By Christian Hoffmann & Bernd Sebastian Kamps

25 April

Today’s Top 10 Papers will be presented at 19:00 CEST
(Central European Summer Time)

24 April

Virology

Sungnak W, Huang N, Bécavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, Published: 23 April 2020. Full-text: https://www.nature.com/articles/s41591-020-0868-6

Elegant paper, confirming the expression of ACE2 in multiple tissues shown in previous studies, with added information on tissues not previously investigated, including nasal epithelium and cornea and its co-expression with TMPRSS2. Potential tropism was analyzed by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. These transcripts were found in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission.

 

Epidemiology

Giordano G, Blanchini F, Bruno R, et al. Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy. Nat Med. 2020 Apr 22. pii: 10.1038/s41591-020-0883-7. PubMed: https://pubmed.gov/32322102. Full-text: https://doi.org/10.1038/s41591-020-0883-7

Interesting new model that predicts the course of the epidemic, considering eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. The model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. Authors demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing pandemic.

 

Peto J, Alwan NA, Godfrey KM, et al. Universal weekly testing as the UK COVID-19 lockdown exit strategy. Lancet. 2020 Apr 20. pii: S0140-6736(20)30936-3. PubMed: https://pubmed.gov/32325027. Full-text: https://doi.org/10.1016/S0140-6736(20)30936-3

They have a dream: These UK researches recommend the evaluation of weekly antigen testing of the whole population after lockdown. As they say, “a voluntary Dunkirk spirit” would be the only way for 10 million tests to be done daily.

 

Transmission

Park SY, Kim YM, Yi S, et al. Coronavirus Disease Outbreak in Call Center, South Korea. Emerg Infect Dis. 2020 Apr 23;26(8). PubMed: https://pubmed.gov/32324530. Full-text: https://doi.org/10.3201/eid2608.201274

Epidemiologic characteristics of a COVID-19 outbreak centered in a call center in South Korea, indicating an attack rate of 8.5% within the whole building. If results were restricted to one floor, the attack rate was as high as 43.5%. Among the 97 confirmed case-patients, 92% were symptomatic at the time of investigation and 4% were presymptomatic. Only 4% remained asymptomatic after 14 days of isolation.

 

Keshtkar-Jahromi M, Sulkowski M, Holakouie-Naieni K. Public Masking: An Urgent Need to Revise Global Policies to Protect against Novel Coronavirus Disease (COVID-19). Am J Trop Med Hyg. 2020 Apr 22. PubMed: https://pubmed.gov/32323645. Full-text: https://doi.org/10.4269/ajtmh.20-0305

Brief review. Authors highly recommend mass masking around the world during the pandemic. Whereas surgical masks are the preferred recommendation for the general public, cloth masks should be considered as a substitute if supplies are limited or surgical masks are not available.

 

Clinical

Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 Apr 20. pii: S0140-6736(20)30937-5. PubMed: https://pubmed.gov/32325026. Full-text: https://doi.org/10.1016/S0140-6736(20)30937-5

The ACE2 receptor is widely expressed on  endothelial  cells. Three cases, indicating direct viral infection  of  the  endothelial  cell  and  diffuse   endothelial   inflammation, induced by SARS-CoV-2   infection.

 

Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute Pulmonary Embolism Associated with COVID-19 Pneumonia Detected by Pulmonary CT Angiography. Radiology. 2020 Apr 23:201544. PubMed: https://pubmed.gov/32324103. Full-text: https://doi.org/10.1148/radiol.2020201544

In 100 patients with severe COVID-19, a high prevalence (23%, 95%CI 15-33%) of acute pulmonary embolism was found. Pulmonary embolus was diagnosed at mean of 12 days from symptom onset. In multivariable analysis, requirement for mechanical ventilation (OR = 3.8, 95%CI 1.02-15) remained associated with acute pulmonary embolus.

 

Comorbidities

Sriram K, Insel PA. Risks of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence. Clin Pharmacol Ther. 2020 Apr 22. PubMed: https://pubmed.gov/32320478. Full-text: https://doi.org/10.1002/cpt.1863

Nice review. Data from 12 animal studies and from 12 human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. Authors conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.

 

Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020 Apr 17. PubMed: https://pubmed.gov/32302265. Full-text: https://doi.org/10.1161/CIRCRESAHA.120.317134

Same direction: In this retrospective, multi-center study of 1128 adult patients with hypertension diagnosed with COVID-19, 188 patients taking ACEI/ARB were compared with 940 patients without using ACEI/ARB. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%). In a Cox model, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group (adjusted HR 0.42; 95%CI, 0.19-0.92).

 

Treatment

Chorin E, Dai M, Shulman E. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nature Medicine. Published: 24 April 2020. Full-Text: https://www.nature.com/articles/s41591-020-0888-2

Check ECG if you do this! In this important study, authors followed the corrected QT (QTc) interval in a consecutive cohort of 84 patients receiving hydroxychloroquine and azithromycin which were administered orally for 5 days. A prolongation of the QTc from a baseline average of 435 ± 24 ms to a maximal average value of 463 ± 32 ms was found, occurring on day 3.6 ± 1.6 of therapy. In a subset of nine (11%) patients, the QTc was severely prolonged to >500 ms, a known marker of high risk of malignant arrhythmia and sudden cardiac death. Five of nine patients with severe QTc prolongation had a normal QTc at baseline.

 

23 April 

Epidemiology

Jiang XL, Zhang XL, Zhao XN, et al. Transmission potential of asymptomatic and paucisymptomatic SARS-CoV-2 infections: a three-family cluster study in China. J Infect Dis. 2020 Apr 22. pii: 5823691. PubMed: https://pubmed.gov/32319519. Full-text: https://doi.org/10.1093/infdis/jiaa206

Detailed cluster analysis, confirming that the transmission by individuals with asymptomatic or paucisymptomatic infections is possible. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his three-month-old daughter. SARS-CoV-2 was detected in the environment of one household.

 

Diagnostics

Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020 Apr 21;369:m1443. PubMed: https://pubmed.gov/32317267. Full-text: https://doi.org/10.1136/bmj.m1443

Among 96 consecutively admitted patients (22 mild, 74 severe COVID-19), RNA viral load was measured in 3,497 respiratory, stool, serum, and urine samples. Infection was confirmed in all patients by testing sputum and saliva samples, in the stool of 59% and in the serum of 41%. The median duration of virus in stool (22 days) was significantly longer than in respiratory (18 days, severe cases: 21 days) and serum samples (16 days). However, main limitation is that RNA PCR cannot distinguish between viable and non-viable virus.

 

Clinical

Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22. pii: 2765184. PubMed: https://pubmed.gov/32320003. Full-text: https://doi.org/10.1001/jama.2020.6775

The numbers are becoming huge now. This case series from New York included 5,700 COVID-19 patients admitted to 12 hospitals between March 1 and April 4, 2020. Median age was 63 years (IQR 52-75), the most common comorbidities were hypertension (57%), obesity (42%), and diabetes (34%). At triage, 31% of patients were febrile, 17% had a respiratory rate greater than 24 breaths/minute, and 28% received supplemental oxygen. Of 2,634 patients with an available outcome, 14%  (median age, 68 years, IQR 56-78, 33% female) were treated in ICU, 12% received invasive mechanical ventilation and 21% died. Mortality for those requiring mechanical ventilation was 88.1%.

 

Pan Y, Yu X, Du X, et al. Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers. J Infect Dis. 2020 Apr 22. pii: 5823633. PubMed: https://pubmed.gov/32318703. Full-text: https://doi.org/10.1093/infdis/jiaa205

Retrospective analysis of 26 persistently asymptomatic patients. The median period from contact to the last positive nucleic acid test was 21.5 days (10-36 days). At least 10 patients had typical ground-glass or patchy opacities on CT.

 

Spinato G, Fabbris C, Polesel J, et al. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 Apr 22. pii: 2765183. PubMed: https://pubmed.gov/32320008. Full-text: https://doi.org/10.1001/jama.2020.6771

Telephone survey, analyzing 202 adult COVID-19 patients with mild symptoms, 5-6 after the positive swab was performed. Any altered sense of smell or taste was reported by 130 patients (64%, 95% CI, 57%-71%, more frequent in women, 73%). This was seen in 12% before, in 23% at same time and in 27% after other symptoms. An altered sense of smell or taste was reported as the only symptom by 6 patients (3.0%).

 

Finsterer J, Stollberger C. Causes of hypogeusia/hyposmia in SARS-CoV2 infected patients. J Med Virol. 2020 Apr 20. PubMed: https://pubmed.gov/32311107. Full-text: https://doi.org/10.1002/jmv.25903

Some thoughts on the pathogenesis of hyposmia. According to the authors, the most likely cause for transient hypogeusia and hyposmia in SARS-CoV2-infected patients is a direct contact and interaction of the virus with gustatory receptors or olfactory receptor cells.

 

Comorbidities

Sattar N, McInnes IB, McMurray JJV. Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation. 2020 Apr 22. PubMed: https://pubmed.gov/32320270. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047659

Brief review on obesity as a unifying risk factor for severe COVID-19 infection, reducing both protective cardiorespiratory reserve as well as potentiating the immune dysregulation. Possible pathomechanisms are discussed.

 

Treatment

Prokunina-Olsson L, Alphonse N, Dickenson RE, et al. COVID-19 and emerging viral infections: The case for interferon lambda. J Exp Med. 2020 May 4;217(5). pii: 151664. PubMed: https://pubmed.gov/32289152. Full-text: https://doi.org/10.1084/jem.20200653

In this Viewpoint, authors present their opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat SARS-CoV-2 infections.

 

Severe COVID-19

Caputo ND, Strayer RJ, Levitan R. Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED´s Experience during the COVID-19 Pandemic. Acad Emerg Med. 2020 Apr 22. PubMed: https://pubmed.gov/32320506. Full-text: https://doi.org/10.1111/acem.13994

Proning helps, even in awake, non-tubated patients. Among 50 patients, the median SpO2 at triage was 80%. After application of supplemental oxygen was given to patients on room air it was 84%. After 5 minutes of proning was added, SpO2 improved to 94%.

 

Pediatric

Lu X, Zhang L, Du H, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr 23;382(17):1663-1665. PubMed: https://pubmed.gov/32187458. Full-text: https://doi.org/10.1056/NEJMc2005073

Of 171 children with confirmed SARS-CoV-2 infection in Wuhan, most appeared to have a milder clinical course. Asymptomatic infections were not uncommon (16%). During the course of hospitalization, 3 patients (all with coexisting conditions) required intensive care support and invasive mechanical ventilation.

 

22 April

Vaccine

Callaway E. Hundreds of people volunteer to be infected with coronavirus. Nature 22 April 2020. Full-text: https://www.nature.com/articles/d41586-020-01179-x

What about a ‘human challenge’ vaccine study? Such a trial would be much faster: a much smaller group of young, healthy volunteers would receive a candidate vaccine and then be intentionally infected with the virus, to judge the efficacy of the immunization. No trial is yet planned, but the debate is on. The approach is also gaining some political support.

 

Epidemiology

Cowling BJ, Ali ST, Ng TWY, et al. Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study. Lancet Public Health. 2020 Apr 17. pii: S2468-2667(20)30090-6. PubMed: https://pubmed.gov/32311320. Full-text: https://doi.org/10.1016/S2468-2667(20)30090-6

Detailed paper from Hong Kong modelling the effects of non-pharmaceutical interventions (NPIs, including border restrictions, quarantine and isolation, distancing, and changes in population behaviour). NPIs were associated with reduced transmission of COVID-19 and were also likely to have substantially reduced influenza transmission. Findings strongly suggest that social distancing and population behavioural changes – that have a social and economic impact that is less disruptive than a total  lockdown – can  meaningfully  control COVID-19.

 

Wu X, Fu B, Chen L, Feng Y. Serological tests facilitate identification of asymptomatic SARS-CoV-2 infection in Wuhan, China. J Med Virol. 2020 Apr 20. PubMed: https://pubmed.gov/32311142. Full-text: https://doi.org/10.1002/jmv.25904

Forget herd immunity! Overall prevalence is still incredibly low. Even in hotspots like Wuhan! From April 3 to 15, SARS-CoV-2-specific IgG positive rate among 1,021 people applying for a permission of resume, only 98 (9.60%) were IgG positive and IgM and NAT (SARS‐CoV‐2 nucleic acid test) negative.

 

Diagnostics

Wilson NM, Norton A, Young FP, Collins DW. Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review. Anaesthesia. 2020 Apr 20. PubMed: https://pubmed.gov/32311771. Full-text: https://doi.org/10.1111/anae.15093

Evidence suggestive of airborne spread is growing. Authors discuss several ‘aerosol-generating procedures’ and current evidence (limited). A precautionary approach should be considered to assure healthcare worker safety.

 

Marty M, Chen K, Verrill KA. How to Obtain a Nasopharyngeal Swab Specimen. NEJM 2020. April 17, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMvcm2010260?query=featured_home

It’s not that trivial to obtain a NP-Swab. Watch this video on protection, preparation, equipment, handling, removing personal protective equipment etc.

 

Xiang F, Wang X, He X, et al. Antibody Detection and Dynamic Characteristics in Patients with COVID-19. Clin Infect Dis. 2020 Apr 19. pii: 5822173. PubMed: https://pubmed.gov/32306047. Full-text: https://doi.org/10.1093/cid/ciaa461

More on antibodies, as a complement approach for PCR. The seroconversion of specific IgM and IgG antibodies were observed as early as the 4th day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, positive predictive value of IgM were 77.3% (51/66), 100% and 100%, and those of IgG were 83.3% (55/66), 95.0% and 94.8%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness.

 

Clinical

Effenberger M, Grabherr F, Mayr L, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020 Apr 20. pii: gutjnl-2020-321388. PubMed: https://pubmed.gov/32312790. Full-text: https://doi.org/10.1136/gutjnl-2020-321388

Faecal calprotectin (FC) has evolved as a reliable faecal biomarker allowing detection of intestinal inflammation in inflammatory bowel diseases and infectious colitis. This report on 40 patients provides some evidence that SARS-CoV-2 infection instigates an inflammatory response in the gut, as elevated FC (largely expressed by neutrophil granulocytes) and diarrhea.

 

Severe COVID-19

Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 Jun 1;217(6). pii: 151683. PubMed: https://pubmed.gov/32302401. Full-text: https://doi.org/10.1084/jem.20200652

Case report of a patient who succumbed to COVID-19. Hypothesis that a powerful function of neutrophils – the ability to form neutrophil extracellular traps (NETs) – may contribute to organ damage and mortality in COVID-19.  Targeting NETs directly and/or indirectly with existing drugs may reduce clinical severity.

 

Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020 Apr 21. PubMed: https://pubmed.gov/32316063. Full-text: https://doi.org/10.1055/s-0040-1710018

Case series of 22 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.

 

Treatment

Bhimray A, Morgan RL, Shumaker. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Published by IDSA, 4/11/2020. Full-text: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

Evidence-based guidelines which are, in the absence of large RCTs, not very helpful. Recommendations for all drugs acknowledge the current “knowledge gap”. HCQ, lopinavir/r, tocilizumab and convalescent plasma should be given “only in the context of a clinical trial”. Well.

 

 

21 April

No new papers today, but the  third edition of COVID Reference (222 pages, free PDF).

20 April

Epidemiology

Normile D. ‘Suppress and lift’: Hong Kong and Singapore say they have a coronavirus strategy that works. Science Mag Apr 13, 2020. Full-text https://www.sciencemag.org/news/2020/04/suppress-and-lift-hong-kong-and-singapore-say-they-have-coronavirus-strategy-works#

Bottom line: The tighter you control the infected, the less restriction you have to impose on the uninfected. With this strategy, Hong Kong and Singapure are very successful. But look at the controls: Hospitalizing all those who test positive, regardless of whether they have symptoms, two weeks of self-quarantine to all close contacts, electronic wristbands etc. You want to see were infected people in Hong Kong are? You’ll find them here: https://chp-dashboard.geodata.gov.hk/covid-19/en.html

 

Cheng KK, Lam TH, Leung CC. Wearing face masks in the community during the COVID-19 pandemic: altruism and solidarity. Lancet. 2020 Apr 16. pii: S0140-6736(20)30918-1. PubMed: https://pubmed.gov/32305074. Full-text: https://doi.org/10.1016/S0140-6736(20)30918-1

Authors review current recommendations and conclude that mass masking  for  source  control  is  a  useful  and   low-cost   adjunct   to   social   distancing   and   hand   hygiene, shifting the  focus  from  self-protection  to  altruism, actively involves every citizen, and is a symbol of social solidarity in the global response to the pandemic.

 

Virology/Pathogenesis

Rockx B, Kuiken T, Herfst S, et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science  17 Apr 2020: eabb7314. Full text: https://science.sciencemag.org/content/early/2020/04/16/science.abb7314

This animal study was performed to understand pathogenesis, showing SARS-CoV-2-infected macaques provide a new model to test therapeutic strategies. Virus was excreted from nose and throat in the absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes.

 

Diagnostics

Atkinson B, Petersen E. SARS-CoV-2 shedding and infectivity. Lancet. 2020 Apr 15. pii: S0140-6736(20)30868-0. PubMed: https://pubmed.gov/32304647. Full-text: https://doi.org/10.1016/S0140-6736(20)30868-0

Brief but important comment on several papers reporting on prolonged viral shedding. PCR  does  not distinguish between infectious virus and non-infectious nucleic acid. This is well-known from many viral infections such as Ebola or Measles.

 

Clinical

Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barre Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302082. Full-text: https://doi.org/10.1056/NEJMc2009191

Observational series from Italy, involving five patients with COVID-19–associated Guillain–Barré syndrome which probably should be distinguished from critical illness neuropathy and myopathy, which tend to appear later in the course of critical COVID-19 illness.

 

Gutierrez-Ortiz C, Mendez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020 Apr 17. pii: WNL.0000000000009619. PubMed: https://pubmed.gov/32303650. Full-text: https://doi.org/10.1212/WNL.0000000000009619

The next paper on neurological complications seen with COVID-19, which are probably due to an aberrant immune response.

 

Chen R, Liang W, Jiang M, et al. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest. 2020 Apr 15. pii: S0012-3692(20)30710-8. PubMed: https://pubmed.gov/32304772. Full-text: https://doi.org/10.1016/j.chest.2020.04.010

It’s not only age. Multivariate analysis of a retrospective cohort of 1590 hospitalized subjects with COVID-19 throughout China revealed the following factors associated with mortality: Age 75 or older (HR: 7.86, 95% CI: 2.44-25.35), Age 65-74 years (HR: 3.43, 95% CI: 1.24-9.5), coronary heart disease (HR: 4.28, 95% CI: 1.14-16.13), cerebrovascular disease(HR: 3.1, 95% CI: 1.07-8.94), dyspnea (HR: 3.96, 95% CI:1.42-11), procalcitonin>0.5ng/ml (HR: 8.72, 95% CI:3.42-22.28), AST>40 U/L (HR: 2.2, 95% CI: 1.1- 6.73). Not very new, but by now the largest cohort with detailed informations.

 

Comorbidities

Brojakowska A, Narula J, Shimony R, Bander J. Clinical Implications of SARS-Cov2 Interaction with Renin Angiotensin System. J Am Coll Cardiol. 2020 Apr 14. pii: S0735-1097(20)35001-4. PubMed: https://pubmed.gov/32305401. Full-text: https://doi.org/10.1016/j.jacc.2020.04.028

Don’t stop your sartans or ACE inhibitors! Authors hypothesize that the benefits of treatment with renin-angiotensin system inhibitors in SARS-COV2 may outweigh the risks and at the very least should not be withheld.

 

Kennedy NA, Jones GR, Lamb CA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020 Apr 17. pii: gutjnl-2020-321244. PubMed: https://pubmed.gov/32303607. Full-text: https://doi.org/10.1136/gutjnl-2020-321244

Making recommendation in the absence of data is not that easy. Authors have made heroic attempts to balance the risk of immune modifying drugs with the risk associated with active disease.

 

Severe COVID-19

Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science  17 Apr 2020: eabb8925. Full-text: https://science.sciencemag.org/content/early /2020/04/16/science.abb8925

Brief but phantastic overview about current knowledge and the pathways leading to cytokine release syndrome.

 

19 April

Epidemiology

Nickbakhsh S, Ho A, Marques DFP, McMenamin J, Gunson RN, Murcia PR. Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence. J Infect Dis. 2020 Apr 15. pii: 5820656. PubMed: https://pubmed.gov/32296837. Full-text: https://doi.org/10.1093/infdis/jiaa185

Interesting and incredible diligent work on seasonal coronaviruses (sCoVs) and other cocirculating viruses over a thirteen years period in Western Scotland, UK. Different sCoVs were detected in 4.0% (2,958/74,519) of tested patients overall, contributing to 10.7% of all respiratory virus detections. All were winter pathogens, on average peaking between January and March, alongside influenza viruses and RSV. However, there were notable variations between sCoV types and between years. A potential for cross-protective immunity was also seen between some subtypes.

 

Diagnosis

Abdalhamid B, Bilder CR, McCutchen EL, Hinrichs SH, Koepsell SA, Iwen PC. Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources. Am J Clin Pathol. 2020 Apr 18. pii: 5822023. PubMed: https://pubmed.gov/32304208. Full-text: https://doi.org/10.1093/ajcp/aqaa064

Experimental pools were created, mixing positive and negative nasopharyngeal specimen. Results: If incidence rate of SARS-CoV-2 infection is 10% or less, group testing will result in the saving of reagents and personnel time with an overall increase in testing capability of at least 69%.

 

Abbasi J. The Promise and Peril of Antibody Testing for COVID-19. JAMA. 2020 Apr 17. pii: 2764954. PubMed: https://pubmed.gov/32301958. Full-text: https://doi.org/10.1001/jama.2020.6170

Comprehensive review on recent (last two weeks) developments in antibody testing, a very rapidly evolving field of research. Brief overview on promises and perils of different testing systems, including ELISA and lateral flow assays.

 

Ashcroft J. Keep older healthcare workers off the covid-19 front line. BMJ. 2020 Apr 17;369:m1511. PubMed: https://pubmed.gov/32303493. Full-text: https://doi.org/10.1136/bmj.m1511

Older age is a risk factor for severe disease. This also applies to HCW. In China 11/23 deceased HCWs had been reactivated from retirement. In Italy, most of the 74 doctors who have died were in their 60s, and only four were women. This brief letter to BMJ addresses this issue. Author declared the following competing interests: “I am an older, male GP”.

 

Clinical

Chow EJ, Schwartz NG, Tobolowsky FA, et al. Symptom Screening at Illness Onset of Health Care Personnel With SARS-CoV-2 Infection in King County, Washington. JAMA. 2020 Apr 17. pii: 2764953. PubMed: https://pubmed.gov/32301962. Full-text: https://doi.org/10.1001/jama.2020.6637

Detailed analysis of symptoms of all laboratory-confirmed SARS-CoV-2 infections in HCP residing in King County. Ccreening only for fever, cough, short-ness of breath, or sore throat might have missed 17% of symptomatic HCP at the time of illness onset; expanding criteria for symptoms screening to include myalgias and chills may still have missed 10%.

 

Chong VCL, Lim EKG, Fan EB, Chan SSW, Ong KH, Kuperan P. Reactive lymphocytes in patients with Covid-19. Br J Haematol. 2020 Apr 16. PubMed: https://pubmed.gov/32297330. Full-text: https://doi.org/10.1111/bjh.16690

Examination of the peripheral blood films of 32 patients found reactive lymphocytes in 72%. This seems to be in stark contrast to the SARS outbreak where reactive lymphocytes of this type only rarely seen.

 

Treatment

Hillaker E, Belfer JJ, Bondici A, Murad H, Dumkow LE. Delayed Initiation of Remdesivir in a COVID-19 Positive Patient. Pharmacotherapy. 2020 Apr 13. PubMed: https://pubmed.gov/32281114. Full-text: https://doi.org/10.1002/phar.2403

Were we wrong with our critical review on remdesivir? Again, we hope so. A case of successful late initiation of remdesivir is presented. Sixty hours after starting the drug, the patient was extubated and was able to transition to room air within 24 hours of extubation.

 

Zhu Z, Lu Z, Xu T, et al. Arbidol Monotherapy is Superior to Lopinavir/ritonavir in Treating COVID-19. J Infect. 2020 Apr 10. pii: S0163-4453(20)30188-2. PubMed: https://pubmed.gov/32283143. Full-text: https://doi.org/10.1016/j.jinf.2020.03.060

Retrospective case series, comparing lopinavir/r (34 cases) and arbidol (16 cases). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15 (44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01).

 

Pregnancy

Chen L, Li Q, Zheng D, et al. Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302077. Full-text: https://doi.org/10.1056/NEJMc2009226

Experience from Wuhan. A total of 109 of 118 women (92%) had mild disease, and 9 (8%) had severe disease (hypoxemia), 1 of whom received noninvasive mechanical ventilation (critical disease). There were 3 spontaneous abortions, 2 ectopic pregnancies, and 4 induced abortions (all owing to patients’ concerns about Covid-19).

 

Alzamora MC, Paredes T, Caceres D, Webb CM, Valdez LM, La Rosa M. Severe COVID-19 during Pregnancy and Possible Vertical Transmission. Am J Perinatol. 2020 Apr 18. PubMed: https://pubmed.gov/32305046. Full-text: https://doi.org/10.1055/s-0040-1710050

Case report from Lima (Peru), describing a severe presentation of COVID-19 in pregnancy requiring invasive ventilatory support, suggesting possible vertical transmission.

 

18 April

Epidemiology

CDC Covid Response Team. Characteristics of Health Care Personnel with COVID-19 – United States, February 12-April 9, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):477-481. PubMed: https://pubmed.gov/32298247. Full-text: https://doi.org/10.15585/mmwr.mm6915e6

During February 12-April 9, among 315,531 COVID-19 cases reported to CDC, 49,370 (16%) included data on whether the patient was a health care worker (HCW). Of 8,945 HCW, detailed data were available. Most HCW (90%) were not hospitalized; however, severe outcomes, including 27 deaths, occurred across all age groups. ICU admission and death were observed in 2.1–4.9% and 0.3-0.6%, respectively. These rates were markedly higher in HCW older then 65 years, with 6.9-16.0 % and 2.0-4.2%.

 

Anfinrud P, Stadnytskyi V, Bax CE, Bax A. Visualizing speech-generated oral fluid droplets with laser light scattering. N Engl J Med. https://doi.org/10.1056/NEJMc2007800.

You remember Depeche Mode’s hit ‘Enjoy the Silence’? Then look at this video, a person saying “stay healthy”, a laser light-scattering experiment in which speech-generated droplets and their trajectories were visualized. The louder the speech, the higher the numbers of flashes. The number of flashes was highest when the “th” sound in the word “healthy” was pronounced. Depeche Mode were right: “Words are very unnecessary/They can only do harm”.

 

Meselson M. Droplets and Aerosols in the Transmission of SARS-CoV-2. N Engl J Med. 2020 Apr 15. PubMed: https://pubmed.gov/32294374. Full-text: https://doi.org/10.1056/NEJMc2009324

These authors emphasize that breathing and talking produce even smaller and much more numerous particles, known as aerosol particles, than those visualized in the (above mentioned) laser experiment. They recommend wearing a suitable mask whenever it is thought that infected persons may be nearby and of providing adequate ventilation of enclosed spaces where such persons are known to be or may recently have been.

 

Diagnostics

Iwen PC, Stiles KL, Pentella MA. Safety Considerations in the Laboratory Testing of Specimens Suspected or Known to Contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Am J Clin Pathol. 2020 Apr 15;153(5):567-570. PubMed: https://pubmed.gov/32190890. Full-text: https://doi.org/10.1093/ajcp/aqaa047

Brief review on laboratory biosafety practices necessary to safely process clinical specimens.

 

Huang Y, Chen S, Yang Z, et al. SARS-CoV-2 Viral Load in Clinical Samples of Critically Ill Patients. Am J Respir Crit Care Med. 2020 Apr 15. PubMed: https://pubmed.gov/32293905. Full-text: https://doi.org/10.1164/rccm.202003-0572LE

Small study on 16 critically ill patients, demonstrating higher viral load and prolonged shedding in lower respiratory tract specimens, as compared with upper respiratory tract specimens.

 

Kim H, Hong H, Yoon SH. Diagnostic Performance of CT and Reverse Transcriptase-Polymerase Chain Reaction for Coronavirus Disease 2019: A Meta-Analysis. Radiology. 2020 Apr 17:201343. PubMed: https://pubmed.gov/32301646. Full-text: https://doi.org/10.1148/radiol.2020201343

There is big debate whether chest CT contributes to COVID-19 diagnosis. Chinese researchers say yes, all others say no. This metaanalysis found a high sensitivity but low specificity. In areas with low prevalence, chest CT has a low positive predictive value (1.5-30.7%).

 

Clinical

Goyal P, Choi JJ, Pinheiro LC, et al. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302078. Full-text: https://doi.org/10.1056/NEJMc2010419

Clinical characteristics of the first 393 consecutive patients who were admitted to two hospitals in New York City, among them 130 needing invasive mechanical ventilation. The latter were more likely to be male, to have obesity, and to have elevated liver-function values and inflammatory markers (ferritin, d-dimer, C-reactive protein, and procalcitonin). Diarrhea (23.7%), and nausea and vomiting (19.1%) were more frequent as in the reports from China (it remains unclear whether this difference reflects geographic variation or differential reporting).

 

Bangalore S, Sharma A, Slotwiner A, et al. ST-Segment Elevation in Patients with Covid-19 – A Case Series. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302081. Full-text: https://doi.org/10.1056/NEJMc2009020

In this case series of 18 patients who had ST-segment elevation, there was variability in presentation, a high prevalence of nonobstructive disease, and a poor prognosis. 6/9 patients undergoing coronary angiography had obstructive disease. Of note, all 18 patients had elevated d-dimer levels.

 

Gong J, Ou J, Qiu X, et al. A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020 Apr 16. pii: 5820684. PubMed: https://pubmed.gov/32296824. Full-text: https://doi.org/10.1093/cid/ciaa443

A risk prediction nomogram for severe COVID-19 was evaluated, including older age, and higher serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width, blood urea nitrogen, direct bilirubin and lower albumin. Interesting, but must be validated in larger trials.

 

Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Apr 15. PubMed: https://pubmed.gov/32294339. Full-text: https://doi.org/10.1056/NEJMc2008597

In this observational series of 58 patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. It remained unclear, which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.

 

 

17 April

Epidemiology

Szarpak L, Smereka J, Filipiak KJ, Ladny JR, Jaguszewski M. Cloth masks versus medical masks for COVID-19 protection. Cardiol J. 2020 Apr 14. pii: VM/OJS/J/68300. PubMed: https://pubmed.gov/32285928. Full-text: https://doi.org/10.5603/CJ.a2020.0054

Some critical thoughts on the use of cloth masks. The physical properties of a cloth mask, reuse, the frequency and effectiveness of cleaning, and increased moisture retention, may potentially increase the infection risk.

 

Diagnostics

He X, Lau EHY, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med. 2020 Apr 15. pii: 10.1038/s41591-020-0869-5. PubMed: https://pubmed.gov/32296168. Full-text: https://doi.org/10.1038/s41591-020-0869-5

Important work on viral shedding: this may begin 2 to 3 days before the appearance of the first symptoms and infectiousness profile may more closely resemble that of influenza than of SARS.  Analyzing a total of 414 throat swabs in 94 patients, highest viral load in throat swabs was found at the time of symptom onset. Infectiousness started from 2.3 days (95% CI, 0.8–3.0 days) before symptom onset and peaked at 0.7 days (95% CI, −0.2–2.0 days) before symptom onset. Authors estimated that 44% (95%CI 25-69%) of secondary cases were infected during the index cases´ presymptomatic stage. Infectiousness was estimated to decline quickly within 7 days.

 

Raptis CA, Hammer MM, Short RG, et al. Chest CT and Coronavirus Disease (COVID-19): A Critical Review of the Literature to Date. AJR Am J Roentgenol. 2020 Apr 16:1-4. PubMed: https://pubmed.gov/32298149. Full-text: https://doi.org/10.2214/AJR.20.23202

Critical review, concluding that current evidence do not substantiate the use of CT as a diagnostic test for COVID-19. At present, CT should be reserved for evaluation of complications of COVID-19 pneumonia or for assessment if alternative diagnoses are suspected.

 

Song C, Wang Y, Li W, et al. Absence of 2019 Novel Coronavirus in Semen and Testes of COVID-19 Patients. Biol Reprod. 2020 Apr 16. pii: 5820830. PubMed: https://pubmed.gov/32297920. Full-text: https://doi.org/10.1093/biolre/ioaa050

The virus was not found in semen of 12 patients recovering from COVID-19 and in a testis sample of one deceased patient.

 

Scorzolini L, Corpolongo A, Castilletti C, Lalle E, Mariano A, Nicastri E. Comment of the potential risks of sexual and vertical transmission of Covid-19 infection. Clin Infect Dis. 2020 Apr 16. pii: 5820874. PubMed: https://pubmed.gov/32297915. Full-text: https://doi.org/10.1093/cid/ciaa445

In six women, SARS-CoV-2 was not detected in amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples.

 

Clinical

Zhan M, Qin Y, Xue X, Zhu S. Death from Covid-19 of 23 Health Care Workers in China. N Engl J Med. 2020 Apr 15. PubMed: https://pubmed.gov/32294342. Full-text: https://doi.org/10.1056/NEJMc2005696

In China, among 3387 healthcare workers infected with SARS-CoV-2, 23 persons had died. Median age was 55 years (range, 29 to 72). Eleven of these persons had been rehired after retirement and 8 were surgeons. Only 2 of the 23 health care workers were physicians in respiratory medicine who had been specifically assigned to treat patients with Covid-19.

 

Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020 Apr 16. PubMed: https://pubmed.gov/32297796. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047349

SARS-CoV-2 has the potential to infect cardiomyocytes, pericytes and fibroblasts via the ACE2 pathway leading to direct myocardial injury, but that pathophysiological sequence remains unproven. A second hypothesis to explain COVID-19 related myocardial injury centers on cytokine excess and/or antibody mediated mechanisms. Clinically, COVID-19 can manifest with an acute cardiovascular syndrome (termed “ACovCS”). This review shows surveillance, diagnostic and management strategies for ACovCS that balances potential patient risks and healthcare staff exposure.

 

Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020 Apr 15. pii: 10.1007/s00277-020-04019-0. PubMed: https://pubmed.gov/32296910. Full-text: https://doi.org/10.1007/s00277-020-04019-0

Review focussing on thrombocytopenia which is commonly seen in COVID-19. Three mechanisms are discussed: direct infection of bone marrow cells by the virus and inhibition of platelet synthesis, platelet destruction by the immune system and platelet aggregation in the lungs, resulting in microthrombi and platelet consumption.

 

Treatment

Smereka J, Puslecki M, Ruetzler K, et al. Extracorporeal membrane oxygenation in COVID-19. Cardiol J. 2020 Apr 14. pii: VM/OJS/J/68313. PubMed: https://pubmed.gov/32285929. Full-text: https://doi.org/10.5603/CJ.a2020.0053

A brief review on ECMO which remains a therapeutic option in some well selected patients with severe COVID-19.

 

Di Giambenedetto S, Ciccullo A, Borghetti A, et al. Off-label Use of Tocilizumab in Patients with SARS-CoV-2 Infection. J Med Virol. 2020 Apr 16. PubMed: https://pubmed.gov/32297987. Full-text: https://doi.org/10.1002/jmv.25897

The humanized anti-IL-6 receptor antibody tocilizumab was given to three patients with severe COVID-19. All showed rapid relief of respiratory symptoms, resolution of fever and reduction in CRP following tocilizumab administration.

 

16 April

Comment on
Compassionate Use of Remdesivir for Patients with Severe Covid-19
N Engl J Med. 2020 Apr 10.

Today, we will not discuss the Top Ten Papers. Instead, we will talk about remdesivir and give you 10 good reasons to be careful. Last Friday, on April 10, the New England Journal of Medicine published data on patients who were treated with 10 days of remdesivir on a compassionate use basis (Grein 2020).

More >>>

15 April

Epidemiology

Gudbjartsson DF, Helgason A, Jonsson H, et al. Spread of SARS-CoV-2 in the Icelandic Population. N Engl J Med. 2020 Apr 14. PubMed: https://pubmed.gov/32289214. Full-text: https://doi.org/10.1056/NEJMoa2006100

SARS-CoV-2 in Iceland. As of April 4, a total of 1,221 of 9,199 tested persons (13.3%) were positive. Why is this of interest? Because the country serves as a perfect epidemiological model. Key findings: The percentage of participants who tested positive in population screening remained stable (0.8%) in March, and the infection rates in two screening groups (recruited through open invitation and through random sampling) were not substantially different. Notably, 43% of the participants who tested positive reported having no symptoms.

 

Stone TE, Kunaviktikul W, Omura M, Petrini M. Editorial: Facemasks and the Covid 19 pandemic: What advice should health professionals be giving the general public about the wearing of facemasks? Nurs Health Sci. 2020 Apr 12. PubMed: https://pubmed.gov/32279450. Full-text: https://doi.org/10.1111/nhs.12724

Bottom line of this editorial (addressed to nurses): surgical facemasks by the general public is not recommended unless you are looking after a sick person in a household setting or are suffering an illness. Far more effective is handwashing and maintaining a safe distance from other people.

 

Perc M, Miksić NG, Slavinec M et al. Forecasting COVID-19. Front. Phys., 08 April 2020 | https://doi.org/10.3389/fphy.2020.00127

Forecasts obtained with a simple iteration method that needs only the daily values of confirmed cases as input. The method takes into account expected recoveries and deaths, and it determines maximally allowed daily growth rates that lead away from exponential increase toward stable and declining numbers. Keeping the daily growth rates at least below 5% is an important target for a promising outlook.

 

Diagnostic

Cheng MP, Papenburg J, Desjardins M, et al. Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus-2: A Narrative Review. Ann Intern Med. 2020 Apr 13. pii: 2764737. PubMed: https://pubmed.gov/32282894. Full-text: https://doi.org/10.7326/M20-1301

Comprehensive review of the current array of tests for SARS-CoV-2, highlighting gaps in current diagnostic capacity, and proposing potential solutions.

 

Wang X, Yao H, Xu X, et al. Limits of Detection of Six Approved RT-PCR Kits for the Novel SARS-coronavirus-2 (SARS-CoV-2). Clin Chem. 2020 Apr 13. pii: 5819547. PubMed: https://pubmed.gov/32282874. Full-text: https://doi.org/10.1093/clinchem/hvaa099

Limits of detection of six commercial kits differed substantially (up to 16-fold difference), with the poorest limits likely leading to false-negative results when RT–PCR were used to detect SARS-CoV-2 infection. According to the authors, manufacturers  should  analyze  the  existing  problems  according  to  the  clinical  application  and  further  improve  their  products. 

 

Stam HJ, Stucki G, Bickenbach J. Covid-19 and Post Intensive Care Syndrome: A Call for Action. J Rehabil Med. 2020 Apr 14. PubMed: https://pubmed.gov/32286675. Full-text: https://doi.org/10.2340/16501977-2677

One aftershock of the pandemic will be huge number of post-intensive care survivors who have been mechanically ventilated and will likely experience short- and medium-term consequences. These patients will require not only adequate screening but early rehabilitation and other interventions.

 

Comorbidities

Daniels MJ, Cohen MG, Bavry AA, Kumbhani DJ. Reperfusion of STEMI in the COVID-19 Era – Business as Usual? Circulation. 2020 Apr 13. PubMed: https://pubmed.gov/32282225. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047122

In the current crisis with limited resources to protect the work force, fibrinolytic therapy (FT) may be considered for patients with myocardial infarction (STEMI). FT may even be preferred over primary percutaneous coronary intervention. Arguments for this strategy are summarized.

 

Zhong Z, Zhang Q, Xia H, et al. Clinical characteristics and immunosuppressants management of coronavirus disease 2019 in solid organ transplant recipients. Am J Transplant. 2020 Apr 13. PubMed: https://pubmed.gov/32282986. Full-text: https://doi.org/10.1111/ajt.15928

COVID-19 was observed in two transplant recipients (liver and kidney), with different treatments and prognoses. Both patients recovered.

 

Treatment

Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 Apr 13. pii: 2764727. PubMed: https://pubmed.gov/32282022. Full-text: https://doi.org/10.1001/jama.2020.6019

Phantastic review on current knowledge on potential therapies (as of April 5).

 

Rome BN, Avorn J. Drug Evaluation during the Covid-19 Pandemic. N Engl J Med. 2020 Apr 14. PubMed: https://pubmed.gov/32289216. Full-text: https://doi.org/10.1056/NEJMp2009457

Thoughts on how clinical trials should be performed during the current pandemic. And how the processes for evaluating and approving drugs can go awry during a public health crisis.

14 April

Virology

Monteil V, Kwon H, Patricia Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020. DOI: 10.1016/j.cell.2020.04.004. https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00739.pdf

This study shows that human recombinant soluble ACE2 (hrsACE2) blocks SARS-CoV-2 infections of different cells, human blood vessel organoids and human kidney organoids. In ARDS patients, hrsACE2 was ineffective but safe at a broad range of doses. Apeiron Biologics plans a randomized study on 200 COVID-19 patients in April.

 

Epidemiology

van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. PubMed: https://pubmed.gov/32182409 . Full-text: https://doi.org/10.1056/NEJMc2004973

This important work had been published a few weeks ago. Today, no less than 6 correspondence letters mainly discuss airborne transmission and viability of SARS-CoV-2 in aerosols. Bottom line: Viability was investigated under experimental conditions and should not be used to draw conclusions about airborne transmission. However, according to the authors, aerosol-generating medical procedures should be examined as well as decontamination techniques.

 

Sutton D, Fuchs K, D´Alton M, Goffman D. Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. N Engl J Med. 2020 Apr 13. PubMed: https://pubmed.gov/32283004. Full-text: https://doi.org/10.1056/NEJMc2009316

Between March 22 and April 4, 2020, all pregnant women who delivered infants were tested in a hospital located on the northern tip of Manhattan, New York City. Nasopharyngeal swabs obtained from 210 asymptomatic women were positive in 29 (13.7%). All four women with symptoms of Covid-19 on admission were positive. In other words: 29/33 women were asymptomatic.

 

Kong WH, Li Y, Peng MW, et al. SARS-CoV-2 detection in patients with influenza-like illness. Nat Microbiol. 2020 Apr 7. pii: 10.1038/s41564-020-0713-1. PubMed: https://pubmed.gov/32265517 . Full-text: https://doi.org/10.1038/s41564-020-0713-1

Re-analysing 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020, authors found 9 to be positive for SARS-CoV-2. The onset date of the earliest case was 4 January 2020, one week after the outbreak was reported by hospitals.

 

Clinical

Zini G, Bellesi S, Ramundo F, d´Onofrio G. Morphological anomalies of circulating blood cells in COVID-19. Am J Hematol. 2020 Apr 12. PubMed: https://pubmed.gov/32279346 . Full-text: https://doi.org/10.1002/ajh.25824

Morphologic changes in the peripheral blood over time in a few COVID-19 patients from Italy. In the early phase of symptom aggravation, a pronounced granulocytic reaction with immaturity, dysmorphism and apoptotic-degenerative morphological evidence was seen. Later the hematologic pictures tended to shift toward impressive reactive lymphocyte activation, often with numerical increase, and heterogeneous morphological expression. 

 

Comorbidities

Wang H, Li T, Barbarino P, et al. Dementia care during COVID-19. Lancet. 2020 Apr 11; 395(10231):1190-1191. PubMed: https://pubmed.gov/32240625 . Full-text: https://doi.org/10.1016/S0140-6736(20)30755-8

A few thoughts on dementia care in this crisis.

 

Treatment

De Meyer S, Bojkova D, Cinati J, et al. Lack of Antiviral Activity of Darunavir against SARS-CoV-2. doi: https://doi.org/10.1101/2020.04.03.20052548

Usually we hesitate to refer to www.medrxiv.org. Preprints published at this website are preliminary reports of work that have not been certified by peer review. Well, it’s time to make an exception. Because this is important: Darunavir, an HIV protease inhibitor, is not active against SARS-CoV-2. There was no vitro antiviral activity against a clinical isolate at clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control, showed potent activity (EC50 = 0.38 μM). However, the clinical trial on 3.040 participants treated with darunavir in Spain is still ongoing (clintrials.gov assessed on April 13).

 

Bartiromo M, Borchi B, Botta A, et al. Threatening drug-drug interaction in a kidney transplant patient with Coronavirus Disease 2019 (COVID-19). Transpl Infect Dis. 2020 Apr 12. PubMed: https://pubmed.gov/32279418 . Full-text: https://doi.org/10.1111/tid.13286

If you give HIV PIs, please be always aware of drug-drug interactions. Ritonavir is a strong pharmacoenhancer. For example, tacrolimus has to be reduced by 10-100 fold to maintain concentration within the therapeutical range. In this case report, a women with kidney transplantation  was treated with lopinavir/r (the “r” indicates ritonavir) for COVID-19 while receiving the full dose tacrolimus. Levels went incredibly high and were still above the therapeutical range, 9 days after stopping both lopinavir/r and tacrolimus. Fortunately, everything turned out alright.

 

Feldmann M, Maini RN, Woody JN, et al. Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed. Lancet. 2020 Apr 9. pii: S0140-6736(20)30858-8. PubMed: https://pubmed.gov/32278362 . Full-text: https://doi.org/10.1016/S0140-6736(20)30858-8

Treating the inflammatory excess in patients with COVID-19: Why anti-tumour necrosis factor (TNF) antibodies could be a good idea.

 

McEnery T, Gough C, Costello RW. COVID-19: Respiratory support outside the intensive care unit. Lancet Respir Med. 2020 Apr 9. pii: S2213-2600(20)30176-4. PubMed: https://pubmed.gov/32278367 . Full-text: https://doi.org/10.1016/S2213-2600(20)30176-4

The debate about the optimal mode of respiratory support (outside ICU) continues. Advocate high flow nasal cannulae (HFNC) over non-invasive ventilation (NIV) or vice versa? In the absence of randomised control trials in the use of either HFNC or NIV in COVID-19, this comment discusses current knowledge.

 

13 April

Virology

Gao Y, Yan L, Huang Y, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020 Apr 10. pii: science.abb7498. PubMed: https://pubmed.gov/32277040. Full-text: https://doi.org/10.1126/science.abb7498

Using cryogenic electron microscopy, authors describe the structure of the RNA-dependent RNA polymerase, another central enzyme of the viral replication machinery. It is also shown how remdesivir and sofosbuvir bind to this polymerase.

 

Epidemiology

Danis K, Epaulard O, Benet T, et al. Cluster of coronavirus disease 2019 (Covid-19) in the French Alps, 2020. Clin Infect Dis. 2020 Apr 11. pii: 5819060. PubMed: https://pubmed.gov/32277759. Full-text: https://doi.org/10.1093/cid/ciaa424

Some clusters are described, including a 9-yr-old child who attended three different schools (why 3 is not described) and one ski class while symptomatic. Coinfected with both picornavirus + influenza A(H1N1), child transmitted only these viruses to others but not SARS-CoV-2, suggesting that these viruses are more easily transmitted than SARS-CoV-2.

 

Asadi S, Bouvier N, Wexler AS, et al. The coronavirus pandemic and aerosols: Does COVID-19 transmit via expiratory particles? Aerosol Sci Technol 2020, April 3. DOI: 10.1080/02786826.2020.1749229. Full-text: www.tandfonline.com/doi/full/10.1080/02786826.2020.1749229

Why is SARS-CoV-2 so highly transmissible? This interesting overview describes current knowledge of airborne transmission. It’s not only the “droplet spray”, typically greater than 5 µm in diameter. Alternatively, a susceptible person can inhale microscopic aerosol particles consisting of the residual solid components of evaporated respiratory droplets, which are tiny enough to remain airborne for hours. Authors conclude that speech plausibly serves as an underrecognized transmission mechanism: “it is up to ‘aerosol scientists’ to provide the technology and hard data to either corroborate or reject that.” So please, get on the scene, aerosol scientists on this planet!

 

Clinical

Yousefzadegan S, Rezaei N. Case Report: Death Due to Novel Coronavirus Disease (COVID-19) in Three Brothers. Am J Trop Med Hyg. 2020 Apr 10. PubMed: https://pubmed.gov/32277694. Full-text: https://doi.org/10.4269/ajtmh.20-0240

Is there a genetic predisposition for severe diseases? This report from Iran describes three brothers aged 54-66 years, all dying from COVID-19 with a relatively similar pattern after less than 2 weeks of illness. All were previously healthy, without histories of underlying diseases.

 

Casini A, Alberio L, Angelillo-Scherrer A, et al. Thromboprophylaxis and laboratory monitoring for in-hospital patients with Covid-19 – a Swiss consensus statement by the Working Party Hemostasis. Swiss Med Wkly. 2020 Apr 11;150:w20247. PubMed: https://pubmed.gov/32277760. Full-text: https://doi.org/10.4414/smw.2020.20247

All in-hospital COVID-19 patients should receive pharmacological thromboprophylaxis according to a risk stratification score, unless contraindicated. In patients with creatinine clearance >30 ml/min, low molecular weight heparin (LMWH) should be administered according to the prescribing information. These guidelines also suggest regularly monitoring prothrombin time, D-dimers, fibrinogen, platelet count, LDH, creatinine and ALT daily or at least 2-3 times per week.

 

Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol. 2020 Apr 12. PubMed: https://pubmed.gov/32279441. Full-text: https://doi.org/10.1002/alr.22579

“Flu plus ‘loss of smell’ means COVID-19”. Among 263 patients presenting during March (single center in San Diego) with flu-like-symptoms, loss of smell was found in 68 % of COVID-19 patients (n=59), compared to only 16 % in negative patients (n=203). Smell and taste impairment were independently and strongly associated with positivity (anosmia: adjusted odds ratio 11, 95%CI: 5‐24). Conversely, sore throat was independently associated with negativity.

 

Comorbidities

Torres T, Puig L. Managing Cutaneous Immune-Mediated Diseases During the COVID-19 Pandemic. Am J Clin Dermatol. 2020 Apr 10. PubMed: https://pubmed.gov/32277351. Full-text: https://doi.org/10.1007/s40257-020-00514-2

Patients with cutaneous immune-mediated diseases (including psoriasis, atopic dermatitis, and hidradenitis suppurativa) may continue their treatment even during the COVID-19 outbreak, preventing disease flares. However, in patients with active COVID-19 infection, it is generally recommended to withhold immunosuppressive or biologic treatment.

 

Coles CE, Aristei C, Bliss J, et al. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic. Clin Oncol (R Coll Radiol). 2020 May;32(5):279-281. PubMed: https://pubmed.gov/32241520. Full-text: https://doi.org/10.1016/j.clon.2020.03.006

In order to reduce hospital visits to a minimum and to ease pressure on workforce, detailed guidelines on radiation therapy for breast cancer are given, mainly focussing on hypofractionation.

 

Treatment, procedures

Lentz RJ, Colt H. Summarizing societal guidelines regarding bronchoscopy during the COVID-19 pandemic. Respirology. 2020 Apr 11. PubMed: https://pubmed.gov/32277733. Full-text: https://doi.org/10.1111/resp.13824

In whom to perform bronchoscopy and how to perform it safely? This paper describes different guidelines (based on expert opinions).

 

Grant WB, Lahore H, McDonnell SL, et al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients. 2020 Apr 2;12(4). pii: nu12040988. PubMed: https://pubmed.gov/32252338. Full-text: https://doi.org/10.3390/nu12040988

Evidence? Well. Serum 25(OH)D concentrations tend to decrease with age, which may be important for COVID-19 because case-fatality rates increase with age. That’s the whole story. After all, the ”hypothesis that vitamin D supplementation can reduce the risk of influenza and COVID-19Â incidence and death should be investigated in trials”.

 

12 April

Virology

Chu H, Chan JF, Wang Y, et al. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis. 2020 Apr 9. pii: 5818134. PubMed: https://pubmed.gov/32270184 . Full-text: https://doi.org/10.1093/cid/ciaa410

Cell experiments on replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Both viruses were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. SARS-CoV-2 generated 3.20 folds more infectious virus particles than SARS-CoV from the infected lung tissues.

 

Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020 Apr 9. pii: 10.1038/s41577-020-0308-3. PubMed: https://pubmed.gov/32273594 . Full-text: https://doi.org/10.1038/s41577-020-0308-3

Some thoughts on the immunopathological changes in patients with COVID-19 and how this may provide potential targets for drug discovery and may be important for clinical management.

 

Wang Q, Zhang Y, Wu L, et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell. 2020 Apr 7. pii: S0092-8674(20)30338-X. PubMed: https://pubmed.gov/32275855 . Full-text: https://doi.org/10.1016/j.cell.2020.03.045

Atomic details of the crystal structure of the C-terminal domain of SARS-CoV-2 spike protein in complex with human ACE2 are presented. hACE2-binding mode of SARS-CoV-2 seems to be similar to SARS-CoV, but some key residue substitutions slightly strengthen the interaction and lead to higher affinity for receptor binding. Antibody experiments indicated notable differences in antigenicity between SARS-CoV and SARS-CoV-2.

 

Epidemiology

Guo ZD, Wang ZY, Zhang SF, et al. Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020. Emerg Infect Dis. 2020 Apr 10;26(7). PubMed: https://pubmed.gov/32275497 . Full-text: https://doi.org/10.3201/eid2607.200885

In hospitals, the virus is everywhere. SARS-CoV-2 was widely distributed in the air and on object surfaces in both the intensive care units and general wards, implying a potentially high infection risk for medical staff. Contamination was greater in ICU. Virus was found on floors, computer mice, trash cans, and sickbed handrails and was detected in air approximately 4 m from patients.  

 

Rossman H, Keshet A, Shilo S, et al. A framework for identifying regional outbreak and spread of COVID-19 from one-minute population-wide surveys. Nat Med. 2020 Apr 9. pii: 10.1038/s41591-020-0857-9. PubMed: https://pubmed.gov/32273611 . Full-text: https://doi.org/10.1038/s41591-020-0857-9

Coronavirus infection spreads in clusters, and early identification of these clusters is critical for slowing down the spread of the virus. Short daily population-wide online surveys that assess the development of symptoms could serve as a strategic and valuable tool for identifying such clusters and informing epidemiologists, public-health officials and policymakers.

 

Diagnostics

Guo WL, Jiang Q, Ye F, et al. Effect of throat washings on detection of 2019 novel coronavirus. Clin Infect Dis. 2020 Apr 9. pii: 5818370. PubMed: https://pubmed.gov/32271374 . Full-text: https://doi.org/10.1093/cid/ciaa416

Throat washing may be used for monitoring due to its noninvasive and reliability. Throat washing was harvested by asking patient to oscillate over posterior pharyngeal wall with 20 ml sterile normal saline. After 5-10 seconds, they had to spit out normal saline from their throat to a sterile container. In 24 paired throat washings and nasopharyngeal swabs specimens, positive testing rate of throat washing was much higher than that of swabs.

 

Xiao AT, Tong YX, Zhang S. False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence. J Med Virol. 2020 Apr 9. PubMed: https://pubmed.gov/32270882 . Full-text: https://doi.org/10.1002/jmv.25855

Negative does not mean absolutely negative. Among 70 COVID-19 patients, 15 (21%) experienced a “turn positive” of SARS-CoV-2 PCR after two consecutive negative results (up to 45 days after symptom onset).

 

Clinical

Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. pii: 2764549. PubMed: https://pubmed.gov/32275288 . Full-text: https://doi.org/10.1001/jamaneurol.2020.1127

This retrospective, observational case series found 78/214 patients (36%) with neurologic manifestations, ranging from fairly specific symptoms (loss of sense of smell or taste, myopathy, and stroke) to more nonspecific symptoms (headache, low consciousness, dizziness, or seizure). Whether these more nonspecific symptoms are manifestations of the disease itself remains to be seen.

 

Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 9. PubMed: https://pubmed.gov/32271988 . Full-text: https://doi.org/10.1111/jth.14830

Among 81 severe COVID-19 patients, incidence of venous thromboembolism (VTE) was 25%. A significant increase of D-dimer was a good index for identifying high-risk groups of VTE.

 

Treatment

Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. PubMed: https://pubmed.gov/32269046 . Full-text: https://doi.org/10.1136/bmj.m1432

In the year 1925, the BMJ cautiously endorsed Moellgaard’s gold treatment for tuberculosis, although it found his pharmacological reasoning “both interesting and instructive”. In 2020, BMJ is similarly cautious about hydroxyl/chloroquine treatment for SARS-CoV-2. In cell and animal studies, the effects on avian influenza, Epstein-Barr, chikungunya or Zika have been variable. Wide use of these drugs will expose patients to rare but potentially fatal harms, including serious cutaneous adverse reactions, fulminant hepatic failure, and ventricular arrhythmias (especially when prescribed with azithromycin).

11 April

Virology

Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020 Apr 8. pii: science.abb7015. PubMed: https://pubmed.gov/32269068 . Full-text: https://doi.org/10.1126/science.abb7015

SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks. However, ferrets and cats are permissive to infection and cats were susceptible to airborne infection. But cat owners may relax. Experiments were done in a small number of cats exposed to high doses of the virus, probably not representing real-life. It remains also unclear if cats secret enough coronavirus to pass it on to people.

 

Wang X, Xu W, Hu G, et al. SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol. 2020 Apr 7. pii: 10.1038/s41423-020-0424-9. PubMed: https://pubmed.gov/32265513 . Full-text: https://doi.org/10.1038/s41423-020-0424-9

It remains unclear whether SARS-CoV-2 can also infect T cells, resulting in lymphocytopenia. Using a model with pseudoviruses, authors showed that SARS-CoV-2 infects (but does not replicate in) T cells through S protein-mediated membrane fusion. T-cell lines were significantly more sensitive to SARS-CoV-2 infection when compared with SARS-CoV. Of note, a very low expression level of hACE2 was found, indicating that a novel receptor might mediate SARS-CoV-2 entry into T cells.

 

Vaccine

Le TT, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape.  Nature reviews drug discovery. 09 April 2020. doi: 10.1038/d41573-020-00073-5. Full-text: https://www.nature.com/articles/d41573-020-00073-5

Brief data-driven overview by seven experts. The conclusion is that efforts are unprecedented in terms of scale and speed and that there is an indication that vaccine could be available by early 2021. As of 8 April 2020, the global vaccine landscape includes 115 candidates, of which the 5 most advanced candidates have already moved into clinical development, including mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio, LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute. The race is on!

 

Diagnostics

Xu K, Chen Y, Yuan J, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis. 2020 Apr 9. pii: 5818308. PubMed: https://pubmed.gov/32271376 . Full-text: https://doi.org/10.1093/cid/ciaa351

In a cohort of 113 symptomatic patients from two hospitals outside Wuhan, the median duration of SARS-CoV-2 RNA detection was 17 days (IQR, 13-22 days) as measured from illness onset. Male sex, delayed hospital admission, and invasive mechanical ventilation were independent risk factors for prolonged SARS-CoV-2 RNA shedding.

 

Okba NMA, Muller MA, Li W, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease 2019 Patients. Emerg Infect Dis. 2020 Apr 8;26(7). PubMed: https://pubmed.gov/32267220 . Full-text: https://doi.org/10.3201/eid2607.200841

Small study, demonstrating that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. Sensitivity varied between the assays (IgA ELISA showed higher sensitivity). It remains crucial to calibrate and standardize assays developed by different laboratories by using well-defined standard references as part of diagnostic assay validation.

 

Clinical

Wang Y, Lu X, Chen H, et al. Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am J Respir Crit Care Med. 2020 Apr 8. PubMed: https://pubmed.gov/32267160 . Full-text: https://doi.org/10.1164/rccm.202003-0736LE

Large single-center case series study on 344 severe and critically ill patients admitted to Tongji hospital from January 25 through February 25, 2020. Of all, 133 (38.7%) patients died at a median of 15 days. Beside older age, hypertension and COPD were more common in non-survivors but not diabetes. No difference was seen between patients with or without ACE inhibitors.

 

Ji D, Zhang D, Xu J, et al. Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score. Clin Infect Dis. 2020 Apr 9. pii: 5818317. PubMed: https://pubmed.gov/32271369. Full-text: https://doi.org/10.1093/cid/ciaa414

CURB-65 severity score may not be suitable for COVID-19. In 208 patients, a risk factors scoring system was developed, for prediction of progression, based on patients’ age, comorbidities, lymphocyte count and serum LDH at presentation. Needs to be validated by larger studies.

 

Treatment

Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. PubMed: https://pubmed.gov/32275812 . Full-text: https://doi.org/10.1056/NEJMoa2007016

A compassionate use program of remdesivir for patients with severe COVID-19 is described. Clinical improvement was observed in 36/53 (68%) patients. Since published yesterday, data are celebrated in the media. Unjustifiably. Although authors have made some efforts to discuss their data carefully, even more caution is needed. We believe that with this “study”, any (yes, any!) clinical benefit of remdesivir remains unproven. Moreover, several issues in this data set seem to be very implausible. We have written a correspondence letter to NEJM and keep you updated.

 

Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020 Apr 6. pii: scitranslmed.abb5883. PubMed: https://pubmed.gov/32253226 . Full-text: https://doi.org/10.1126/scitranslmed.abb5883

The ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against all CoVs, as well as increased potency against resistance mutations to the nucleoside analog inhibitor remdesivir. But how long will it take to bring this compound into clinical trials?

 

Jin Z, Du X, Xu Y, et al. Structure of M(pro) from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9. pii: 10.1038/s41586-020-2223-y. PubMed: https://pubmed.gov/32272481 . Full-text: https://doi.org/10.1038/s41586-020-2223-y

Virtual drug screening to identify new drug leads that target the COVID-19 virus main protease M(pro) which plays a pivotal role in mediating viral replication and transcription. Six compounds inhibited M(pro) with IC50 values ranging from 0.67 to 21.4 muM, among them with disulfiram and carmofur (a pyrimidine analogue used as an antineoplastic agent) two approved drugs.

10 April

Diagnostics

Yuan J, Kou S, Liang Y, Zeng J, Pan Y, Liu L. PCR Assays Turned Positive in 25 Discharged COVID-19 Patients. Clin Infect Dis. 2020 Apr 8. pii: 5817588. PubMed: https://pubmed.gov/32266381. Full-text: https://doi.org/10.1093/cid/ciaa398

Among 172 discharged COVID-19 patients, 25 (14.5%) had positive testing again 2 to 13 days after discharge, without aggravation of symptoms. Two negative RT-PCR tests 24 hours apart may not be sufficient for viral clearance evaluation, suggesting the need for additional measures to confirm illness resolution.      

 

Hope MD, Raptis CA, Henry TS. Chest Computed Tomography for Detection of Coronavirus Disease 2019 (COVID-19): Don´t Rush the Science. Ann Intern Med. 2020 Apr 8. pii: 2764546. PubMed: https://pubmed.gov/32267912. Full-text: https://doi.org/10.7326/M20-1382

Can chest CT be used as a primary tool for detecting COVID-19 in epidemic areas? Some early studies from China said so. The authors comment that this is a cautionary tale about the consequences of rushing the scientific review process: harsh criticism on faulty design, incomplete methods, biased patient cohorts, confounding and scant discussion, calling into question the broad conclusions that were made in these studies. Bottom line: CT should not be used to screen for or as a first-line test to diagnose COVID-19, all the more considering that safely CT performing is problematic.

 

Nair A, Rodrigues JCL, Hare S, et al. A British Society of Thoracic Imaging statement: considerations in designing local imaging diagnostic algorithms for the COVID-19 pandemic. Clin Radiol. 2020 May;75(5):329-334. PubMed: https://pubmed.gov/32265036. Full-text: https://doi.org/10.1016/j.crad.2020.03.008

Same issue. The British Society of Thoracic Imaging has explored different scenarios integrating CT into a diagnostic algorithm. Of note, the clinical value, even in the absence of PCR availability, remains unclear. Again: CT can help, but probably not as a tool for diagnosing COVID-19.

 

Clinical

Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr 8. PubMed: https://pubmed.gov/32268022. Full-text: https://doi.org/10.1056/NEJMc2007575

Case series on 3 patients with critical illness, developing antiphospholipid antibodies. These antibodies may rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in critically patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy.

 

Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Apr 6. pii: 10.1007/s00405-020-05965-1. PubMed: https://pubmed.gov/32253535. Full-text: https://doi.org/10.1007/s00405-020-05965-1

This important study shows that in Europe, otolaryngological symptoms are much more common than in Asia (it remains unclear whether this is a true difference). Among 417 mild-to-moderate COVID-19 patients (from 12 European hospitals), 86% and 88% reported olfactory and gustatory dysfunctions, respectively. The vast majority was anosmic (hyposmia, parosmia, phantosmia did also occur), and the early olfactory recovery rate was 44%. Females were more affected than males. Olfactory dysfunction appeared before (12%), at the same time (23%) or after (65%) the appearance of other symptoms. There is no doubt that sudden anosmia or ageusia need to be recognized as important symptoms of COVID-19.

 

Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020 Apr 7. PubMed: https://pubmed.gov/32266761. Full-text: https://doi.org/10.1111/cns.13372

Neuroinvasive propensity has been demonstrated as a common feature of human coronaviruses. These viruses can invade brainstem via a synapse‐connected route from the lung and airways. With regard to SARS‐CoV‐2, early occurrences such as olfactory symptoms (see above) should be further evaluated for CNS involvement. Potential late neurological complications in cured COVID-19 patients are discussed. No data are available yet. However, after reading this, you will ask yourself whether herd immunity (infection of broader populations) is such a good idea.

 

Epidemiology

Stafford N. Covid-19: Why Germany´s case fatality rate seems so low. BMJ. 2020 Apr 7;369:m1395. PubMed: https://pubmed.gov/32265194. Full-text: https://doi.org/10.1136/bmj.m1395

Guess why? It’s probably testing and nothing else. The more people with no or mild symptoms you test, the lower the fatality rate. Reliable PCR methods have been reported by the end of January. In Germany’s public health system, testing is not restricted to a central laboratory as in many other nations but can be conducted at quality controlled laboratories throughout the country. Within a few weeks, overall capacity reached half a million PCR tests a week. The same low fatality rate is seen in South Korea, another country with high testing rates.

 

Nussbaumer-Streit B, Mayr V, Dobrescu AI, et al. Quarantine alone or in combination with other public health measures to control COVID-19: a rapid review. Cochrane Database Syst Rev. 2020 Apr 8;4:CD013574. PubMed: https://pubmed.gov/32267544. Full-text: https://doi.org/10.1002/14651858.CD013574

A Word from Cochrane. Current evidence for COVID-19 “is limited”. However, findings “consistently indicate that quarantine is important in reducing incidence and mortality”. In order to maintain the best possible balance of measures, “decision makers must constantly monitor the outbreak situation and the impact of the measures implemented”. Well.

 

Pregnancy

Zaigham M, Andersson O. Maternal and Perinatal Outcomes with COVID-19: a systematic review of 108 pregnancies. Acta Obstet Gynecol Scand. 2020 Apr 7. PubMed: https://pubmed.gov/32259279. Full-text: https://doi.org/10.1111/aogs.13867

Systematic review among 108 pregnancies published in 18 articles. 91% were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported.

 

Bourne T, Kyriacou C, Coomarasamy A, et al. ISUOG Consensus Statement on rationalization of early-pregnancy care and provision of ultrasonography in context of SARS-CoV-2. Ultrasound Obstet Gynecol. 2020 Apr 8. PubMed: https://pubmed.gov/32267981. Full-text: https://doi.org/10.1002/uog.22046

Statement how to rationalize ultrasound and to manage early-pregnancy complications in this crisis.

9 April

Virology

Kim YI, Kim SG, Kim SM, et al. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 Apr 5.. PubMed: https://pubmed.gov/32259477 . Full-text: https://doi.org/10.1016/j.chom.2020.03.023

Ferrets shed the virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. They may represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.

 

Clinical

Miller DG, Pierson L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Ann Intern Med. 2020 Apr 7. pii: 2764413. PubMed: https://pubmed.gov/32259194 . Full-text: https://doi.org/10.7326/M20-1281

The American Association of Medical Colleges (AAMC) recommended that “unless there is a critical health care workforce need locally, we strongly suggest that medical students not be involved in any direct patient care activities”. The authors disagree (for good reasons).

 

Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology. 2020 Apr 3. pii: S0016-5085(20)30448-0. PubMed: https://pubmed.gov/32251668 . Full-text: https://doi.org/10.1053/j.gastro.2020.03.065

In a meta-analysis of 60 studies, comprising 4,243 patients, the pooled prevalence of gastrointestinal symptoms was 17.6% (95% CI, 12.3%-24.5%). Prevalence was lower in studies from China than other countries. Pooled prevalence of stool samples that were positive for virus RNA was 48.1% and could persist for up to ≥33 days from illness onset even after viral RNA negativity in respiratory specimens. Stool viral RNA was detected at higher frequency among those with diarrhea.

 

Shanafelt T, Ripp J, Trockel M. Understanding and Addressing Sources of Anxiety Among Health Care Professionals During the COVID-19 Pandemic. JAMA. 2020 Apr 7. pii: 2764380. PubMed: https://pubmed.gov/32259193 . Full-text: https://doi.org/10.1001/jama.2020.5893

This viewpoint summarizes key considerations for supporting the health care workforce.

 

Comorbidities

Dave M, Seoudi N, Coulthard P. Urgent dental care for patients during the COVID-19 pandemic. Lancet. 2020 Apr 3. pii: S0140-6736(20)30806-0. PubMed: https://pubmed.gov/32251619 . Full-text: https://doi.org/10.1016/S0140-6736(20)30806-0

Don’t forget the dentists! And test them with the same high priority as that of medical health­care workers in hospitals!

 

Sun J, Aghemo A, Forner A, Valenti L. COVID-19 and liver disease. Liver Int. 2020 Apr 6. doi: https://doi.org/10.1111/liv.14470 . [Epub ahead of print]

“Since December 2019, patients with unexplained pneumonia have been found in Wuhan, Hubei Province, China, which was caused by a novel coronavirus that had not been previously identified (1). Tentatively defined as 2019 novel coronavirus (2019-nCoV), the pathogen has now been named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2), while the disease termed Coronavirus Disease 2019 (COVID-19).” This abstract was published on April 6, with references. In all seriousness. Come on guys, we all know that! It is to be feared that nobody will read your interesting mini-review on mechanisms and clinical implications of liver injury, unmet clinical needs and main research questions.

 

Treatment

Praveen D, Chowdary PR, Aanandhi MV. Baricitinib – a januase kinase inhibitor – not an ideal option for management of COVID-19. Int J Antimicrob Agents. 2020 Apr 4:105967. PubMed: https://pubmed.gov/32259575 . Full-text: https://doi.org/10.1016/j.ijantimicag.2020.105967

Several studies have speculated that baricitinib could act on AT2 cells and AAK1 mediated endocytosis. The authors argue that the drug would not be an ideal option, due to the fact that baricitinib causes lymphocytopenia, neutropenia and viral reactivation. Sounds reasonable.

 

Perinel S, Launay M, Botelho-Nevers E, et al. Towards Optimization of Hydroxychloroquine Dosing in Intensive Care Unit COVID-19 Patients. Clin Infect Dis. 2020 Apr 7. pii: 5816960. PubMed: https://pubmed.gov/32255489 . Full-text: https://doi.org/10.1093/cid/ciaa394

Ongoing clinical trials with HCQ use different dosing regimens. In this PK study on 13 patients critically ill with COVID-19, 200 mg three times daily dosing regimen were  inappropriate  to reach a supposed target  blood level of 1-2 mg/L. Authors proposed 800 mg once daily on day 1, followed by 200 mg twice daily for 7 days. However, further PK studies are needed.

 

Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest. 2020 Apr 7. pii: 138745. PubMed: https://pubmed.gov/32254064 . Full-text: https://doi.org/1387454

An overview of treatment with convalescent plasma on current evidence of benefit, regulatory considerations, logistical work flow (recruitment of donors etc.) and proposed clinical trials.

 

Procedures

Loftus RW, Dexter F, Parra MC, Brown JR. Importance of oral and nasal decontamination for patients undergoing anesthetics during the COVID-19 era. Anesth Analg. 2020 Apr 3. PubMed: https://pubmed.gov/32250978 . Full-text: https://doi.org/10.1213/ANE.0000000000004854

According to authors, the evidence shows a favourable risk/benefit profile for patient decolonization with nasal povidone and oral chlorhexidine rinse to help mitigate the perioperative spread.

8 April

Epidemiology

Ghinai I, McPherson TD, Hunter JC, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet. 2020 Apr 4;395(10230):1137-1144. PubMed: https://pubmed.gov/32178768 . Full-text: https://doi.org/10.1016/S0140-6736(20)30607-3

Infection of health-care workers (HCWs) is not inevitable. A female in her 60s who travelled to Wuhan on Dec 25, 2019, and returned to Illinois on Jan 13, 2020, transmitted infection to her husband.  Although both were hospitalised in the same facility and shared hundreds (n=348) of contacts with HCWs, nobody else became infected, supporting recommendations regarding appropriate infection control.

 

Bae S, Kim MC, Kim JY, et al. Effectiveness of Surgical and Cotton Masks in Blocking SARS-CoV-2: A Controlled Comparison in 4 Patients. Ann Intern Med. 2020 Apr 6. pii: 2764367. PubMed: https://pubmed.gov/32251511 . Full-text: https://doi.org/10.7326/M20-1342

Very small study, but both surgical and cotton masks appeared to be ineffective in preventing the virus dissemination from the coughs of patients with COVID-19 to the environment and external mask surface.

 

Diagnostics

Chapman AR, Bularga A, Mills NL. High-Sensitivity Cardiac Troponin Can Be An Ally in the Fight Against COVID-19. Circulation. 2020 Apr 6. PubMed: https://pubmed.gov/32251612 . Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047008

Nice review on how to use and interpret troponin results in COVID-19 patients. According to the authors, clinicians must recognize that troponin is not a test for myocardial infarction, and it never was. No biomarker has ever had the ability to detect acute atherothrombotic occlusion in a coronary artery. Elevations of cardiac troponin can inform the diagnosis of a number of cardiac conditions related to COVID-19.

 

Clinical

Omer SB, Malani P, Del Rio C. The COVID-19 Pandemic in the US: A Clinical Update. JAMA. 2020 Apr 6. pii: 2764366. PubMed: https://pubmed.gov/32250388. Full-text: https://doi.org/10.1001/jama.2020.5788

Short but interesting viewpoint on current clinical insights and key questions. Is PCR always positive? What about reinfection, immunity? What do we know about transmission?

 

Comorbidities

Schiffrin EL, Flack J, Ito S, Muntner P, Webb C. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 6. pii: 5816609. PubMed: https://pubmed.gov/32251498 . Full-text: https://doi.org/10.1093/ajh/hpaa057

Is hypertension a true risk factor for severe COVID-19 courses? According to the authors,  there  is  as  yet (March 29) “no  evidence”  that  hypertension  is  related  to  outcomes  of COVID-19, or that ACE inhibitor or ARB use is harmful, or for that matter beneficial.

 

Pasha SB, Fatima H, Ghouri YA. Management of Inflammatory Bowel Diseases in the Wake of COVID-19 Pandemic. J Gastroenterol Hepatol. 2020 Apr 4. PubMed: https://pubmed.gov/32246874 . Full-text: https://doi.org/10.1111/jgh.15056

Some thoughts on how to manage patients suffering from Inflammatory Bowel Diseases, regarding their ongoing immunosuppressive therapies which could render them more susceptible to acquire COVID-19 infection and develop severe courses.

 

Treatment

Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. PNAS 2020, April 6. https://doi.org/10.1073/pnas.2004168117

A single dose (200 mL) of convalescent plasma was given to 10 patients (9 treated with umifenovir, 6 with methylprednisolone, 1 with remdesivir). In all 7 patients with viremia, serum SARS-CoV-2 RNA decreased to an undetectable level within 2-6 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within three days. Using antibodies from convalescents could be an option in severe cases. It’s now time for larger studies.

 

Du YX, Chen XP. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. Clin Pharmacol Ther. 2020 Apr 4. PubMed: https://pubmed.gov/32246834 . Full-text: https://doi.org/10.1002/cpt.1844

This mini-review (not free accessible, unfortunately) focusses on the pharmacokinetics of favipiravir and potential drug-drug interactions (DDIs). As the parent drug undergoes metabolism in the liver mainly by aldehyde oxidase (AO), potent AO inhibitors such as cimetidine, amlodipine, or amitriptyline are expected to cause relevant DDIs.

 

Pregnancy, pediatrics

Choi SH, Kim HW, Kang JM, Kim DH, Cho EY. Epidemiology and Clinical Features of Coronavirus disease 2019 in Children. Clin Exp Pediatr. 2020 Apr 6. pii: cep.2020.00535. PubMed: https://pubmed.gov/32252139 . Full-text: https://doi.org/10.3345/cep.2020.00535

In this nice review published on April 6, it is summarized “what is known about COVID-19 in children and adolescents until now”. No, not until now. Until March 12, 2020 (a far-off age).  What has happened since then?

 

Poon LC, Yang H, Kapur A, et al. Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals. Int J Gynaecol Obstet. 2020 Apr 4. PubMed: https://pubmed.gov/32248521 . Full-text: https://doi.org/10.1002/ijgo.13156

For those of you who are not gynaecologists: No, it’s not Luís Figo. It’s FIGO, the International Federation of Gynaecology and Obstetrics which gives “interim” recommendations about how to deal with pregnant women: 46 pages on ambulatory antenatal care, management in the setting of the obstetrical triage, intra/postpartum management and neonatal care. Among others, IRCCS, PAHO, ECDC, SIN, SEGO, RCOG, SOGC, SOAP, ISUOG and RANZCOG have also contributed.

 

7 April

Epidemiology

Klompas M, Morris CA, Sinclair J, Pearson M, Shenoy ES. Universal Masking in Hospitals in the Covid-19 Era. N Engl J Med. 2020 Apr 1. PubMed: https://pubmed.gov/32237672. Full-text: https://doi.org/10.1056/NEJMp2006372

Thoughts on universal masking in hospitals. Pros and cons. Bottom line: The main value is probably psychological: giving health care workers the confidence to absorb and implement prevention practices.

 

Tian H, Liu Y, Li Y, et al. An investigation of transmission control measures during the first 50 days of the COVID-19 epidemic in China. Science. 2020 Mar 31. pii: science.abb6105. PubMed: https://pubmed.gov/32234804. Full-text: https://doi.org/10.1126/science.abb6105

“All models are wrong, but some are useful”, statistician George Box supposedly once said. This model shows how non-pharmaceutical measures have worked in China. Without the Wuhan travel ban, there would have been 744,000 cases by February 19, day 50 of the epidemic. With the Wuhan travel ban alone, the number of cases would have decreased to 202,000. Other control measures such as the national emergency response, together with the travel ban, limited the number of cases, 96 % fewer than expected in the absence of interventions.

 

Normile D. As normalcy returns, can China keep COVID-19 at bay? Science. 2020 Apr 3;368(6486):18-19. PubMed: https://pubmed.gov/32241931. Full-text: https://doi.org/10.1126/science.368.6486.18

Thoughts and opinions on how China is now addressing an issue every country and location in the world will eventually (hopefully) face: how to normalize and restore societal activities, while at the same time minimizing disease-related dangers from the outbreak.

 

Diagnostics

Pan Y, Long L, Zhang D, et al. Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads. Clin Chem. 2020 Apr 4. pii: 5815979. PubMed: https://pubmed.gov/32246822. Full-text: https://doi.org/10.1093/clinchem/hvaa091

Don’t put your swabs in the sun! In this small study, all samples were inactivated by incubation in a water bath at 56˚ for 30 minutes. O note, 7/15 specimens with low virus levels converted into false negative. Longer storage also caused false-negative result in a few cases.

 

Virology

Monto AS, DeJonge P, Callear AP, et al. Coronavirus occurrence and transmission over 8 years in the HIVE cohort of households in Michigan. J Infect Dis. 2020 Apr 4. pii: 5815743. PubMed: https://pubmed.gov/32246136. Full-text: https://doi.org/10.1093/infdis/jiaa161

Let’s pray that SARS-CoV-2 remembers its origins. And that it behaves like other human coronaviruses (hCoVs). A longitudinal surveillance cohort study of children and their households from Michigan found that hCoV infections were sharply seasonal, showing a peak for different HCoV types (229E, HKU1, NL63, OC43) in February. Over 8 years, almost no HCoV infections occurred after March. Will SARS-CoV-2 remember this? It’s April….

 

Yuan M, Wu NC, Zhu X, et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science. 2020 Apr 3. PubMed: https://pubmed.gov/32245784. Full-text: https://doi.org/10.1126/science.abb7269

Insights into antibody recognition and how SARS-CoV-2 can be targeted by the humoral response, revealing a conserved epitope shared between SARS-CoV and SARS-CoV-2. This epitope could be used for vaccines and the development of cross-protective antibodies.

 

Clinical

Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6. PubMed: https://pubmed.gov/32250385. Full-text: https://doi.org/10.1001/jama.2020.5394

Important work, providing sobering evidence about the burden of critical illness. Over a period of 28 days, 1,591 COVID-19 patients (88 % requiring endotracheal intubation and ventilatory support) were admitted to 72 Italian ICUs, an average of 22 patients per ICU (median length of stay was 9 days). Of note, 82 % were male and median age was only 63 years (IQR 56-70), suggesting that older age alone is not a risk factor for admission to the ICU. As of March 25, ICU mortality was 26 %. However, 58 % were still in the ICU. Scarifying study, telling us a lot about the fragility of health care systems in even the wealthiest countries.

 

Wunsch H. The outbreak that invented intensive care. Nature, World View, April 3, 2020. Full-text: https://www.nature.com/articles/d41586-020-01019-y

Interesting article on Copenhagen’s polio epidemic in 1952, when over 300 patients (see below) developed respiratory paralysis within a few weeks, completely overwhelming the ventilator facilities. Does this remind you of something?

 

West JB. The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiology. J Appl Physiol 2005 Aug;99(2):424-32. PubMed: https://pubmed.gov/16020437. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1351016/

Yes, it’s old. But, please, read this incredible story on hope and despair, on enormous medical challenges and true heroes, highly topical after almost 60 years. A comprehensive review about a forgotten epidemic occurring 1952 at the Belgdam Hospital in Copenhagen, Denmark: About 3,000 polio patients were admitted between August and December, among them 1,250 with paralysis and 345 with respiratory failure – due to bulbar or bulbospinal polio affecting brainstem or nerves that control breathing. The heroic solution was to recruit 1,500 medical and dental students, providing round-the-clock manual ventilation using rubber bags, with only the patient’s appearance to guide them. For a total of 165.000 hours. Think about it. The students were flying literally by sight. Sometimes, only the patients’ rolling up eyes signalled them that more ventilation was needed. Watery eyes while reading this heart-breaking article. A perfect story for anti-vaxxers (if these damned trolls would take notice). And about how fast we forget.

 

Procedures

Lyons C, Callaghan M. The use of high-flow nasal oxygen in COVID-19. Anaesthesia. 2020 Apr 4. PubMed: https://pubmed.gov/32246843. Full-text: https://doi.org/10.1111/anae.15073

Careful and well-balanced review about the pros and cons of this treatment strategy.

6 April

No papers today. But the second edition and editions in Spanish, Italian, French and Portugues.

5 April

Epidemiology

Scott SE, Zabel K, Collins J, et al. First Mildly Ill, Non-Hospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States — Maricopa County, Arizona, 2020. Clinical Infectious Diseases 2020, 02 April, ciaa374, https://doi.org/10.1093/cid/ciaa374

Is symptom severity a proxy for infectivity? Case report of a patient with mild illness and positive tests for up to 18 days after diagnosis, without evidence of transmission to 16 close contacts, among them 10 high-risk contacts.

 

Lu J, Gu J, Li K, et al. COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020. Emerg Infect Dis. 2020 Apr 2;26(7). PubMed: https://pubmed.gov/32240078. Full-text: https://doi.org/10.3201/eid2607.200764

Outbreak in a restaurant. The distances between index patient and persons at other tables were all >1 m, suggesting that droplet transmission was prompted by air-conditioned ventilation.

 

Kwon SY, Kim EJ, Jung YS, Jang JS, Cho NS. Post-donation COVID-19 identification in blood donors. Vox Sang. 2020 Apr 2. PubMed: https://pubmed.gov/32240537. Full-text: https://doi.org/10.1111/vox.12925

Korean study of seven asymptomatic blood donors who were later identified as COVID-19 confirmed cases. None out of 9 recipients of platelets or red blood cell transfusions tested positive for SARS-CoV-2 RNA. Transfusion transmission is unlikely.

 

Chang L, Zhao L, Gong H, Wang L, Wang L. Severe Acute Respiratory Syndrome Coronavirus 2 RNA Detected in Blood Donations. Emerg Infect Dis. 2020 Apr 3;26(7). PubMed: https://pubmed.gov/32243255. Full-text: https://doi.org/10.3201/eid2607.200839

With screening of 2,430 donations in real-time, including 1,656 platelet and 774 whole blood donations from Wuhan, authors found plasma samples positive for viral RNA from 4 asymptomatic donors. It remains unclear whether detectable RNA signifies infectivity.

 

Diagnostics

Vetrugno L, Bove T, Orso D, et al. Our Italian Experience Using Lung Ultrasound for Identification, Grading and Serial Follow-up of Severity of Lung Involvement for Management of Patients with COVID-19. Echocardiography. 2020 Apr 1. PubMed: https://pubmed.gov/32239532. Full-text: https://doi.org/10.1111/echo.14664

Experience from Italy with lung ultrasound as a bedside tool to improve evaluation of lung involvement, and also reduce the use of chest x-rays and CT. A point scoring system is employed by region and ultrasound pattern.

 

Clinical

Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility – King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):377-381. PubMed: https://pubmed.gov/32240128. Full-text: https://doi.org/10.15585/mmwr.mm6913e1

Outbreak in a long-term care facility: Test them all, immediately! Following identification of a case of SARS-CoV-2 in a health care worker, 13/23 residents who tested positive were asymptomatic or presymptomatic on the day of testing.

 

Comorbidities

Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 Apr 3. pii: 2764299. PubMed: https://pubmed.gov/32242890. Full-text: https://doi.org/10.1001/jamacardio.2020.1282

This mini-review outlines the mechanisms by which RAAS inhibitors (ACEIs/ARBs) may be of benefit in COVID-19. Overview of the current recommendations for their use in infected patients. According to the authors, the biological plausibility of salutary effects of RAAS inhibitors is intriguing and several trials of starting losartan in patients with COVID-19 are currently being planned.

 

Al-Shamsi HO, Alhazzani W, Alhuraiji A, et al. A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group. Oncologist. 2020 Apr 3. PubMed: https://pubmed.gov/32243668. Full-text: https://doi.org/10.1634/theoncologist.2020-0213

Detailed and important review for oncologists, addressing current challenges associated with managing cancer patients during theCOVID-19 pandemic.

 

Volkow ND. Collision of the COVID-19 and Addiction Epidemics. Ann Intern Med. 2020 Apr 2. pii: 2764313. PubMed: https://pubmed.gov/32240293. Full-text: https://doi.org/10.7326/M20-1212

Don’t forget or marginalize persons with substance use disorders during this crisis.

 

Fried JA, Ramasubbu K, Bhatt R, et al. The Variety of Cardiovascular Presentations of COVID-19. Circulation. 2020 Apr 3. PubMed: https://pubmed.gov/32243205. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047164

Four COVID-19 cases with cardiovascular presentations are described. In patients presenting with what appears to be a typical cardiac syndrome, COVID-19 infection should be in the differential during the current pandemic, even in the absence of fever or cough.

 

 

4 April

Epidemiology

Ferretti L, Wymant C, Kendall M, et al. Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing. Science 31 Mar 2020. https://doi.org/10.1126/science.abb6936

Using an analytically solvable model, authors show that viral spread is too fast to be contained by manual contact tracing. Spread could be controlled if this process was faster, more efficient and happened at scale. A contact-tracing App which builds a memory of proximity contacts and immediately notifies contacts of positive cases can achieve epidemic control if used by enough people, without need for lockdowns.

 

Flaxman S, Mishra S, Gandy A. Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries. March 30. https://doi.org/10.25561/77731

Infection-control measures such as national lockdowns in many European countries are reducing the spread of the coronavirus. Across 11 countries, between 21,000 and 120,000 deaths were probably avoided by the end of March, according to a model by a group at Imperial College London.

 

Leung NH, Chu Dk, Shiu EY. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Med 2020, April 3. https://doi.org/10.1038/s41591-020-0843-2

Do face masks work? Yes, but it depends. This important study from Hong Kong (performed 2013-16) quantified virus in respiratory droplets and aerosols in exhaled breath. In total, 111 participants (infected with seasonal coronavirus, influenza or rhinovirus) were randomized to wear (or not) a simple surgical face mask. Results suggested that masks could be used by ill people to reduce onward transmission. But note the small numbers: in respiratory droplets, seasonal coronavirus was found in 0/11 droplets (aerosols: 0/11) from participants wearing face masks, compared to 3/10 (aerosols: 4/10) without masks. Influenza viruses were detected in 1/27 (aerosols 6/27!) with face masks, compared to 6/23 (8/23) without. For rhinovirus, there were no significant differences at all. Of note, authors also identified virus in some participants who did not cough at all during the 30-min exhaled breath collection, suggesting droplet and aerosol routes of transmission from individuals with no obvious signs or symptoms.

 

Chin AW, Chu JT, Perera MR, et al. Stability of SARS-CoV-2 in different environmental conditions.The Lancet Microbe 2020, April 02. Full-text: https://doi.org/10.1016/S2666-5247(20)30003-3

Don’t put your masks in the fridge for recycling! Heating is probably better. This important work shows that the virus was highly stable at 4°C (almost no reduction on day 14) but sensitive to heat (70°C: inactivation 5 min, 56°: 30 min, 37°: 2 days). It also depends on the surface: No infectious virus could be recovered from printing and tissue papers after 3 hours, from treated wood and cloth on day 2, from glass and banknote on day 4, stainless steel and plastic on day 7. Strikingly, a detectable level of infectious virus (∼0·1% of the original inoculum) could still be present on the outer layer of a surgical mask on day 7.

 

Clinical

Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020 Apr 2. pii: 2449. PubMed: https://pubmed.gov/32240279. Full-text: https://doi.org/10.4193/Rhin20.114

Case report and series on isolated sudden onset anosmia, urgeing to consider this presentation.

 

Comorbities

Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-760. PubMed: https://pubmed.gov/32228222. Full-text: https://doi.org/10.1080/22221751.2020.1746200

First study argueing against any deleterious effect of RAAS inhibitors (ACE inhibitors or sartans) in COVID-19! Among 42 of 417 patients admitted to Shenzhen Hospital while on antihypertensive therapy, those receiving RAAS inhibitors had a lower rate of severe diseases than patients without (5/17 compared to 12/25) and a trend toward a lower level of IL-6 in peripheral blood.

 

The Lancet Oncology. COVID-19: global consequences for oncology. Lancet Oncol. 2020 Apr;21(4):467. PubMed: https://pubmed.gov/32240603. Full-text: https://doi.org/10.1016/S1470-2045(20)30175-3

Thoughts on how the pandemic affects treatment of patients with cancer and how it will hit the wider oncology community. Substantial changes for research, education, and collaboration are expected, including reduced international travel and increased remote networking and telemedicine.

 

Procedures

Tay JK, Koo ML, Loh WS. Surgical Considerations for Tracheostomy During the COVID-19 PandemicLessons Learned From the Severe Acute Respiratory Syndrome Outbreak. JAMA Otolaryngol Head Neck Surg. Published online March 31, 2020. Full-text: https://doi.org/10.1001/jamaoto.2020.0764

Patients with prolonged ventilation may require tracheostomy to optimize weaning from ventilatory support. Review of the literature and practical issues.

 

Diagnostics

Petherick A. Developing antibody tests for SARS-CoV-2. The Lancet 2020, April 4, Vol. 395, No. 10230. Full-text: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30788-1/fulltext

Brief report about current knowledge and development on antibody testing.

 

Treatment

Chen C, Huang J, Cheng Z, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. Posted March 27, medRxiv 2020.03.17.20037432. Full-text: https://doi.org/10.1101/2020.03.17.20037432

Important open-label, randomized trial conducted in 3 hospitals from China, comparing arbidol and favipiravir in 236 patients with COVID-19 pneumonia. Primary outcome was the 7 day clinical recovery rate (recovery of fever, respiratory rate, oxygen saturation and cough relief). In “ordinary” COVID-19 patients (not critical), the recovery rates were 56% with arbidol (n=111) and 71 % (n=98) with favipiravir (p=0.02) that was well tolerated, except for some elevated serum uric acid levels. Striking! But can we trust? In the whole study population, no difference was evident. Many cases were not confirmed by PCR. There were also imbalances between subgroups of “ordinary” patients and even favipiravir was incorrectly spelt 7 times: 3x famiravir, 4x fabiravir (come on guys – did anybody read the manuscript?). This paper needs a careful (and major) review…

 

.

3 April

Virology

Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020 Mar 27;367(6485):1444-1448. PubMed: https://pubmed.gov/32132184. Full-text: https://doi.org/10.1126/science.abb2762

Using cryo–electron microscopy, it is shown how SARS-CoV-2 binds to human cells. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Authors present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. The structures provide a basis for the development of therapeutics targeting this crucial interaction.

 

Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. Published: 30 March 2020. Full-text: https://www.nature.com/articles/s41586-020-2180-5

To elucidate the SARS-CoV-2 RBD and ACE2 interaction at a higher resolution/atomic level, authors used X-ray crystallography. Binding mode was very similar to SARS-CoV, argueing for convergent evolution of both viruses. The epitopes of two SARS-CoV antibodies targeting the RBD were also analysed with the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

 

Shang J, Ye G, Shi K. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020, March 30. https://doi.org/10.1038/s41586-020-2179-y

How well does SARS-CoV-2 recognize hACE2? Better than other coronaviruses. Compared to SARS-CoV and RaTG13 (isolated from bats), ACE2-binding affinity is higher. Functionally important epitopes in SARS-CoV-2 RBM are described that can potentially be targeted by neutralizing antibody drugs.

 

Epidemiology

Luo C, Yao L, Zhang L, et al. Possible Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Public Bath Center in Huai´an, Jiangsu Province, China. JAMA Netw Open. 2020 Mar 2;3(3):e204583. PubMed: https://pubmed.gov/32227177. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.4583

A cluster-spreading event in Huai’an (China), in which a patient may have transmitted the virus to 8 other individuals via bathing in a public bath center (sauna, bath, 25 to 41 °C and humidity of approximately 60%). Transmissibility appears not to be reduced in warm and humid conditions.

 

Cereda D, Tirani M, Rovida F, et al. The early phase of the COVID-19 outbreak in Lombardy, Italy. Preprint. Full-text: https://arxiv.org/abs/2003.09320

Still looking for patient zero in Italy (not found). However, this important study of 6,000 laboratory-confirmed cases tracks how the outbreak unfolded in the region. By the time the first case was detected, the virus had already spread (since January) to most towns and cities in southern Lombardy.

 

Comorbidities

Bousquet J, Akdis C, Jutel M, et al. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement. Allergy. 2020 Mar 31. PubMed: https://pubmed.gov/32233040. Full-text: https://doi.org/10.1111/all.14302

A joint statement of the European Academy of Allergology and Clinical Immunology, following the results of the questionnaire. Bottom line: Stopping intranasal steroids is not advised, until we know better.

 

Clinical

Back A, Tulsky JA, Arnold RM. Communication Skills in the Age of COVID-19.  Ann Intern Med 2020, April 2. DOI: https://doi.org/10.7326/M20-1376

Thoughts about how to communicate as a clinician in this crisis. Talking maps for communication tasks that none of us have faced before, including facilitating virtual goodbyes between family members and dying patients with restricted access. And explaining decisions on why a particular patient will not receive a scarce resource: “I can see how it feels unfair”. Phew. Could anyone ever have imagined that?

 

Procedures

Zhang Y, Zhang X, Liu L, Wang H, Zhao Q. Suggestions for infection prevention and control in digestive endoscopy during current 2019-nCoV pneumonia outbreak in Wuhan, Hubei province, China. Endoscopy. 2020 Apr;52(4):312-314. PubMed: https://pubmed.gov/32212122. Full-text: https://doi.org/10.1055/a-1128-4313

Brief workflow to prevent SARS-CoV-2 transmission in the endoscopy center.

 

Diagnostics

Qiu L, Liu X, Xiao M, et al. SARS-CoV-2 is not detectable in the vaginal fluid of women with severe COVID-19 infection. Clin Infect Dis 2020, April 2, ciaa375, full-text: https://doi.org/10.1093/cid/ciaa375

Is the virus everywhere? No. Not in the vaginal fluid (of 10 women with severe COVID-19).

 

Saito M, Adachi E, Yamayoshi S, et al. Gargle lavage as a safe and sensitive alternative to swab samples to diagnose COVID-19: a case report in Japan. Clinical Infectious Diseases 2020, April 2, ciaa377, https://doi.org/10.1093/cid/ciaa377

Case report of a patient who did not produce sputum. Gargle lavage testing was sensitive. If confirmed by larger studies, this can be done by patients themselves without putting healthcare professionals at increased risk.

 

 

2 April

Epidemiology

Chan KH, Yuen KY. COVID-19 epidemic: disentangling the re-emerging controversy about medical face masks from an epidemiological perspective.  Int J Epidem March 31, 2020. dyaa044. Full-text: https://doi.org/10.1093/ije/dyaa044

Review of data and inconsistencies in official guidelines and expert opinions about face masks, confusing both the public and health care professionals. Still tangling, after reading this review.

 

Dudly JP, Lee NT. Disparities in Age-Specific Morbidity and Mortality from SARS-CoV-2 in China and the Republic of Korea. Clin Inf Dis 2020, March 31. Full-text: https://doi.org/10.1093/cid/ciaa354

Morbidity in China exhibited a Gaussian distribution (peak 50-59 years), while morbidity in ROK had a bimodal distribution (peak 20-29 years). Careless youth? Authors speculate that this was possibly due to differences in public health intervention practices and age-related sociocultural factors (lower rates of compliance among younger people with social distancing and self-quarantine recommendations).

 

Patrick GT, Whittaker C, Watson O, et al. The Global Impact of COVID-19 and Strategies for Mitigation and Suppression. Imperial College London 2020, published March 26. Full-text: https://doi.org/10.25561/77735.

Elegant models, illustrating the potential impact of the COVID-19 pandemic globally and highlighting the challenging decisions faced by governments. In the absence of interventions, COVID-19 would have resulted in 7.0 billion infections and 40 million deaths globally this year. Mitigation strategies focussing on shielding the elderly (60% reduction in social contacts) and slowing but not interrupting transmission (40% reduction) could reduce this burden by half, saving 20 million lives.

 

Wells CR, Sah P, Moghadas SM, et al. Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak. Proc Natl Acad Sci U S A. 2020 Mar 13. pii: 2002616117. PubMed: https://pubmed.gov/32170017 . Full-text: https://doi.org/10.1073/pnas.2002616117

Complex epidemiological models, showing that border controls, airport screening and travel restrictions likely slowed the rate of exportation from mainland China to other countries, but were insufficient to contain the global spread of COVID-19. Rapid contact tracing remains essential.

 

Clinical

Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. Published online March 31, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.1291

In a case series from China, 12/38 patients (32%, more common in severe COVID-19 cases) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. Two patients had positive PCR results from conjunctival swabs.

 

Bonow RO, Fonarow GC, O´Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. 2020 Mar 27. pii: 2763844. PubMed: https://pubmed.gov/32219362 . Full-text: https://doi.org/10.1001/jamacardio.2020.1105

Brief review on the potential for direct and indirect adverse effects of SARS-CoV-2 on the heart and especially so in those with already established heart disease.

 

Comorbidities

Kaiser UB, Mirmira RG, Stewart PM. Our Response to COVID-19 as Endocrinologists and Diabetologists. J Clin Endocrin Metabol, 105, May 2020, published 31 March 2020, dgaa148, https://doi.org/10.1210/clinem/dgaa148

Thoughts on diabetes management, glucocorticoid use, pituitary or other neuroendocrine diseases.

 

CDC COVID-19 Response Team. Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020. MMWR Morb Mortal Wkly Rep. ePub: 31 March 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6913e2

No, the situation in the US does not differ from other countries. Among 7,162 patients with underlying health conditions or potential risk factors reported to the CDC, those with these conditions were more likely admitted to the hospital and to an ICU. And yes, “persons with underlying health conditions who have symptoms of COVID-19 should immediately contact their health care provider”.

 

Diagnostics

Wölfel R, Corman VM, Guggemos W. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020, April 1. Full-text: https://doi.org/10.1038/s41586-020-2196-x

Important work, showing active virus replication in upper respiratory tract tissues (in contrast to SARS). In a detailed virological analysis of nine cases, pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 10⁸ RNA copies per throat swab, day 4), more than 1000 times higher than seen with SARS-CoV. Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Shedding of viral RNA from sputum outlasted the end of symptoms.

 

Treatment

Liu S, Zheng Q, Wang Z. Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus. Bioinformatics April 1, 2020. btaa224, Full-text: https://doi.org/10.1093/bioinformatics/btaa224

Some new ideas on treatment. Using a computer-aided drug discovery protocol, possible covalent drugs targeting 3CLpro protease of SARS-CoV-2 were identified. For drug repurposing, the following ones (indication) might have priority: Telcagepant (migraine), Vidupiprant (asthma), Poziotinib (breast cancer), and Fostamatinib (rheumatoid arthritis).

 

1 April

Virology

Ceraolo C, Giorgi FM. Genomic variance of the 2019-nCoV coronavirus. J Med Virol. 2020 May;92(5):522-528. PubMed: https://pubmed.gov/32027036. Full-text: https://doi.org/10.1002/jmv.25700

Analysis of 56 genomic sequences from distinct patients, showing high sequence similarity (>99%).  A few variable genomic regions exist, mainly at the ORF8 locus (coding for accessory proteins).

 

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544. PubMed: https://pubmed.gov/32123347. Full-text: https://doi.org/10.1038/s41564-020-0695-z

Consensus statement (a little bit wordiness), defining the place of SARS-CoV-2 (provisionally named 2019-nCoV) within the Coronaviridae.

 

Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020 Apr;5(4):562-569. PubMed: https://pubmed.gov/32094589. Full-text: https://doi.org/10.1038/s41564-020-0688-y

Important work on viral entry, using a rapid and cost-effective platform with allows to functionally test large groups of viruses for zoonotic potential. Host protease processing during viral entry is a significant barrier for several lineage B viruses. However, bypassing this barrier allows several coronaviruses to enter human cells through an unknown receptor.

 

Clinical

Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020; (published online March 30.) Full-text: https://doi.org/10.1016/S1473-3099(20)30243-7

Defining the case fatality rate (CFR) remains challenging and simply dividing the number of deaths by the number of cases can be misleading. Using individual-case data and after careful modelling, CFR was 1.38% (95% CI, 1.23–1.53) in this analysis. The mean duration from symptom onset to death was 17.8 days (95% 16.9–19.2).

 

Comorbidities

Yao H, Chen JH, Xu YF. Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry. 2020 Apr;7(4):e21. Full-text: https://doi.org/10.1016/S2215-0366(20)30090-0

Don’t forget people with mental health conditions! A few thoughts on these patients who could be more substantially affected, resulting in relapses or worsening of an already existing mental health condition because of high susceptibility to stress compared with the general population.

 

Chen Q, Liang M, Li Y, et al. Mental health care for medical staff in China during the COVID-19 outbreak. Lancet Psychiatry. 2020 Apr;7(4):e15-e16. PubMed: https://pubmed.gov/32085839. Full-text: https://doi.org/10.1016/S2215-0366(20)30078-X

And don’t forget the staff! Some thoughts on how to maintain staff mental health during such a crisis.

 

Jin XH, Zheng KI, Pan KH, Xie YP, Zheng MH. COVID-19 in a patient with chronic lymphocytic leukaemia. Lancet Haematol. 2020 Apr;7(4):e351-e352. Full-text: https://doi.org/10.1016/S2352-3026(20)30074-0

Interesting case report on a patient with CLL. Clinical and biochemical features of COVID-19 might be partly masked by coexisting CLL. Longer incubation period was presumed.

 

Diagnostics

Chen C, Gao G, Xu Y, et al. SARS-CoV-2–Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19. Ann Intern Med. 2020, March 30. DOI: 10.7326/M20-0991. Full-text: https://annals.org/aim/fullarticle/2764036/sars-cov-2-positive-sputum-feces-after-conversion-pharyngeal-samples

Among 133 patients, 22 patients who had positive RT-qPCR results for SARS–CoV-2 in the sputum or feces (up to 39 and 13 days, respectively) after pharyngeal swabs became negative. Although uncontrolled, this study raises concern about whether patients with negative pharyngeal swabs are truly virus-free, or sampling of additional body sites is needed.

 

Therapy and Procedures

Kim AH, Sparks JA, Liew JW. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19. Ann Intern Med 2020. DOI: https://doi.org/10.7326/M20-1223

Harsh criticism at the Gautret-Study (on a potential benefit of hydroxychloroquine), making clear that essential standards of data generation and interpretation were lacking, leading to undesirable downstream effects.

 

Yazdany J, Kim AH. Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know. Ann Intern Med. 2020. DOI: 10.7326/M20-1334. Full-text: https://annals.org/aim/fullarticle/2764199/use-hydroxychloroquine-chloroquine-during-covid-19-pandemic-what-every-clinician

Extensive comment on someone’s swanky twitter claiming that the combination of HCQ and azithromycin has “a real chance to be one of the biggest game changers in the history of medicine” (March 21). Careful review about the risks of HCQ and how pretentious dissemination of overpromised data may cause severe harm.

 

 

31 March

Diagnostics

Yu F, Yan L, Wang N, et al. Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients. Clin Infect Dis. 2020 Mar 28. pii: 5812997. PubMed: https://pubmed.gov/32221523. Full-text: https://doi.org/10.1093/cid/ciaa345

Is sputum sufficient for diagnosis? In a total of 323 samples from 76 pts, the average viral load in sputum (17429 copies/test) was significantly higher than in throat swabs (2552) and nasal swabs (651). Viral load was also higher in the early and progressive stages than in the recovery stage. If these data were confirmed, collection of specimen would be much easier.

 

Zhao J, Yuan Q, Wang H, et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020 Mar 28. pii: 5812996. PubMed: https://pubmed.gov/32221519. Full-text: https://doi.org/10.1093/cid/ciaa344

More on antibody response. Among 173 patients, the seroconversion rate (median time) for Ab, IgM and IgG was 93.1% (11 days), 82.7% (12 days) and 64.7% (14 days), respectively. A higher titer of Ab was independently associated with a worse clinical classification.

 

Comorbidities

Vaduganathan M, Vardeny O, Michel T, McMurray JV, Pfeffer MA, Solomon SD. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. NEJM, March 30, 2020. DOI: 10.1056/NEJMsr2005760. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?

Phantastic review of an interdisciplinary expert panel on the use, risks and benefit of RAAS inhibitors (ACE inhibitors and sartans) in the COVID-19 era. Bottom line: We don’t know enough. Until further data are available, RAAS inhibitors should be continued.

 

Joob B, Wiwanitkit V. SARS-CoV-2 and HIV. J Med Virol. 2020 Mar 27. PubMed: https://pubmed.gov/32220066. Full-text: https://doi.org/10.1002/jmv.25782

A few new thoughts on HIV infection and COVID-19.

 

Zhu F, Cao Y, Xu S, Zhou M. Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China [published online ahead of print March 11, 2020]. J Med Virol. https://doi.org/10.1002/jmv.25732

First case report of patient with undiagnosed HIV-Infection (low CD4 counts), recovering from a coronavirus‐related pneumonia. Argues against deleterious effect of HIV.

 

Pregnancy

Li Y, Zhao R, Zheng S, et al. Lack of Vertical Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, China. Emerg Infect Dis. 2020 Jun 17;26(6). PubMed: https://pubmed.gov/32134381. Full-text: https://doi.org/10.3201/eid2606.200287

Case report on a caesarean section, suggesting that mother-to-child transmission is unlikely.

 

Epidemiology

Hellewell J, Abbott S, Gimma A, et al. Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. Lancet Glob Health. 2020 Apr;8(4):e488-e496. PubMed: https://pubmed.gov/32119825. Full-text: https://doi.org/10.1016/S2214-109X(20)30074-7

Excellent work with implications for future outbreaks and the time after lockdown. Using a stochastic transmission model, contact tracing and isolation of cases was sufficient to control a new outbreak.

 

Clinical

Bhatraju PK, Ghassemieh BJ, Nichols M. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. NEJM March 30, 2020. DOI: https://doi.org/10.1056/NEJMoa2004500

More than “Ok, COVID-19 has reached the US”: This paper describes in detail the demographic characteristics, coexisting conditions, imaging findings, and outcomes among 21 critically ill patients admitted at ICUs.

 

Nickel CH, Bingisser R. Mimics and chameleons of COVID-19. Swiss Med Wkly. 2020 Mar 23;150:w20231. PubMed: https://pubmed.gov/32202647. https://doi.org/10.4414/smw.2020.20231

An old patient with COVID-19 and non-specific symptoms is described, as well as another case with heart failure, mimicking COVID-19. Both cases underline the need for extensive testing.

 

Vaccine

Lurie N, Saville M, Hatchett R, Halton J. Developing Covid-19 Vaccines at Pandemic Speed. NEJM March 30, 2020. DOI: https://doi.org/10.1056/NEJMp2005630

Excellent review on vaccine development. Outlook on new platforms for RNA and DNA vaccines that can be made quickly because they require no culture or fermentation, instead using synthetic processes.  Hope and despair.

 

30 March

Fauci AS, Lane HC, Redfield RR. Covid-19 – Navigating the Uncharted. N Engl J Med. 2020 Mar 26;382(13):1268-1269. PubMed: https://pubmed.gov/32109011. Full-text: https://doi.org/10.1056/NEJMe2002387

Brief overview of current research topics, given by opinion leaders.

 

Hospital

Sorbello M, El-Boghdadly K, Di Giacinto I, et al. The Italian COVID-19 outbreak: experiences and recommendations from clinical practice. Anaesthesia. 2020 Mar 27. PubMed: https://pubmed.gov/32221973. Full-text: https://doi.org/10.1111/anae.15049

Detailed practical recommendations, based on experiences made during the Italian outbreak. Key elements of clinical management, airway management, personal protective equipment and non-technical aspects are described.

 

Cook TM, El-Boghdadly K, McGuire B, McNarry AF, Patel A, Higgs A. Consensus guidelines for managing the airway in patients with COVID-19. Anaesthesia. 2020 Mar 27. PubMed: https://pubmed.gov/32221970. Full-text: https://doi.org/10.1111/anae.15054

Consented principles from the UK Association of Anaesthetists for airway management, including emergency tracheal intubation, predicted or unexpected difficult tracheal intubation, cardiac arrest, anaesthetic care and tracheal extubation.

 

Matthay MA, Aldrich JM, Gotts JE. Treatment for severe acute respiratory distress syndrome from COVID-19. Lancet Respir Med. 2020 Mar 20. pii: S2213-2600(20)30127-2. PubMed: https://pubmed.gov/32203709. Full-text: https://doi.org/10.1016/S2213-2600(20)30127-2

Brief overview of therapeutic options for severe acute respiratory distress syndrome.

 

Clinical

Chen G, Wu D, Guo W, et al. Clinical and immunologic features in severe and moderate Coronavirus Disease 2019. J Clin Invest. 2020 Mar 27. pii: 137244. PubMed: https://pubmed.gov/32217835. Full-text: https://doi.org/137244

First study on immunologic characteristics of 21 patients (retrospective). Total lymphocytes but also CD4+ and CD8+T cells decreased in nearly all patients, and were markedly lower in severe cases (294, 178 and 89 x 106/L) than moderate cases (641, 382 and 254 x 106/L). Immunological markers may be of importance due to their correlation with disease severity in COVID-19.

 

Risk factors, comorbidities

McMichael TM, Currie DW, Clark S, et al. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. N Engl J Med. 2020 Mar 27. PubMed: https://pubmed.gov/32220208. Full-text: https://doi.org/10.1056/NEJMoa2005412

Important paper that highlights the severity of COVID-19 in older people. A total of 167 confirmed cases affecting 101 residents in a long-term care facility, 50 health care personnel (HCP), and 16 visitors. The case fatality rate for residents was 33.7% (34 of 101) and 0 % among HCP.

 

Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J. 2020 Mar 26. pii: 13993003.00547-2020. PubMed: https://pubmed.gov/32217650. Full-text: https://doi.org/10.1183/13993003.00547-2020

More on the role of comorbidities. 1,590 hospitalised patients from 575 hospitals across mainland China. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (95%CI) 1.424-5.048], diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were risk factors of reaching endpoints.

 

Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. pii: 2763843. PubMed: https://pubmed.gov/32219357. Full-text: https://doi.org/10.1001/jamacardio.2020.1096

Interesting case report on myopericarditis with systolic dysfunction which highlights cardiac involvement as a complication, even without symptoms and signs of interstitial pneumonia.

 

Kutikov A, Weinberg DS, Edelman MJ, Horwitz EM, Uzzo RG, Fisher RI. A War on Two Fronts: Cancer Care in the Time of COVID-19. Ann Intern Med. 2020 Mar 27. pii: 2764022. PubMed: https://pubmed.gov/32219410. Full-text: https://doi.org/10.7326/M20-1133

Inspiring thoughts on treatment and care for patients with cancer. No new data.

 

Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. PubMed: https://pubmed.gov/32217556. Full-text: https://doi.org/10.1136/bmj.m1091

Retrospective case series of 113 deceased patients. The median time from disease onset to death was 16 (IQR 12.0-20.0) days. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (100%), type I respiratory failure (51%), sepsis (100%), acute cardiac injury (77%), heart failure (49%), alkalosis (40%), hyperkalaemia (37%), acute kidney injury (25%), and hypoxic encephalopathy (20%).

 

Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;368:m1185. PubMed: https://pubmed.gov/32220865. Full-text: https://doi.org/10.1136/bmj.m1185

Discussion of a possible link between NSAIDs and both respiratory and cardiovascular adverse effects in COVID-19. Recommends pragmatic approach: regular NSAID use should probably not be recommended first line.

 

Pregnancy, pediatric patients

Wang SS, Zhou X, Lin XG, et al. Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China. Curr Med Sci. 2020 Mar 26. pii: 10.1007/s11596-020-2174-4. PubMed: https://pubmed.gov/32219626. Full-text: https://doi.org/10.1007/s11596-020-2174-4

Updated and very detailed recommendations for the clinical management for pregnant women and their newborns with SARS-CoV-2. Experience from Wuhan. No data.

 

Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA. 2020 Mar 26. pii: 2763854. PubMed: https://pubmed.gov/32215589. Full-text: https://doi.org/10.1001/jama.2020.4861

Among 6 mothers with confirmed COVID-19, SARS-CoV-19 was not detected in the serum or throat swab by RT-PCR in any of their newborns. However, virus-specific antibodies (IgG) were detected in 5 neonatal blood sera samples.