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[23 November] Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes +++ SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation +++ SARS-CoV-2 transmission between mink (Neovison vison) and humans, Denmark +++ and more…

The daily Top 10 – the best papers published in the best medical and scientific journals: Monday, Tuesday, Wednesday, Thursday, Friday, Saturday and even Sunday.

 

23 November

Epidemiology

Taylor CA, Boulos C, Almond D. Livestock plants and COVID-19 transmission. PNAS November 19, 2020. Full-text: https://doi.org/10.1073/pnas.2010115117

Livestock processing poses a particular public health risk extending far beyond meatpacking companies and their employees. The authors estimate livestock plants to be associated with 236.000 to 310.000 COVID-19 cases (6 to 8% of total US cases) and 4300 to 5.200 deaths (3 to 4% of total US cases) as of July 21. They also illustrate potential contributions of plant size, industrial concentration, plant shutdowns, and policy actions to this phenomenon. High numbers were found among large processing facilities and large meatpacking companies. According to the authors, their results “motivate investigation into supply chains, operating procedures, and labor relations within the meatpacking industry”. They also discuss some implications. Interestingly, one was seemingly beyond the intellectual grasp of the authors: that consumers could abstain from buying meat produced by these large meatpacking companies.

Figure 1. Mean county-level COVID-19 cases per thousand (A) and deaths per thousand (B) over time based on proximity to a livestock facility. The band “0–50 km” excludes the… | Continue reading at https://doi.org/10.1073/pnas.2010115117. Reproduced with permission.

 

Virology

Hammer AS, Quaade ML, Rasmussen TB, Fonager J, Rasmussen M, Mundbjerg K, et al. SARS-CoV-2 transmission between mink (Neovison vison) and humans, Denmark. Emerg Infect Dis Nov 18, 2020. 2021 Feb. Full-text: https://doi.org/10.3201/eid2702.203794

Anne Sophie Hammer and colleagues describe the outbreaks on three Danish mink farms. A high proportion of mink were infected within a few days, which may provide major virus exposure to persons working with mink. Full-length virus genome sequencing revealed novel viral variants in mink. These variants subsequently appeared within the local human community.

 

Immunology

Karki ER, Sharma BR, Tuladhar S, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell November 18, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.11.025

More on the cytokine storm: Rajenda Karki and colleagues evaluated the role of pro-inflammatory cytokines that are highly upregulated in patients with COVID-19 in inducing inflammatory cell death, inflammation, tissue and organ damage, and mortality. They show that the specific combination of TNF-α and IFN-γ is critical for these processes. In mice, the combination of anti-TNF-α and anti-IFN-γ neutralizing antibodies protected against death in SARS-CoV-2 infection and models of sepsis, hemophagocytic lymphohistiocytosis (HLH), and cytokine shock.

 

Hekman RM, Hume AJ, Goel RK, et al. Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2. Molecular Cell November 18, 2020.  Full-text: https://doi.org/10.1016/j.molcel.2020.11.028

SARS-CoV-2 infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange. As AT2 injury is central to COVID-19 pathogenesis, there is an urgent need to delineate the mechanisms of SARS-CoV-2-driven lung pathology. Primary AT2s are difficult to maintain in culture, but human induced pluripotent stem cell-derived alveolar epithelial type 2 cells (iAT2s) have been developed and extensively characterized. Using these cells, Ryan Hekman and colleagues from Boston performed a quantitative phosphoproteomic survey, demonstrating diverse host responses to infection of alveolar epithelial cells and suggesting a dynamic disease signature that evolves as the virus disrupts host programs and rewires modules. Time course analysis revealed rapid remodeling of diverse host systems, including signaling, RNA processing, translation, metabolism, nuclear integrity, protein trafficking, and cytoskeletal-microtubule organization, leading to cell cycle arrest, genotoxic stress, and innate immunity.

Graphical Abstract. Reproduced with permission.

 

Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID-19. Science Immunology 18 Nov 2020: Vol. 5, Issue 53, eabe8063. Full-text: https://doi.org/10.1126/sciimmunol.abe8063

In their brilliant perspective, Annika C. Karlsson and colleagues from Stockholm, Sweden summarize and speculate on a specific set of questions related to T cell immunity against respiratory viral infections, with a focus on COVID-19 severity, immunity, long-term consequences, and vaccination.

Figure 1. The unknowns about T cells in COVID-19 in relation to disease severity, memory formation and vaccination | (A) Clinical and virological factors likely to be related to the development and function of antigen-specific T cell responses against SARS-CoV-2. The impact of factors including…  | Continue reading at https://doi.org/10.1126/sciimmunol.abe8063. Reproduced with permission.

 

Cervia C, Nilsson J, Zurbuchen Y, et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol. 2020 Nov 19:S0091-6749(20)31623-7. Full-text: https://doi.org/10.1016/j.jaci.2020.10.040

Using immunoassays specific for SARS-CoV-2 spike proteins, Carlo Cervia and colleagues from Zurich, Switzerland determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of PCR positive patients and of negative HCWs. Serum IgA titers in mild COVID-19 cases were often transiently positive, whereas serum IgG titers remained negative or became positive 12-14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Interestingly, some HCWs with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases.

 

Vaccines

Lederer K, Castaño D, Atria DG, et al.  SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. Cell November 21, 2020.  Full-text: https://doi.org/10.1016/j.immuni.2020.11.009

A systematic comparison between two vaccine platforms, nucleoside modified mRNA lipid nanoparticle and recombinant protein formulated with the MF59-like adjuvant AddaVax (rRBD-AddaVax), evaluating quantitatively and qualitatively the germinal center (GC) responses to SARS-CoV-2 upon immunization. The authors found that SARS-CoV-2 mRNA vaccines had a superior capacity, in comparison to rRBD-AddaVax, to elicit potent SARS-CoV-2 specific GC B cell responses after the administration of a single vaccine dose. Importantly, they demonstrated that GC B cells and Tfh cells strongly correlated with the production of nAbs.

Graphical abstract. Reproduced with permission.

 

Clinical

Manzano GS, Woods, JK, Amato AA. Covid-19–Associated Myopathy Caused by Type I Interferonopathy. NEJM November 20, 2020. Full-text: https://doi.org/10.1056/NEJMc2031085

Myalgias and elevated creatine kinase levels are seen in many patients. Whether the elevation in creatine kinase level is caused by viral infection of muscle, toxic effects of cytokines, or another mechanism is unclear. Giovanna S. Manzano and colleagues from Boston describe a COVID-19 patient with myopathy who had a muscle-biopsy specimen showing evidence of virus-induced type I interferonopathy.

 

Treatment

Bozzi G, Mangioni D, Minoia F, et al. Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study. J Allergy Clin Immunol. 2020 Nov 18:S0091-6749(20)31621-3. PubMed: https://pubmed.gov/33220354. Full-text: https://doi.org/10.1016/j.jaci.2020.11.006

IL-1 receptor antagonist anakinra is one of the cytokine-blocking agents employed for COVID-19 treatment. Of 120 patients with hyperinflammation (33% on mechanical ventilation), 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 14% in treated patients and 36% in controls (p = 0,005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0,33, p = 0.007 and HR 0,18, p = 0,001, respectively). Randomized, controlled trials including use of either agent alone are needed to confirm these results.

 

Milewska A, Chi Y, Szczepanski A, et al. HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. J Virology November 20, 2020. Full-text: https://doi.org/10.1128/JVI.01622-20

The cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of all known human coronaviruses. Using in vitro and ex vivo models of human airway epithelium, the authors show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection.

 

22 November

Epidemiology

Thompson CN, Baumgartner J, Pichardo C, et al. COVID-19 Outbreak — New York City, February 29–June 1, 2020. MMWR 2020;69:1725–1729. Full-text:  http://dx.doi.org/10.15585/mmwr.mm6946a2

During March–May 2020, approximately 203.000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). The crude fatality rate (CFR) among confirmed cases was 9.2% overall and 32.1% among hospitalized patients. Incidence, hospitalization rates, and mortality were highest among Black/African American and Hispanic/Latino persons, as well as those who were living in neighborhoods with high poverty, aged ≥ 75 years, and with underlying medical conditions. Of note, the overall CFR of 9,2% is an overestimate because of under-ascertainment of cases, given the restrictive testing guidance and limited availability of tests during the first 2 months of the epidemic.

 

Virology

Volz E, Hill V, McCrone JT, et al. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity. Cell November 18, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.11.020

Investigating the hypothesis for positive selection of Spike D614G in more than 25.000 whole genome SARS-CoV-2 sequences from the UK, not all approaches showed a conclusive signal of positive selection. However, population genetic analysis indicated that 614G increased in frequency relative to 614D in a manner consistent with a selective advantage. 614G was also associated with higher viral load and younger age of patients.

 

Transmission

Van Dyke ME, Rogers TM, Pevzner E, et al. Trends in County-Level COVID-19 Incidence in Counties With and Without a Mask Mandate — Kansas, June 1–August 23, 2020. MMWR Morb Mortal Wkly Rep. ePub: 20 November 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6947e2

Masks work! The governor of Kansas issued an executive order requiring wearing masks in public spaces, effective July 3, 2020, which was subject to county authority to opt out. After July 3, COVID-19 incidence decreased in 24 counties with mask mandates but continued to increase in 81 counties without mask mandates. By August 17–23, 2020, the 7-day rolling average COVID-19 incidence had decreased by 6% to 16 cases per 100.000 among mandated counties and increased by 100% to 12 per 100.000 among non-mandated counties.

 

Vaccine

Lewis JR. What Is Driving the Decline in People’s Willingness to Take the COVID-19 Vaccine in the United States? JAMA Health Forum. 2020; 1(11):e201393. Full-text: https://doi.org/10.1001/jamahealthforum.2020.1393

People in the US are ready to move on from the COVID-19 pandemic, but when it comes to a vaccine, many have a wait-and-see attitude. Jarrett Ramos Lewis addresses the reasons. As we move toward having an approved COVID-19 vaccine, it is important to understand that for many, it will take time to feel comfortable and confident in getting the vaccine. While the politicization of the vaccine is to blame for some of that delay, the increased reluctance of people to get a COVID-19 vaccine runs much deeper than politics.

 

Diagnostics

Oved K, Olmer L, Shemer-Avni Y, et al. Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation. EClinical Med November 19, 2020. Full-text: https://doi.org/10.1016/j.eclinm.2020.100651

Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and Mt. Sinai ELISA were used to analyze negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients. Immunoassay sensitivities were between 81,5% – 89,4% while specificities were between 97,7% – 100%, resulting in a profound impact on the expected Positive Predictive Value in low (< 15%) prevalence scenarios. No meaningful increase was detected in the false positive rate in children compared to adults. A positive correlation between disease severity and antibody titers, and no decrease in antibody titers in the first 8 weeks after PCR positivity was observed. The authors also identified a subgroup of symptomatic SARS-CoV-2 positive patients (~5%), who remained seronegative across a wide range of antigens, isotypes, and technologies.

 

Clinical

Van den Borst B, Peters JB, Brink M, et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis 21 November 2020, ciaa1750. Full-text: https://doi.org/10.1093/cid/ciaa1750

More on “long COVID-19”. All patients discharged after COVID-19 from the Radboud University Medical Centre, Nijmegen, The Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, non-admitted patients with mild disease but with symptoms persisting > 6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest CT/X-ray, 6-minute walk test, body composition, and questionnaires. Among 124 patients (27 mild, 51 moderate, 26 severe and 20 critical), lung diffusion capacity was below the lower limit of normal in 42% of discharged patients, and 22% had low exercise capacity. Problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains of functional impairment (64%), fatigue (69%) and quality of life (72%).

 

Kennedy M, Helfand BKI, Gou RY, et al. Delirium in Older Patients With COVID-19 Presenting to the Emergency Department. JAMA Netw Open, November 19. 2020;3(11):e2029540. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.29540

In this retrospective cohort study of 817 patients older than 65 years with COVID-19 presenting at emergency departments (ED) of 7 US sites, 28% had delirium at presentation, and delirium was the sixth most common of all presenting signs and symptoms. Among delirious patients, 37% had no typical COVID-19 symptoms or signs, such as cough or fever. Factors associated with delirium (with adjusted relative risk, aRR between 1.1 and 2) were older than 75 years, living in a nursing home or assisted living, had prior use of psychoactive medication, vision impairment, hearing impairment, stroke, and Parkinson’s disease. Not very surprising: delirium was associated with ICU stay (aRR 1.67) and death (aRR 1.24).

 

Severe COVID-19

Fiacchini G, Tricò D, Ribechini A, et al. Evaluation of the Incidence and Potential Mechanisms of Tracheal Complications in Patients With COVID-19. JAMA Otolaryngol Head Neck Surg. Published online November 19, 2020. Full-text: https://doi.org/10.1001/jamaoto.2020.4148

Giacomo Fiacchini and colleagues from Pisa, Italy demonstrate a high tracheal complication rate of invasive mechanical ventilation. In their cohort study of 98 patients with COVID-19 and severe respiratory failure, the incidence of full-thickness tracheal lesions or tracheoesophageal fistulas after prolonged (≥ 14 days) invasive mechanical ventilation was significantly higher in patients with COVID-19 (46,7%) than matched controls (2,2%). Attempts to prevent these lesions should be made and quickly recognized when they occur to avoid potentially life-threatening complications in ventilated patients with COVID-19.

 

Sun L, Hymowitz M, Pomeranz HD. Eye Protection for Patients With COVID-19 Undergoing Prolonged Prone-Position Ventilation. JAMA Ophthalmol. Published online November 19, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.4988

Clinicians should also be aware of the possible presence of elevated intraocular pressure from periorbital edema due to direct compression of the eye and orbit, and optic disc edema and retinal hemorrhages, which may be associated with a hypercoagulable state, in patients in prolonged prone position. Lucy Sun and colleagues report on two patients with periorbital edema in the prone position with bilateral findings of optic disc edema and retinal hemorrhages as well as a substantial increase in intraocular pressure.

 

Pregnancy

Adhikari EH, Moreno W, Zofkie AC, et al. Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Netw Open November 19. 2020;3(11):e2029256. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.29256

Good news from Dallas, USA: in this cohort study of 252 SARS-CoV-2–positive and 3122 negative pregnant women tested in outpatient and inpatient settings at a large county medical center, adverse pregnancy outcomes were similar. Neonatal infection occurred in 3% of infants, predominantly among infants born to asymptomatic or mildly symptomatic women. Placental abnormalities were not associated with disease severity, and the rate of hospitalization was similar to rates among non-pregnant women.

 

Pediatrics

Roarty C, Tonry C, McFetridge L, et al. Kinetics and seroprevalence of SARS-CoV-2 antibodies in children. Lancet Infect Dis November 19, 2020.  Full-text: https://doi.org/10.1016/S1473-3099(20)30884-7

Antibody titers in children exposed to SARS-CoV-2 remain at a detectable level for at least 62 days.

 

 

21 November

Epidemiology

Firestone MJ, Wienkes H, Garfin J, et al. COVID-19 Outbreak Associated with a 10-Day Motorcycle Rally in a Neighboring State — Minnesota, August–September 2020. MMWR Morb Mortal Wkly Rep. ePub: 20 November 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6947e1

August 2020? Too soon for news about SARS-CoV-2 to have spread through western South Dakota, USA. Unaware of the pandemic, approximately 460.000 persons attended a motorcycle rally with numerous indoor and outdoor events over a 10-day period. The results: 51 confirmed primary event-associated cases, 21 secondary cases, and five tertiary cases. An additional nine likely rally-associated secondary or tertiary cases occurred. Four patients were hospitalized, and one died.

 

Cao S, Gan Y, Wang C, et al. Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China. Nat Commun 11, 5917 (2020). Full-text: https://doi.org/10.1038/s41467-020-19802-w

Which government wouldn’t like to have correct estimates of the prevalence of SARS-CoV-2 infection following the release of lockdown restrictions? Here is what happened in Wuhan between May 14 and June 1, 2020, where authorities ordered a city-wide SARS-CoV-2 screening program. All city residents aged six years or older were eligible and 9.899.828 (92,9%) participated. No new symptomatic cases and 300 asymptomatic cases (detection rate 0,303/10.000) were identified. There were no positive tests amongst 1174 close contacts of asymptomatic cases.

 

Al-Mandhari AS, Brennan RJ Abubakar A, Hajjeh R. Tackling COVID-19 in the Eastern Mediterranean Region. Lancet 2020, published 19 November. Full-text: https://doi.org/10.1016/S0140-6736(20)32349-7

Most countries in the Eastern Mediterranean region saw fairly slow transmission of SARS-CoV-2 during the early months of the pandemic but in May, as social measures, such as restrictions and partial or full lockdowns, were relaxed during the holy month of Ramadan, disease transmission accelerated.

 

Immunology

Bourdon M, Manet C, Montagutelli X. Host genetic susceptibility to viral infections: the role of type I interferon induction. Genes Immun (2020). https://doi.org/10.1038/s41435-020-00116-2

The innate immune response is the major front line of defense against viral infections. It involves hundreds of genes with antiviral properties whose expression is induced by type I interferons (IFNs) and are therefore called interferon-stimulated genes (ISGs). The authors review the role of the molecular partners of the type I IFNs induction pathway and their implication in the control of viral infections and of their complications. Be prepared: not all mechanisms are yet fully understood.

 

Meyerholz DK, Perlman S. Does common cold coronavirus infection protect against severe SARS-CoV-2 disease? J Clin Invest 2020, published 20 November. Full-text: https://doi.org/10.1172/JCI144807

Read this comment by David Meyerholz and Stanley Perlman on a paper we presented on 9 October [Sagar M, Reifler K, Rossi M, et al. Recent endemic coronavirus infection is associated with less severe COVID-19. J Clin Invest. 2020 Sep 30:143380. PubMed: https://pubmed.gov/32997649. Full-text: https://doi.org/10.1172/JCI143380] where Joseph Mizgerd, Manish Sagar and colleagues showed that individuals with a previously detected eCoV infection had less severe COVID-19 illness.

 

Diagnostics

Qian J, Boswell SA, Chidley C, et al. An enhanced isothermal amplification assay for viral detection. Nat Commun 11, 5920 (2020). Full-text: https://doi.org/10.1038/s41467-020-19258-y

Michael Springer, Jason Qian and colleagues from Harvard Medical School report the development of a molecular diagnostic test for SARS-CoV-2 based on an enhanced recombinase polymerase amplification (eRPA) reaction. eRPA has a detection limit on patient samples down to 5 viral copies, requires minimal instrumentation, and is highly scalable and inexpensive. The protocol reported here was developed and optimized in less than 3 weeks, with an additional 4 weeks for sample preparation optimization, and patient sample acquisition. Good news for future pandemics.

 

Arizti-Sanz J, Freije CA, Stanton AC, et al. Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2. Nat Commun 11, 5921 (2020). Full-text: https://doi.org/10.1038/s41467-020-19097-x

Cameron Myhrvold, Jon Arizti-Sanz and colleagues from Princeton University describe SHINE (Streamlined Highlighting of Infections to Navigate Epidemics), an extraction-free, rapid, and sensitive detection tool for SARS-CoV-2 RNA. The results can be visualized with an in-tube fluorescent readout — reducing contamination risk as amplification reaction tubes remain sealed — and interpreted by a companion smartphone application. Validation on 50 nasopharyngeal patient samples showed 90% sensitivity and 100% specificity with a sample-to-answer time of 50 min.

 

Clinical

Datta SD, Talwar A, Lee JT. A Proposed Framework and Timeline of the Spectrum of Disease Due to SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health Implications. JAMA. Published online November 18, 2020. Full-text: https://doi.org/10.1001/jama.2020.22717

Morbidity from SARS-CoV-2 goes beyond acute infection. Amish Talwar, Deblina Datta and James Lee from the CDC propose a framework of three distinct illness periods associated with SARS-CoV-2 infection: 1) acute infection; 2) a rare post-acute hyperinflammatory illness after roughly two weeks; and 3) a stage of late inflammatory and virological sequelae. These illness periods also capture distinct phases of host-viral interaction.

 

Severe COVID

Al-Salameh A, Lanoix JP, Bennis Y, et al. The association between body mass index class and coronavirus disease 2019 outcomes. Int J Obes (2020). Full-text: https://doi.org/10.1038/s41366-020-00721-1

Being overweight (and not only obesity) is associated with ICU admission, but is not associated with death. This is the result of a retrospective study from Amiens University Hospital, France. In total, 433 consecutive patients were included, and BMI data were available for 329: 20 were underweight (6,1%), 95 had a normal weight (28,9%), 90 were overweight (27,4%), and 124 were obese (37,7%). The ORs for ICU admission were similar for overweight (3.16) and obesity (3.05).

 

 

20 November

Epidemiology

Van Dorp L, Tan CCS, Datt Lam S, et al. Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation. bioRxiv 2020, posted 16 November. Full-text: https://doi.org/10.1101/2020.11.16.384743

If you introduce SARS-CoV-2 in mink farms, it spreads and mutates rapidly. This is the result of a study which looked into 239 viral genomes isolated from farmed animals in the Netherlands and Denmark. The authors identified 23 recurrent mutations including three mutations in the Receptor Binding Domain of the SARS-CoV-2 spike protein that independently emerged at least four times but are only rarely observed in human lineages. Reassuringly, the authors state that the low prevalence of mink-adapted mutations in strains circulating in humans to date (November 2020) suggests that they are not expected to increase transmission of SARS-CoV-2 in humans.

 

Virology

Klein S, Cortese M, Winter SL, et al. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat Commun 11, 5885 (2020). Full-text: https://doi.org/10.1038/s41467-020-19619-7

How is the unusually large SARS-CoV-2 genome incorporated into the virion? Find the answer in this paper by Petr Chlanda, Ralf Bartenschläger, Steffen Klein and colleagues. The authors characterized the viral replication compartment and report critical insights into the budding mechanism of SARS-CoV-2.

 

Transmission

Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J, Ho A. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Lancet Microbe 2020, published 19 November. Full-text: https://doi.org/10.1016/S2666-5247(20)30172-5

After this meta-analysis of 79 studies (5340 individuals) on SARS-CoV-2, the authors report that no study detected live virus beyond day 9 of illness, despite persistently high viral loads. Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. Please communicate this finding to state authorities (for example, in Italy) which require negative RT-PCR tests before allowing citizens who recovered from SARS-CoV-2 infection to go back to normal life.

 

Heidt A. COVID-19 Diagnostics: How Do Saliva Tests Compare to Swabs? The Scientist 2020, published 9 October. Full-text: https://www.the-scientist.com/news-opinion/covid-19-diagnostics-how-do-saliva-tests-compare-to-swabs–68035

A lay press article going in the same direction. From hospitals and college campuses to remote villages in French Guiana, scientists pit the two approaches against one other.

 

Immunology

Yu X, Cragg MS. Engineered antibodies to combat viral threats. Nature 2020, published 18 November. Full-text: https://www.nature.com/articles/d41586-020-03196-2

A Nature News and Views article by Xiaojie Yu and Mark Cragg. As the COVID-19 pandemic rages globally, interest in antiviral treatments has never been higher. Antibodies are key defense components and engineering them to better exploit their natural functions might boost therapeutic options.

 

Vaccine

Editorial. COVID-19 vaccines: no time for complacency. Lancet 2020, published 21 November. Full-text: https://doi.org/10.1016/S0140-6736(20)32472-7

“‘Yes. Yes. Yes.’ That was the response of John Bell, Regius Professor of Medicine at the University of Oxford, when asked whether we could be confident that life will be returning to normal by spring.” Of course, we will not return to normal life within 6 months. Let’s lean back and be satisfied that in less than a year, we have characterized a novel illness, sequenced a new viral genome, developed diagnostics, produced treatment protocols, and established the efficacy of drugs and vaccines in randomized controlled trials. There is no hurry. If we can achieve some kind of pre-COVID-19 ‘normalcy’ by 2022, it would be a feat remembered by generations.

 

Diagnostics

Karp DG, Danh K, Espinoza NF, et al. A serological assay to detect SARS-CoV-2 antibodies in at-home collected finger-prick dried blood spots. Sci Rep 10, 20188 (2020). Full-text: https://doi.org/10.1038/s41598-020-76913-6

The authors report a self-collection kit for at-home finger-prick dried blood spot collection. The results suggest 100% sensitivity and specificity. If proven successful at a large scale, such methods could facilitate the conduct of unbiased serosurveys in hard-to-reach populations.

 

Clinical

Meduri A, Oliverio GW, Mancuso G, et al. Ocular surface manifestation of COVID-19 and tear film analysis. Sci Rep 10, 20178 (2020). https://doi.org/10.1038/s41598-020-77194-9

No SARS-CoV-2 in tears – that’s the result of a study in 29 hospitalized patients. Ocular symptoms, reported in a third of the patients, included eye burning, foreign body sensation and three reported tearing. Seven patients presented conjunctival hyperemia and/or chemosis, and eleven patients presented blepharitis signs such as lid margin hyperemia and/or telangiectasia, crusted eyelashes, and alterations of the meibomian orifices.

 

Severe COVID

Jain A, Chaurasia R, Sengar NS, et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10, 20191 (2020). https://doi.org/10.1038/s41598-020-77093-z

A higher fatality rate in vitamin D deficient patients (21% vs 3.1%)? Vitamin D levels markedly low in patients with severe COVID-19? These are the conclusions of a study including asymptomatic 91 COVID-19 patients (Group A) and 63 severely ill patients requiring ICU admission (Group B). The prevalence of vitamin D deficiency was 32.96% and 96.82% respectively in Group A and Group B.

 

Gu SX, Tyagi T, Jain K, et al. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nat Rev Cardiol (2020). https://doi.org/10.1038/s41569-020-00469-1

The authors summarize evidence pointing to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19. Discover potential therapeutic strategies in the management of patients with COVD-19.

 

Spanish

If you read Spanish, please read Camhaji E, Barragán A, Cullell JM, Breña  CM, Galindo J. 100.000 muertos en México – Radiografía de un país. El País 2020, published 20 November. Full-text: https://elpais.com/mexico/2020-11-20/100000-muertos-en-mexico-radiografia-de-un-pais-roto.html

México rompe la barrera psicológica de un millón de casos confirmados y 100.000 fallecimientos por coronavirus con hartazgo, desgaste y más dudas que certezas sobre el fin de la pandemia.

 

González B. ¿Por qué los colegios no se han convertido en un foco de contagios de covid? – El País 2020, published 19 November. Full-text: https://elpais.com/buenavida/salud/2020-11-18/por-que-los-colegios-no-se-han-convertido-en-un-foco-de-contagios-de-covid.html

Los expertos analizan distintas teorías que explican que las clases en cuarentena sean solo en torno al 1.5% del total.

 

19 November

Immunology

Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv 2020, posted 16 November. Full-text: https://doi.org/10.1101/2020.11.15.383323

As we approach the end of Year 1 of the SARS-CoV-2 pandemic, we realize that although millions of people were infected during spring 2020, there is now, 8 months later, no sizeable epidemic of re-infections. This observation suggests that SARS-CoV-2 infection might confer a solid immunity. Now, Shane Crotty, Alessandro Sette, Daniela Weiskopf, Jennifer Dan and colleagues analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 185 COVID-19 cases, including 41 cases at > 6 months post-infection. The result: Spike IgG was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. These findings might suggest that after SARS-CoV-2 infection (or after vaccination), the vast majority of people could be protected against severe COVID-19 for years.

Read also the NYTimes article by Mandavilli A. Immunity to the Coronavirus May Last Years, New Data Hint. The New York Times 2020, published 17 November. Full-text: https://www.nytimes.com/2020/11/17/health/coronavirus-immunity.html

 

Epidemiology

Xing Y, Wong GWK, Ni W, Hu X, Xing Q. Rapid Response to an Outbreak in Qingdao, China. N Engl J Med 2020, published 18 November. Full-text: https://doi.org/10.1056/NEJMc2032361

Three COVID-19 cases in Qingdao in October: a taxi driver who was admitted to Qingdao Central Hospital for a transient ischemic attack on October 10; his wife who had been working part-time as a nursing assistant at Qingdao Chest Hospital; and a man with pulmonary tuberculosis who was treated at the same hospital. These were the first cases after a 2-month period without local SARS-CoV-2 transmission in China. What would you have done during the next 7 days? The Chinese authorities tested 10.9 million people and identified another 9 cases related to the initial cluster. The outbreak was controlled without a lockdown.

 

Prevention

Bundgaard H, Bundgaard JS, Raaschou-Pedersen DET, et al. Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial. Ann Intern Med. 2020 Nov 18. PubMed: https://pubmed.gov/33205991. Full-text: https://doi.org/10.7326/M20-6817

Ammunition for your friends who deny the usefulness of wearing face masks? This Danish study finds that wearing surgical masks doesn’t really reduce the SARS-CoV-2 infection rate among wearers. Don’t read the article without reading the comment by Laine C, Goodman SN, Guallar E. The Role of Masks in Mitigating the SARS-CoV-2 Pandemic: Another Piece of the Puzzle. Ann Intern Med. 2020 Nov 18. PubMed: https://pubmed.gov/33205993. Full-text: https://doi.org/10.7326/M20-7448 and the editorial by Frieden TR, Cash-Goldwasser S. Of Masks and Methods. Ann Intern Med. 2020 Nov 18. PubMed: https://pubmed.gov/33205992. Full-text: https://doi.org/10.7326/M20-7499. And maybe we should ask researchers from South-East Asia to repeat the study.

Continue wearing face masks!

 

Vaccine

Ramasamy MN, Minassian AM, Ewer KJ, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet 2020, published 18 November. Full-text: https://doi.org/10.1016/S0140-6736(20)32466-1

Phase II results of a single-blind, randomized, controlled trial that describe the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in a wide range of participants, including adults aged 70 years and older. The results are encouraging: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose.

See also the comment by Andrew MK, McElhaney JE. Age and frailty in COVID-19 vaccine development. Lancet 2020, published 18 November. Full-text: https://doi.org/10.1016/S0140-6736(20)32481-8

 

 

Knipe DM, Levy O, Fitzgerald KA, Mühberger E. Ensuring vaccine safety. Science 2020, published 17 November. Full-text: https://doi.org/10.1126/science.abf0357

Vaccines are among the most successful medical and public health measures ever implemented and prevent ~6 million deaths globally per year. Efficient SARS-CoV-2 vaccines might prevent a similar number of deaths over the coming years. However, caution the authors, the urgent need for COVID-19 vaccines must be balanced with the imperative of ensuring safety and public confidence in vaccines by following the established clinical safety testing protocols throughout vaccine development, including both pre- and post-deployment.

 

Wadman M. Fever, aches from Pfizer, Moderna jabs aren’t dangerous but may be intense for some. Science 2020, published 18 November. Full-text: https://www.sciencemag.org/news/2020/11/fever-aches-pfizer-moderna-jabs-aren-t-dangerous-may-be-intense-some

Both the BioNTech/Pfizer and the Moderna/NIH mRNA vaccine reached 95% efficacy in clinical trials of tens of thousands of people. The trials revealed no serious safety concerns. We will learn to accept fever and aches as signs that the vaccine works. Even bone and muscle aches and an almost unbearable 38.9°C fever that lasts 12 hours…

 

Clinical

Dhawan  R, Gopalan D, Howard L, et al. Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19. Lancet Repiratory Medicine 2020, published 17 October. Full-text: https://doi.org/10.1016/S2213-2600(20)30407-0

The long-term outcomes in survivors of COVID-19 are unknown at present. As pulmonary thrombosis and thromboembolism occur during clinical SARS-CoV-2 infection, the authors propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential hemodynamic sequelae that might affect quality of life for a long time.

 

Education

Rubin EJ, Baden LR, Morrissey S. Covid-19 in Europe and New Information on Vaccines. Audio interview (26:44). N Engl J Med 2020; 383: e134. Access: https://doi.org/10.1056/NEJMe2033666

The editors discuss both recent vaccine trial results and the state of the pandemic in Europe.

 

Spanish

Sámano J. España abochorna a Alemania. El País 2020, published 17 November. Full-text: https://elpais.com/deportes/2020-11-17/espana-abochorna-a-alemania.html

La nueva generación de la Roja lo borda con una goleada de época a la selección de Löw y jugará la fase final de la Liga de las Naciones.

 

Ansede M. El mayor estudio hasta la fecha sugiere que las defensas contra el coronavirus pueden durar años. El País 2020, published 19 November. Full-text: https://elpais.com/ciencia/2020-11-18/el-mayor-estudio-hasta-la-fecha-sugiere-que-las-defensas-contra-el-coronavirus-pueden-durar-anos.html

Un análisis exhaustivo de 185 personas que han superado la covid muestra una respuesta inmune potente y duradera.

 

Domínguez N. Las incógnitas sobre la primera vacuna “eficaz” contra el coronavirus. El País 2020, published 19 November. Full-text: https://elpais.com/ciencia/2020-11-14/las-incognitas-sobre-la-primera-vacuna-eficaz-contra-el-coronavirus.html

El anuncio de una inyección efectiva en un 90% realizado por Pfizer esta semana deja más preguntas que respuestas.

 

French

Simonnet G. « L’être humain n’accepte plus d’être malade » | Le Monde 2020, published 19 November. Full-text : https://www.lemonde.fr/idees/article/2020/11/19/guy-simonnet-l-etre-humain-n-accepte-plus-d-etre-malade_6060282_3232.html

Rappelant que « le vivant est avant tout incertitude », le neurobiologiste Guy Simonnet souligne qu’une « tolérance zéro maladie » ne peut qu’être la source d’une nouvelle vulnérabilité.

 

Caramel L. « Peu de malades ont développé des formes graves du Covid-19 en Afrique » – Le Monde 2020, published 19 November. Full-text : https://www.lemonde.fr/afrique/article/2020/11/18/peu-de-malades-ont-developpe-des-formes-graves-du-covid-en-afrique_6060239_3212.html

Laurence Caramel, journaliste au « Monde Afrique », a répondu à vos questions sur les raisons de l’« exception africaine » face à la pandémie mondiale.

 

Audureau W. Covid-19 : pourquoi bars et restaurants sont considérés comme étant à risque F – Le Monde 2020, published 18 November. Full-text : https://www.lemonde.fr/les-decodeurs/article/2020/11/18/pourquoi-bars-et-restaurants-sont-consideres-comme-etant-a-risques_6060234_4355770.html

S’il est globalement très difficile de remonter le fil, plusieurs études de cas ont démontré le risque de ces lieux, malgré les démentis des restaurateurs.

 

18 November

Epidemiology

Denny TN, Andrews L, Bonsignori M, et al. Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus — Duke University, Durham, North Carolina, August 2–October 11, 2020. MMWR Morb Mortal Wkly Rep. ePub: 17 November 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6946e1

Test them all? In fall 2020, Duke University’s COVID-19 prevention strategy included risk reduction behaviors, but also frequent testing using pooled SARS-CoV-2 PCR testing, and contact tracing. Of 10,265 students who received testing 68,913 times, 84 had positive results. Of these, 51% were asymptomatic, and some had high viral loads. This plan allowed campus to remain open for 10 weeks of classes without substantial outbreaks among residential or off-campus populations. Importantly, no evidence from contact tracing linked transmission with in-person classes. Pooled testing permitted a nearly 80% savings in use of reagents and laboratory resources compared with testing each individual specimen.

 

Immunology

Samuel RM, Majd H, Richter MN, et al. Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men. Cell Stem Rep November 17, 2020.  Full-text: https://doi.org/10.1016/j.stem.2020.11.009

Finasteride for COVID-19? Ryan M. Samuel and colleagues from San Francisco identified a link between male sex hormone signaling and regulation of the SARS-CoV-2 receptor ACE2 and co-receptor TMPRSS2, possibly explaining the higher complication rates in men. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. Of note, treatment with anti-androgenic drugs such as finasteride reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection. Finally, clinical data on COVID-19 patients demonstrated that prostate diseases, which are linked to elevated androgen, are significant risk factors and genetic variants that increase androgen levels are associated with higher disease severity.

 

Li A, Ling Y, Song Z, et al. Early plasma IL-37 responses accompanied with low inflammatory cytokines correlate with benign clinical outcomes during SARS-CoV-2 infection. J Infect Dis. 2020 Nov 17:jiaa713. PubMed: https://pubmed.gov/33197260. Full-text: https://doi.org/10.1093/infdis/jiaa713

Ang Li and colleagues from Shanghai examined early responses of IL-37, a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients prior to any clinical intervention and determined its correlation with clinical prognosis. Higher early IL-37 responses correlated with earlier viral RNA negative conversion, chest CT image improvement and cough relief, consequently resulting in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower IL-6 and IL-8 and higher IFN-α, and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and CRP. Moreover, IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in hACE2-transgenic mice infected with SARS-CoV-2.

 

Woldemeskel BA, Kwaa AK, Garliss CC, Laeyendecker O, Ray SC, Blankson JN. Healthy donor T cell responses to common cold coronaviruses and SARS-CoV-2. J Clin Invest. 2020 Nov 16:143120. PubMed: https://pubmed.gov/32966269. Full-text: https://doi.org/10.1172/JCI143120

Bezawit A. Woldemeskel and colleagues from Baltimore used the ELISPOT assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses and SARS-CoV-2 in 21 healthy donors seronegative for SARS-CoV-2. An in vitro expansion culture assay was also used to analyze memory T cell responses. Responses to the spike protein of the 3 common cold coronaviruses were found in many of the donors. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses.

 

Vaccine

Zhang Y, Zeng G, Pan H. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet November 17, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30843-4

Phase I/II study of an inactivated vaccine candidate against COVID-19. In total, 743 participants at the Suining County of Jiangsu province, China, received at least one dose (n = 143 for Phase 1 and n = 600 for Phase 2; safety population). At day 28 after the days 0 and 28 vaccination schedule, seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group which is the suggested dose for efficacy assessment in future Phase III trials. Adverse events such as mild injection-site pain, occurred in 81 (17%) of 480 vaccine recipients.

 

Bar-Zeev N, Kochhar S. Expecting the unexpected with COVID-19 vaccines. Lancet November 17, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30870-7

According to this detailed comment, like all Phase II trials, the results must be interpreted with caution until Phase III results are published. Neutralising titers were substantially lower than those seen in 117 convalescent patients who previously had COVID-19 tested in the same laboratory. A demonstration of longevity of response and of empiric protection from this vaccine candidate will be important.

 

Clinical

Bois MC, Boire NA, Layman AJ, et al. COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. Circulation. 2020 Nov 16. PubMed: https://pubmed.gov/33197204. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050754

What are the underlying mechanisms of cardiac complications? This small, but detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series of 15 COVID-19 cases showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently had cardiac fibrin microthrombi (12/16), without universal acute ischemic injury. Moreover, myocarditis was present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

 

Vaira LA, Hopkins C, Sandison A, et al. Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia. J Laryngol Otol. 2020 Nov 16:1-13. PubMed: https://pubmed.gov/33190655. Full-text: https://doi.org/10.1017/S0022215120002455

Interesting case report of a patient who presented with anosmia persisting for more than three months after infection. MRI did not reveal any pathological findings: the olfactory bulb and clefts were of normal volume, without signal anomalies. However, the biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

 

Alvarez-Garcia J, Lee S, Gupta A, et al. Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2020 Nov 17;76(20):2334-2348. PubMed: https://pubmed.gov/33129663. Full-text: https://doi.org/10.1016/j.jacc.2020.09.549

Retrospective analysis of 6439 patients admitted for COVID-19 at 5 hospitals in New York City between February 27 and June 26, 2020. Compared with patients without heart failure (HF), those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%), and mortality (40.0% vs. 24.9%). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.

 

Collateral damage

De Luca G, Verdoia M, Cercek M, et al. Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI. J Am Coll Cardiol. 2020 Nov 17;76(20):2321-2330. PubMed: https://pubmed.gov/33183506. Full-text: https://doi.org/10.1016/j.jacc.2020.09.546

A total of 6609 patients underwent primary percutaneous coronary intervention (PPCI) in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.81; 95% confidence interval: 0.78 to 0.84). Furthermore, the pandemic was associated with a significant increase in “door-to-balloon” and total ischemia times, which may have contributed to higher mortality during the pandemic.

 

Co-morbidities

Shah GL, DeWolf S, Lee YJ, et al. Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. J Clin Invest. 2020 Nov 16:141777. PubMed: https://pubmed.gov/32897885. Full-text: https://doi.org/10.1172/JCI141777

Gunjan L. Shah from Memorial Sloan Kettering Cancer Center and colleagues retrospectively investigated 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days). Overall survival at 30 days was 78%. Mortality was largely driven by patients with active malignancy, especially relapsed leukemia, in whom the goals of care were affected both by COVID-19 severity and the decision to forgo anti-cancer treatment during an active infection. Immune profiling revealed reductions and rapid recovery in lymphocyte populations across lymphocyte subsets. Many patients were able to recover from COVID-19 infection and mount an antibody response with similar overall survival to the general hospitalized population.

 

17 November

Epidemiology

Mahale P, Rothfuss C, Bly S, et al. Multiple COVID-19 Outbreaks Linked to a Wedding Reception in Rural Maine — August 7–September 14, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1686–1690. Full-text: http://dx.doi.org/10.15585/mmwr.mm6945a5

Do you have a niece who, despite all the warnings, is unwaveringly sticking to her plans to get married in January? Who says that only 50 guests (ok, 55) will come and that temperature checks for all guests will be conducted at the facility entrance? That there will be enough space, with 10 tables, with 4–6 guests seated around each table? That signs posted at the entrance will instruct visitors to wear masks? Then give her this paper to read. A wedding reception in a small rural town in Maine was the likely source of COVID-19 outbreaks in the local community, a long-term care facility, and a correctional facility. Outcome: 177 cases, seven hospitalizations, and seven deaths. Read here why people should avoid large gatherings, practice physical distancing, wear masks, stay home when ill, and self-quarantine after exposure to a person with confirmed SARS-CoV-2 infection.

(If your niece doesn’t want to read a scientific paper, provide her with “15 Benefits of A Summer Wedding”: https://www.nichemarket.co.za/blog/extravaganza/benefits-summer-wedding. Benefit No. 16 is found probably below, in the vaccine section.)

Graphical abstract:

 

 

Ali H, Kondapally K, Pordell P, et al. COVID-19 Outbreak in an Amish Community — Ohio, May 2020. MMWR Morb Mortal Wkly Rep 2020;69:1671–1674. Full-text:  http://dx.doi.org/10.15585/mmwr.mm6945a2

How social gatherings likely contributed to rapid transmission of SARS-CoV-2 in an Amish community. In May, after a cluster of seven COVID-19 cases was identified, 23/30 (77%) additional residents tested by RT-PCR received positive test results. Rapid and sustained transmission of SARS-CoV-2 was associated with multiple social gatherings. Although Amish communities might be experiencing challenges with preventing and mitigating SARS-CoV-2 transmission, the authors conclude that leveraging Amish cultural beliefs of communal responsibility could help limit the spread of SARS-CoV-2.

 

Wang EA, Western B, Berwick DM. COVID-19, Decarceration, and the Role of Clinicians, Health Systems, and Payers. A Report From the National Academy of Sciences, Engineering, and Medicine. JAMA November 16, 2020. Full-text: https://doi.org/10.1001/jama.2020.22109

By August 2020, 90 of the largest 100 cluster outbreaks in the United States had occurred in prisons and jails. Reducing the incarcerated population (“decarceration”) is an important and urgent strategy for mitigating viral transmission in prisons and jails. In their courageous viewpoint, Emily Wang and colleagues argue that decarceration in the service of both public health and safer communities will require sustained engagement from clinicians, health systems, and Medicaid authorities.

 

Immunology

Knierman MD, Lannan MB, Spindler LJ, et al. The Human Leukocyte Antigen Class II Immunopeptidome of SARS-CoV-2 Spike Glycoprotein. Cell Rep November 13, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108454

Using mass spectrometry, Michael D Knierman and colleagues from Lilly performed a precise and comprehensive immunopeptidomic investigation with SARS-CoV-2 spike glycoprotein. They identified 526 unique sequences from SARS-CoV-2 spike glycoprotein extracellular domain in a complex with HLA class II molecules on antigen presenting cells from a panel of healthy donors. The identified sequences spanned the entire spike protein and several sequences were isolated from a majority of the donors sampled, indicating promiscuous binding. This is good news, as both the depth and breadth of the HLA-II peptides indicate that mutational drift is not expected to dramatically alter the ability of an infected individual to mount a new B cell response.

 

Vaccine

Callaway E. COVID vaccine excitement builds as Moderna reports third positive result. Nature NEWS November 16, 2020. Full-text: https://doi.org/10.1038/d41586-020-03248-7

Moderna’s vaccine comprises RNA instructions for cells to produce a modified form of the coronavirus spike protein, the immune system’s key target against coronaviruses. Of note, the vaccine remains stable in conventional refrigerators for a month and ordinary freezers for six months. Ewen Callaway summarizes preliminary data showing that the immunization is 94% effective and seems to prevent severe infections.

 

Diagnostics

Gniffke EP, Harrington WE, Dambrauskas N, et al. Plasma From Recovered COVID-19 Patients Inhibits Spike Protein Binding to ACE2 in a Microsphere-Based Inhibition Assay. J Infect Dis. 2020 Nov 13;222(12):1965-1973. PubMed: https://pubmed.gov/32798222 . Full-text: https://doi.org/10.1093/infdis/jiaa508

A new microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to ACE2. Plasma from 22 patients who had recovered from mild COVID-19 and expressed anti–spike protein trimer immunoglobulin G (IgG) inhibited ACE2–spike protein binding to a greater degree than controls. The degree of inhibition was correlated with anti–spike protein IgG levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of patients recovered from COVID-19 or vaccine recipients in a cell-free assay system.

 

Clinical

Coate KC, Cha , Shrestha S. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Microvasculature and Ducts of Human Pancreas but are Not Enriched in β Cells. Cell Metabolism November 13, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.11.006

Isolated reports of new-onset diabetes in COVID-19 cases have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. Katie Coate and colleagues show here that it’s not that easy. In pancreatic sections, ACE2 and TMPRSS2 protein (the main cell entry factors) were not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. Contrasting with previous reports, this careful investigation suggests that the interaction of diabetes and SARS-CoV-2 is mediated by systemic inflammation and/or metabolic changes in other organs such as liver, muscle or adipose tissue (and not by a direct infection of β cells in the pancreas).

 

Shi Z, de Vries HJ, Vlaar AP, et al. Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. JAMA Intern Med November 16, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6278

This study focused on the diaphragm, the main muscle of respiration. Consecutive diaphragm muscle specimens from 26 deceased COVID-19 patients were compared with autopsy diaphragm specimens of 8 patients who had been critically ill without COVID-19. There was an increased expression of genes involved in fibrosis and histological evidence for the development of fibrosis in the diaphragm. Of note, this myopathic phenotype was distinctly different from that of control ICU patients, with comparable duration of mechanical ventilation and ICU length of stay. It is hypothesized that severe myopathy may lead to diaphragm weakness and might contribute to ventilator weaning failure, persistent dyspnea, and fatigue in COVID-19 survivors.

 

Miller DG, Piesron L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Annals Int Med 2020, November 17. Full-text: https://doi.org/10.7326/L20-1195

Interesting discussion about in-person medical student involvement during the COVID-19 pandemic. Some authors argue for it, others against it. Both sides have good arguments.

 

Collateral Damage

Leske S, Kõlves K, Cromton D, et al. Real-time suicide mortality data from police reports in Queensland, Australia, during the COVID-19 pandemic: an interrupted time-series analysis. Lancet Psychiatry, November 16, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30435-1

Do suicide rates increase during infectious disease outbreaks? Probably not (at least in Australia). In this study, analyzing suspected suicide rates in 2020 relative to 2015–19 to assess any early effects of the COVID-19 pandemic in Queensland, no evidence of a change in suspected suicide rates was seen.

 


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