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By Christian Hoffmann &
Bernd S. Kamps
26 May
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Summary
First, investigate if social connectedness is a risk factor for the spreading of COVID-19 among older adults; analyze a South African outbreak involving 39 patients and 80 staff; and detect SARS-CoV-2 in human breastmilk.
Afterwards, examine factors associated with hospital admission and critical illness among 5279 people in New York; manage different cases of STEMI/NSTEMI ACS with potential or known COVID-19 infection; evaluate if CRP performs better than other parameters (age, neutrophil count, platelet count) in predicting adverse outcome; and discuss with your colleagues if we should one day measure the “viral load”?
Finally, apply past lessons learned from sepsis to immunotherapies for COVID-19; explain why lopinavir concentrations in 12 COVID-19 patients are higher than in HIV-infected patients; and compare individual quarantine with active monitoring targeted by contact tracing.
Epidemiology
Peak CM, Kahn R, Grad YH, et al. Individual quarantine versus active monitoring of contacts for the mitigation of COVID-19: a modelling study. Lancet Infect Dis. 2020 May 20. PubMed: https://pubmed.gov/32445710. Full-text: https://doi.org/10.1016/S1473-3099(20)30361-3
Complex models, comparing individual quarantine (separation from others of an individual who is believed to be exposed to the disease but not currently showing symptoms) with active monitoring targeted by contact tracing (assessing for symptoms at regular intervals such as twice-daily visits by HCW or phone-based self-monitoring, and if symptoms are detected, the individual is promptly isolated). Bottom line: It depends. It depends on the assumptions regarding the serial interval, the amount of transmission that occurs before symptom onset, and the feasibility setting. With a short mean serial interval of 4.8 days and hence substantial pre-symptomatic infectiousness, individual quarantine was considerably more effective than active monitoring at reducing onward transmission. With longer serial intervals both active monitoring and individual quarantine effectively reduce transmission.
Liotta G, Marazzi MC, Orlando S. Is social connectedness a risk factor for the spreading of COVID-19 among older adults? The Italian paradox. PLOS May 21, 2020. Full-text:
One hypothesis about the fatal spread of SARS-CoV-2 in Italy is that the supposed closeness between younger and older generations in Italian families may have played a major role. In this study, this was not confirmed. Paradoxically, it seemed that the variables associated with social isolation were risk factors for higher rates among the elderly. Social relationships may be protective against increased mortality rates during a crisis impacting the frailest populations. Instead, availability of beds in nursing homes were one of the determinants of infection rate among individuals aged >80.
Transmission
Nordling L. Study tells ‘remarkable story’ about COVID-19’s deadly rampage through a South African hospital. May 25, 2020. Full-text: https://www.sciencemag.org/news/2020/05/study-tells-remarkable-story-about-covid-19-s-deadly-rampage-through-south-african
Screen the staff! Incredible story about a man who sought help for coronavirus symptoms on March 9, spending only a few hours at the emergency department of a hospital in Durban, South Africa. He was kept separate in a triage area, but that room was reached through the main resuscitation bay, where a stroke patient occupied a bed. Both patients were seen by the same doctor. After likely transmitting the virus to the stroke patient, the results, eight weeks later were: 39 patients and 80 staff linked to the hospital had been infected, and 15/39 patients had died. Lesson learnt: Nosocomial outbreaks may be a major amplifier of COVID-19 transmission.
Groß R, Conzelmann C, Müller JA, et al. Detection of SARS-CoV-2 in human breastmilk. Lancet. 2020 May 21:S0140-6736(20)31181-8. PubMed: https://pubmed.gov/32446324. Full-text: https://doi.org/10.1016/S0140-6736(20)31181-8
SARSCoV2 RNA in milk samples from an infected mother (two mothers were examined) was found on 4 consecutive days. Detection of viral RNA in milk coincided with mild COVID19 symptoms and a SARSCoV2 positive diagnostic test of the newborn.
Diagnostics
Han MS, Byun JH, Cho Y, Rim JH. RT-PCR for SARS-CoV-2: quantitative versus qualitative. Lancet Infect Dis. 2020 May 20:S1473-3099(20)30424-2. PubMed: https://pubmed.gov/32445709. Full-text: https://doi.org/10.1016/S1473-3099(20)30424-2
Should we measure the “viral load”? Unfortunately, there is wide heterogeneity and inconsistency of the standard curves calculated from studies that provided Ct values from serial dilution samples and the estimated viral loads. According to the authors, precautions are needed when interpreting the Ct values of SARS-CoV-2 RT-PCR results shown in COVID-19 publications to avoid misunderstanding of viral load kinetics for comparison across different studies.
Luo X, Zhou W, Yan X, et al. Prognostic value of C-reactive protein in patients with COVID-19. Clin Infect Dis. 2020 May 23:ciaa641. PubMed: https://pubmed.gov/32445579. Full-text: https://doi.org/10.1093/cid/ciaa641
In 359 patients, CRP performed better than other parameters (age, neutrophil count, platelet count) in predicting adverse outcome. Besides, admission serum CRP level was identified as a moderate discriminator of disease severity.
Clinical
Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020 May 22;369:m1966. PubMed: https://pubmed.gov/32444366. Full-text: https://doi.org/10.1136/bmj.m1966
Of 5,279 cases confirmed in a large medical center in New York, 52% were admitted to hospital, of whom 1,904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age with an odds ratio of 37.9 for ages 75 years and older. Other risks were heart failure (OR 4.4), male sex (2.8), chronic kidney disease (2.6), and BMI >40 (2.5). Admission oxygen saturation of <88% (3.7), troponin level >1 (4.8), CRP >200 (5.1), and D dimer level >2500 (3.9) were more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone.
Cormorbidities
Valente S, AnselmiF, Cameli M. Acute coronary syndromes during COVID-19. European Heart Journal, 2020, May 25. Full-text: https://doi.org/10.1093/eurheartj/ehaa457.
Brief guide for clinicians for managing different cases of STEMI/NSTEMI ACS with potential or known COVID-19 infection, based on recent worldwide evidence and standardization protocols.
Treatment
Remy KE, Brakenridge SC, Francois B, et al. Immunotherapies for COVID-19: lessons learned from sepsis. Lancet Respir Med. 2020 Apr 28. PubMed: https://pubmed.gov/32444269. Full-text: https://doi.org/10.1016/S2213-2600(20)30217-4
The hypothesis that quelling the cytokine storm with anti-inflammatory therapies directed at reducing interleukin-6 (IL-6), IL-1, or even tumour necrosis factor α (TNFα) might be beneficial has led to several ongoing trials. The authors are less enthusiastic and urge caution. Past attempts to block the cytokine storm associated with other microbial infections and with sepsis have not been successful and, in some cases, have worsened outcomes. Moreover, there is concern that suppressing the innate and adaptive immune system to address increased cytokine concentrations, could enable unfettered viral replication, suppress adaptive immunity, and delay recovery processes. There is growing recognition that potent immunosuppressive mechanisms are also prevalent in such patients. Giving immunosuppressive agents seems not to be a good idea.
Gregoire M, Le Turnier P, Gaborit BJ, et al. Lopinavir pharmacokinetics in COVID-19 patients. J Antimicrob Chemother. 2020 May 22. PubMed: https://pubmed.gov/32443151. Full-text: https://doi.org/10.1093/jac/dkaa195
Lopinavir concentrations in 12 COVID-19 patients at the Nantes University Hospital, France, were extremely high compared with those usually observed in HIV-infected patients (trough: 18,000 ng/mL versus 5365 ng/mL with 400/100 mg q12h).