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By Christian Hoffmann &
Bernd S. Kamps
This is bad-news-day. If you are not in a good mood, come back tomorrow.
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First, calculate the number of COVID-19 cases, deaths, and demand for hospital services in the UK in the absence of non-pharmaceutical interventions; retract an article about the effectiveness of surgical and cotton masks; and discuss the ethical issues of COVID-19 human challenge studies.
Afterwards, test the clinical performance of several serologic assays; study the effect of extensive wildlife trade bans on zoonotic disease burden; and describe the psychosocial burden of COVID-19.
Finally, investigate the airborne spread of SARS-CoV-2 and a potential role for air disinfection; and write an editor’s comment on a study you just published and don’t trust anymore.
Davies NG, Kucharski ADJ, Eggo RM, et al. Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study. Lancet, June 02, 2020. Full-text: https://doi.org/10.1016/S2468-2667(20)30133-X
Herd immunity? Forget it. Using a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66 million people in England, Wales, Scotland, and Northern Ireland, the authors projected a median unmitigated burden of 23 million (95% prediction interval 13–30) clinical cases and 350,000 deaths (170,000–480, 000) due to COVID-19 in the UK by December, 2021. Bad news because extreme measures are probably required to bring the epidemic under control.
Jamrozik E, Selgelid MJ. COVID-19 human challenge studies: ethical issues. Lancet Infect Dis. 2020 May 29:S1473-3099(20)30438-2. PubMed: https://pubmed.gov/32479747. Full-text: https://doi.org/10.1016/S1473-3099(20)30438-2
Human challenge studies could accelerate vaccine development, helping to test multiple candidate vaccines. This personal view on ethical issues explains why this will be difficult. This is bad news. However, this is also somewhat good news (exception today!), as the authors argue that human challenge studies can “reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks.”
Eskew EA, Carlson CJ. Overselling wildlife trade bans will not bolster conservation or pandemic preparedness. Lancet Planetary Health, June 01, 2020. Full-text: https://doi.org/10.1016/S2542-5196(20)30123-6
Nice comment about a wildlife trade ban. Many (including us) have been quick to advocate for complete restriction of commercial trade, particularly in wet markets (like Wuhan) given their potential role as hotspots of cross-species viral transmission. This collective rhetoric suggests that eliminating wildlife trade is a simple, effective defense against zoonotic pandemics. According to the authors, stopping pandemics is not as simple as stopping wildlife trade. The bad news is that even with extensive wildlife trade bans, crippling zoonotic disease burden remains a near certainty.
Baer S, Kim MC, Kim JY. Notice of Retraction: Effectiveness of Surgical and Cotton Masks in Blocking SARS-CoV-2. Annals Int Med 2020, June 2. https://doi.org/10.7326/L20-0745
Come on, guys. “We are retracting our article….we had not fully recognized the concept of limit of detection (LOD) of the in-house RT-PCR used in the study (2.63 log copies/mL), and we regret our failure to express the values below LOD as “<LOD (value).” The LOD is a statistical measure of the lowest quantity of the analyte that can be distinguished from the absence of that analyte. Therefore, values below the LOD are unreliable and our findings are uninterpretable.“ We regret, too.
Baer 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
This was our comment on this study in April: “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.”
Nardell EA, Nathavitharana RR. Airborne Spread of SARS-CoV-2 and a Potential Role for Air Disinfection. JAMA. 2020 Jun 1. PubMed: https://pubmed.gov/32478797. Full-text: https://doi.org/10.1001/jama.2020.7603
We will have to deal with upper-room germicidal UV filters (GUV). According to the authors, preparation for future respiratory viral pathogens should include consideration of the use of upper-room GUV to help mitigate airborne transmission. Sounds complicated, expensive. Bad news.
Tang MS, Hocl KG, Logsdon NM, et al. Clinical Performance of the Roche SARS-CoV-2 Serologic Assay. Clinical Chemistry, June 2, 2020. hvaa132, https://doi.org/10.1093/clinchem/hvaa132.
The authors compared the clinical performance of several serologic assays (Abbott, EUROIMMUN and the Roche Elecsys assay). The Abbott assay demonstrated the fewest false negative results > 14d post-symptom onset and the fewest false positive results. While the Roche assay detected more positive results earlier after onset of symptoms, none of the assays demonstrated high enough clinical sensitivity before day 14 from symptom onset to diagnose acute infection. This is bad news because we still have to rely on PCR during the first two weeks.
Kola, Lola. Global mental health and COVID-19. Lancet Psychiatry June 02, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30235-2
Intelligent comment. The psychosocial burden of COVID-19 will become increasingly evident in the coming months as the effects of social measures such as physical distancing, loneliness, death of friends and family members, and job losses manifest. Bad news, no good prospects (but the best author name of the month!).
Rubin EJ. Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med 2020, June 2. Full-text: https://doi.org/10.1056/NEJMoa2007621
Ooops. They don’t trust their own authors (Mehra 2020). “Recently, substantive concerns have been raised about the quality of the information in that database”, editor Eric Rubin writes, washing NEJM’s hands in innocence. “We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions.” Ok. Let’s wait and see what happens. But bad news because even in a journal like NEJM, bad data quality is possible.
Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med. Full-text: https://doi.org/10.1056/NEJMoa2007621
This was the original work of concern. Bad news that we cannot trust it. This was our comment: “The first study analyzed a total of 8,910 COVID-19 patients (from 169 hospitals located in 11 countries) for whom discharge status was availably by March 29 (Mehra 2020). A total of 515 (5.8%) died in the hospital. Factors independently associated with an increased risk of in-hospital death were an age greater than 65 years (odds ratio, 1.93), coronary artery disease (2.70), heart failure (2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (2.96; 95% CI, 2.00 to 4.40), and current smoking (1.79; 95% CI, 1.29 to 2.47). No increased risk was found for the use of ACE inhibitors (0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (1.23; 95% CI, 0.87 to 1.74). Of note, use of either ACE inhibitors or statins was associated with better survival. However, these associations should be considered with extreme caution as the study design cannot exclude the possibility of confounding.”
Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med 2020, June 3. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
In total, 821 asymptomatic participants were randomized to receive hydroxychloroquine or placebo within 4 days after exposure (88% with a high-risk exposure). Incidence of confirmed SARS-CoV-2 was 11.8% with CQ and 14.3% with placebo. Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
This is bad news because after high-risk or moderate-risk exposure to Covid-19, HCQ did not prevent infection when used as postexposure prophylaxis within 4 days after exposure.