Results of a multicenter randomized control trial of convalescent plasma therapy for COVID-19 were reported by Ling Li (Chinese Academy of Medical Sciences and Peking Union Medical College) et al. in JAMA. The open-label study in seven medical centers in Wuhan, China, involved 103 patients with severe or life-threatening, laboratory-confirmed, COVID-19, 52 of whom received convalescent plasma. The authors did not find any significant clinical benefits of convalescent plasma treatment, though it should be noted that the study was terminated early and underpowered due to the difficulties of recruiting patients given the successful control of the Wuhan outbreak.
A randomized, double-blind, placebo-controlled trial of prophylactic hydroxychloroquine treatment in 821 asymptomatic people, 719 of whom were at a high-risk exposure to SARS-CoV-2 (predominantly healthcare workers exposed in the absence of appropriate personal protection equipment), in multiple centers in the USA and Canada found no benefit of the drug. The study, published in the New England Journal of Medicine, reported no severe adverse reactions in the treatment group. Overall, 107 participants developed COVID-19, who were diagnosed by either a PCR test or symptomatic criteria, but there was no significant difference in incidence between the hydroxychloroquine-treated (49 of 414) and placebo (58 of 407) groups.
Following an open letter from dozens of researchers questioning the provenance and validity of its data as well as the analytical techniques used, The Lancet first posted an expression of concern about Mehra et al.’s article on hydroxychloroquine and chloroquine treatment of COVID-19, and the paper has now been retracted. Although the lead author, Mandeep Mehra, is at Harvard Medical School, the data in the study was obtained from the Surgisphere Corporation. Problems with Surgisphere potentially extend beyond the hydroxycholoroquine controversy, with the New England Journal of Medicine publishing its own editorial expression of concern, this one focusing on an angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor blocker COVID-19 study that also relied on data compiled by the company.
The histamine H2 receptor antagonist famotidine (the active compound in the heartburn drug Pepcid) was associated to a reduced risk of intubation and death in 84 patients with COVID-19 in an earlier retrospective study posted as a non-peer-reviewed preprint. Work led by Darrell Ricke at Massachusetts Institute of Technology compares the biochemical action and pharmacokinetics of famotidine with those of cimetidine, a H2 antagonist that has not shown clinical benefits in patients with COVID-19, as well as relating a case report of a COVID-19 patient treated with famotidine. The study, a preprint which has not yet been peer-reviewed, shows that famotidine has stronger binding to H2 than cimetidine (confirming previous data) and that famotidine serum levels exceed its half-maximum inhibitory concentration (IC50) at all dosing regimens, while cimetidine failed to reach its IC50 when used at its standard dose. Unlike cimetidine, famotidine acts a partial agonist of arrestin recruitment. The authors propose that mast cell activation and histamine release may be central to lung pathology in patients with COVID-19.
Epidemiology and public health
Christian Drosten at Charité Institute of Virology, Berlin, and colleagues estimated SARS-CoV-2 infectivity in different age groups based on the viral load determined by PCR. The study, which used two different PCR systems (Roche LightCycler 480 II and Roche cobas 6800/8800) and analysed data from 3,303 SARS-CoV-2-positive cases (out of a total of 77,996 people tested), predicts that 30–50% of PCR-positive individuals are likely to be infectious. Although some variation was detected in the cobas system, LC480 analysis found no differences in viral load across age groups. Overall, the work suggests that infected children may be as likely as adults to transmit SARS-CoV-2. The work was uploaded as a preprint and has not been peer-reviewed.
The efficacy of face masks in reducing SARS-CoV-2 transmission has been contentious. A highly publicized study in Annals of Internal Medicine questioning the utility of surgical or cotton masks has recently been retracted. Derek Chu (McMaster University, Canada) and colleagues, writing in The Lancet, have performed a systematic literature review and meta-analysis of 172 observational and 44 comparative studies to evaluate the efficacy of personal protective equipment in COVID-19 prevention. Face masks were associated with protection in both healthcare and community transmission settings, with N95 respirators showing the greatest degree of protection and multilayer masks also showing significant protection. The paper also examines the importance of eye protection (associated with a 78% reduction in risk of infection) and physical distancing (82% reduction in risk at 1 meter).