Tsai A, Diaware O, Nahass RG, et al. Impact of tocilizumab administration on mortality in severe COVID-19. Sci Rep 10, 19131 (2020). Full-text: https://doi.org/10.1038/s41598-020-76187-y
Another study that does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. In this single-center propensity-score matched cohort study, 132 patients were included in the matched dataset (tocilizumab = 66; no tocilizumab = 66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group.
Sokolowska, M. Outsmarting SARS-CoV-2 by empowering a decoy ACE2. Sig Transduct Target Ther 5, 260 (2020), published 3 November. Full-text: https://doi.org/10.1038/s41392-020-00370-w
There are currently a few therapeutic approaches which focus on blocking SARS-CoV-2 binding to its key receptor, an angiotensin-converting enzyme 2 (ACE2), or on inhibition of virus spike cleavage. Milena Sokolowska discusses soluble recombinant human ACE2 (rhACE2) and a paper we presented on August 4: Chan KK, Dorosky D, Sharma P, et al. Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. Science 2020, published 4 August. Full-text: https://science.sciencemag.org/content/early/2020/08/03/science.abc0870
Mattay MA, Thompson BT. Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties. Lancet Resp Med October 29, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30503-8
An important comment on unanswered questions regarding the use of dexamethasone. Michael Matthay and Taylor Thompson discuss the limitations of the pragmatic RECOVERY trial (huge number of excluded patients, no data on oxygen support, no use of remdesivir, no data on viral clearance etc). They also discuss the steps need to be taken to learn more about the effects of dexamethasone in hospitalised patients with COVID-19.
Chen P, Nirula A, Heller B, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med 2020, published 28 October. Full-text: https://doi.org/10.1056/NEJMoa2029849
Bamlanivimab (LY-CoV555) is a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. In this interim analysis, the patients who received LY-CoV555 had fewer hospitalizations and a lower symptom burden than those who received placebo, with the most pronounced effects observed in high-risk cohorts. Be prepared: the results are not spectacular.
Ledford H. The race to make COVID antibody therapies cheaper and more potent. Nature 2020, published 23 October. Full-text: https://www.nature.com/articles/d41586-020-02965-3
Injections of antibodies might prevent mild COVID-19 from becoming severe, but the treatments are expensive and difficult to make.
Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P; PLACID Trial Collaborators. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 Oct 22;371:m3939. PubMed: https://pubmed.gov/33093056. Full-text: https://doi.org/10.1136/bmj.m3939
Convalescent plasma (giving neutralizing antibodies of people who made it through SARS-CoV-2 infection) has been one of the biggest hopes. This open label randomized controlled trial (RCT; the largest to date with results) investigated the effectiveness of CP in adults with moderate COVID-19 in 39 public and private hospitals across India. In total, 235 patients were assigned to two doses of 200 mL CP and 229 to best standard of care only (control arm). Progression to severe disease or all-cause mortality at 28 days after enrolment occurred in 44 (19%) participants receiving CP and in 41 (18%) in the control arm. Moreover, CP treatment did not show anti-inflammatory properties and there were no difference between patients with or without neutralizing antibodies at baseline (who had produced their own antibodies or not). The main limitation: The authors did not measure the antibody titers in CP before transfusion because validated, reliable commercial tests were not available when the trial started. Let’s hope that low antibody titers were the reason for the lack of efficacy.
Pathak EB. Convalescent plasma is ineffective for covid-19. BMJ. 2020 Oct 22;371:m4072. PubMed: https://pubmed.gov/33093025. Full-text: https://doi.org/10.1136/bmj.m4072
A strong statement, after all (and some thoughts on how to deal with the bad results of the PLACID trial).
Chowdhury JF, Moores LK, Connors JM. Anticoagulation in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Oct 22;383(17):1675-1678. PubMed: https://pubmed.gov/33085867. Full-text: https://doi.org/10.1056/NEJMclde2028217
The case of a 78-year-old man with hypertension and hyperlipidemia who was brought to the emergency department 48 hours ago. Now that the patient’s condition has worsened, with progressive hypoxemia, elevated inflammatory markers, and an increase in d-dimer level, it is to decide whether a) the prophylactic doses of anticoagulants should be maintained or whether b) they should be replaced by an increased dose (and if so, what agent). Lisa Moores says a), Jean Connors says b). Both have good arguments. This is bad news, because after 9 months, we still don’t know what to do.