Postexposure prophylaxis drug, vaccine complications, and anticoagulation in COVID-19

The monoclonal antibody combination of casirivimab and imdevimab gained both evidence support and authorization for COVID-19 postexposure prophylaxis. An industry-funded trial, published Aug. 4 by the New England Journal of Medicine (NEJM), randomized 1,505 people to either the combination or placebo, administered by subcutaneous injection within 96 hours of a household contact receiving a diagnosis of SARS-CoV-2. Symptomatic infection rates were 1.5% in the treatment group and 7.8% in the placebo group, and among symptomatic infected participants, the median time to resolution of symptoms was two weeks shorter in the intervention group than in the placebo group. The results support use of the combination drug “to prevent SARS-CoV-2 infection and symptomatic disease in persons in whom immediate protection is warranted,” the authors said. The FDA revised the emergency use authorization for the combination of casirivimab and imdevimab on July 30 to allow its use as postexposure prophylaxis for COVID-19 in adults and children ages 12 years and older who are at high risk for progression to severe COVID-19. It should only be used as postexposure prophylaxis for patients who are not fully vaccinated or who are not expected to have an adequate immune response to vaccination, the agency noted. The NIH also updated its treatment guidelines on the use of monoclonal antibodies for COVID-19 on Aug. 4.

A study published by JAMA on Aug. 4 reported on myocarditis and pericarditis associated with COVID-19 vaccination. Among the more than 2 million studied people who had received at least one COVID-19 shot, researchers found 20 cases of myocarditis (19 resulting in hospitalization) and 37 of pericarditis (13 hospitalized). About two-thirds of cases occurred in men, and the median ages were 36 years for myocarditis and 59 years for pericarditis. None of the patients died. The study found that the mean monthly numbers of myocarditis or myopericarditis cases were 16.9 (95% CI, 15.3 to 18.6) during the prevaccine period versus 27.3 (95% CI, 22.4 to 32.9) during the vaccine period and that those of pericarditis were 49.1 (95% CI, 46.4 to 51.9) and 78.8 (95% CI, 70.3 to 87.9), respectively. The study authors also observed that myocarditis developed rapidly in younger patients, mostly after the second shot, whereas pericarditis affected older patients later, after either the first or second dose.

Finally, two new studies, both from an international research collaborative and published by NEJM on Aug. 4, provided mixed data on the effects of therapeutic-dose anticoagulation in COVID-19. The first reported on 2,219 patients who were hospitalized but not critically ill with COVID-19 and randomized to either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The trial was stopped when prespecified criteria was met showing the superiority of therapeutic dosing. However, therapeutic dosing did not improve outcomes in critically ill COVID-19 patients, according to the other study, which randomized 1,098 such patients to either a therapeutic dose of heparin or usual thromboprophylaxis before it was stopped for futility. An accompanying editorial offered an interpretation of the mixed findings. “First, the available evidence does not support use of therapeutic-dose heparin or [low-molecular-weight heparin] LMWH for thrombosis prevention in critically ill patients. Other antithrombotic or even profibrinolytic strategies may be warranted. Second, whether intermediate or therapeutic doses of thromboprophylactic drugs are effective and safe in moderately ill patients with Covid-19 remains an important question,” the editorialist wrote, noting that there is still “lack of insight into the mechanisms by which heparin or LMWH does (or does not) provide protection and the question of whether the individual patient's bleeding risk outweighs the benefit.”