February 12, 2021

Background: Publication of the RECOVERY trial results on Dexamethasone were game changing - the drug had a clear reduction in mortality in patients requiring oxygen. Since then, we have had little to celebrate in terms of therapeutics in those with moderate to severe disease. The beneficial effects of corticosteroids in COVID-19 patients with hypoxic lung damage suggests other, more specific immunomodulatory agents may provide additional patient-oriented improvements.

Enter Tocilizumab.  This is a recombinant anti-IL6 receptor monoclonal antibody that inhibits binding of IL-6 to receptors that signal inflammation.  The results of tocilizumab from randomized trials thus far have shown mixed results for benefit.  Many of the trials not showing benefit were smaller, however the larger REMAP-CAP trial [2] did report benefit in patients requiring organ support. Further data is clearly needed to guide clinicians.

January 23, 2021

Background: One of the many massive challenges of the COVID19 pandemic has been the lack of targeted therapeutics. Extensive efforts have been invested into research with only glimmers of benefit for most drugs. The exception to this has been dexamethasone which was shown in the RECOVERY trial to have remarkable impacts on death in patients requiring O2 (NNT = 29) and in those requiring invasive ventilation (NNT = 8.5). A number of other drugs showed promise in observation and retrospective studies (HCQ, convalescent plasma) only to prove ineffective in well-done RCTs. Others (i.e. remdesivir) have shown inconsistent results at best. 

Monoclonal antibody infusions have gained national attention as a potential therapeutic. This drug class works by binding to domains on SARS-CoV2 spike protein blocking its ability to bind to ACE2 receptors on cells and thus stopping cellular invasion. Previously, we reviewed the interim analysis of BLAZE-1 which demonstrated a small reduction in viral load with one of the three studied doses. However, this difference fell below the author’s preset threshold, raised questions of biological plausibility and found no difference in any clinically meaningful outcome. Additionally, we recently reviewed the REGN-CoV2 antibody cocktail data which also failed to demonstrate any meaningful benefits. Today, we dive into the full BLAZE-1 data as the study has been completed.

January 22, 2021

Background: Facilities around the world have seen surges of COVID-19 pneumonia  patients who have required protracted hospitalizations leading to overwhelmed hospital systems. Awake proning is a practice that was adopted early in the pandemic as a means to avoid, or at least delay, endotracheal intubation to lessen the burden of ICU care.  Proning helps improve lung recruitment, reduce ventilation/perfusion mismatch, and reduces alveolar strain in intubated patients.  Numerous small trials and anecdotes of awake proning have shown improvements in oxygenation and respiratory rate.However, whether these surrogate physiological endpoint improvements translate to better clinical outcomes (i.e. intubation and mortality) is still largely unknown.

January 2, 2021

Background: Antibodies targeted at the SARS-CoV2 spike protein are an essential part of the body’s immune response to COVID19 infection. The recent emergency use authorization (EUA) Pfizer and Moderna vaccines act by introducing mRNA into the body that instructs cells to create a polyclonal spike protein antibody response. These antibodies bind to numerous locations on the SARS-CoV2 spike protein limiting the virus’s ability to enter and infect host cells. However, the vaccine is yet to be available in adequate numbers to immunize the general population and the pandemic continues.

Since the start of the COVID19 pandemic, extensive efforts have been made by pharmaceutical companies to create monoclonal antibodies that can be administered to people during the viremic phase of illness. The goal of these drugs is to give patients antibodies prior to their body mounting a response in an effort to prevent progression of disease. We have previously reviewed the EUA drug bamlanivimab (LY-CoV555) - a monoclonal antibody. In that review, we note the absence of any difference in patient centered outcome as well as serious methodological flaws. Here we review a monoclonal antibody cocktail - REGN-COV2 (casirivimab/imdevimab).

December 26, 2020

Background Information: With rising cases, an increasing death toll, and a significant strain on hospital systems globally, the COVID-19 pandemic seemed to have no end in sight. The aggressive pursuit of a vaccine has led to multiple clinical trials starting before the end of this year. In fact, there are 48 vaccines under clinical evaluation and 11 of these are currently being evaluated in phase 3 clinical efficacy trials.1 Among those includes, the replication-deficient chimpanzee adenoviral vector developed at Oxford University (ChAdOx1). Following the initiation of a phase 1 clinical trial in the UK (COV001), three additional randomized controlled trials were initiated across the UK (COV002), Brazil (COV003) and South Africa (COV005). Upon completion of enrollment, the authors of the following paper sought to perform a combined interim analysis of the four trials to assess ChAdOx1’s efficacy and safety