July 6, 2020

Background: Hydroxychloroquine (HCQ) is an antimalarial and immunomodulatory drug that is postulated to exert an antiviral effect by increasing intracellular pH resulting in decreased viral binding at the ACE2 receptor. Azithromycin is a macrolide antibiotic that also has anti-inflammatory and immunomodulatory properties which could help decrease viral replication and viral binding. Both of these medications have been used to treat COVID patients based on in vitro findings. However, in vitro studies often do not extrapolate to patient oriented outcomes. In June 2020 the US FDA revoked the prior emergency use authorization to HCQ and chloroquine (CQ) in patients with COVID-19. We now have yet another retrospective observational trial of HCQ, azithromycin, and the drugs in combination.

June 23, 2020

Background: We have been in need of a sign of hope in the fight against SARS-CoV-2 as it runs from city to city overwhelming health systems.  The majority of patients will be either asymptomatic or have only mild disease.  These patients will improve for the most part with symptomatic care.  There is a smaller portion of patients admitted to the hospital and ICU requiring oxygen therapy or invasive mechanical ventilation (IMV).  In this group of patients, there has not been much promise in the way of treatments improving mortality.  Patients requiring oxygen therapy (HFNC, NIV, IMV, ECMO) are mostly in the pulmonary and hyperinflammatory stage of disease (see below figure). One theoretical option in this hyperinflammatory stage of disease is corticosteroids to help quell the immune response and potentially improve mortality outcomes.

June 8, 2020

Background: Despite the initial excitement around the use of chloroquine (CQ) and hydroxychloroquine (HCQ), there is mounting evidence that neither drug is effective in COVID-19 treatment. Laboratory studies have shown antiviral and immunomodulatory properties in vitro but these have not held up in clinical application. However, one potential area of use that needs more investigation is the use of HCQ for post-exposure prophylaxis (PEP). As the pandemic continues, PEP becomes an increasingly important topic in stopping repeat surges of the disease. To date, there is no high-quality evidence on prophylactic HCQ after exposure.

June 6, 2020

Background: Convalescent plasma therapy is not a new or novel therapeutic option.  It involves taking the plasma from patients who have recovered from an illness and using it to treat patients who currently have the same illness. This approach has been evaluated in the treatment of SARS, MERS, and ebola but, none of the studies in these disease showed definitive results.  Thus far, the amount of evidence on convalescent plasma therapy in COVID-19 is also limited.  There was a case series of 5 patients [2] and a systematic review of 5 trials with 27 patients [3]. Neither study was earth-shattering. However, both showed  improved weaning from mechanical ventilation and no adverse events in the convalescent plasma group.  With a total of 32 patients, we should not put any weight in either of these trials.  We now have our first randomized clinical trial on convalescent plasma therapy.

June 2, 2020

Background: We have covered the two previous RCTs on remdesivir on REBEL EM (RCT #1 and RCT #2). In the first trial by Wang et al [2], there was no statically significant improvement in clinical outcomes, but, there were trends toward shorter duration of illness. In the ACTT-1 preliminary report [3], despite all the methodological issues, there was a 4 day decrease in clinical improvement (although not in patients requiring HFNC/NIV/IMV/ECMO).  Neither trial was perfect, however in the middle of pandemic, a several day decrease in recovery time may be beneficial in reducing hospital crowding if the difference holds true in subsequent studies and if the correct target population is known.  We now have our 3rd RCT on remdesivir [1], just published in the NEJM comparing 5 days vs 10 days of remdesivir in patients with severe COVID-19.
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