Combination Drug Therapy in COVID-19: Are We Using Sound Science in the Management of These Patients?

Background: Multiple case reports have shown promising results with remdesivir, tocilizumab and convalescent plasma. We evaluated the efficacy and safety of combination therapy with remdesivir, tocilizumab, steroids, antibiotics and convalescent plasma in COVID-19 patients. Objectives: To assess whether a multi-pronged approach to tackling SARS-CoV-2 had an impact on our primary end goal of decreasing the need for mechanical ventilation and identify some of the complexities involved with combination treatment regimens. Methods: In this retrospective, single center study, six confirmed SARS-CoV-2 patients with similar demographics and comorbidities treated with a combination of remdesivir, tocilizumab, antibiotics, steroids and convalescent plasma were followed. Results: At the time of initiation of treatment, all six patients were requiring at least 3 liters of supplemental oxygenation via nasal cannula. All patients received remdesivir for 5 - 10 days, tocilizumab for a total of 4 doses each across 2 days, methylprednisone and antibiotics. Commonly used antibiotics were cefepime, azithromycin, ceftriaxone and piperacillin/tazobactam. Convalescent plasma was given to three out of the six patients. Despite combination therapy with remdesivir, tocilizumab, steroids, antibiotics and convalescent plasma, four out of the six patients (66.67%) deteriorated and required invasive mechanical ventilation. Conclusions: There are currently no set treatment guidelines for COVID 19. Most institutions appear to be utilizing some form of combination therapy against COVID-19. In this study, invasive mechanical ventilation was avoided in only two of six patients despite robust use of combination therapy in all patients. Our study suggests that multiple medications may not be the answer. Instead, a clearer understanding of the pathophysiology along with timing at which medications are introduced might play a more important role. We propose judicious use of combination therapy in a methodical and sequential use in patients requiring three or more liters of supplemental oxygen. Use of any of these medications, either by itself or in combination, after mechanical ventilation has minimal if any benefits and should be used as a last resort. Currently, a few clinical trials in the recruiting stage are underway that look at various combination therapies that could provide a more comprehensive understanding regarding the efficacy of combination therapy against SARS-CoV-2.