Other COVID-19 pharmacologic therapies under study
Treatments of note in the review included the following:
- Tocilizumab. This monoclonal antibody IL-6 receptor antagonist, approved by the FDA for treatment of rheumatoid arthritis and for cytokine release syndrome related to chimeric antigen receptor (CAR) T-cell therapy, has yielded success in small series of patients with severe cases of COVID-19, according to authors. In one 21-patient report, 91% had clinical improvement, usually after a single dose. In China, tocilizumab is included in COVID-19 treatment guidelines, and several randomized clinical trials are underway in China including patients with COVID-19 with severe pneumonia.
- Immunoglobulin therapy. Antibodies from recovered COVID-19 patients could help with free virus and infected cell immune clearance, the authors said, adding that further studies are warranted beyond a few small published case series that suggest promise. Furthermore, on March 24 the FDA released guidance for screening donors for COVID-19 convalescent plasma and on emergency investigational new drug applications based on this modality.
- Lopinavir/ritonavir. Despite demonstrated in vitro activity against other novel coronaviruses, there is no published in vitro data for lopinavir/ritonavir in SARS-CoV-2, and likely a “limited role” for this combination anticipated in treating COVID-19, according to the review authors. In an open-label randomized clinical trial published in the New England Journal of Medicine (2020 Mar 18. doi: 10.1056/NEJMoa2001282), there were no differences in clinical improvement, viral clearance, or mortality for antiviral treatment versus standard care. Delayed treatment initiation may explain the ineffectiveness, though a subgroup analysis didn’t show a shorter time to clinical improvement for those who got the treatment earlier.
- Ribavirin. Likewise, this antiviral medication has efficacy and safety data suggesting “limited value” for treatment of COVID-19. Treatment of SARS yielded “inconclusive results” for ribavirin, which was also associated with substantial toxicity that included hemolytic anemia in 60% of SARS patients.
- Oseltamivir. While it may treat influenza, it has no documented activity against SARS-CoV-2 in vitro: “This agent has no role in the management of COVID-19 once influenza has been excluded,” said Dr. Sanders and coauthors.
- Corticosteroids. They could decrease inflammatory responses in the lung, but they could also lead to delays in viral clearance and increases in secondary infection risk. Guidelines for COVID-19 say to avoid corticosteroids, and the authors of the review concur, saying that potential harms and lack of proven benefit mean they usually should not be used outside of a randomized clinical trial setting.
- Vaccines. Clearly, vaccines represent the “most effective long-term strategy” to prevent future COVID-19 outbreaks, though at least 12-18 months would be required until vaccines can be widely deployed, authors said.
Dr. Sanders reported no potential conflicts. Senior author James B. Cutrell, MD, also of the University of Texas Southwestern Medical Center, reported nonfinancial support from Gilead and Regeneron outside of the study. No other authors reported disclosures.