A comprehensive review conducted by researchers at the Keck School of Medicine of USC has revealed that most COVID-19 therapies approved by the U.S. Food and Drug Administration (FDA) cause minimal serious side effects. The findings, published in Open Forum Infectious Diseases, provide reassurance about the safety profile of treatments that have been developed and authorized during the pandemic.
The research team evaluated the full spectrum of evidence available from U.S. biomedical science, incorporating 54 studies that spanned both inpatient and outpatient treatment settings, clinical trials, and observational research.
Oral Antivirals Show Strong Safety Profile
According to the study, oral antiviral medications such as Paxlovid demonstrated no significant association with serious adverse events. This finding is particularly important for high-risk patients who may be prescribed these treatments.
"The main message is, if your doctor puts you on Paxlovid, you don't have to worry about serious side effects," said Susanne Hempel, PhD, professor of clinical population and public health sciences and director of the Southern California Evidence Review Center (ERC) at the Keck School of Medicine, who oversaw the work. "There are no serious adverse events for any of the oral medications that you're taking at home for COVID-19."
Varying Safety Profiles Among Treatment Types
The research revealed different safety profiles across treatment categories:
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Monoclonal antibodies targeting the spike protein, including Evusheld, which were previously administered intravenously in hospitals but are no longer authorized by the FDA due to lack of effectiveness against newer variants, showed no association with serious adverse events.
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Tocilizumab (Actemra), an intravenous monoclonal antibody that works through a different mechanism, was associated with infection and low white blood cell counts in some studies.
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Convalescent plasma transfusions from recovered COVID-19 patients were linked with higher risks of internal bleeding, infection, and blood clots.
Importantly, the researchers noted that all serious adverse events identified in the study aligned with current product labeling, suggesting that manufacturers have appropriately documented these risks.
Rigorous Methodology Enhances Confidence in Findings
The study's methodology was particularly robust, as it only included investigations comparing COVID-19 therapy with standard care, placebo, or no treatment. This approach allowed researchers to reasonably exclude effects of the disease itself from their analysis.
The research team also went beyond peer-reviewed literature to include data submitted to the FDA and to the National Library of Medicine's clinicaltrials.gov site, providing a more comprehensive assessment of treatment safety.
Informing Public Health Policy
The study was conducted to help develop a countermeasure injury compensation table, which is used to determine whether patients and families who report adverse events are eligible for public benefits.
"Given the unique nature of the pandemic and the rapid production of treatments for COVID-19, the findings are very reassuring," said co-author and infectious disease expert Jeffrey Klausner, MD, MPH, professor of clinical population and public health sciences in the Keck School of Medicine. "With a severe public health emergency like COVID-19, it is critical that there exists a government compensation program for treatment-related injuries that is based on the best scientific evidence. Now we know with additional certainty that the treatments are safe without a high frequency of serious side effects."
Focus on Serious Adverse Events
The researchers concentrated specifically on serious side effects, using a standard scale developed by the National Institutes of Health. On this five-point scale, a rating of three or above indicates severe conditions requiring hospitalization, with the highest grade of five signifying a fatal event.
Margaret Maglione, MPP, first author and project leader at the ERC, emphasized the thoroughness of the safety monitoring process: "Manufacturers must submit very detailed records to the FDA for emergency authorization, so every adverse event should have been reported. We did not identify any serious adverse events that were not already described on the product packaging."
Clinical Implications for High-Risk Patients
While most people who contract COVID-19 can recover without prescription medications, physicians often prescribe treatments for patients with risk factors such as advanced age, obesity, cardiovascular issues, diabetes, or compromised immune systems. The findings from this study provide reassurance for these vulnerable populations and their healthcare providers.
The research underscores the importance of continued safety monitoring of COVID-19 treatments while confirming that the current therapeutic options, particularly oral antivirals, have favorable safety profiles for appropriate patients.
