Department of Research & Evaluation News

In December 2021, the Pfizer-BioNTech medication Paxlovid received emergency authorization as a treatment to prevent severe health problems from COVID-19 that could lead to hospitalization and death. But recently, small studies with less than a dozen people began to show up in the media linking the medication to a rebound in COVID-19 symptoms following recovery.

On May 13, 2022, Sara Tartof, PhD, an epidemiologist at the Kaiser Permanente Southern California Department of Research & Evaluation, received an email from the Centers for Disease Control and Prevention with a request. Could the scientists at Research & Evaluation harness their research knowledge and robust electronic health records to see if there were any serious issues?

Within 3 weeks, Debbie Malden, DPhil, and Dr. Tartof were able to quickly look at this question in the Kaiser Permanente Southern California patient population.

“We were able to describe the proportion of those who were admitted to the hospital or visited the emergency department for COVID-19-related illness after being treated with Paxlovid for mild to moderate COVID-19 symptoms,” said Dr. Malden, who is an epidemiologist with Research & Evaluation and an Epidemic Intelligence Service officer with the Centers for Disease Control and Prevention. “Our analysis found that less than 1% of patients who received Paxlovid ended up in the hospital or emergency department for COVID-19 in the 5 to 15 days following treatment.”

The study, “Hospitalization and Emergency Department Encounters for COVID-19 Following Paxlovid Treatment — California, December 2021–May 2022,” was published in the CDC’s Morbidity and Mortality Weekly Report on June 21, 2022.

It found among 5,287 Kaiser Permanente Southern California patients 12 years and older who received Paxlovid between December 31, 2021, and May 26, 2022:

• 73% had received 3 or more doses of COVID-19 vaccine before the date of infection, and 8% were unvaccinated.
• During the 5 to 15 days after Paxlovid treatment was dispensed, 6 hospitalizations and 39 emergency department visits considered related to SARS-CoV-2 infection were identified, representing less than 1% of all patients who were treated with Paxlovid during the study period.
• Among these 45 people, 21 (47%) were 65 years and older and 35 (78%) had at least one underlying health condition, such as diabetes, cancer, liver disease, or cardiovascular disease.
• Although there were 2 deaths to patients who had received Paxlovid, those deaths were attributed to underlying conditions and not the medication or COVID-19 rebound.

Paxlovid is prescribed for people who have conditions that might make them at higher risk of severe disease from COVID-19. It is typically given within the first few days after COVID symptoms appear. So, the patients included the study were mainly people who had underlying conditions or lifestyle factors that would make them at higher risk of severe disease from COVID-19.

“Even without a control group to compare those numbers to, we can tell with these low numbers that there is not an issue of significant concern,” said Dr. Tartof, the senior author of the study. “While this was a first pass to identify quickly whether there was a significant issue, we will be following this question with further research.”

This study also contributes to the knowledge about Paxlovid because the original clinical trial that was used to grant emergency use authorization was based upon patients who were unvaccinated. This Kaiser Permanente study included both vaccinated and unvaccinated patients.

The ability to do a quick turnaround to look at potential issues is a result of several years of dedicated work. Since March 2020, scientists, clinicians, and staff from Kaiser Permanente Southern California have been on the leading edge of research on the novel coronavirus. Findings from the research on COVID-19 vaccines have had global implications.

The size and diversity of the Kaiser Permanente Southern California member population, the integration of Kaiser Permanente’s care and lab systems, the depth of information in its electronic health record system, and the expertise of Kaiser Permanente Southern California vaccine research scientists offered the research teams unique advantages as they sought answers the whole world wanted to know about the performance of these new vaccines.

Kaiser Permanente has long partnered with CDC to study the safety of vaccines. The Vaccine Safety Datalink is a collaboration between CDC’s Immunization Safety Office and 9 health care organizations, the largest of which is Kaiser Permanente Southern California.

Research & Evaluation also works with the CDC through its Epidemic Intelligence Service training program. Dr. Malden is the third EIS officer for the CDC embedded within the Department of Research & Evaluation for the 2-year training program.

In addition to Dr. Malden and Dr. Tartof, other authors on this study include Vennis Hong, MS, and Bradley Ackerson, MD, of the Department of Research & Evaluation; Bruno Lewin, of the Department of Research & Evaluation and the Kaiser Permanente Bernard J. Tyson School of Medicine; Marc Lipsitch, DPhil, COVID-19 Response, CDC, Atlanta, Georgia, and Center for Communicable Disease, Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; and Joseph A. Lewnard, PhD, School of Public Health, University of California, Berkeley, California.