Study suggests reinfections from the virus that causes COVID-19 likely have similar severity as original infection

NIH-funded analysis of health record data shows severe reinfections often follow severe first infections.

What

Using health data from almost 213,000 Americans who experienced reinfections, researchers have found that severe infections from the virus that causes COVID-19 tend to foreshadow similar severity of infection the next time a person contracts the disease. Additionally, scientists discovered that long COVID was more likely to occur after a first infection compared to a reinfection. The study, funded by the National Institutes of Health’s (NIH) Researching COVID to Enhance Recovery (RECOVER) Initiative, is published in Communications Medicine.

The analysis used data from electronic health records of 3.1 million Americans who are part of the National COVID Cohort Collaborative (N3C). Researchers focused on 212,984 people who reported a reinfection. Those individuals were originally infected between March 1, 2020-Dec. 31, 2022, and experienced a second infection by March 2023. Most participants (203,735) had COVID-19 twice, but a small number (478) had it three times or more. COVID-19 vaccines, though not available during the entire study period, correlated with a protective effect.

About 27% of those with severe cases, defined as receiving hospital care for a coronavirus infection, also received hospital care for a reinfection. Adults with severe cases were more likely to have underlying health conditions and be ages 60 or older. In contrast, about 87% of those who had mild COVID cases that did not require hospital care the first time also had mild cases of reinfections.

Reinfections were defined as having occurred at least two months after a first infection. They were found to occur most frequently when omicron variants were circulating in late 2021 and early 2022. Waning immunity and increased exposure to the coronavirus, including the highly-infectious variants, likely accounted for the uptick.

Scientists also discovered that regardless of the variant, long COVID cases were more likely to occur after a first infection compared to a reinfection. Long COVID was defined in the review as those experiencing long-term COVID-19 symptoms, such as feeling tired, coughing, or having problems sleeping, breathing, or thinking, after an acute coronavirus infection.

Researchers also found that lower levels of albumin, a protein made by the liver, may indicate a higher risk for reinfection. This finding could indicate lower albumin as a possible risk marker for reinfection. Scientists believe this deserves further attention, such as by considering trials to test if nutritional interventions may prevent reinfection or its severity.

The study is funded by NIH’s RECOVER Initiative. Additional support came from the N3C Data Enclave, which is supported by the National Center for Advancing Translational Sciences, also part of NIH.

Who

David C. Goff, M.D., Ph.D., a senior scientific program director for the RECOVER Observational Consortium Steering Committee and director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, is available for interviews on this paper.

Study

Hadley E, Yoo YJ, Patel S, et al. Insights from an N3C RECOVER EHR-based cohort study characterizing SARS-CoV-2 reinfections and Long COVID. Commun Med. 2024; doi: 10.1038/s43856-024-00539-2.

HHS Long COVID Coordination: This work is a part of the National Research Action Plan (PDF, 1.3 MB), a broader government-wide effort in response to the Presidential Memorandum directing the Secretary for the Department of Health and Human Services to mount a full and effective response to long COVID. Led by Assistant Secretary for Health Admiral Rachel Levine, the Plan and its companion Services and Supports for Longer-term Impacts of COVID-19 report (PDF, 1.6 MB) lay the groundwork to advance progress in the prevention, diagnosis, treatment, and provision of services for individuals experiencing long COVID.

About RECOVER: The National Institutes of Health Researching COVID to Enhance Recovery (NIH RECOVER) Initiative brings together clinicians, scientists, caregivers, patients, and community members to understand, diagnose, and treat long COVID. RECOVER has created one of the largest and most diverse groups of long COVID study participants in the world. In addition, RECOVER clinical trials are testing potential interventions across five symptom focus areas. For more information, please visit recoverCOVID.org.

About the National Institutes of Health (NIH):
NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

###