COVID variant success involves more than viral load

Since SARS-CoV-2 first emerged in late 2019, the virus has undergone a remarkable evolutionary journey. Over the course of the COVID-19 pandemic, successive variants—including Alpha, Delta and Omicron—rapidly displaced their predecessors and fueled new waves of infection around the globe. Scientists have closely tracked these viral turnovers in an effort to understand what makes one variant more successful than another. While factors such as transmissibility and the virus’s ability to escape the immune system are known to contribute to a variant’s spread, the role of viral replication during natural infection remains less clear. Untangling how viral and host factors shape the amount of virus present during infection could provide important insight into both transmission and the evolutionary forces that drive the emergence of new variants.

A new study published in Communications Medicine led by the Hyrien Lab in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center examined whether viral factors or host characteristics play a larger role in determining how much SARS-CoV-2 accumulates during infection and how long infected individuals continue to shed virus. To answer this question, the team analyzed samples from 953 participants enrolled across more than 50 sites in the United States, Latin America and Southern Africa collected between July 2020 and March 2022—a period that captured multiple waves of SARS-CoV-2 evolution, from pre-Alpha strains through early Omicron variants.

"The SARS-CoV-2 pandemic was marked by substantial changes in viral variant as many variants emerged and displaced previously circulating variants," said lead author William Hahn. "Our study included a diverse cohort which captured the early phases of the pandemic and then continued recruiting as the virus adapted to humans with subsequent variant waves."

Throughout the pandemic, viral load emerged as one of the most widely used measures of SARS-CoV-2 infection. The amount of virus detected in a patient's upper airway has been linked to transmission risk and, in some studies, disease severity. Similarly, the length of time a person continues to shed detectable virus can influence how long they remain capable of infecting others. Because of these connections, researchers have often looked to viral load and shedding duration as potential indicators of a variant's ability to spread and compete with other strains.

The researchers measured viral load in nasal swabs collected over time, allowing them to compare both the highest observed viral levels and the duration of viral shedding across participants. They then examined whether these viral kinetics were associated with host characteristics such as age, sex, body mass index, HIV status and other medical conditions, or with the viral variant responsible for infection. While host factors showed little association with either viral load or shedding duration, viral variant was strongly linked to differences in both measures. Some variants produced higher observed viral loads or longer periods of shedding than others.

But one result stood out. Variants associated with the highest viral loads were not necessarily the variants that went on to dominate the pandemic. "Our findings suggest that you cannot simply extrapolate from which viruses have higher replication kinetics to more holistic measures of viral fitness," Hahn said. "The variants that had the highest amount of virus and longest shedding period were not the viruses that were the evolutionary winners and were quickly supplanted."

The findings suggest that commonly used measures such as viral load and shedding duration should be interpreted cautiously when evaluating the fitness of emerging viral variants. The study also highlights how much remains to be learned about the factors that drive viral evolution. Although demographic and clinical characteristics explained little of the variation observed in viral shedding, the researchers noted striking differences between individuals, with some participants clearing detectable virus within days while others continued shedding for weeks. Future studies examining immune responses may help explain these patterns and provide a more complete picture of how viral and host factors interact during infection.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Lawrence Corey and Ollivier Hyrien contributed to this research.

The spotlighted research was funded by the National Institutes of Health.

Hahn WO, Fisher LH, Ward A, Grant S, Yen C, Kaur Randhawa A, Li X, Ramirez S, Espy N, Hural J, Hanke J, Roychoudhury P, Kelley CF, Rouphael N, Cantos VD, Pinto J, Cahn PE, Manentsa M, Makhema J, Samaneka W, Bhondai-Mhuri M, Stranix-Chibanda L, Losso MH, Garcia EAR, Innes C, Chinula L, Lama JR, Gallardo-Cartagena JA, Kabengele C, Chilengi R, Nchabeleng M, Tieu H, Hoagland B, Grinsztejn B, Brumskine WL, Ahmed K, Wallis CL, Greninger AL, Corey L, Hyrien O. 2026. Viral variant but not host factors associate with SARS-CoV-2 viral kinetics. Communications Medicine. https://doi.org/10.1038/s43856-026-01588-5.