This study investigates the seasonal transmission pattern of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) in the United States to help public health activities like optimizing vaccine treatments and healthcare system preparedness. Viruses like respiratory syncytial virus (RSV) and influenza normally peak once every winter. Rhinoviruses and parainfluenza showed biannual peaks. SARS-CoV-2 transmission remains less predictable due to the continuous emergence of novel variants and the fluctuating immunity of people. Earlier studies have consistently shown winter peaks, accompanied by additional surges, with some research estimating up to three peaks annually. Different variants have led to both winter and mid-year rises in the cases. This research utilized regional and national data on laboratory test positivity and tracked the weekly proportions of distinct S1 spike genotypes to investigate the link between COVID-19 seasonality and antigenic diversity.
This study analysed regional and national SARS-CoV-2 test positivity in the United States between October 2020 and September 2024. It used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS). Investigators determined the proportion of cases occurring in late winter and summer to identify peak positive rates and applied discrete Fourier transform (DFT) analysis to investigate the dominant seasonal pattern. They investigated the weekly prevalence of viral lineages and the S1 spike protein genotypes quantified using the Simpson diversity index (SDI). They examined the link between positive rates and SDI changes by using Spearman cross-correlation over the past 2 years.
SARS-CoV-2 circulated all years but showed consistent peaks in the late summer from July to September and in winter from December to February, except winter 2020 to 2021. Most areas experienced two annual peaks, where Region 8 recorded a single peak from summer 2023 to winter 2023-2024. Around 65% of total cases were identified during the combined late winter and summer months, with regional variation ranging from 54% to 77%. Spectral analysis showed two dominant periodicities (51 and 26 weeks). This indicated bimodal seasonality, which is supported by enhanced model fit with increased frequency.
This study observed that the predominance of a single S1 spike protein sequence often aligned with seasonal surges and higher positivity rates, although this was less evident in 2023. Declines in spike protein diversity, measured by the Simpson Diversity Index (SDI), typically preceded positivity peaks by about two weeks, with a stronger negative correlation observed after October 2022. Notably, in the late summer surges of 2023 and 2024, no single dominant variant emerged, and multiple S1 sequences co-circulated at lower proportions.
This analysis confirmed that SARS-CoV-2 exhibits a biannual pattern in the U.S., with peaks in late summer and winter, a trend likely to continue due to the virus’s rapid evolution and changes in spike S1 diversity. Spectral analysis identified dominant frequencies that support this semiannual seasonality, along with additional minor periodicities. Before November 2022, each surge was typically linked to a predominant S1 sequence; however, from 2023 onwards, late summer surges showed higher antigenic diversity, with no single dominant variant. Declines in S1 diversity often preceded surges, suggesting that tracking diversity could help predict future peaks.
SARS-CoV-2 transmission is influenced by viral evolution, population immunity resulting from vaccination and prior infections, as well as seasonal factors such as climate and human behavior. With immunity from vaccination and infections expected to be widespread by 2025, antibody levels increase with repeated exposures, although protection wanes, especially in older or immunocompromised individuals, highlighting the potential need for biannual vaccination strategies.
This study has several limitations, including variability in laboratory methods, reliance on passive surveillance data, and declining genomic sequencing, all of which can affect the interpretation of trends. Nonetheless, continued genomic monitoring and diversity assessments can help to forecast the seasonal surges, inform vaccine scheduling, and strengthen healthcare preparedness for COVID-19.
Reference: Rose EB, Paden CR, Cook PW, Ma KC, Winn A, Castro J, et al. Estimated COVID-19 periodicity and correlation with SARS-CoV-2 spike protein S1 antigenic diversity, United States. Emerg Infect Dis. 2025 Aug. doi:10.3201/eid3108.250451
