Estimated COVID-19 Periodicity and Correlation with SARS-CoV-2 Spike Protein S1 Antigenic Diversity, United States

Abstract

Emergence of antigenically diverse SARS-CoV-2 variants may be correlated with temporal circulation patterns. We analyzed positive SARS-CoV-2 tests in the United States reported to a national, laboratory-based surveillance network and unique amino acid sequences of the S1 region of the spike protein reported to national genomic surveillance during October 2020-September 2024. We estimated SARS-CoV-2 dominant periodicities using a discrete Fourier transform, described S1 variation using the Simpson diversity index (SDI), and estimated Spearman cross-correlation coefficients between percentage change in SDI and percentage positivity. SARS-CoV-2 activity consistently peaked during July-September and December-February, and dominant periodicities were at weeks 52.2 and 26.1. Percentage positivity and percentage change in SDI were negatively correlated (ρ = -0.30; p<0.001). SARS-CoV-2 peaks occurred in late summer and winter, a pattern likely related to rapid SARS-CoV-2 evolution and cyclical diversity. Monitoring associations between percentage positivity and SDI can help forecast expected surges and optimize prevention and preparedness.

Keywords: COVID-19; SARS; SARS-CoV-2; United States; antigenic variation; coronavirus; coronavirus disease; respiratory infections; seasons; severe acute respiratory syndrome coronavirus 2; spike protein; viruses; zoonoses.

Figure 1

Weekly smoothed (3-week) percentages of positive SARS-CoV-2 tests reported to the National Respiratory and Enteric Surveillance System (NREVSS), nationally and by Health and Human Services (HHS) Region, United States, October 2020–September 2024. The data represent SARS-CoV-2 nucleic acid amplification test results, which include reverse transcription PCR tests from the NREVSS sentinel network of laboratories in the United States, including clinical, public health, and commercial laboratories. These data exclude antigen, antibody, and at-home test results. Blue (December–February) and gray (July–September) vertical bands indicate time periods with increased percentage positivity. Seasonal peaks are indicated by dots at the week when smoothed percent positivity peaked. Regional colors are grouped by geography (e.g., Regions 1, 2, and 3 are shades of green and comprise the Northeast). All HHS Regions had 2 seasonal peaks a year, except HHS Region 8, which only had 1 peak between summer 2023 and winter 2023–2024. HHS Region 1: Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont; HHS Region 2: New Jersey, New York, Puerto Rico, and the Virgin Islands; HHS Region 3: Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia; HHS Region 4: Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee; HHS Region 5: Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin; HHS Region 6: Arkansas, Louisiana, New Mexico, Oklahoma, and Texas; HHS Region 7: Iowa, Kansas, Missouri, and Nebraska; HHS Region 8: Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming; HHS Region 9: Arizona, California, Hawaii, Nevada, American Samoa, Commonwealth of the Northern Mariana Islands, Federated States of Micronesia, Guam, Marshall Islands, and Republic of Palau; HHS Region 10: Alaska, Idaho, Oregon, and Washington. Data from US-affiliated Pacific Islands are not included in NREVSS.

Figure 2

National smoothed (3-week) percentages of positive SARS-CoV-2 tests reported to the National Respiratory and Enteric Surveillance System (NREVSS), United States, October 2020–September 2024. Data represent SARS-CoV-2 nucleic acid amplification test results, which include reverse transcription PCR tests from the NREVSS sentinel network of laboratories in the United States, including clinical, public health, and commercial laboratories. These data exclude antigen, antibody, and at-home test results. A) Periodogram, in which the height of each point indicates strength of the periodicity at the corresponding frequency. Dots indicate 5 dominant periodicities, at frequencies corresponding to surges every 104.5, 52.2, 26.1, 20.9, and 17.4 weeks. Weeks represent time intervals (i.e., weeks do not represent a year of calendar time in the context of this analysis). B) Fitted harmonic function using the 52.2- and 26.1-week periodicities determined by discrete Fourier transform (green line). C) Fitted harmonic function using the 104.5-, 52.2-, 26.1-, 20.9-, and 17.4-week periodicities determined by discrete Fourier transform (pink line).

Figure 3

Weekly numbers of sequenced SARS-CoV-2 isolates, proportions with unique S1 spike sequences, and national percentages of positive SARS-CoV-2 tests and percentage changes in SDI, United States, October 2020–September 2024. A) Numbers of sequenced isolates (gray bars) and proportions of isolates with each unique S1 sequence (colored lines). Unique S1 sequences with a maximum proportion of <0.02 during the study period are included in the total number of isolates but not shown as proportion lines to improve visibility of patterns. B) National smoothed (3-week) percentages of positive SARS-CoV-2 tests reported to the NREVSS and percentage changes in SDI of S1 spike proteins. NREVSS, National Respiratory and Enteric Surveillance System; SDI, Simpson diversity index.