Vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19) and related hospitalizations (1,2), and surviving a previous infection protects against B.1.1.7 (Alpha) and B.1.617.2 (Delta) variant reinfections† (2). Since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in the United States in late December 2021, reported reinfections have increased§ (3). Early reinfections (those occurring within 90 days of previous infection) are not well understood (4). Because some persons have prolonged detection of viral RNA after infection,¶ repeat positive nucleic acid amplification test (NAAT) results within 90 days could reflect prolonged shedding from earlier infection, presenting technical challenges to documenting and characterizing early reinfections. This report describes 10 patients from four states, with whole genome sequencing (WGS)–confirmed Omicron variant infections within 90 days of a previous Delta infection. This activity was reviewed by CDC, approved by respective institutional review boards, and was conducted consistent with applicable federal law and CDC policy.**
An early reinfection was defined as a SARS-CoV-2 WGS test result (performed at a state, university, or contracted commercial laboratory††) from a new NAAT-positive specimen, collected during October 2021–January 2022 and <90 days after a first positive specimen from a previous WGS-confirmed SARS-CoV-2 infection, that demonstrated a different lineage from the first infection. Vermont Department of Health case investigators noted an increase in suspected early reinfections; five of these cases were confirmed through Vermont’s passive WGS surveillance system, which sequences the highest percentage (15.8%) of total state cases nationwide.§§ Wisconsin Department of Health Services was notified by university researchers of suspected early reinfections in members of a household enrolled in a longitudinal respiratory disease surveillance study.¶¶ Public Health – Seattle & King County was notified after Washington testing guidance for K–12 schools led to identification of a suspected early reinfection in a student at a school sporting event. Rhode Island screening protocols for hospitals and long-term care facilities led to collection of two NAAT-positive specimens within 90 days from a long-term care facility resident.
Ten patients with early reinfections were identified (Table). WGS identified Delta variant in all specimens from first infections and Omicron in all reinfection specimens.*** Median age at first infection was 11 years. Eight patients were aged <18 years, one was a long-term care facility resident, and one was a health care worker†††; five were male. Intervals between initial and subsequent specimen collections ranged from 23 to 87 days (median = 54.5 days). Patient E had completed a 2-dose mRNA COVID-19 vaccination series 6–10 weeks before the first infection; patients A and B each had received a single dose of mRNA COVID-19 vaccine between infections. The seven remaining patients were unvaccinated. In Wisconsin, household transmission during patient G’s reinfection likely resulted in reinfections of patients F and H.§§§,¶¶¶ Nine patients were symptomatic during first infection (median duration = 9 days; range = 0–20 days).**** Among eight patients with available clinical data during reinfection, six were symptomatic during reinfection (median duration = 5 days; range = 0–10 days).
Expansion of SARS-CoV-2 WGS, through public health surveillance and longitudinal research,†††† might enable rapid identification of reinfections with distinct lineages and detection of novel variants. Current CDC guidance for identifying early reinfections requires demonstration of different lineages by genetic sequencing.§§§§ Limited capacity for strain testing, including WGS, diminishes opportunities for first and reinfection NAAT specimens from the same person to undergo additional testing.¶¶¶¶ Moreover, antigen tests are increasingly performed at home, resulting in specimens being unavailable for strain testing. Thus, most early reinfections are likely not identified.
The findings from this case series might not be generalizable to the U.S. population and are specific to the transition period between Delta and Omicron variant predominance. Nonetheless, this study highlights potential limits of infection-induced immunity against novel variants.
One patient in this case series had received a full primary COVID-19 vaccine series but was not yet eligible for a booster. No other eligible patient was up to date on recommended COVID-19 vaccinations,***** which provides additional protection, even among those with previous infection (2,5). These patients might have had increased risk for SARS-CoV-2 infection because of low vaccination rates††††† and high rates of close contact§§§§§ in school-aged cohorts, and higher frequency and intensity of exposures in health care and congregate settings. Although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for preventing future SARS-CoV-2 infections (2,5).