Long COVID Burden Highest Among Individuals Infected During Pre-Omicron Period

Results of a study published in Clinical Infectious Diseases suggest that prior COVID-19 infection with pre-Omicron variants is the strongest risk factor for the occurrence of postacute sequelae symptoms.

Researchers in Switzerland conducted a prospective cross-sectional analysis between July/August 2020 and May/June 2022 among health care workers (HCWs) at 9 centers. Participants were provided with questionnaires to obtain information on COVID-19 vaccination status, characteristics, risk factors for COVID-19 infection, and acute symptoms associated with prior COVID-19 infection. The primary outcome was the total number of postacute sequelae symptoms. Logistic regression was used to compare individual symptom frequency between infected vs uninfected (controls) participants. A multivariable negative-binomial regression model was used to assess the relationship between viral variant and vaccination status on number of symptoms, with baseline health, social determinants, employment details, and COVID-19 vaccine receipt included as potential confounders.

The final analysis included 2912 HCWs, of whom the median age was 44 years, 81% were women, and 1685 (57.9%) reported prior COVID-19 infection. Of participants who reported infection, the majority were infected during the Omicron period (64.2%), followed by the wild-type period (18.7%) and the Alpha/Delta periods (17.1%).

Previously infected participants reported a mean of 0.55 symptoms. Overall, infected vs uninfected participants reported a significantly higher mean number of symptoms (0.39, 95% CI 0.34-0.45).

The mean number of symptoms was found to decrease with each subsequent iteration of viral variant. COVID-19 infection onset during the wild-type period was associated with the highest mean number of symptoms (1.12; 95% CI, 0.88-1.45; P <.001), followed by onset during the Alpha/Delta (0.67; 95% CI, 0.51-0.89; P <.001) and Omicron BA.1 periods (0.52; 95% CI, 0.45-0.61; P =.001).

Similar findings were observed after the analysis was restricted to unvaccinated participants.

For participants previously infected with Omicron BA.1, the mean number of reported symptoms was 0.49 (95% CI, 0.41-0.58 P =.30) among those who received 3 or more COVID-19 vaccine doses and 0.71 (95% CI, 0.53-0.95 P =.028) among those who received 1 to 2 doses. For unvaccinated participants with prior Omicron BA.1 infection, the mean number of symptoms was 0.36 (95% CI, 0.22-0.60).

Fatigue and asthenia were the most commonly reported symptoms among infected (14.7%) and uninfected (9.4%) participants. Among vaccinated and unvaccinated participants, the most consistently reported symptoms across all viral variants were loss of smell/taste and brain fog and loss of smell/taste and hair loss, respectively.

Results of the multivariable analysis indicated a positive association between mean number of reported symptoms and prior infection during the wild-type (adjusted rate ratio [aRR], 2.81; 95% CI, 2.08-3.83) and Alpha/Delta periods (aRR, 1.93; 95% CI, 1.10-3.46). Other factors positively associated with mean number of symptoms were BMI, having a preexisting condition, current receipt of any medication, and cumulative exposure to COVID-19-infected patients.

Limitations of this study include potential misclassification of viral variants and potential underestimation of postacute sequelae prevalence. These findings also may not be applicable to individuals infected with more recent Omicron variants.

Based on these findings, the researchers noted that “Future research should primarily address the needs of individuals infected early on in the pandemic…”

Disclosures: Multiple authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Infectious Disease Advisor