Symptoms Compatible With Long Coronavirus Disease (COVID) in Healthcare Workers With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection-Results of a Prospective Multicenter Cohort

Abstract

Background: The burden of long-term symptoms (ie, long COVID) in patients after mild COVID-19 is debated. Within a cohort of healthcare workers (HCWs), frequency and risk factors for symptoms compatible with long COVID are assessed.

Methods: Participants answered baseline (August/September 2020) and weekly questionnaires on SARS-CoV-2 nasopharyngeal swab (NPS) results and acute disease symptoms. In January 2021, SARS-CoV-2 serology was performed; in March, symptoms compatible with long COVID (including psychometric scores) were asked and compared between HCWs with positive NPS, seropositive HCWs without positive NPS (presumable asymptomatic/pauci-symptomatic infections), and negative controls. The effect of time since diagnosis and quantitative anti-spike protein antibodies (anti-S) was evaluated. Poisson regression was used to identify risk factors for symptom occurrence.

Results: Of 3334 HCWs (median, 41 years; 80% female), 556 (17%) had a positive NPS and 228 (7%) were only seropositive. HCWs with positive NPS more frequently reported ≥1 symptom compared with controls (73% vs 52%, P < .001); seropositive HCWs without positive NPS did not score higher than controls (58% vs 52%, P = .13), although impaired taste/olfaction (16% vs 6%, P < .001) and hair loss (17% vs 10%, P = .004) were more common. Exhaustion/burnout was reported by 24% of negative controls. Many symptoms remained elevated in those diagnosed >6 months ago; anti-S titers correlated with high symptom scores. Acute viral symptoms in weekly questionnaires best predicted long-COVID symptoms. Physical activity at baseline was negatively associated with neurocognitive impairment and fatigue scores.

Conclusions: Seropositive HCWs without positive NPS are only mildly affected by long COVID. Exhaustion/burnout is common, even in noninfected HCWs. Physical activity might be protective against neurocognitive impairment/fatigue symptoms after COVID-19.

Keywords: asymptomatic; healthcare workers; long COVID; risk factors; serology.

Figure 1.

Study flow showing the total population and the subpopulations analyzed for specific analyses. Abbreviations: anti-S, anti-spike protein antibodies; COVID, coronavirus disease; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Percentage of HCWs reporting symptom and total number of reported symptoms (upper right corner) by HCWs with a positive SARS-CoV-2 swab (red), seropositive HCWs without a positive swab (orange), and seronegative HCWs without a positive swab (light blue). Statistics: Positive HCWs are compared with negative HCWs, respectively (***P < .001; **P = .001–.01; *P = .01–.05). Abbreviations: HCW, healthcare worker; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Sum score for the post-concussion (RMEAD), fatigue severity (FSS), depression (PHQ), and anxiety (GAD) scores by HCWs with a positive SARS-CoV-2 swab (red), seropositive HCWs without a positive swab (orange), and seronegative HCWs without a positive swab (light blue). Statistics: Positive HCWs are compared with negative HCWs, respectively (***P < .001; *P = .01–.05). Abbreviations: FSS, Fatigue Severity Scale; GAD, General Anxiety Disorder; HCW, healthcare worker; PHQ, Patient Health Questionnaire; RMEAD, Rivermead Post-Concussion Questionnaire; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; serol., serology.

Figure 4.

Percentage of healthcare workers reporting individual symptoms and total number of reported symptoms (upper right corner) according to weeks since positive SARS-CoV-2 swab, compared with negative controls. Statistics: P values from tests for trends over the 4 categories, without negative controls. Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 5.

Sum score for symptoms, the post-concussion (RMEAD), fatigue severity (FSS), depression (PHQ), and anxiety (GAD) scores according to quartile of SARS-CoV-2 anti-spike titers. Results are adjusted for time since positive swab. Statistics: P values from tests for linear trends over the 4 categories. Abbreviations: FSS, Fatigue Severity Scale; GAD, General Anxiety Disorder; PHQ, Patient Health Questionnaire; Q, quartile; RMEAD, Rivermead Post-Concussion Questionnaire; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 6.

Forest plot showing the multiplicative effect of potential influential factors on the number of long-COVID symptoms, as determined through multivariable Poisson regression. Factors in blue are negatively and those in red are positively associated with the number of symptoms. Abbreviation: BMI, body mass index; CI, confidence interval; COVID, coronavirus disease; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.