Abstract
BackgroundWith the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections.MethodsBased on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza.ResultsIn the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33–10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34–6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05–9.75]) and seasonal influenza (6.01 [95% CI 3.53–10.26], p for difference = 0.902) cohorts.ConclusionCOVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.
Highlights
With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections
Severe COVID-19 cases were characterized by high case fatality, the majority (~ 81%) of COVID-19 patients only experienced flu-like symptoms and spontaneously recovered without specific medical interventions [2]
Compared with matched unexposed individuals, individuals with COVID-19 were more likely to have a history of life-threatening infections (10.99% vs 7.33%, p < 0.001) and be overweight (31.84% vs 26.54% for Body mass index (BMI) ≥ 29.9, p < 0.001)
Summary
With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections. Previous studies have revealed that patients with viral respiratory infections may suffer an increased risk of secondary infections, including severe secondary infections with high mortality [4]. It is plausible that COVID19 can alter people’s susceptibility to other severe secondary infections This hypothesis is supported by a recent finding suggesting a profound impact of SARS-CoV-2 on immune systems [6], which seemed sustained even among individuals who have recovered from the primary infection [7, 8]. By using seasonal influenza as a control of the “exposure” condition, we explored to what extent the observed associations were exclusive to COVID-19
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