Post-viral symptoms and conditions are more frequent in COVID-19 than influenza, but not more persistent (preprint)

Post-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as Influenza. We addressed this topic by investigating a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last Influenza outbreak in 2018 and followed them up to 18 months. We found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the Influenza cohort. Persistence of post-viral symptoms was however similar between COVID-19 and Influenza. We conclude that post-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms.

Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study (preprint)

Objectives: To investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19. Method: A cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. Results: In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjoegren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases. Conclusions: SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19 (preprint)

Background: Long-term health sequelae of the coronavirus disease 2019 (COVID-19) are a major public health concern. However, evidence on post-acute COVID-19 syndrome (post COVID-19) is still limited, particularly for children and adolescents. Utilizing comprehensive healthcare data on more than 45 percent of the German population from January 2019 through December 2020, we investigated post COVID-19 in children/adolescents and adults. Methods: From a total of 38 million individuals, we identified all patients with laboratory confirmed diagnosis of COVID-19 through June 30, 2020. A control cohort was assigned using 1:5 exact matching on age, sex, and propensity score matching on prevalent medical conditions. COVID-19 and control cohorts were followed for incident morbidity outcomes documented at least three months after the date of COVID-19 diagnosis, which was used as the index date for both groups. Overall, 96 pre-defined outcomes were aggregated into 13 diagnosis/symptom complexes and three domains (physical health, mental health, physical/mental overlap domain). We used Poisson regression to estimate incidence rate ratios (IRRs) with 95%-confidence intervals (95%-CI). Results: The study population included 157,134 individuals (11,950 children/adolescents and 145,184 adults) with confirmed COVID-19. COVID-19 and control cohort were well-balanced regarding covariates. For all health outcomes combined, incidence rates (IRs) in the COVID-19 cohort were significantly higher than those in the control cohort in both children/adolescents (IRR=1.30, 95%-CI=[1.25-1.35], IR COVID-19=436.91, IR Control=335.98) and adults (IRR=1.33, 95%-CI=[1.31-1.34], IR COVID-19=615.82, IR Control=464.15). The relative magnitude of increased documented morbidity was similar for the physical, mental, and physical/mental overlap domain. In the COVID-19 cohort, incidence rates were significantly higher in all 13 diagnosis/symptom complexes in adults and in ten diagnosis/symptom complexes in children/adolescents. IRR estimates were similar for the age groups 0-11 and 12-17. Incidence rates in children/adolescents were consistently lower than those in adults. Among the specific outcomes with the highest IRR and an incidence rate of at least 1/100 person-years in the COVID-19 cohort in children and adolescents were malaise/fatigue/exhaustion (IRR=2.28, 95%-CI=[1.71-3.06], IR COVID-19=12.58, IR Control=5.51), cough (IRR=1.74, 95%-CI=[1.48-2.04], IR COVID-19=36.56, IR Control=21.06), and throat/chest pain (IRR=1.72, 95%-CI=[1.39-2.12], IR COVID-19=20.01, IR Control=11.66). In adults, these included dysgeusia (IRR=6.69, 95%-CI=[5.88-7.60], IR COVID-19=12.42, IR Control=1.86), fever (IRR=3.33, 95%-CI=[3.01-3.68], IR COVID-19=11.53, IR Control=3.46), and dyspnea (IRR=2.88, 95%-CI=[2.74-3.02], IR COVID-19=43.91, IR Control=15.27). Conclusions: This large, matched cohort study indicates substantial new-onset post COVID-19 morbidity in pediatric and adult populations based on routine health care documentation. Further investigation is required to assess the persistence and long-term health impact of post COVID-19 conditions, especially in children and adolescents.