Severe SARS-CoV-2 infections associated with greater risk of long term symptoms

1. In a retrospective cohort analysis, patients with severe SARS-CoV-2 infection were more likely to experience additional symptoms (e.g., fatigue, shortness of breath) in the 31-150 days following a positive test. 

2. It was also found that more severe SARS-CoV-2 infections were linked to increased incidence of diabetes, hematologic disorders, and respiratory diseases in the months following a positive test. 

Evidence Rating Level: 2 (Good)

The SARS-CoV-2 pandemic has caused millions of infections and deaths worldwide since the first recorded cases. However, there is also a relatively large proportion (between 10 to 50%) of individuals who develop new and persistent symptoms and conditions after infection with SARS-CoV-2 (often referred to as post-acute sequelae of SARS-CoV-2 infection [PASC] or long-COVID). However, these symptoms are heterogenous in nature and have not been appropriately studied in children and non-hospitalized adults. The current study made use of electronic health records data to examine whether select symptoms and conditions could be isolated in relation to acute infection of SARS-CoV-2. Two cohorts were stratified based on age at time of infection (a youth cohort, 0-19 years old, and an adult cohort, ≥ 20 years old). Participants included over 3 million adults (316,249 with a positive viral test and 2,775,331 with only negative viral tests) and over 675,000 youth (62,131 with a positive viral test and 613,512 with only negative tests). Patients who were hospitalized with a positive viral test had higher prevalences of all symptom outcomes 31-150 days after a SARS-CoV-2 test. Fifty-three percent of hospitalized adults with positive tests had at least one symptom compared to 44% of hospitalized adults with negative viral tests. Hospitalized adults with a positive test were at higher risk of being diagnosed with at least one symptom (adjusted odds ratio [aOR], 1.17 [95% CI, 1.11–1.23]), three or more symptoms (aOR, 1.16[95% CI, 1.08 – 1.26]), fatigue (aOR, 1.12 [95% CI, 1.05 – 1.18]), or shortness of breath (aOR, 1.50[95% CI, 1.38–1.63]) 31 to 150 days after SARS-CoV-2 testing. Children who were hospitalized with a positive test had increased odds of being diagnosed with at least one symptom (aOR, 1.18[95% CI, 1.08–1.28]) or shortness of breath (aOR, 1.40 [95% CI, 1.15–1.70]) 31–150 days later. Among those who were not hospitalized, those with positive tests were at higher risk of being diagnosed with fatigue or shortness of breath (aORfatigue, 1.11[95% CI, 1.05–1.16]; aORSOB, 1.22[95% CI, 1.15–1.29]) in the 31-150 days post-positive test. With respect to the development of new conditions, if adults were hospitalized with a positive test, there was an observed increase in incidence of type 1 or 2 diabetes (adjusted hazard ratio [aHR], 1.25[95% CI, 1.17–1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11–1.28]), and respiratory diseases (aHR, 1.44[95% CI, 1.30–1.60]). They were not significantly more likely than their negative test counterparts to develop mental health conditions, major adverse cardiovascular events, or neurological disorders. If non-hospitalized with a positive test, adults were more likely to develop new hematologic disorders (aHR, 1.12[95% CI, 1.02–1.23]) compared to those who tested negative and did not go to hospital. The generalizability of this study is higher than previous studies due to its inclusion of adults, children, and both hospitalized and non-hospitalized individuals. The findings demonstrate that patients with more severe COVID infections were more likely to develop PASC and long-COVID symptoms. They were also more likely to develop chronic diseases in the months following infection. Future studies should validate these results and further study those who were not hospitalized for long-term sequelae. 

Click to read the study in BMC Infectious Diseases

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