By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: The incidence of most selected new-onset medical conditions did not significantly differ among those who had been hospitalized with COVID-19, influenza, or sepsis.
SOURCE: Quinn KL, Stukel TA, Huang A, et al. Comparison of medical and mental health sequelae following hospitalization for COVID-19, influenza, and sepsis. JAMA Intern Med 2023;183:806-817.
The occurrence of prolonged symptoms and new-onset medical conditions after survival from COVID-19 is the focus of much research funding. However, the research is hampered by a lack of consensus of the definition of long COVID. In addition, it is uncertain whether the incidence of prolonged symptoms and signs are different from those seen after other serious infectious diseases.
Quinn et al examined the incidence of 13 medical conditions in individuals who survived hospitalization for either COVID-19 between April 1, 2020, and Oct. 31, 2021, (n = 26,499), historical controls with influenza (n = 17,516) or sepsis (282,473), and contemporary controls with sepsis (n = 52,878). The new-onset conditions of interest included a variety of cardiovascular conditions and procedures, venous thromboembolic disease, neurologic disorders, rheumatoid arthritis, and mental health disorders.
Although some differences were present at 30 days post-discharge, beyond that time the only significant difference by one year was a greater incidence of venous thromboembolism in those who had been hospitalized for COVID-19 when compared to influenza controls (adjusted hazard ratio, 1.77; 95% CI, 1.36-2.31). Required ICU care did not significantly affect the results.
COMMENTARY
While there is a great focus on long COVID, a variety of other infections are associated with subsequent prolonged illness. Quinn et al found that for a wide variety of new-onset conditions, there was no significant difference in prolonged illness between those who were hospitalized with COVID-19, influenza, or sepsis — with one exception. COVID-19 was associated with a greater risk of thromboembolic disease at 12 months in comparison with influenza — but not when compared with prior sepsis hospitalization.
Several factors must be taken into consideration. Some comparisons did not involve contemporaneous cohorts. Of note is that only 7% of the COVID-19 patients had received at least one dose of vaccine against this infection. Perhaps a more highly vaccinated cohort may have experienced different frequencies of subsequent conditions. The COVID-19 cohort recorded a higher in-hospital mortality rate than the other groups, which also may have altered results. This also could introduce an “immortal time bias” — but this seems to me to be irrelevant in understanding the incidence of illness in survivors. The only individuals who could be the subject of such a study as this had to have survived.
In addition to these issues, several conditions thought to be somewhat specific to long COVID, such as olfactory disturbances, dysgeusia, and autonomic dysfunction, were not included in this study. The authors of a recent study developed a scoring system for diagnosing long COVID, but it remains to be seen whether its use will help resolve some of the confounding issues revolving around this diagnosis and its study.1
Effective antiviral therapy of the acute infection with Paxlovid is reported to be associated with a reduced incidence of subsequent long COVID.2 Although it failed the primary endpoint of preventing the occurrence of severe COVID-19 by day 14 of therapy of the acute infection (albeit, while demonstrating efficacy in secondary endpoints of ED visit, hospitalization, or death), metformin administration to acutely infected outpatients was associated with a lower risk of clinician-diagnosed long COVID.3
REFERENCES
1. Thaweethai T, Jolley SE, Karlson EW, et al; RECOVER Consortium. Development of a definition of postacute sequelae of SARS-CoV-2 infection. JAMA 2023;329:1934-1946.
2. Xie Y, Choi T, Al-Aly Z. Association of treatment with nirmatrelvir and the risk of post-COVID-19 condition. JAMA Intern Med 2023;183:554-564.
3. Bramante CT, Buse JB, Liebovitz DM, et al. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): A multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial. Lancet Infect Dis 2023; Jun 8:S1473-3099(23)00299-2. doi: 10.1016/S1473-3099(23)00299-2. [Online ahead of print].
The incidence of most selected new-onset medical conditions did not significantly differ among those who had been hospitalized with COVID-19, influenza, or sepsis.
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