Rates of infection with other pathogens after a positive COVID-19 test versus a negative test in US veterans…, 2025, Cai, Xu, Xie, Al-Aly

Rates of infection with other pathogens after a positive COVID-19 test versus a negative test in US veterans November, 2021, to December, 2023: a retrospective cohort study
Miao Cai; Evan Xu; Yan Xie; Ziyad Al-Aly

BACKGROUND
SARS-CoV-2 infection leads to post-acute sequelae that can affect nearly every organ system, including the immune system. However, whether an infection with SARS-CoV-2 is associated with increased risk of future infections with other pathogens is not yet fully characterised. In this study, we aimed to test the association between a positive test for COVID-19, compared with a negative test, and rates of future infections with other pathogens.

METHODS
We used the US Department of Veterans Affairs health-care databases to build a spatiotemporally aligned cohort of 231 899 people with a positive COVID-19 test and 605 014 with a negative COVID-19 test (test-negative control group) between Nov 1, 2021, and Dec 31, 2023. We first did a discovery approach to map the associations between those with a positive COVID-19 test versus a negative test and laboratory-based outcomes of infectious illnesses. We then compared rates of a prespecified set of infectious disease outcomes between those with and without a positive COVID-19 test. To evaluate the specificity of the findings to COVID-19, we compared the rates of a prespecified set of infectious disease outcomes in a spatiotemporally aligned cohort of people admitted to hospital for COVID-19 (n=12 450) versus those admitted for seasonal influenza (n=3293). Outcomes were ascertained 30 days after the date of the first test until the end of follow-up (365 days after the first test plus 30 days, death, or July 18, 2024, whichever came first). An inverse probability weighting approach was used to balance demographic and health characteristics across cohorts. Log-binomial regression models were used to estimate risk ratios (RRs) and 95% CIs.

FINDINGS
In the 12 months of follow-up, compared with participants who had a negative test for COVID-19, people with COVID-19 who did not require admission to hospital during the acute phase of infection had increased test positivity rates for bacterial infections (in blood, urine, and respiratory cultures) and viral diseases (including Epstein–Barr virus, herpes simplex virus reactivation, and respiratory viral infections). People who were positive for COVID-19 and admitted to hospital also had increased rates of bacterial infections in blood, respiratory, and urine biospecimens, and viral infections in blood and respiratory biospecimens. Analyses of prespecified outcomes showed that, compared with the test-negative control group, participants with a positive COVID-19 test who were not admitted to hospital had significantly increased rates of outpatient diagnosis of infectious illnesses (RR 1·17 [95% CI 1·15–1·19]), including bacterial, fungal, and viral infections; outpatient respiratory infections (1·46 [1·43–1·50]); and admission to hospital for infectious illnesses (1·41 [1·37–1·45]), including for sepsis and respiratory infections; the rates of prespecified outcomes were generally higher among those who were admitted to hospital for COVID-19 during the acute phase. Compared with people admitted to hospital for seasonal influenza, those admitted for COVID-19 had higher rates of admission to hospital for infectious illnesses (1·24 [1·10–1·40]), admission to hospital for sepsis (RR 1·35 [1·11–1·63]), and in-hospital use of antimicrobials (1·23 [1·10–1·37]).

INTERPRETATION
Our results suggest that a positive test for COVID-19 (vs a negative test) was associated with increased rates of diagnosis of various infections in the 12 months following an acute SARS-CoV-2 infection. The putative long-term effects of COVID-19 on the immune system and the propensity for infection with other pathogens should be further evaluated in future studies.

FUNDING
US Department of Veterans Affairs.


Link | PDF (The Lancet Infectious Diseases)

 

Editorial in Long-term infectious sequelae after SARS-CoV-2 infection should be considered in mild cases too (2025, The Lancet Infectious Diseases)

 

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