More infections diagnosed after COVID-19

Patients with an acute SARS-CoV-2 infection tend to have a subsequent increase in diagnosed infections over the next 12 months, according to new research.

In a large US cohort, 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) during the 1-year follow-up were higher among people who contracted COVID-19 but did not require hospital admission during the acute phase of infection than among those who had tested negative for COVID-19. [Lancet 2025;doi:10.1016/S1473-3099(24)00831-4]

Analyses of prespecified outcomes showed that a positive COVID-19 test without hospital admission was significantly associated with increased rates of outpatient diagnosis of infectious illnesses such as bacterial, fungal, and viral infection (risk ratio [RR], 1.17, 95 percent confidence interval [CI], 1.15–1.19) compared with a negative test.

Likewise, significantly increased rates of outpatient respiratory infections (RR, 1.46, 95 percent CI, 1.43–1.50) and admission to hospital for infectious illnesses such as sepsis and respiratory infections (RR, 1.41, 95 percent CI, 1.37–1.45) were associated with a positive COVID-19 test.

A marked increase in the frequency of subsequent infections was also seen among people who were hospitalized for COVID-19 during the acute phase. When compared with those admitted for seasonal influenza, people admitted for COVID-19 had higher rates of hospitalization for infectious illnesses (RR, 1.24, 95 percent CI, 1.10–1.40), hospitalization for sepsis (RR, 1.35, 95 percent CI, 1.11–1.63), and in-hospital use of antimicrobials (RR, 1.23, 95 percent CI, 1.10–1.37).

For the analysis, the investigators used the US Department of Veterans Affairs (VA) healthcare databases and included 231,899 people with a positive COVID-19 test and 605,014 with a negative COVID-19 test (test-negative control group) between November 2021 and December 2023. They also established a spatiotemporally aligned cohort comprising 12,450 people admitted to hospital for COVID-19 and 3,293 people admitted for seasonal influenza to ascertain the specificity of the findings to COVID-19.

What sets apart the present work “is the identification of increased infection rates among patients who were not admitted to hospital,” commented Prof Gabriel Chodick from the Tel-Aviv University in Tel Aviv, Israel, in an accompanying editorial. [Lancet 2025;doi:10.1016/S1473-3099(25)00074-X]

“Previous research has primarily shown elevated rates of infection in patients with long-COVID or in those requiring admission to hospital, [and the evidence from this study] suggests effects extending beyond the acute phase of infection, affecting even mild cases,” Chodick continued. “These findings have important implications for understanding the potential impact of COVID-19 on long-term immune function and susceptibility to pathogens.”

He noted that the current study builds upon another analysis of VA healthcare data, which showed increased frequency of various noncommunicable conditions—such as pulmonary diseases, hyperglycaemia, diabetes, kidney disease, and gastrointestinal complications— in patients with COVID-19 who were not admitted to hospital. [J Clin Invest 2021;131:e140491]

“This growing body of research on post-acute COVID-19 sequelae supports a bidirectional relationship between noncommunicable diseases and infectious diseases, resulting in persistently increased risk of adverse outcomes in the months and years after initial SARS-CoV-2 infection,” Chodick said.