Mortality Risk Increases in COVID-19 Co-Infection with Influenza and Adenoviruses

Maaike C Swets, MD

Preventative measures put in place to inhibit the spread of SARS-CoV-2 have also been effective in reducing transmission of other endemic respiratory viruses. Investigators expect that as many countries relax these measures, SARS-CoV-2 will join other viruses in circulating the population leading to a probably increase in co-infections.

Because the clinical outcome of respiratory viral co-infection with SARS-CoV-2 is unknown, a team of investigators decided to examine co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses with SARS-CoV-2 infection.

The data indicated that co-infection with influenza viruses increased a patient's odds of receiving invasive mechanical ventilation when compared with SARS-CoV-2 monoinfection.

The Risks of Co-Infection

Investigators, led by Maaike C Swets, Roslin Institute, University of Edinburgh, assessed 212,466 adults who were admitted to a UK hospital with SARS-CoV-2 infection between February 2020-December 2021 using the International Severe Acute Respiratory and Emerging Infection Consortium–WHO Clinical Characterisation Protocol.

Testing for respiratory viral co-infections was performed in 6965 patients with SARS-CoV-2. A viral co-infection was detected in 8.4% (583) of patients; 227 of them had influenza viruses, 220 patients had respiratory syncytial virus, and 136 patients had adenoviruses.

A higher risk of death was significantly associated with SARS-CoV-2 and influenza virus, or adenovirus co-infections. Invasive mechanical ventilation was more likley to be implemented in patients with co-infection of influenza viruses.

The Strengths and Limitations

According to investigators, with 583 confirmed co-infections and 6382 confimed SARS-CoV-2 monoinfections, this study was the largest evaluation of individuals with COVID-19 who were tested for endemic respiratory viruses. Also, patients were recruited throughout an 18-month period.

Investigators noted some limitations of the study, including a risk of selection bias, particularly referring to the severity of illness in a patients. Those who were more unwell increased the probability of testing for co-infections.

Influenza virus co-infection still maintained a significant association with invasive mechanical ventilation after investigators performed corrections for the selection bias and other differences with inverse probablility weighting analysis. The odds ratio was larger than in the unweighted analysis but the confidence intervals were wider.

The authors concluded that co-infections will be on the rise with pubilc health restrictions being lifted, especially during winter. The increased risk among patients with co-infections has several implications for policy, according to the team.

"First, our results provide further support for vaccination against both SARS-CoV-2 and influenza viruses," investigators wrote. "Second, they suggest that testing for influenza viruses is important in hospital inpatients with COVID-19 to identify patients at risk and a cohort of patients who might have different responses to immunomodulatory and antiviral therapy."

The study "SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses" was published in The Lancet.