Coinfection Dynamics in Respiratory Viral Infections

Coinfection occurs when two or more respiratory viruses infect the same host concurrently, altering transmission patterns, disease severity and immune responses. Studies reveal that interactions between influenza viruses, rhinoviruses, coronaviruses and other pathogens can lead to synergistic or antagonistic effects. Synergy may enhance viral replication, prompt exaggerated inflammatory responses and increase the risk of pneumonia, acute respiratory distress syndrome and mortality. Conversely, viral interference can suppress one pathogen through innate immunity activation, delaying or attenuating secondary infection. Non-pharmaceutical interventions, behavioural shifts and vaccination campaigns also influence coinfection dynamics by modifying susceptibility and contact rates. Understanding the timing and order of sequential infections is crucial, as early exposure to one virus can shape the host’s antiviral defences and affect the outcome of a subsequent challenge. Advances in genomic surveillance and multiplex diagnostics are beginning to map the global burden of coinfections, guiding more integrated surveillance systems and informing combined vaccination strategies to mitigate the collective impact of cocirculating respiratory viruses.

Research from Nature Portfolio

High-throughput virome capture sequencing in a cohort of SARS-CoV-2 patients demonstrated that roughly one in twelve individuals harboured an additional respiratory virus, most commonly rhinovirus or influenza. This work underscored the feasibility of simultaneously obtaining full SARS-CoV-2 genomes and identifying co-pathogens without targeted assays, highlighting the prevalence of undetected coinfections and their potential to complicate clinical management. In a mammalian model, sequential infection with influenza A virus followed two days later by SARS-CoV-2 caused severe lung damage, prolonged viral shedding and near-complete mortality. Strikingly, prior immunity to influenza—but not to SARS-CoV-2—prevented the lethal outcome, indicating that antibody-mediated protection against one virus can modulate the course of coinfection. Together, these studies provide foundational evidence that cocirculation of influenza and SARS-CoV-2 poses a compounded threat and that maintaining high influenza vaccine coverage may reduce severe comorbidity.

Coinfection Dynamics in Respiratory Viral Infections publication trend

The graph below shows the total number of articles in coinfection dynamics in respiratory viral infections across all publications each year (not limited to Nature Index journals).

Technical terms

Coinfection: Concurrent infection of a single host by two or more pathogens, which can alter disease severity, transmission and immune responses.

Test-negative design: An observational study method in which patients who test negative for a target pathogen serve as controls to estimate the effect of another infection on disease risk.

Neutralizing antibody: An antibody that binds to a virus and blocks its ability to infect host cells, playing a critical role in protective immunity.

References

1. Respiratory viral co-infections among SARS-CoV-2 cases confirmed by virome capture sequencing. Scientific Reports (2021).
2. Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity. Nature Communications (2021).
3. Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design. International Journal of Epidemiology (2021).
4. Influenza co-infection associated with severity and mortality in COVID-19 patients. Virology Journal (2021).
5. Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4+ T Cell Responses. Journal of Virology (2022).
6. COVID-19 and Respiratory Virus Co-Infections: A Systematic Review of the Literature. Viruses (2023).