Possible Viral Interference Leading to Protection from Subsequent Respiratory Viral Infections – Results of an Observational Study at a Singapore Teaching Hospital.

Respiratory infections, affecting mainly young children and the elderly, pose significant global health threats. While protection from related strains of viruses like influenza is well-documented, cross-protection among different viruses remains less understood. The disappearance of influenza during the COVID-19 pandemic prompted investigation into viral interference and non-pharmaceutical interventions' role. Studies suggest interactions between different viruses and host responses influence infection rates. In a large retrospective review, we assessed the impact of initial respiratory infections on subsequent viral infections, studying prevalent viruses including Influenza, Adenovirus, EV/RV, Parainfluenza, RSV, and coronaviruses. This aimed to elucidate the dynamics of viral interference independent of pandemic-related interventions. We analysed all patients tested for positive respiratory viruses between January 2016– December 2019 just prior to the pandemic in the National University Hospital laboratory, Singapore. Nasal, throat, and/ or nasopharyngeal swabs were collected by treating clinicians and tested by either multiplex PCR or immunofluorescence. Survival plots were created to study the time for a second viral infection following the initial respiratory viral detection. RSV (HR: 0.63, 95%CI: 0.43–0.92; p<0.01) and influenza (HR: 0.41, 95%CI: 0.27-0.61; p<0.001) -positive cases showed a greater delay in subsequent respiratory infections compared to other pathogens, suggesting relative protection, while enterovirus/ rhinovirus (HR: 2.05, 95%CI: 1.52-2.77; p<0.001) and Parainfluenza (HR: 1.76, 95%CI: 1.18-2.63; p<0.001) showed heightened susceptibility. No significant associations were found for Adenovirus (HR 0.66; 95% CI 0.30 to 1.44; p=1), seasonal coronaviruses (HR 1.39; 95% CI 0.75 to 2.59; p=1), and other viruses (Bocavirus, Metapneumovirus) (HR 1.37; 95% CI 0.85 to 2.21; p=0.539). In our retrospective analysis, we discovered a notable trend: patients previously infected with Influenza or RSV showed reduced likelihood of subsequent viral infections within four years. While this aligns with findings by Chen et al., our study diverged in revealing that prior RSV infection, not adenovirus, conferred protective effects. This discrepancy may stem from demographic variations; our cohort encompassed diverse demographics, primarily children prone to RSV-related hospitalizations. Variations in circulating viruses and host immune responses could also influence outcomes. Notably, laboratory studies indicate cross-protection mechanisms, with Rhinovirus and Influenza inhibiting SARS-CoV-2 replication. This underscores the complexity of viral interactions and immune responses, warranting further investigation, especially regarding cytokine involvement. Our findings shed light on the intricate dynamics of viral interference, urging comprehensive exploration to elucidate underlying mechanisms and implications for clinical practice. We found that it is possible that prior infections with Influenza virus or RSV conferred significant cross-protection against subsequent circulating respiratory viral infections for the next 4 years. Larger studies are needed to explore mechanisms behind this possible broad-spectrum antiviral response in human hosts as this may have implications for vaccination strategies. [ABSTRACT FROM AUTHOR]