The pitfalls of inferring virus–virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2

There is growing experimental evidence that many respiratory viruses—including influenza and SARS-CoV-2—can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio—defined as the ratio of co-infection prevalence to the product of single-infection prevalences—should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza–SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection—such as a high reproduction number or a short infectious period—that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.

Viral Coinfection and Nasal Cytokines in Children With Clinically Diagnosed Acute Sinusitis

Objective: Children with no pathogenic bacteria in the nasopharynx are unlikely to have acute bacterial sinusitis. We evaluated whether information on clinical presentation, viral co-detection, and mucosal cytokine levels could be used to predict presence of bacteria in the nasopharynx.Method: We obtained nasopharyngeal (NP) swabs from children diagnosed with acute sinusitis. NP swabs were processed for bacterial culture, viral PCR testing, and cytokine expression. We examined whether results of the bacterial culture could be predicted based on the presence of clinical information, presence of viruses or mucosal cytokine levels.Results: We enrolled 174 children; 123 (71%) had a positive culture for potentially pathogenic bacteria and 51 (29%) had normal flora. 122/174 (70%) tested positive for one or more viruses. Compared to children with normal flora, children with pathogenic bacteria were more likely to have viruses (p < 0.01), but this relationship disappeared when we adjusted for age. Children with pathogenic bacteria in their nasopharynx and children with normal flora had similar levels of nasal cytokines.Conclusion: In children with clinically diagnosed acute sinusitis, clinical presentation, levels of nasal cytokines, and presence of viruses do not differentiate children with and without pathogenic bacteria in their nasopharynx.

Non-SARS Non-MERS Human Coronaviruses: Clinical Characteristics and Outcome

Human coronaviruses (HCoVs) have become evident sources of human respiratory infections with new emerging HCoVs as a significant cause of morbidity and mortality. The common four coronaviruses (229E, HKU1, NL63, and OC43) are known to cause respiratory illness in humans, but their clinical impact is poorly described in the literature. We analyzed the data of all patients who tested positive for at least one of the four HCoVs from October 2015 to January 2020 in a tertiary care center. HCoVs were detected in 1062 specimens, with an incidence rate of 1.01%, out of all documented respiratory illnesses. Detection of these viruses was reported sporadically throughout the years, with a peak of occurrence during winter seasons. OC43 had the highest incidence (53.7%), followed by NL63 (21.9%), HKU1 (12.6%), and 229E (11.8%). Most of these infections were community-acquired, with symptoms of both upper and lower respiratory tract. Co-detection with other viruses were observed, mostly with rhinovirus. 229E was the most frequent (26.4%) HCoV in patients requiring intensive care, while NL63 and 229E were the most common in patients requiring invasive ventilation. The highest 30-day mortality rate was observed in patients infected with 229E (6.4%). HCoVs are common circulating pathogens that have been present for decades, with 229E being the most virulent in this study cohort.