Broad respiratory testing to identify SARS-CoV-2 viral co-circulation and inform diagnostic stewardship in the COVID-19 pandemic

Abstract

Background: SARS-CoV-2 infection can present with a broad clinical differential that includes many other respiratory viruses; therefore, accurate tests are crucial to distinguish true COVID-19 cases from pathogens that do not require urgent public health interventions. Co-circulation of other respiratory viruses is largely unknown during the COVID-19 pandemic but would inform strategies to rapidly and accurately test patients with respiratory symptoms.Methods: This study retrospectively examined 298,415 respiratory specimens collected from symptomatic patients for SARS-CoV-2 testing in the three months since COVID-19 was initially documented in the province of Alberta, Canada. By focusing on 52,285 specimens that were also tested with the Luminex Respiratory Pathogen Panel for 17 other pathogens, this study examines the prevalence of 18 potentially co-circulating pathogens and their relative rates in prior years versus since COVID-19 emerged, including four endemic coronaviruses. Results: SARS-CoV-2 was identified in 2.2% of specimens. Parallel broad multiplex testing detected additional pathogens in only 3.4% of these specimens: significantly less than in SARS-CoV-2-negative specimens (p < 0.0001), suggesting very low rates of SARS-CoV-2 co-infection. Furthermore, the overall co-infection rate was significantly lower among specimens with SARS-CoV-2 detected (p < 0.0001). Finally, less than 0.005% of all specimens tested positive for both SARS-CoV-2 and any of the four endemic coronaviruses tested, strongly suggesting neither co-infection nor cross-reactivity between these coronaviruses. Conclusions: Broad respiratory pathogen testing rarely detected additional pathogens in SARS-CoV-2-positive specimens. While helpful to understand co-circulation of respiratory viruses causing similar symptoms as COVID-19, ultimately these broad tests were resource-intensive and inflexible in a time when clinical laboratories face unprecedented demand for respiratory virus testing, with further increases expected during influenza season. A transition from broad, multiplex tests toward streamlined diagnostic algorithms targeting respiratory pathogens of public health concern could simultaneously reduce the overall burden on clinical laboratories while prioritizing testing of pathogens of public health importance. This is particularly valuable with ongoing strains on testing resources, exacerbated during influenza seasons.

Evaluation of human coronavirus OC43 and SARS‐COV‐2 in children with respiratory tract infection during the COVID‐19 pandemic

“…In a recently published study conducted in Canada, Marshal et al examined respiratory specimens of 298,415 COVID‐19 symptomatic patients for 18 possible cocirculating pathogens, including four endemic coronaviruses. This study found very low rates of SARS‐COV‐2 coinfection and significantly lower rates of coinfection for SARS‐COV‐2 virus in comparison with SARS‐COV‐2‐negative specimens 27 . In the study conducted by Hazra et al, 2535 specimens were simultaneously tested for SARS‐CoV‐2 and other pathogens, including HCoV‐OC43, on symptomatic patients.…”

Decline of Influenza and Respiratory Viruses With COVID-19 Public Health Measures

“…The effect observed because of the intervention is suggestive of a correlation rather than direct causation, as not all variables could be controlled. The model used in this study did not adjust for viral coinfections (found to be very low, approximately 3%), 49 as well as the effect of influenza vaccination. In Alberta, influenza vaccination coverage was constant, at approximately 30% over the study period, and the annual effectiveness was largely comparable for these years.…”

Respiratory virus coinfections with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) continue to be rare one year into the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada (June 2020–May 2021)

“…As with other regions, ERV was the most common additional respiratory virus detected among SARS-CoV-2 positive samples, 2 which is consistent with our observations earlier in the pandemic. 4 As ERV is a common single target on multiplex respiratory assays, many studies have not been able to differentiate the two. However, published data from Australia, Austria, Canada, and the United Kingdom demonstrate rhinovirus as the predominant seasonal circulating respiratory virus since the SARS-CoV-2 pandemic started; 1,7,8 therefore, we speculate that rhinovirus is likely predominant here.…”

“…During the first three months of the pandemic in Alberta, Canada (March-May 2020), when all specimens submitted for COVID-19 testing also underwent respiratory viral multiplex testing, only 3.4% of those positive for SARS-CoV-2 were found to have a co-infecting respiratory virus. 4 The most prevalent of these respiratory viruses was either enterovirus or rhinovirus (ERV); the viral panel utilized could not distinguish these two.…”