Routine Testing for Non-SARS-CoV-2 Pathogens May Not Rule Out COVID-19

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Routine testing for non-SARS-CoV-2 pathogens is unlikely to provide clinical benefit unless a positive result would alter the disease management.

Routine testing for respiratory pathogens other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not be helpful in ruling out novel coronavirus disease 2019 (COVID-19) in the absence of widespread testing capabilities, according to a research letter published in JAMA.1

On March 14, 2020, the Centers for Disease Control and Prevention recommended that, in light of the low availability of tests to detect SARS-CoV-2, patients suspected of having COVID-19 be tested for other respiratory pathogens. This guideline was issued, based on reports from China suggesting that patients with COVID-19 were rarely infected by another respiratory pathogen.2  

To determine the rates of coinfection with SARS-CoV-2 and other respiratory pathogens in Northern California, researchers at Stanford Health Care, California, tested 1217 specimens from 1206 unique patients for SARS-CoV-2 and other respiratory pathogens using real-time reverse transcriptase–polymerase chain reaction between March 3 and March 25, 2020.

Of the 1217 specimens, 116 (9.5%) were positive for SARS-CoV-2 and 318 (26.1%) were positive for ≥1 non-SARS-CoV-2 pathogen. Of the 116 specimens that were positive for SARS-CoV-2, 24 specimens (20.7%) were positive for ≥1 additional pathogen vs 294 of the 1101 (26.7%) specimens that were negative for SARS-CoV-2 (difference, 6.0%; 95% CI, -2.3% to 14.3%).

The most common coinfections included rhinovirus/enterovirus (6.9%), respiratory syncytial virus (5.2%), and non-SARS-CoV-2 Coronaviridae (4.3%). The rates of infection for each of the other respiratory pathogens tested were comparable in patients with or without coinfection of SARS-CoV-2.

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Study limitations included the fact that samples were solely collected from patients in Northern California, and that specific patterns of coinfection that may help predict infection with SARS-CoV-2 may not be identified here because of restricted multiple testing of samples and capture of spatiotemporal variation — essential in viral epidemiology — resulting from a limited sample size.

“These results suggest higher rates of coinfection between SARS-CoV-2 and other respiratory pathogens than previously reported, with no significant difference in rates of SARS-CoV-2 infection in patients with and without other pathogens,” the researchers wrote. “The presence of a non-SARS-CoV-2 pathogen may not provide reassurance that a patient does not also have SARS-CoV-2.”


1. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens [published online April 15, 2020]. JAMA. doi:10.1001/jama.2020.6266

2. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.