Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs.

Methods: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2.

Results: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%).

Conclusions: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

Keywords: COVID-19; coinfection; multiplex; nucleic acid testing; respiratory virus.

Figure 1.

Comparison of cycle thresholds in the S-gene, E-gene, and N-gene reverse-transcription quantitative nucleic acid tests (RT-QNATs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) loads. Nasopharyngeal/oropharyngeal swabs were submitted for routine testing with the S-gene and E-gene RT-QNATs (n = 7663). Samples with concordant positive or discordant results were subsequently tested with the in-house N-gene RT-QNAT. A, Cycling thresholds of concordant positive and discordant samples are displayed (median, 25^th and 75^th percentiles; n = 7663). B, SARS-CoV-2 loads and number of cases determined with the S-gene RT-QNAT in positive samples (median, 25^th and 75^th percentiles; n = 927).

Figure 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and community-acquired respiratory virus (CARV) epidemiology during the beginning of the epidemic spread from January to March 2020. A, Weekly SARS-CoV-2 (n = 8592) and CARV (n = 2394) prevalence in symptomatic children and adults. B, Weekly prevalence of cumulated SARS-CoV-2 (n = 8592) and CARV (N = 2394) cases in symptomatic children and adults (bar chart), and cumulated SARS-CoV-2 and CARV cases by calendar week 13 (pie chart). C, Weekly SARS-CoV-2 and CARV prevalence in nasopharyngeal/oropharyngeal swabs tested in parallel (n = 1816), and cumulated SARS-CoV-2 and CARV cases by calendar week 13 (pie chart). Abbreviations: HAdV, human adenovirus; HCoV, human coronavirus (229E, OC43, NL63, and HKU1); HMPV, human metapneumovirus; HPIV, human parainfluenza virus (types 1–4); HRSV, human respiratory syncytial virus; HRV, human rhinovirus; IV-A/B, influenza virus A and B; M. pne, Mycoplasma pneumoniae; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 3.

Age distribution of patients positive for community-acquired respiratory virus (CARV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nasopharyngeal/oropharyngeal swabs were analyzed in parallel for different CARVs with multiplex nucleic acid test and SARS-CoV-2 with reverse-transcription quantitative nucleic acid test. Patient age of CARV- or SARS-CoV-2–positive patients is displayed (median, 25^th and 75^th percentiles; n = 1816), and compared using Mann–Whitney U test (Table 3; Supplementary Tables 4–6). Abbreviations: HAdV, human adenovirus; HCoV, human coronavirus (229E, OC43, NL63, and HKU1); HMPV, human metapneumovirus; HPIV, human parainfluenza virus (types 1–4); HRSV, human respiratory syncytial virus; HRV, human rhinovirus; IV-A/B, influenza virus A and B; M. pne, Mycoplasma pneumoniae; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.