ABSTRACT
Introduction: SARS-CoV-2-detection is critical for clinical and epidemiological assessment of the ongoing CoVID-19 pandemic. Aim: To cross-validate manual and automated high-throughput (Roche-cobas6800-Target1/Target2) testing for SARS-CoV-2-RNA, to describe detection rates following lockdown and relaxation, and to evaluate SARS-CoV-2-loads in different specimens. Method: The validation cohort prospectively compared Basel-S-gene, Roche-E-gene, and Roche-cobas6800-Target1/Target2 in 1344 naso-oropharyngeal swabs (NOPS) taken in calendar week 13 using Basel-ORF8-gene-assay for confirmation. Follow-up-cohort-1 and -2 comprised 12363 and 10207 NOPS taken over 10 weeks until calendar week 24 and 34, respectively. SARS-CoV-2-loads were compared in follow-up NOPS, lower respiratory fluids, and plasma. Results: Concordant results were obtained in 1308 cases (97%) including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman r>0.95; p<0.001) for all assays. Discordant samples (N=36) had significantly lower SARS-CoV-2-loads (p<0.001). Following lockdown, weekly detection rates declined to <1% reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% with similarly high SARS-CoV-2-loads, but patients were significantly younger than during lockdown (34 vs 52 years, p<0.001). SARS-CoV-2-loads in follow-up NOPS declined by 3log10 copies/mL within 10 days post-diagnosis (p<0.001). SARS-CoV-2-loads in NOPS correlated weakly with those in time-matched lower respiratory fluids and plasma, but remained detectable in 14 and 7 cases of NOPS with undetectable SARS-CoV-2, respectively. Conclusion: Evaluated manual and automated assays are highly concordant and correlate quantitatively. Following successful lockdown, declining positive predictive values require dual-target-assays for clinical and epidemiologic assessment. Confirmatory and quantitative follow-up testing should be considered within <5 days, using lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.
Subject(s)
COVID-19ABSTRACT
Background. SARS-CoV-2 emerged in China in December 2019 as new cause of severe viral pneumonia (CoVID-19) reaching Europe by late January 2020. We validated the WHO-recommended assay and describe the epidemiology of SARS-CoV-2 and community-acquired respiratory viruses (CARVs). Methods. Naso-oropharyngeal swabs (NOPS) from 7663 individuals were prospectively tested by the Basel-S-gene and the WHO-based E-gene-assay (Roche) using Basel-N-gene-assay for confirmation. CARVs were tested in 2394 NOPS by multiplex-NAT, including 1816 together with SARS-CoV-2. Results. Basel-S-gene and Roche-E-gene-assays were concordant in 7475 cases (97.5%) including 825 (11%) positive samples. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 NOPS. Adults were more likely to test positive for SARS-CoV-2, while children were more likely to test CARV-positive. CARV co-infections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced other CARVs within 3 weeks reaching 48% of all detected respiratory viruses followed by rhino/enterovirus (13%), influenzavirus (12%), coronavirus (9%), respiratory syncytial (6%) and metapneumovirus (6%). Conclusions. The differential diagnosis for respiratory infections was broad during the early pandemic, affecting infection control and treatment decisions. We discuss the role of pre-existing immunity and competitive CARV replication for the epidemiology of SARS-CoV-2 infection among adults and children.