Variation of SARS-CoV-2 viral loads by sample type, disease severity and time: a systematic review

Background. To describe whether SARS-CoV-2 viral loads (VLs) and cycle thresholds (CTs) vary by sample type, disease severity and symptoms duration. Methods. Systematic searches were conducted in MEDLINE, EMBASE, BioRxiv and MedRxiv. Studies reporting individual SARS-CoV-2 VLs and/or CT values from biological samples. Paired reviewers independently screened potentially eligible articles. CT values and VLs distributions were described by sample type, disease severity and time from symptom onset. Differences between groups were examined using Kruskal-Wallis and Dunn's tests (post-hoc test). The risk of bias was assessed using the Joanna Briggs Critical Appraisal Tools. Results. 14 studies reported CT values, 8 VLs and 2 CTs and VLs, resulting in 432 VL and 873 CT data points. VLs were higher in saliva and sputum (medians 4.7x108 and 6.5x104 genomes per ml, respectively) than in nasopharyngeal and oropharyngeal swabs (medians 1.7x102 and 4.8x103). Combined naso/oropharyngeal swabs had lower CT values (i.e. higher VLs) than single site samples (p=<0.0001). CT values were also lower in asymptomatic individuals and patients with severe COVID-19 (median CT 30 for both) than among patients with moderate and mild symptoms (31.4 and 31.3, respectively). Stool samples were reported positive for a longer period than other specimens. Conclusion. VLs are higher in saliva and sputum and in individuals who are asymptomatic of with severe COVID-19. Diagnostic testing strategies should consider that VLs vary by sample type, disease severity and time since symptoms onset.