key: cord-0694712-4ww6aabi authors: da Silva, Severino Jefferson Ribeiro title: Comparing studies of SARS‐CoV‐2 viral loads requires caution date: 2022-02-04 journal: J Med Virol DOI: 10.1002/jmv.27631 sha: 7ac5a2dda2f35081a6b75be55e1e483f2d6a1b5b doc_id: 694712 cord_uid: 4ww6aabi Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), research groups around the world are unraveling key factors of the associated disease, coronavirus disease 2019 (COVID-19). In light of this, many studies have sought to elucidate predictors for COVID-19 severity in order to guide clinical management and prognosis of the disease 1 . This article is protected by copyright. All rights reserved. ities. [1] [2] [3] [4] Moreover, many studies have evaluated the association between viral load and COVID-19 severity with controversial findings. 3, [5] [6] [7] [8] [9] [10] [11] [12] In summary, a cumulative body of data obtained during the COVID-19 pandemic course has demonstrated high, little, or no statistical correlation between viral load and severity in COVID-19 patients. Taken together, these results published until now demonstrate that this is a question that remains unclear and undefined. Throughout the COVID-19 pandemic, many studies have suggested that the high viral load was associated with a higher risk of severe disease in COVID-19 patients. 5, 8 In one of the first reports assessing the relationship between viral load and COVID-19 severity, Liu et al. 5 analyzed the C t values in patients classified with mild and severe disease using 76 respiratory specimens. After quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis, the results demonstrated that the viral load in nasopharyngeal specimens of COVID-19 severe cases was around 60 times higher than mild cases, and this positive correlation was maintained during the first 12 days of infection. 5 In a similar study, SARS-CoV-2 RNA viral shedding was evaluated in 3497 samples (serum, respiratory, stool, and urine) from 96 consecutively admitted COVID-19 patients in a hospital in Zhejiang province, China. 8 Viral load in respiratory specimens, with exception of stool and serum, of individuals with severe disease was higher than in individuals with mild disease. 8 In severe ill patients, male gender and old age was associated with longer viral shedding. 8 Similarly, these findings also corroborate with outcomes reported by other research teams across the world. 10, [13] [14] [15] In contrast, several reports have pointed that the high viral load was not associated with a higher risk of severe disease in COVID-19 patients. 9, 16, 17 For instance, a multicenter cross-sectional retrospective study was conducted by Abdulrahman et al. 9 using data obtained from Bahrain's National COVID-19 Task force's centralized database to explore whether a correlation exists between viral load and COVID-19 severity. A multivariable logistic regression was applied to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. In summary, the results showed that the C t values obtained from RT-qPCR showed no statistical significance for an association with the requirement for oxygenation on admission among COVID-19 patients. 9 In the midst of the COVID-19 pandemic, what factors have led to this controversial association between viral load and COVID-19 severity? 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