key: cord-0730109-7dc2gox0 authors: Jacot, Damien; Greub, Gilbert; Jaton, Katia; Opota, Onya title: Viral load of SARS-CoV-2 across patients and compared to other respiratory viruses date: 2020-09-07 journal: Microbes Infect DOI: 10.1016/j.micinf.2020.08.004 sha: be0ec0a0b9932e952efea17da99cdc4138acce7c doc_id: 730109 cord_uid: 7dc2gox0 RT-PCRs to detect SARS-CoV-2 RNA is key to manage the COVID-19 pandemic. We analyzed SARS-CoV-2 viral loads from 22’323 RT-PCR results according to samples types, gender, age, and health units. Viral load did not show any difference across age and appears to be a poor predictor of disease outcome. SARS-CoV-2 viral load showed similar high viral loads than the one observed for RSV and influenza B. The importance of viral load to predict contagiousness and to assess disease progression is discussed. At the beginning of January 2020, the cluster of SARS-CoV-2 cases identified in Wuhan City, Hubei 22 Province (China) rapidly spread to other regions in China and to other countries, causing a world 23 pandemic (1, 2) . Quantitative reverse transcription polymerase chain reaction (RT-PCR) represents a 24 key diagnostic tool for patients with suspected SARS-CoV-2 infection. Viral-specific genes, such as 25 the Envelope (E), the RdRP/Helicase (Hel), the spike protein encoding gene (S), as well as 26 Nucleocapsid (N) were used as molecular targets and combination of these genes have been 27 recommended by the WHO (3, 4) . We introduced the E, RdRP, and N genes RT-PCRs in our fully 28 automated molecular diagnostic platform (MDx platform) (5). A lower sensitivity of the RT-PCRS 29 targeting the RdRP and N genes, compared to that targeting the E gene was observed leading us to 30 use solely the E gene, as RT-PCR target. Latter during the pandemic, the cobas® SARS-CoV-2 test 31 (Roche, Basel, Switzerland) became available targeting the ORF1/a, a non-structural region for 32 specific detection of SARS-CoV-2 and a conserved region in the E gene, for pan-Sarbecovirus 33 detection. The pan-Sarbecovirus primers and probe can also detect the SARS-CoV-1 virus, however 34 not currently circulating (6). 35 We determined the correlation between the cycle threshold (Ct) value and viral load and 36 investigated the distribution of viral loads across sex, age, and healthcare departments and as well 37 as against other respiratory viruses. The report of RT-PCR SARS-CoV-2 viral loads raised also several 38 questions regarding the use of this information for the laboratory as an internal quality assessment 39 tool, as well as (i) to predict contagiousness of patients and hence to guide epidemiological 40 decisions, especially for hospitalized patients and (ii) to predict the patient prognosis and assess for the E-gene PCR was those described by Corman and colleague (4) . Cts of the MDx platform 54 targeting the E gene were converted to viral load using either a plasmid containing the target 55 sequence of the PCR obtained from RD-Biotech (Besançon, France) or using purified viral RNA, kindly Ct values were obtained on the MDx platform and converted to viral loads, as previously reported 72 (5). For Influenza A and B and RSV the Xpert® Xpress Flu/RSV was used and converted to viral load 73 according to Zou et al. (7) . Only nasopharyngeal and nose swabs were included. Statistical analysis: 74 Data were process with Rstudio and plotted using ggplot2. Median is presented in all graphs. Statistical significance of viral loads were assessed using a parametric paired t-test and the two-76 tailed p-values interpretation are written on the graphs. 80 We observed a broad distribution of viral load values ( individuals, when tested, were likely to be proportionally more frequently positive than the rest of 98 the population, while young children showed very low percentages of positivity despite being rarely 99 tested ( Fig. S1C-D) . Interestingly, viral loads categorization based on 5-year brackets ages showed no 100 significant differences across age groups (Fig. 2C) . Although limited by the low samples size, the 101 pediatric age groups showed viral loads values comparable to adults. 103 We focused on the Intensive care unit (ICU), the internal medicine (IM) department, the emergency 104 unit (EU) and patients addressed to a screening unit (SU) specifically developed during the outbreak. This stratification per unit was used to investigate possible differences in viral loads in patients with showed that this value is not significantly higher than the one obtain for all other patients (Fig. 2D) . The clinical relevance and usefulness of viral load measures appears to be mainly restricted to 160 specifically classifying the patient as being in the first phase of the disease with high viral load or 161 rather in the 2 nd phase of the disease when viral load tends to decrease and when inflammation 162 predominates (12). This may be useful to help treatment decision, i.e. to use for instance anti-IL6 or 163 steroids in presence a cytokine storm or during a macrophage activation syndrome. Indeed, COVID-164 19 disease severity is not directly linked to viral replication in the upper and lower respiratory tracts 165 but is also to an unregulated inflammatory process induced by the host immune response (12). Interpretation of a unique viral load value in a given patients should be done cautiously since (i) 167 there is a trend to a natural gradual decrease of the viral load in the nasopharyngeal samples over (ii) clinical presentation, since a patient with cough and/or nasal discharge will be more contagious. 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