key: cord-0935001-uujuujjf authors: Alteri, Claudia; Cento, Valeria; Vecchi, Marta; Colagrossi, Luna; Fanti, Diana; Vismara, Chiara; Puoti, Massimo; Perno, Carlo Federico title: Nasopharyngeal SARS-CoV-2 load at hospital admission as predictor of mortality date: 2020-07-16 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa956 sha: 6aeba4b24f56bbcc8dc920cb54d5df077de59b58 doc_id: 935001 cord_uid: uujuujjf nan SARS-CoV-2 demonstrated a strikingly fast, and intense, replication kinetics, whose contribution to the clinical evolution of the COVID-19 is starting to be investigated [3] [4] [5] [6] . The nasopharyngeal SARS-CoV-2 loads expressed by cycle-thresholds (CTs) of RT-PCR, the standard-of-care for COVID-19 molecular diagnosis [7, 8] , is a widelyavailable parameter to be correlated with the severity of COVID-19. To prove this hypothesis, we investigated the correlation between the initial nasopharyngeal SARS-CoV-2 loads and 30-day in-hospital mortality, in 206 consecutive adult patients with a laboratory-confirmed SARS-CoV-2 infection, admitted to Niguarda Hospital (Milan, Italy) since March 5, and who have either died or been discharged by April 23, 2020 (Study protocol: 92-15032020). Dynamic-ranges of categorized Ctvalues of viral RdRp, E and N genes were assessed by quantitative droplet-digital PCR. The median (interquartile-range, IQR) time from symptoms-onset to hospital admission was 6 (4-9) days. By then, 188/206 (91.3%) patients presented an interstitial pneumonia with ground-glass opacities. Survivors (N=153) and nonsurvivors (N=53) significantly differed in several anamnestic, clinical, virological and laboratory characteristics (Appendix). These included both the mean and the absolute Ct values of RdRp, N and E genes, that were significantly lower in non-A c c e p t e d M a n u s c r i p t 4 survivors compared to survivors (p=0.001), reflecting higher viral-loads in the nasal/throat compartment of the former patients. Of note, the 20.7% of non-survivors had initial Cts<20 (viral-loads≥10 7 copies/mL), vs. only 5.3% of survivors (p<0.001). Kaplan-Meier curves showed a progressive increase of 30-day mortality, by increase in nasopharyngeal SARS-CoV-2 load (Figure 1 ). Thirty-days after disease-onset, the survival rate have dropped down to 35.3% in patients with Cts<20 (viral-loads≥10 7 copies/mL), vs. 81·0% in patients with Cts>35 (viral-loads<10 3 copies/mL) (p=0.001). Notably, the 36.4% of patients with initial Cts<20 died within seven days, vs. 14.3% and 0.0% of patients with initial Cts 20-24.9 and higher (Cts>25) (p=0·006). In Cox proportional hazard models (Appendix), out of 19 variables analyzed, Cts <20 Overall, we identified the high initial nasopharyngeal viral-load as an independent risk factor for in-hospital mortality, and for a significantly faster worsening of clinical conditions towards death. These results strengthen the recently reported correlation between viral-load and severe disease [5, 6] and provide initial evidence of a role for viral-load in influencing the definitive outcome. As RT-PCR on nasopharyngeal swabs is used worldwide, clinically validated Cts cut-offs (i.e.<20) represent a readyto-use prognostic marker to help stratifying patients for the risk of in-hospital death, and consequently implement appropriate measures to contain fatalities. A c c e p t e d M a n u s c r i p t 5 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. The Lancet Infectious Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China SARS-CoV-2 viral load in sputum correlates with risk of COVID-19 progression Viral dynamics in mild and severe cases of A c c e p t e d M a n u s c r i p t