Pre-test symptom duration and cycle threshold values for SARS-CoV-2 reverse transcription-PCR (RT-PCR) predict COVID-19 mortality

Miller, Emily Happy; Zucker, Jason; Castor, Delivette; Annavajhala, Medini K; Sepulveda, Jorge L; Green, Daniel A; Whittier, Susan; Scherer, Matthew; Medrano, Nicola; Sobieszczyk, Magdalena E; Yin, Michael T; Kuhn, Louise; Uhlemann, Anne-Catrin

BACKGROUND: The relationship between SARS-CoV-2 viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with COVID-19. METHODS: We conducted an observational study between March 10–May 30, 2020 at a large quaternary academic medical center in New York City. Patient characteristics, laboratory values, and clinical outcomes were abstracted from the electronic medical records. Of all patients tested for SARS-CoV-2 during this time (N=16,384), there were 5,467 patients with positive tests, of which 4,254 had available Ct values and were included in further analysis. Univariable and multivariable logistic regression models were used to test associations between Ct values, duration of symptoms prior to testing, patient characteristics and mortality. The primary outcome is defined as death or discharge to hospice. RESULTS: Lower Ct values at diagnosis (i.e. higher viral load) were associated with significantly higher mortality among both in- and out-patients. Interestingly, patients with a shorter time since the onset of symptoms to testing had a worse prognosis, with those presenting less than three days from symptom onset having 2-fold increased odds of death. After adjusting for time since symptom onset and other clinical covariates, Ct values remained a strong predictor of mortality. CONCLUSIONS: SARS-CoV-2 RT-PCR Ct value and duration of symptoms are strongly associated with mortality. These two factors add useful information for clinicians to risk stratify patients presenting with COVID-19.