135 COVID-19 patients admitted to Yale-New Haven Hospital (YNHH) between March 18th and May 5th, 2020 were included in this study. Nasopharyngeal swabs were collected, as recently described23 (link), approximately every four days for SARS-CoV-2 RT-qPCR analysis where clinically feasible. Paired whole blood for flow cytometry analysis was collected simultaneously in sodium heparin-coated vacutainers and kept on gentle agitation until processing. All blood was processed the same day as collection from patients. Patients were scored for COVID-19 disease severity through review of electronic medical records (EMR) at each longitudinal time point. Scores were assigned by a clinical infectious disease physician according to a custom developed disease severity scale. Moderate disease status (Clinical Score 1, 2 and 3) was defined as: (1) SARS-CoV-2 infection requiring hospitalization without supplemental oxygen, (2) infection requiring non-invasive supplemental oxygen (<3 L / min, sufficient to maintain greater than 92% SpO2), (3) infection requiring non-invasive supplemental oxygen (> 3L supplemental oxygen to maintain SpO2 > 92%, or, required > 2L supplemental oxygen to maintain SpO2 > 92% and had a high sensitivity C-reactive protein (CRP) > 70) and received tocilizumab. Severe disease status (Clinical score 4 and 5) was defined as infection meeting all criteria for clinical score 3 while also requiring admission to the YNHH Intensive Care Unit (ICU) and > 6L supplemental oxygen to maintain SpO2 > 92% (4); or infection requiring invasive mechanical ventilation / extracorporeal membrane oxygenation (ECMO) in addition to glucocorticoid / vasopressor administration (5). Clinical score 6 was assigned for deceased patients. Of note, the use of tocilizumab can increase circulating levels of IL-6 through inhibition of IL-6Rα-mediated degradation. Analysis of our cohort indicate higher plasma levels of IL-6 in both moderate and severe patients that received tocilizumab treatment (Extended data Fig. 1d) .
For all patients, days from symptom onset were estimated according to the following scheme: (1) highest priority was given explicit onset dates provided by patients; (2) next highest priority was given to the earliest reported symptom by a patient, and (3) in the absence of direct information regarding symptom onset, we estimated a date through manual assessment of the electronic medical record (EMRs) by an independent clinician. Demographic information was aggregated through a systematic and retrospective review of patient EMRs and was used to constructExtended Table 1 . Symptom onset and etiology was recorded through standardized interview with patients or patient surrogates upon enrollment in our study, or alternatively through manual EMR review if no interview was possible due to clinical status. The clinical data was collected using EPIC EHR and REDCap 9.3.6 software.
For all patients, days from symptom onset were estimated according to the following scheme: (1) highest priority was given explicit onset dates provided by patients; (2) next highest priority was given to the earliest reported symptom by a patient, and (3) in the absence of direct information regarding symptom onset, we estimated a date through manual assessment of the electronic medical record (EMRs) by an independent clinician. Demographic information was aggregated through a systematic and retrospective review of patient EMRs and was used to construct
