ABSTRACT
T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately. In SARS-COV-2 PCR+ individuals, a wave of TCRs strongly but transiently expand, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains but not with circulating human coronaviruses. Many expanding CDR3s were present at high frequency in pre-pandemic repertoires. Early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the preinfection naive repertoire. High-frequency naive precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection.
ABSTRACT
PURPOSE: To evaluate the sensitivity, specificity, and severity of chest x-rays (CXR) and chest CTs over time in confirmed COVID-19+ and COVID-19- patients and to evaluate determinants of false negatives. METHODS: In a retrospective multi-institutional study, 254 RT-PCR verified COVID-19+ patients with at least one CXR or chest CT were compared with 254 age- and gender-matched COVID-19- controls. CXR severity, sensitivity, and specificity were determined with respect to time after onset of symptoms; sensitivity and specificity for chest CTs without time stratification. Performance of serial CXRs against CTs was determined by comparing area under the receiver operating characteristic curves (AUC). A multivariable logistic regression analysis was performed to assess factors related to false negative CXR. RESULTS: COVID-19+ CXR severity and sensitivity increased with time (from sensitivity of 55% at ≤2 days to 79% at >11 days; p<0.001 for trends of both severity and sensitivity) whereas CXR specificity decreased over time (from 83% to 70%, p=0.02). Serial CXR demonstrated increase in AUC (first CXR AUC=0.79, second CXR=0.87, p=0.02), and second CXR approached the accuracy of CT (AUC=0.92, p=0.11). COVID-19 sensitivity of first CXR, second CXR, and CT was 73%, 83%, and 88%, whereas specificity was 80%, 73%, and 77%, respectively. Normal and mild severity CXR findings were the largest factor behind false-negative CXRs (40% normal and 87% combined normal/mild). Young age and African-American ethnicity increased false negative rates. CONCLUSION: CXR sensitivity in COVID-19 detection increases with time, and serial CXRs of COVID-19+ patients has accuracy approaching that of chest CT.