ABSTRACT
We evaluated the performance of rapid antigen (RAg) and antibody (RAb) microfluidic diagnostics with serial sampling of 71 participants at 6 visits over 2 months following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Rapid tests showed strong agreement with laboratory references (κAg = 81.0%; κAb = 87.8%). RAg showed substantial concordance to both virus growth in culture and PCR positivity 0-5 days since symptom onset (κAg-culture = 60.1% and κAg-PCR = 87.1%). PCR concordance to virus growth in culture was similar (κPCR-culture = 70.0%), although agreement between RAg and culture was better overall (κAg-culture = 45.5% vs κPCR-culture = 10.0%). Rapid antigen and antibody testing by microfluidic immunofluorescence platform are highly accurate for characterization of acute infection.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19 Testing , Clinical Laboratory Techniques , Microfluidics , Sensitivity and Specificity , Antibodies , Polymerase Chain ReactionABSTRACT
BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture. RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms. CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.
Subject(s)
COVID-19 , Adult , Humans , COVID-19/diagnosis , SARS-CoV-2 , Longitudinal Studies , Diagnostic Techniques and Procedures , RNA, Viral , COVID-19 TestingABSTRACT
microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.
