Browsing by Author "Castanha, Priscila MS"

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    SARS-CoV-2 Viremia is Associated with COVID-19 Severity and Predicts Clinical Outcomes.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-08-10) Jacobs, Jana L; Bain, William; Naqvi, Asma; Staines, Brittany; Castanha, Priscila MS; Yang, Haopu; Boltz, Valerie F; Barratt-Boyes, Simon; Marques, Ernesto TA; Mitchell, Stephanie L; Methé, Barbara; Olonisakin, Tolani F; Haidar, Ghady; Burke, Thomas W; Petzold, Elizabeth; Denny, Thomas; Woods, Chris W; McVerry, Bryan J; Lee, Janet S; Watkins, Simon C; St Croix, Claudette M; Morris, Alison; Kearney, Mary F; Ladinsky, Mark S; Bjorkman, Pamela J; Kitsios, Georgios D; Mellors, John W

    Background

    SARS-CoV-2 viral RNA (vRNA) is detected in the bloodstream of some patients with COVID-19 ("RNAemia") but it is not clear whether this RNAemia reflects viremia (i.e., virus particles) and how RNAemia/viremia is related to host immune responses and outcomes.

    Methods

    SARS-CoV-2 vRNA was quantified by ultra-sensitive RT-PCR in plasma samples (0.5-1.0 ml) from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-ICU), and 23 ICU patients, and vRNA levels compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in pelleted plasma.

    Results

    SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6% and 11.1% of ICU, non-ICU, and outpatients respectively. Virions were detected in plasma pellets by electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (p<0.0001); and for inpatient, plasma vRNA levels were strongly associated with higher WHO score at admission (p=0.01), maximum WHO score (p=0.002) and discharge disposition (p=0.004). A plasma vRNA level >6,000 copies/ml was strongly associated with mortality (HR: 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (p<0.01) but not with plasma neutralizing antibody titers (p=0.8).

    Conclusions

    Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia quantified by ultrasensitive RT-PCR correlate strongly with disease severity, patient outcome and specific inflammatory biomarkers but not neutralizing antibody titers.