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. 2020 Dec 2;6(1):138.
doi: 10.1038/s41420-020-00375-y.

Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity

Affiliations

Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity

Vineet Agarwal et al. Cell Death Discov. .

Abstract

Longitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient's nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3-41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.

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Conflict of interest statement

A.D.B. is a consultant for Abbvie, is on scientific advisory boards for nference and Zentalis, and is founder and President of Splissen therapeutics. E.S.T. is on the consulting/advisory board of Roche Diagnostics/Accelerate Diagnostics; has speaking associated engagement with Bio-Rad Diagnostics and research associated engagement with Ortho-Clinical Diagnostics. One or more of the investigators associated with this project and Mayo Clinic have a Financial Conflict of Interest in technology used in the research and that the investigator(s) and Mayo Clinic may stand to gain financially from the successful outcome of the research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies. The authors from nference have financial interests in nference.

Figures

Fig. 1
Fig. 1. Analyzing the distributions of SARS-CoV-2 PCR tests and their characteristics.
Distributions of a number of PCR tests per individual, b number of PCR tests taken by SARS-CoV-2-positive patients, c age of SARS-CoV-2-positive patients, d age of hospitalized SARS-CoV-2-positive patients, e age of ICU-admitted SARS-CoV-2-positive patients, f age of deceased SARS-CoV-2-positive patients, g the number of patients by sequence of SARS-COV-2 PCR positive and negative results, and h the number of switches between SARS-CoV-2-positive and SARS-CoV-2-positive status in longitudinal testing of SARS-CoV-2-positive patients; box indicates the count of patients that switched from SARS-CoV-2-positive to SARS-CoV-2-positive and back to SARS-CoV-2-positive status at least once.
Fig. 2
Fig. 2. Distribution of SARS-CoV-2-positive patients’ infection durations.
Distribution of the SARS-CoV-2-positive patients by a duration between the day of diagnosis to second contiguous negative test after last positive test. b duration between the day of diagnosis to the last positive test.
Fig. 3
Fig. 3. Distribution of upper bound of the duration to seropositive status based on SARS-CoV-2 IgG test and comparison to SARS-CoV-2-positive status based on PCR test.
a Histogram of duration (in days) between the day of diagnosis based on SARS-CoV-2 PCR test and day of seropositive status based on SARS-CoV-2 IgG test. b Comparison of seropositive status (based on antibody test) and SARS-CoV-2-positive status (based on PCR test). Cases that are both IgG-seropositive and PCR positive are boxed. c Scatter plot of lower bound of viral RNA shedding (x-axis) versus the upper bound of IgG-seropositivity status (y-axis).
Fig. 4
Fig. 4. Distributions of RT-PCR Crossing point (Cp) values.
Distributions of RT-PCR Crossing point (Cp) values: a all reported SARS-CoV-2-positive tests; b the last reported SARS-CoV-2-positive test for each patient who continue to shed viral RNA beyond 21 days of initial diagnosis; and c the last reported SARS-CoV-2-positive test for each patient who continue to shed viral RNA beyond 28 days of initial diagnosis.

Update of

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