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[Preprint]. 2020 Jul 7:2020.06.02.20120774.
doi: 10.1101/2020.06.02.20120774.

Long-term SARS-CoV-2 RNA Shedding and its Temporal Association to IgG Seropositivity

Vineet Agarwal  1 , A J Venkatakrishnan  1 , Arjun Puranik  1 , Christian Kirkup  1 , Agustin Lopez-Marquez  1 , Douglas W Challener  2 , John C O'Horo  2 , Matthew J Binnicker  2 , Walter K Kremers  2 , William A Faubion Jr  2 , Andrew D Badley  2 , Amy W Williams  2 , Gregory J Gores  2 , John D Halamka  2   3 , William G Morice 2nd  2   4 , Venky Soundararajan  1
Affiliations

Long-term SARS-CoV-2 RNA Shedding and its Temporal Association to IgG Seropositivity

Vineet Agarwal et al. medRxiv. .

Update in

  • Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity.
    Agarwal V, Venkatakrishnan AJ, Puranik A, Kirkup C, Lopez-Marquez A, Challener DW, Theel ES, O'Horo JC, Binnicker MJ, Kremers WK, Faubion WA Jr, Badley AD, Williams AW, Gores GJ, Halamka JD, Morice WG 2nd, Soundararajan V. Agarwal V, et al. Cell Death Discov. 2020 Dec 2;6(1):138. doi: 10.1038/s41420-020-00375-y. Cell Death Discov. 2020. PMID: 33298894 Free PMC article.

Abstract

Analysis of 851 COVID-19 patients with a SARS-CoV-2-positive PCR at follow-up shows 99 patients remained SARS-CoV-2-positive after four weeks from initial diagnosis. Surprisingly, a majority of these long-term viral RNA shedders were not hospitalized (61 of 99), with variable PCR Crossing point values over the month post diagnosis. 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). Juxtaposing IgG/PCR tests revealed that 14 of 90 patients are non-hospitalized and seropositive yet shed viral RNA. This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term shedders.

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Figures

Figure 1.
Figure 1.
Distributions of (a) number of PCR tests per individual, (b) number of PCR tests taken by COVIDpos patients, (c) age of COVIDpos patients, (d) age of hospitalized COVIDpos patients, (e) age of ICU-admitted COVIDpos patients, (f) age of deceased COVIDpos patients, (g) the number of patients by sequence of SARS-COV-2 PCR positive and negative results, and (h) the number of switches between COVIDpos and COVIDneg status in longitudinal testing of COVIDpos patients; box indicates the count of patients that switched from COVIDpos to COVIDneg and back to COVIDpos status at least once.
Figure 2.
Figure 2.
Distribution of the COVIDpos 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.
Figure 3.
Figure 3.
Distribution of upper-bound of the duration to sero-positive status based on SARS-CoV-2 IgG test and comparison to COVIDpos status based on SARS-CoV-2 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 sero-positive status (based on antibody test) and COVIDpos status (based on PCR test). Cases that are both IgG-sero-positive 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).
Figure 4.
Figure 4.
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.
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