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      Persistence of SARS‐CoV‐2 nasopharyngeal swab PCR positivity in COVID‐19 convalescent plasma donors

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          Abstract

          Background

          Nucleic acid persists after symptom resolution and infectivity for many viral infections via delayed clearance of nucleic acid fragments, non‐infectious particles, or transmissible virus. For Coronavirus Disease 2019 (COVID‐19), the relationship between nasopharyngeal (NP) swab positivity, the development of antibodies against COVID‐19, and clinical history are unclear.

          Study design and methods

          Individuals who recovered from COVID‐19 and volunteered to donate convalescent plasma (CP) were screened by NP swab PCR, responded to a questionnaire, and were tested for anti‐COVID‐19 antibodies.

          Results

          A proportion of 11.8% of individuals tested positive for SARS‐CoV‐2 by NP swab PCR greater than 14 days after the resolution of symptoms of active disease, including one donor who had asymptomatic disease and tested positive by NP swab 41 days after her initial diagnosis. Clinical history did not show a significant correlation with persistence of NP swab positivity. Also, NP swab positivity >14 days from symptom resolution did not correlate with anti‐COVID‐19 serology results. IgG anti‐SARS‐CoV‐2 spike antibody strength correlated with hospitalization for COVID‐19 using two different assays. Total anti‐SARS‐CoV‐2 nucleocapsid antibody strength correlated with time from symptom resolution to sample collection and symptom duration.

          Conclusions

          SARS‐CoV‐2 nucleic acid is detectable long after the resolution of symptoms in a significant percentage of previously diagnosed individuals, which is important to consider when interpreting PCR swab results. Persistence of PCR positivity does not correlate with antibody strength or symptoms of COVID‐19. If anti‐spike antibody is used to assess CP potency, individuals who suffered severe COVID‐19 disease symptoms may represent better donors.

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          Most cited references16

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          Presumed Asymptomatic Carrier Transmission of COVID-19

          This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.
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            Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

            Could administration of convalescent plasma transfusion be beneficial in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19)? In this uncontrolled case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS), administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status. These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials. Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; P ao 2 /F io 2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Patients received transfusion with convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), P ao 2 /F io 2 , viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and P ao 2 /F io 2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials. This case series describes clinical outcomes in 5 Chinese patients with laboratory-confirmed COVID-19, ARDS, and high viral loads despite antiviral treatment who were given human plasma with SARS-CoV-2 antibodies obtained from previously infected and recovered patients.
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              When to use the Bonferroni correction.

              The Bonferroni correction adjusts probability (p) values because of the increased risk of a type I error when making multiple statistical tests. The routine use of this test has been criticised as deleterious to sound statistical judgment, testing the wrong hypothesis, and reducing the chance of a type I error but at the expense of a type II error; yet it remains popular in ophthalmic research. The purpose of this article was to survey the use of the Bonferroni correction in research articles published in three optometric journals, viz. Ophthalmic & Physiological Optics, Optometry & Vision Science, and Clinical & Experimental Optometry, and to provide advice to authors contemplating multiple testing.
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                Author and article information

                Contributors
                thomas.gniadek@gmail.com
                Journal
                Transfusion
                Transfusion
                10.1111/(ISSN)1537-2995
                TRF
                Transfusion
                John Wiley & Sons, Inc. (Hoboken, USA )
                0041-1132
                1537-2995
                24 August 2020
                : 10.1111/trf.16015
                Affiliations
                [ 1 ] Department of Pathology and Laboratory Medicine NorthShore University HealthSystem Evanston Illinois USA
                [ 2 ] NorthShore University HealthSystem Evanston Illinois USA
                [ 3 ] NorthShore University Health System, Swedish Hospital Chicago Illinois USA
                Author notes
                [*] [* ] Correspondence

                Thomas J. Gniadek, Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, 2650 Ridge Ave, Evanston, IL 60201.

                Email: thomas.gniadek@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-4092-9397
                Article
                TRF16015
                10.1111/trf.16015
                7461313
                32840002
                79ceeb26-3068-4db3-b979-55381b3765e7
                © 2020 AABB

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 17 May 2020
                : 21 July 2020
                : 21 July 2020
                Page count
                Figures: 3, Tables: 1, Pages: 7, Words: 3740
                Funding
                Funded by: Private donations to the NorthShore Foundation, including a donation from The Rice Foundation
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.8 mode:remove_FC converted:01.09.2020

                Hematology
                Hematology

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