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      Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient

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          Abstract

          We describe a case of chronic coronavirus disease 2019 (COVID-19) in a patient with lymphoma and associated B-cell immunodeficiency. Viral cultures and sequence analysis demonstrate ongoing replication of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for at least 119 days. The patient had 3 admissions related to COVID-19 over a 4-month period and was treated twice with remdesivir and convalescent plasma with resolution of symptoms. The patient’s lack of seroconversion and prolonged course illustrate the importance of humoral immunity in resolving SARS-CoV-2 infection. This case highlights challenges in managing immunocompromised hosts, who may act as persistent shedders and sources of transmission.

          Abstract

          A detailed study of chronic COVID-19 in a patient with hematologic malignancy. The patient shed infectious virus for >119 days. This case highlights unique challenges in infection control and the clinical management of immunocompromised hosts.

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          Most cited references13

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          Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

          The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
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            Predicting infectious SARS-CoV-2 from diagnostic samples

            Abstract Background RT-PCR has become the primary method to diagnose viral diseases, including SARS-CoV-2. RT-PCR detects RNA, not infectious virus, thus its ability to determine duration of infectivity of patients is limited. Infectivity is a critical determinant in informing public health guidelines/interventions. Our goal was to determine the relationship between E gene SARS-CoV-2 RT-PCR cycle threshold (Ct) values from respiratory samples, symptom onset to test (STT) and infectivity in cell culture. Methods In this retrospective cross-sectional study, we took SARS-CoV-2 RT-PCR confirmed positive samples and determined their ability to infect Vero cell lines. Results Ninety RT-PCR SARS-CoV-2 positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median TCID50/ml was 1780 (282-8511). There was no growth in samples with a Ct > 24 or STT > 8 days. Multivariate logistic regression using positive viral culture as a binary predictor variable, STT and Ct demonstrated an odds ratio for positive viral culture of 0.64 (95% CI 0.49-0.84, p 24. Conclusions SARS-CoV-2 Vero cell infectivity was only observed for RT-PCR Ct 24 and duration of symptoms >8 days may be low. This information can inform public health policy and guide clinical, infection control and occupational health decisions. Further studies of larger size are needed.
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              Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors - Preliminary Report.

              Background Ebola virus has been detected in the semen of men after their recovery from Ebola virus disease (EVD), but little information is available about its prevalence or the duration of its persistence. We report the initial findings of a pilot study involving survivors of EVD in Sierra Leone. Methods We enrolled a convenience sample of 100 male survivors of EVD in Sierra Leone, at different times after their recovery from EVD, and recorded self-reported information about sociodemographic characteristics, the EVD episode, and health status. Semen specimens obtained at baseline were tested by means of a quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay with the use of the target-gene sequences of NP and VP40. Results A total of 93 participants provided an initial semen specimen for analysis, of whom 46 (49%) had positive results on quantitative RT-PCR. Ebola virus RNA was detected in the semen of all 9 men who had a specimen obtained 2 to 3 months after the onset of EVD, in the semen of 26 of 40 (65%) who had a specimen obtained 4 to 6 months after onset, and in the semen of 11 of 43 (26%) who had a specimen obtained 7 to 9 months after onset; the results for 1 participant who had a specimen obtained at 10 months were indeterminate. The median cycle-threshold values (for which higher values indicate lower RNA levels) were 32.0 with the NP gene target and 31.1 with the VP40 gene target for specimens obtained at 2 to 3 months, 34.5 and 32.3, respectively, for specimens obtained at 4 to 6 months, and 37.0 and 35.6, respectively, for specimens obtained at 7 to 9 months. Conclusions These data showed the persistence of Ebola virus RNA in semen and declining persistence with increasing months since the onset of EVD. We do not yet have data on the extent to which positivity on RT-PCR is associated with virus infectivity. Although cases of suspected sexual transmission of Ebola have been reported, they are rare; hence the risk of sexual transmission of the Ebola virus is being investigated. (Funded by the World Health Organization and others.).
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                Author and article information

                Journal
                J Infect Dis
                J Infect Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                22 October 2020
                : jiaa666
                Affiliations
                [1 ] Division of Infectious Diseases, University of Michigan , Ann Arbor, Michigan, USA
                [2 ] Division of Hospital Medicine, University of Michigan , Ann Arbor, Michigan, USA
                [3 ] Department of Microbiology and Immunology, University of Michigan , Ann Arbor, Michigan, USA
                [4 ] Department of Pathology, University of Michigan , Ann Arbor, Michigan, USA
                [5 ] Department of Epidemiology, University of Michigan , Ann Arbor, Michigan, USA
                Author notes
                Correspondence: Adam S. Lauring, University of Michigan, 1150 W Medical Center Dr, MSRB1 5510B, Ann Arbor, MI 48109-5680 ( alauring@ 123456med.umich.edu ).
                Author information
                http://orcid.org/0000-0003-2507-6987
                Article
                jiaa666
                10.1093/infdis/jiaa666
                7797758
                33089317
                80177480-91fb-4b42-b2d7-86d3f4b94167
                © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                History
                : 21 September 2020
                : 15 October 2020
                Page count
                Pages: 5
                Funding
                Funded by: University of Michigan, DOI 10.13039/100007270;
                Funded by: Centers for Disease Control and Prevention, DOI 10.13039/100000030;
                Award ID: U01 IP000974
                Categories
                Brief Report
                AcademicSubjects/MED00290
                Custom metadata
                PAP
                corrected-proof

                Infectious disease & Microbiology
                sars-cov-2,covid-19,immunocompromise,evolution,antibody
                Infectious disease & Microbiology
                sars-cov-2, covid-19, immunocompromise, evolution, antibody

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