The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study
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Abstract
Background
Immunocompromised patients show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. We report a case of prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of coronavirus disease 2019 (COVID-19) in a patient with mantle cell lymphoma who underwent treatment with rituximab, bendamustine, cytarabine with consequent lymphopenia and hypogammaglobulinemia.
Methods
Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). On 5 positive nasopharyngeal swabs, we performed viral culture and next-generation sequencing. We analyzed the patient’s adaptive and innate immunity to characterize T- and NK-cell subsets.
Results
SARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive for 268 days. All 5 performed viral cultures were positive, and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in 3 out of 4 COVID-19 clinical relapses and cleared each time after remdesivir treatment. The T- and NK-cell dynamic was different in aviremic and viremic samples, and no SARS-CoV-2-specific antibodies were detected throughout the disease course.
Conclusions
In our patient, SARS-CoV-2 persisted with proven infectivity for >8 months. Viremia was associated with COVID-19 relapses, and remdesivir treatment was effective in viremia clearance and symptom remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood; these are probably recruited in inflammatory tissue for viral eradication. In addition, we found a high level of NK-cell repertoire perturbation with relevant involvement during SARS-CoV-2 viremia.
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SciScore for 10.1101/2021.01.23.21249554: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources SARS-CoV-2 IgG and IgM antibody testing was performed using Thermo Scientific− COVID-19 Total Antibody ELISA test. IgMsuggested: NoneExperimental Models: Cell Lines Sentences Resources RT-PCR on nasopharyngeal swabs was performed with Allplex 2019 nCOV Seegene – Three Target assay [sensitivity 98·2%, specificity 100%].10 Viral isolation and culture from nasopharyngeal swab samples was performed on VERO E6 cells (Figure 1). VERO E6suggested: RRID:CVCL_XD71)… SciScore for 10.1101/2021.01.23.21249554: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources SARS-CoV-2 IgG and IgM antibody testing was performed using Thermo Scientific− COVID-19 Total Antibody ELISA test. IgMsuggested: NoneExperimental Models: Cell Lines Sentences Resources RT-PCR on nasopharyngeal swabs was performed with Allplex 2019 nCOV Seegene – Three Target assay [sensitivity 98·2%, specificity 100%].10 Viral isolation and culture from nasopharyngeal swab samples was performed on VERO E6 cells (Figure 1). VERO E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources We obtained full genome sequences from the supernatant at different time points with Miseq Illumina (Illumina, Inc. San Diego) using 2×150 paired-end sequencing. Miseq Illuminasuggested: NoneWe mapped and aligned the results to the reference genome obtained from Gisaid (https://www.gisaid.org/, accession ID: EPI_ISL_412973)11 using Geneious software, v. 9.1.5 (http://www.geneious.com).12 We used Nextclade and Pangolin systems (freely available at https://clades.nextstrain.org/ and https://pangolin.cog-uk.io/, respectively)13,14 for strain classification. Geneioussuggested: (Geneious, RRID:SCR_010519)We assessed T cells and NK cells activity on one viremic (Day 84) and one aviremic (Day 146) blood samples by BD Fortessa X20 flow cytometer (BD Biosciences) with the BD FACSDiva software (version 8.0; BD Biosciences) and by Activation Induced Marker (AIM) assay,15 a cytokine-independent approach using specific peptide megapools (MP), identified by bioinformatic approaches. BD FACSDivasuggested: (BD FACSDiva Software, RRID:SCR_001456)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 15. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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