SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

Turner, Jackson S.; Day, Aaron; Alsoussi, Wafaa B.; Liu, Zhuoming; O’Halloran, Jane A.; Presti, Rachel; Patterson, Bruce K.; Whelan, Sean P. J.; Ellebedy, Ali H.; Mudd, Philip A.

doi:10.3389/fimmu.2020.618402

Cited by 17 publications

(14 citation statements)

References 16 publications

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“…Despite the increased T-cell response magnitudes observed in individuals from the prolonged group, it is possible that their T-cell responses may be less functional, therefore allowing a persistence of SARS-CoV-2 virus. This was previously observed in a single individual with prolonged symptoms, persistent PCR+ test results and an impaired IFNg T-cell response (61). This scenario, along with our findings, indicates that COVID-19 vaccination may provide therapeutic benefits to a subset of PASC patients (62).…”

Section: Magnitude Of Sars-cov-2-specific Immune Response Correlates To Symptom Durationsupporting

confidence: 86%

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Files¹,

Sarkar²,

Fram.³

et al. 2021

JCI Insight

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A subset of COVID-19 patients exhibit Post-Acute Sequalae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median=74 days) compared to 30 who had symptom resolution in 20 days or less.Individuals with prolonged symptom duration maintained antigen-specific T-cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and cTfh populations during late convalescence while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 S-protein. Significant correlations between symptom duration and both SARS-CoV-2-specific T cells and antibodies were observed.Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2-specific immune responses are maintained in patients suffering from prolonged post-COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.

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Section: Magnitude Of Sars-cov-2-specific Immune Response Correlates To Symptom Durationsupporting

confidence: 86%

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Files¹,

Sarkar²,

Fram.³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

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“…It has recently been reported that prolonged viral shedding can be observed after immunosuppressive therapy for cancer [10]. Moreover, it was noted that a diminished CD8 + T-cell response, which is seen in people with frailty [11], correlates with prolonged viral shedding [12]. Therefore, frailty might explain the prolonged viral shedding in our case.…”

Section: Discussionsupporting

confidence: 52%

The long-quarantined case of COVID-19 with prolonged viral shedding and intermittent fever for more than 70 days

et al. 2021

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A 79-year old Japanese woman was diagnosed with coronavirus disease (COVID-19), caused by SARS coronavirus 2 (SARS-CoV-2), based on a positive reverse transcription-PCR (RT-PCR) test result. Chest computed tomography revealed mild interstitial pneumonia. She had intermittent persistent inflammatory reactions with fever. Laboratory findings and RT-PCR test results showed SARS-CoV-2 positivity for more than 70 days. To the best of our knowledge, this relatively mild case has the longest duration of viral shedding recorded, as confirmed by RT-PCR analysis. This case demonstrates that the viral shedding in COVID-19 can be prolonged, even in mild disease, and highlights the difficulties in distinguishing viral shedding from SARS-CoV-2 infectivity.

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“…Although patients improved using CCR5 antagonists, the levels of these cytokines decreased but not to normal levels suggesting persistent cytokinemia following discharge from hospitals. In addition, studies including those from our laboratory, have suggested that PASC may be caused by persistent SARS-CoV-2 itself ( 5 ). Here, we sought to identify possible immunologic signatures of COVID-19 severity and to determine whether PASC might represent a distinct immunologic condition compared to Mild to Moderate (MM) or Severe COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

et al. 2021

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Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against CCR5 are being investigated. Here, we explored the role of CCR5 and its ligands across the immunologic spectrum of COVID-19. We used a bioinformatics approach to predict and model the immunologic phases of COVID so that effective treatment strategies can be devised and monitored. We investigated 224 individuals including healthy controls and patients spanning the COVID-19 disease continuum. We assessed the plasma and isolated peripheral blood mononuclear cells (PBMCs) from 29 healthy controls, 26 Mild-Moderate COVID-19 individuals, 48 Severe COVID-19 individuals, and 121 individuals with post-acute sequelae of COVID-19 (PASC) symptoms. Immune subset profiling and a 14-plex cytokine panel were run on all patients from each group. B-cells were significantly elevated compared to healthy control individuals (P<0.001) as was the CD14+, CD16+, CCR5+ monocytic subset (P<0.001). CD4 and CD8 positive T-cells expressing PD-1 as well as T-regulatory cells were significantly lower than healthy controls (P<0.001 and P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF were all significantly elevated compared to healthy controls (all P<0.001). Conversely GM-CSF and CCL4 were in significantly lower levels than healthy controls (P=0.01). Data were further analyzed and the classes were balanced using SMOTE. With a balanced working dataset, we constructed 3 random forest classifiers: a multi-class predictor, a Severe disease group binary classifier and a PASC binary classifier. Models were also analyzed for feature importance to identify relevant cytokines to generate a disease score. Multi-class models generated a score specific for the PASC patients and defined as S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, a score for the Severe COVID-19 patients was defined as S2 = (IL-6+sCD40L/1000 + VEGF/10 + 10*IL-10)/(IL-2 + IL-8). Severe COVID-19 patients are characterized by excessive inflammation and dysregulated T cell activation, recruitment, and counteracting activities. While PASC patients are characterized by a profile able to induce the activation of effector T cells with pro-inflammatory properties and the capacity of generating an effective immune response to eliminate the virus but without the proper recruitment signals to attract activated T cells.

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SARS-CoV-2 Viral RNA Shedding for More Than 87 Days in an Individual With an Impaired CD8+ T Cell Response

Cited by 17 publications

References 16 publications

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

The long-quarantined case of COVID-19 with prolonged viral shedding and intermittent fever for more than 70 days

Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

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