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

Baang, Ji Hoon; Smith, Christopher; Mirabelli, Carmen; Valesano, Andrew L; Manthei, David M; Bachman, Michael A.; Wobus, Christiane E.; Adams, Michael R.; Washer, Laraine; Martin, Emily T.; Lauring, Adam S.

doi:10.1093/infdis/jiaa666

Cited by 268 publications

(241 citation statements)

References 14 publications

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“…T lymphocytes (18% vs 68%) which is attributable to CD8+ T cells' ability to migrate into tissues affected by inflammation to control the virus. This case report adds to existing literature on COVID-19 relapses and prolonged SARS-CoV-2 shedding in immunocompromised patients, [3][4][5][6][7] highlighting the need for special attention in this particular population both in terms of clinical management comprising isolation measures and immunosuppressive treatment, 5,30 and for future immunotherapeutic perspective, including vaccination.…”

Section: T-sne Analysis Performed On Cd8+ T Cells Further Highlightedmentioning

confidence: 85%

“…2 In immunocompromised patients, prolonged viral shedding with proven viral infectivity is increasingly been reported 3-7 and in two cases it was associated with disease relapse. [3][4] Adaptive and innate immunity play a vital role in viral clearance: during many acute infections, including SARS-CoV-2, the presence of CD8+ cytotoxic T cells capable of secreting an array of molecules such granzymes to eradicate virus from the host has been described. 8 At the same time, CD4+ helper T cells can assist cytotoxic T cells and enhance their ability to clear pathogens.…”

Section: Introductionmentioning

confidence: 99%

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The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Sepulcri

Dentone

Mikulska

et al. 2021

Preprint

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BackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient.MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets.FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 ± 1·3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course.InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms 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 that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.FundingNone.

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Section: T-sne Analysis Performed On Cd8+ T Cells Further Highlightedmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Sepulcri

Dentone

Mikulska

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…With such limited substrate for selection to act upon, the short window of time between treatment and transmission could limit the spread of a variant selected within a host. Even during prolonged infections in immunocompromised hosts, there is only limited evidence of resistance to various COVID-19 therapeutics 32–34 .…”

Section: Discussionmentioning

confidence: 99%

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

Valesano

Rumfelt

Dimcheff

et al. 2021

Preprint

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Analysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified a viral load threshold that minimizes false positives. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.

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“…The apparent absence of substantial SARS-CoV-2 adaptations during the early pandemic would simply be a consequence of the durations of the chronic infections within which the progenitors of these lineages evolved. Chronic infections lasting between three and five months have been well documented [50][51][52][53] . Chronic infections that occurred in April 2020 when the first global peak of infections occurred might be expected to only yield substantially adapted variants by July or August 2020 which is approximately concordant with estimates of the times when the most recent common ancestors of viruses in the V2 lineage arose 7 .…”

Section: What Might Have Caused the Sudden Emergence Of The 501y Linementioning

confidence: 99%

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Martin

Weaver

Tegally

et al. 2021

Preprint

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The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.

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

Cited by 268 publications

References 14 publications

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

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