Alterations in T and B cell function persist in convalescent COVID-19 patients

Shuwa, Halima Ali; Shaw, Tovah N.; Knight, Sean; Wemyss, Kelly; McClure, Flora A.; Pearmain, Laurence; Prise, Ian; Jagger, Christopher; Morgan, David; Khan, Saba; Brand, Stephan; Mann, Elizabeth R.; Ustianowski, Andrew; Bakerly, Nawar Diar; Dark, Paul; Brightling, Christopher; Brij, SO; Felton, Timothy; Simpson, Angela; Grainger, John; Hussell, Tracy; Konkel, Joanne E.; Menon, Madhvi; Ahmed, Rohan; Avery, Miriam; Birchall, Katharine; Charsley, Evelyn; Chenery, Alistair; Chew, Christine; Clark, Richard; Connolly, Emma; Connolly, Karen L.; Dawson, Simon; Durrans, Laura; Durrington, Hannah; Egan, Jasmine; Filbey, Kara J.; Fox, Claire; Francis, Helen; Franklin, Miriam; Glasgow, Susannah; Godfrey, Nicola J.; Gray, Kathryn J.; Grundy, Seamus; Guerin, Jacinta; Hackney, Pamela; Hayes, C. G.; Hardy, Emma; Harris, Jade; John, Anu; Jolly, Bethany; Kästele, Verena; Kerry, Gina; Liu, Sylvia; Lin, Li-Jing; Mathioudakis, Alex G.; Mitchell, Joanne; Moizer, Clare; Moore, Katrina; Moss, Stuart B.; Baker, Syed Murtuza; Oliver, Rachel; Padden, Grace; Parkinson, Christina; Phuycharoen, Michael; Saha, Ananya; Salcman, Barbora; Scott, Nicholas A.; Sharma, Seema; Shaw, Jane; Shaw, Joanne; Shepley, Elizabeth; Smith, Lara; Stephan, Simon; Stephens, Richard; Tavernier, G; Tudge, Rhys; Wareing, Louis; Warren, Roanna; Williams, Thomas; Willmore, L; Younas, Mehwish

doi:10.1016/j.medj.2021.03.013

Cited by 113 publications

(159 citation statements)

References 49 publications

(65 reference statements)

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“…In line with our findings, a very high proportion of T cells from acute COVID-19 patients express cytotoxic molecules such as Perforin and Granzyme B, with samples of severe patients displaying the highest expression levels (Shuwa et al, 2021). The increased cytotoxic profile persisted for up to six months and was associated with poorer recovery.…”

Section: Proportion Of Activated Cd16 + T Cells and Complement Protein Expression Determines Outcome Of Covid-19supporting

confidence: 90%

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg

Astaburuaga-García

Bonaguro

et al. 2021

Preprint

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Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

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Section: Proportion Of Activated Cd16 + T Cells and Complement Protein Expression Determines Outcome Of Covid-19supporting

confidence: 90%

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Georg

Astaburuaga-García

Bonaguro

et al. 2021

Preprint

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“…Descriptions of peripheral blood B cells in the initial weeks of an acute SARS-CoV-2 infection have reported modest relative B cell lymphopenia, and variable increases in plasmablast frequencies, in some cases exceeding 30% of total B cells, reminiscent of findings in other severe acute viral illnesses such as Ebola virus infection ( Kaneko et al., 2020 ; Mathew et al., 2020 ; McElroy et al., 2015 ). These B cell subset changes are consistent but transient, as reported in a longer follow-up study of COVID-19 patients that analyzed plasmablast frequencies within 7 days of hospitalization, at discharge, and after 3 to 6 months of convalescence ( Shuwa et al., 2021 ). This study confirmed the finding of elevated plasmablasts in acute COVID-19 but reported that plasmablasts returned to baseline frequencies in convalescent samples 3 to 6 months after infection.…”

Section: B-lineage Cells In Sars-cov-2 Infectionsupporting

confidence: 80%

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Röltgen

Boyd

2021

Cell Host & Microbe

115

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Antibodies, and the B cell and plasma cell populations responsible for their production, are key components of the human immune system’s response to SARS-CoV-2, which has caused the coronavirus disease 2019 (COVID-19) pandemic. Here, we review findings addressing the nature of antibody responses against SARS-CoV-2 and their role in protecting from infection or modulating COVID-19 disease severity. In just over a year, much has been learned, and replicated in independent studies, about human immune responses to this pathogen, contributing to the development of effective vaccines. Nevertheless, important questions remain about the duration and effectiveness of antibody responses, differences between immunity derived from infection compared to vaccination, the cellular basis for serological findings, and the extent to which viral variants will escape from current immunity.

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“…Another study concludes that changes in B and T cell function following hospitalisation due to COVID-19 could affect immunity in the longer term (up to 6 months) and contribute to some persistent symptoms observed in patients convalescing from COVID-19. (23) Our findings are that 90% (67 out of 74) of patients with LC still have specific cellular immunity more than 7 months after primary infection (78% after more than 9), and there is scope to consider that in the majority of LC patients, cellular immunity could go on for a longer period. The fact that there is prolonged specific T cell activity could be an indirect indicator of viral persistence in LC patients.…”

Section: Specific Cellular Response To Sars-cov-2 In Lc Patientsmentioning

confidence: 70%

“…The fact that there is prolonged specific T cell activity could be an indirect indicator of viral persistence in LC patients. (23) Half of the surveyed LC patients appear to have a 'defective' CD4+ T lymphocyte response, which would prevent CD8+ T lymphocytes from activating adequately, thereby affecting proper antibody production.…”

Section: Specific Cellular Response To Sars-cov-2 In Lc Patientsmentioning

confidence: 99%

Analysis of cell-mediated immunity in people with long COVID

Montes¹,

Domènech²,

Guerrero³

et al. 2021

Preprint

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Introduction: The objective of this study is to analyse the specific immune response against SARS-CoV-2 in those affected by Long Covid (LC), attributable to T cells (cell-mediated immunity) and to carry out a parallel analysis of the humoral response and lymphocyte typing. Methodology: Descriptive cross-sectional study of 74 patients with LC for at least 4 months since diagnosis. The collected data were: information on the COVID-19 episode and the persistent symptoms, medical history and a specific cell-mediated immunity to SARS-CoV-2 through flow cytometry, assessing the release of interferon-gamma (IFN-Ɣ) by T4 lymphocytes, T8 lymphocytes and NK cells. Descriptive and comparative analyses were carried out. Results: Patients with LC had negative serology for Covid-19 in 89% of cases but 96% showed specific cellular immunity to SARS-CoV-2 an average of 9.5 months after infection: 89% of this response corresponded to T8 lymphocytes, 58% to NK cells, and 51% to T4 lymphocyte (20% negligibly positive). Most of them had altered immune cell typing and we found that T4 lymphocyte counts were low in 34% of cases and NK cell high in 64%. Macrophage populations were detected in the peripheral blood of 7% of them. Patients displayed a higher percentage of illnesses related to ″abnormal″ immune responses, either preceding SARS-CoV-2 infection (43%) or following it in 23% of cases. Conclusion: The immune system appears to have an important involvement in the development of LC and viral persistence could be the cause or consequence of it. Further analysis with a control group should be performed.

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Alterations in T and B cell function persist in convalescent COVID-19 patients

Cited by 113 publications

References 49 publications

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Analysis of cell-mediated immunity in people with long COVID

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