SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Braun, Julian; Loyal, Lucie; Frentsch, Marco; Wendisch, Daniel; Georg, Philipp; Kurth, Florian; Hippenstiel, Stefan; Dingeldey, Manuela; Kruse, Beate; Fauchère, Florent; Baysal, Emre; Mangold, Maike; Henze, Larissa; Lauster, Roland; Mall, Marcus; Beyer, Kirsten; Röhmel, Jobst; Voigt, Sebastian; Schmitz, Jürgen; Miltenyi, Stefan; Demuth, Ilja; Müller, Marcel A.; Hocke, Andreas C.; Witzenrath, Martin; Suttorp, N; Kern, Florian; Reimer, Ulf; Wenschuh, Holger; Drosten, Christian; Corman, Victor M.; Giesecke‐Thiel, Claudia; Sander, Leif Erik; Thiel, Andreas

doi:10.1038/s41586-020-2598-9

Cited by 1,237 publications

(1,438 citation statements)

References 37 publications

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“…Interestingly, the SARS-CoV-2-responsive CD4 + T cells from unexposed donors also responded to similar epitopes present in endemic coronaviruses 229E and OC43 36 . Therefore, cross-reactive T cells might be the base for this cellular activation in the absence of humoral responses, although the dynamics of this cross-reactivity is not understood yet.…”

Section: Discussionmentioning

confidence: 87%

“…It has been described the generation of immunogenic CD4 + and CD8 + responses against SARS-CoV-2 antigens that correlate with the presence of speci c antibodies against the virus 34,35 . However, up to 35% of unexposed donors (without detectable anti-SARS-CoV-2 speci c antibodies) showed SARS-CoV-2reactive CD4 + T cells, while 83% of antibody-bearing patients displayed comparable cellular responses 36 .…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

IgG seroprevalence against SARS-CoV-2 in a cohort of 449 non-hospitalized, high-risk exposure individuals.

Martínez¹,

García²,

Salas³

et al. 2020

Preprint

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COVID-19 pandemic caused by SARS-CoV-2 led the Spanish government to impose a national lockdown in an attempt to control the spread of the infection. Mobility restrictions but also the requirement of a medical prescription to gain access to serological testing for COVID-19 were included among the measures. Under this scenario, between April 15th to June 15th, 2020, we performed a seroprevalence observational study including 449 individuals that fulfill prescription requirements: manifesting COVID-19 compatible symptoms, being in contact with a COVID-19 confirmed case or belonging to essential occupations including healthcare workers, firefighters or public safety personnel such as police. Importantly, none of the participants was hospitalized. Altogether, we studied this specific, non-commonly addressed cohort for SARS-CoV-2 seroprevalence, uncovering intrinsic features of great demographic interest. The overall rate of IgG seropositivity was 33.69% (95% CI: 29.27 – 38.21). This seroprevalence was comparable between different occupations performed by the participants. However, contacts with confirmed cases associated positively with IgG+ results, with stronger correlation if being a household member. The number of symptoms also correlated positively with IgG+ prevalence. Ageusia/anosmia, pneumonia and cutaneous manifestations were the top-three symptoms that most strongly associated with IgG+ seroprevalence. However, while pneumonia and cutaneous manifestations were barely present in our cohort, fever, ageusia/anosmia and asthenia were the most frequently symptoms described within IgG+ subjects. Therefore, our data illustrate how specific cohorts display heterogeneous characteristics that should be taken into account when identifying population seroprevalence against SARS-CoV-2 and key defining symptoms for COVID-19.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 98%

IgG seroprevalence against SARS-CoV-2 in a cohort of 449 non-hospitalized, high-risk exposure individuals.

Martínez¹,

García²,

Salas³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…On the other hand, previous studies suggested the potential role of pre-existing immunity in fighting COVID-19 [6,23,24]. Therefore, the predicted MHC-II T cell promiscuous epitopes of the SARS-CoV-2 S protein were compared to those from the other six HCoVs.…”

Section: Resultsmentioning

confidence: 99%

“…The cryo-EM structure of the S protein [20] and the neutralizing antibodies binding to the S protein [21,22] were determined. Besides neutralizing antibodies, studies have also shown the importance of CD4 T cell response in the control of SARS-CoV-2 infection and possible preexisting immunity in healthy individuals without exposure to SARS-CoV-2 [6,23,24]. Overall, successful vaccination is likely linked to a robust and long-term humoral response to the SARS-CoV-2 S protein, which could be further enhanced by the rational structural design of the protein.…”

Section: Covid-19 Vaccines Currently In Clinical Trials Including Othmentioning

confidence: 99%

Rational Design of SARS-CoV-2 Spike Glycoproteins To Increase Immunogenicity By T Cell Epitope Engineering

Ong

Huang

Pearce

et al. 2020

Preprint

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The current COVID-19 pandemic caused by SARS-CoV-2 has resulted in millions of confirmed cases and thousands of deaths globally. Extensive efforts and progress have been made to develop effective and safe vaccines against COVID-19. A primary target of these vaccines is the SARS-CoV-2 spike (S) protein, and many studies utilized structural vaccinology techniques to either stabilize the protein or fix the receptor-binding domain at certain states. In this study, we extended an evolutionary protein design algorithm, EvoDesign, to create thousands of stable S protein variants without perturbing the surface conformation and B cell epitopes of the S protein. We then evaluated the mutated S protein candidates based on predicted MHC-II T cell promiscuous epitopes as well as the epitopes' similarity to human peptides. The presented strategy aims to improve the S protein's immunogenicity and antigenicity by inducing stronger CD4 T cell response while maintaining the protein's native structure and function. The top EvoDesign S protein candidate (Design-10705) recovered 31 out of 32 MHC-II T cell promiscuous epitopes in the native S protein, in which two epitopes were present in all seven human coronaviruses. This newly designed S protein also introduced nine new MHC-II T cell promiscuous epitopes and showed high structural similarity to its native conformation. The proposed structural vaccinology method provides an avenue to rationally design the antigen's structure with increased immunogenicity, which could be applied to the rational design of new COVID-19 vaccine candidates.

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“…cytokines) 11 . The innate immune system seems to be insu cient to rapidly clear SARS-CoV-2 infection by itself, as SARS-CoV-2-speci c T and B cell responses develop in most patients [12][13][14] . Virus-speci c T cell responses and neutralizing antibodies, typically generated in a T cell dependent manner, are considered essential for viral clearance 15 .…”

Section: Introductionmentioning

confidence: 99%

T cell anergy in COVID-19 reflects virus persistence and poor outcomes

Renner

Müller

Tiefenböck

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

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SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Cited by 1,237 publications

References 37 publications

IgG seroprevalence against SARS-CoV-2 in a cohort of 449 non-hospitalized, high-risk exposure individuals.

IgG seroprevalence against SARS-CoV-2 in a cohort of 449 non-hospitalized, high-risk exposure individuals.

Rational Design of SARS-CoV-2 Spike Glycoproteins To Increase Immunogenicity By T Cell Epitope Engineering

T cell anergy in COVID-19 reflects virus persistence and poor outcomes

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