Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients

Tan, Anthony T.; Linster, Martin; Tan, Chee Wah; Bert, Nina Le; Chia, Wan Ni; Kunasegaran, Kamini; Zhuang, Yan; Tham, Christine Y.L.; Chia, Adeline; Smith, Gavin J. D.; Young, Barnaby Edward; Kalimuddin, Shirin; Low, Jenny Guek Hong; Lye, David C.; Wang, Lin‐Fa; Bertoletti, Antonio

doi:10.1016/j.celrep.2021.108728

Cited by 672 publications

(699 citation statements)

References 29 publications

Supporting

Mentioning

612

Contrasting

Unclassified

Order By: Relevance

“…Surprisingly, more recently infected asymptomatic individuals possessed a SARS-CoV-2-specific T cell frequency of a magnitude indistinguishable from the one detected in COVID-19 patients (mild, moderate, and severe) tested during acute infection (SARS-CoV-2 PCR positive) or within 1 mo after viral clearance. This finding, even though analyzed with a single assay that might miss some fraction of SARS-CoV-2-specific T cells incapable of producing IFN-γ, further supports the accumulating evidence that the quantity of SARS-CoV-2-specific T cells is not proportional to disease severity during the early phase of infection (Rydyznski Moderbacher et al, 2020;Tan et al, 2021a). This is in contrast to the positive correlation between SARS-CoV-2-specific T cell frequency and presence/severity of symptoms reported by others.…”

Section: Discussionsupporting

confidence: 74%

“…However, the positive relation between SARS-CoV-2-specific T cell quantity and disease severity was not confirmed in recent studies measuring SARS-CoV-2-specific T cells in the early phases of COVID-19. Early induction and more robust SARS-CoV-2-specific CD4 and CD8 T cell response has been associated with milder disease development (Rydyznski Moderbacher et al, 2020;Tan et al, 2021a). In addition, a protective role of T cells has been demonstrated in animal models of coronavirus infections, in which virus-specific T cells clear the virus with limited lung pathology (Zhao et al, 2010;2016).…”

Section: Introductionmentioning

confidence: 99%

“…SARS-CoV-2-specific antibodies (Long et al, 2020b) and T cells are induced in asymptomatic individuals (Sekine et al, 2020), but the reported lower magnitude of antibodies (Long et al, 2020b) and T cell responses (Sekine et al, 2020;Reynolds et al, 2020) has been interpreted as a sign that asymptomatic individuals are mounting a normal innate immunity (Zhao et al, 2020 Preprint), but a weak adaptive antiviral immunity (Long et al, 2020b). Because antibody titers and frequency of SARS-CoV-2-specific T cells in the blood can undergo dynamic changes after viral clearance (Tan et al, 2021a), we reasoned that a proper quantitative comparison between SARS-CoV-2-specific T cells of symptomatic and asymptomatic individuals should be performed at similar time points after infection. The absence of symptoms makes such evaluation difficult.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Bert

Clapham

Tan

et al. 2021

Journal of Experimental Medicine

Self Cite

301

208

View full text Add to dashboard Cite

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Bert

Clapham

Tan

et al. 2021

Journal of Experimental Medicine

Self Cite

301

208

View full text Add to dashboard Cite

show abstract

“…In parallel with the results of studies conducted by other researchers, in our results, the symptoms and severity of the clinical picture in COVID-19 are directly related to the host's IFN response [5,36]. In the literature, it was proposed that early induction of IFN-γ-secreting SARS-CoV-2specific T cells occurs in the COVID-19 cases with mild to moderate disease and accelerated viral clearance [37]. Intestinal SARS-CoV-2 colonization associated with IFN response as the critical step of the inclusion into the virobiota usually follows the resolution of the clinical symptomatic viral infection.…”

Section: Induction Phase Of the Sars-cov-2 Genomic Incorporationsupporting

confidence: 84%

Current community transmission and future perspectives on the COVID-19 process

Turk

Malkan

et al. 2021

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: COVID-19 syndrome due to the SARS-CoV-2 virus is a currently challenging situation ongoing Worldwide. Since the current pandemic of the SARS-CoV-2 virus is a great concern for everybody in the World, the frequently asked question is how and when the COVID-19 process will be concluded. The aim of this paper is to propose hypotheses in order to answer this essential question. As recently demonstrated, SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome. Our main hypothesis is that the ultimate aim of the SARS-CoV-2 virus is the incorporation to human genome and being an element of the intestinal virobiota. Materials and methods: We propose that the SARS-CoV-2 genomic incorporation to be a part of human virobiota is essentially based on three pathobiological phases which are called as the "induction", "consolidation" and "maintenance phases". The phase of "recurrence" complicate any of these three disease phases based on the viral load, exposure time, and more contagious strains and/or mutants. We have performed the "Random Walk Model" in order to predict the community transmission kinetics of the virus. Results: Chimerism-mediated immunotherapy at the individual and community level with the help of vaccination seems to be the only option for ending the COVID-19 process. After the SARS-CoV-2 virus integrated into the human genome via the induction, consolidation and maintenance phases as an element of intestinal virobiota, the chimerism would be concluded. The "viral load", the "genomic strain of the SARS-2 CoV-2" and "host immune reaction against the SARS-CoV-2" are the hallmarks of this long journey. Conclusion: Elucidation of the functional viral dynamics will be helpful for disease management at the individual and community based long-term management strategies.

show abstract

“…Under these temperatures, gene expression is modified in DCs, with upregulation of 43 genes and downregulation of 24 genes involved in post-transcriptional modifications, protein folding, cell death/survival, and migration [49], as well as interleukin (IL)-12 production [50], which could bias the immune response toward a Th1 phenotype [51,52]. An early Th1 immune response is important since Th1 cells are able to produce cytokines and recruit innate immune cells [53], which has been associated with rapid viral clearance and mild disease in COVD-19 [54]. Notably, children who have milder disease after SARS-CoV-2 infection have predominantly increased levels of IL-17A and IFN-c, whereas adults typically do not, possibly reflecting a protective role for Th17 cells [55].…”

Section: Hyperthermia and The Immune Responsementioning

confidence: 99%

Exploring the rationale for thermotherapy in COVID-19

Mancilla-Galindo

Galindo-Sevilla

2021

International Journal of Hyperthermia

View full text Add to dashboard Cite

Increased transmissibility of the pandemic severe acute respiratory coronavirus 2 (SARS-CoV-2) has been noted to occur at lower ambient temperatures. This is seemingly related to a better replication of most respiratory viruses, including SARS-CoV-2, at lower-than-core body temperatures (i.e., 33 C vs 37 C). Also, intrinsic characteristics of SARS-CoV-2 make it a heat-susceptible pathogen. Thermotherapy has successfully been used to combat viral infections in plants which could otherwise result in great economic losses; 90% of viruses causing infections in plants are positive-sense singlestranded ribonucleic acid (þssRNA) viruses, a characteristic shared by SARS-CoV-2. Thus, it is possible to envision the use of heat-based interventions (thermotherapy or mild-temperature hyperthermia) in patients with COVID-19 for which moderate cycles (every 8-12 h) of mild-temperature hyperthermia (1-2 h) have been proposed. However, there are potential safety and mechanistic concerns which could limit the use of thermotherapy only to patients with mild-to-moderate COVID-19 to prevent disease progression rather than to treat patients who have already progressed to severe-to-critical COVID-19. Here, we review the characteristics of SARS-CoV-2 which make it a heat-susceptible virus, potential host mechanisms which could be enhanced at higher temperatures to aid viral clearance, and how thermotherapy could be investigated as a modality of treatment in patients with COVID-19 while taking into consideration potential risks.

show abstract

Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients

Cited by 672 publications

References 29 publications

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Current community transmission and future perspectives on the COVID-19 process

Exploring the rationale for thermotherapy in COVID-19

Contact Info

Product

Resources

About