Pre-existing T cell memory as a risk factor for severe COVID-19 in the elderly

Bächer, Petra; Rosati, Elisa; Esser, Daniela; Martini, Gabriela Rios; Saggau, Carina; Schiminsky, Esther; Dargvainiene, Justina; oumlder, Ina Schr; Wieters, Imke; Eberhardt, Fabian; Neb, Holger; Khodamoradi, Yascha; Sonntagbauer, Michael; Vehreschild, Maria J.G.T.; Conrad, Claudio; Tran, Florian; Rosenstiel, Philip; Markewitz, Robert; Wandinger, Klaus‐Peter; Rybniker, Jan; Kochanek, Matthias; Leypoldt, Frank; Cornely, Oliver A.; Köehler, Philipp; Franke, André; Scheffold, Alexander

doi:10.1101/2020.09.15.20188896

Cited by 28 publications

(62 citation statements)

References 45 publications

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“…With every T cell stimulation approach tested, responses were also seen in a proportion of pre-pandemic controls. Epitope mapping studies will be required to investigate possible cross-reactive components of these responses with other human coronaviruses as other studies have highlighted (2,3,20) and to assess the impact of any such cross-reactivity on disease outcome, whether positive or negative (21,22).…”

Section: Sars-cov-2 Multispecific T Cell Responsementioning

confidence: 99%

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

et al. 2020

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Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

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Section: Sars-cov-2 Multispecific T Cell Responsementioning

confidence: 99%

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

et al. 2020

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“…While most of the scientific literature assumed preexisting T cells could be beneficial, there is also the possibility that preexisting immunity might actually be detrimental (Sette and Crotty [ 12 ]). According to Bacher et al [ 13 ], cross-reactive T cells have a low avidity, negatively impacting the response quality against neoantigens such as SARS-CoV-2 and inappropriate immune reactions. But these authors suggest that preexisting memory T cells targeting HCoVs epitopes and having a low cross-reactivity with SARS-CoV-2 epitopes could prevent the activation of naïve T cells and the selection of high-affinity clones.…”

Section: Evolution Of the Epidemicmentioning

confidence: 99%

Evolution of SARS-CoV-2: Review of Mutations, Role of the Host Immune System

Banoun

2021

Nephron

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Since the reporting of the first cases of coronavirus in China and the publication of the first sequence of SARS-CoV-2 in December 2019, the virus has undergone numerous mutations. In Europe, the spring outbreak (March–April) was followed by a drop in the number of cases and deaths. The disease may have evolved into a milder form. The increase in PCR-positive cases in late summer 2020 did not lead to the expected increase in hospitalizations, ICU admissions, and deaths, based on the severity of the disease in the spring. This difference in disease severity could be due to factors independent of the virus or to the evolution of the virus. This review attempts to identify the mutations that have appeared since the beginning of the pandemic and their role in the temporal evolution of the pandemic. There are a cell and humoral type cross-reactivity in a large part of the population to common cold coronaviruses (HCoVs) and SARS-CoV-2. Evolutionarily important mutations and deletions have emerged in the SARS-CoV-2 genes encoding proteins that interact with the host immune system. In addition, one of the major mutations (in viral polymerase) is logically associated with a higher frequency of mutations throughout the genome. This frequency fluctuates over time and shows a peak at the time when the epidemic was most active. The rate of mutations in proteins involved in the relationship to the immune system continues to increase after the first outbreak. The cross-reactivity on the 1 hand and the viral mutations observed on the other hand could explain the evolution of the pandemic until the summer of 2020, partly due to the evolution of the virus in relation to the host immune system. The immunization campaign began in December 2020: concerns are emerging about a possible escape of the circulating variants vaccines in early 2021. These variants could also escape immunity acquired through infection with the 2020 strains.

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“…The T cell response was shown to be critical for protection in SARS-1-infected mice [6]. Pa-tients with X-linked agammaglobulinemia, a genetic dis-2 in healthy donors [14,18,21,22]. sequencing study after yellow fever vaccination (donor 130 M1 samples in [23]).…”

mentioning

confidence: 99%

Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection

Minervina

Komech

Titov

et al. 2021

eLife

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108

144

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COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However, neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T-cell response nor the diversity of resulting immune memory is well understood. In this study, we use longitudinal high-throughput T-cell receptor (TCR) sequencing to track changes in the T-cell repertoire following two mild cases of COVID-19. In both donors, we identified CD4+ and CD8+ T-cell clones with transient clonal expansion after infection. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurrence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors, the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T-cell clones were detected in the memory fraction at the pre-infection time point, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.

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Pre-existing T cell memory as a risk factor for severe COVID-19 in the elderly

Cited by 28 publications

References 45 publications

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

Evolution of SARS-CoV-2: Review of Mutations, Role of the Host Immune System

Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection

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