Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children

Manthiram, Kalpana; Xu, Qunying; Milanez-Almeida, Pedro; Martins, Andrew J.; Radtke, Andrea J.; Hoehn, Kenneth B.; Chen, Jinguo; Liu, Can; Tang, Juanjie; Grubbs, Gabrielle; Stein, Sydney; Ramelli, Sabrina; Kabát, Juraj; Behzadpour, Hengameh; Karkanitsa, Maria; Spathies, Jacquelyn; Kalish, Heather; Kardava, Lela; Kirby, Martha; Cheung, Foo; Preite, Silvia; Duncker, Patrick C.; Romero, Nahir; Preciado, Diego; Gitman, Lyuba; Koroleva, G. I.; Smith, Grace; Shaffer, Arthur L.; McBain, Ian; Pittaluga, Stefania; Germain, Ronald N.; Apps, Richard; Sadtler, Kaitlyn; Moir, Susan; Chertow, Daniel S.; Kleinstein, Steven H.; Khurana, Surender; Tsang, John S.; Mudd, Pamela; Schwartzberg, Pamela L.

doi:10.21203/rs.3.rs-1276578/v1

“…The problem of long COVID-19 is emerging as a key pathological consequence of SARS-CoV-2 infection [54,55]. Although the set of etiological factors is very broad [56], the residual persistence of viral RNA is considered among them [57]. We identified the thresholds in the increase of the innate and adaptive responses parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic synchrony/coordination of the responses, i.e., to the loss of an optimal pattern of their cascade.…”

Section: Discussionmentioning

confidence: 99%

Predicting the Kinetic Coordination of Immune Response Dynamics in SARS-CoV-2 Infection: Implications for Disease Pathogenesis

Grebennikov

¹

,

Karsonova

²

,

Loguinova

³

et al. 2022

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A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter evaluation. The calibration of the mathematical model of SARS-CoV-2 infection is based on combining the parameter guesses from our earlier study of influenza A virus infection, some recent quantitative models of SARS-CoV-2 infection and clinical data-based parameter estimation of a subset of the model parameters. Hence, the calibrated mathematical model represents a theoretical exploration type of study, i.e., ‘in silico patient’ with mild-to-moderate severity phenotype, rather than a completely validated quantitative model of COVID-19 with respect to all its state-space variables. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the kinetics of immune responses with the clinical phenotypes of COVID-19. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to the pathogenesis of COVID-19, i.e., the sensitivity of the peak viral load to the parameters characterizing the antiviral specific response components, the kinetic coordination of the individual innate and adaptive immune responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e., the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds for variations of the innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination between them were identified.

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“…The 10-fold increase of the differentiation rate of antigen-specific B cells into plasma Although the set of etiological factors is very broad [44], the residual persistence of viral 154 RNA is considered among them [48]. We identified the thresholds in the increase of the game' [51] or race between viral replication and activation of immune system arms [52], i.e.,…”

mentioning

confidence: 99%

Predicting the Cross-Coordinated Immune Response Dynamics in Sars-Cov-2 Infection: Implications for Disease Pathogenesis

Grebennikov¹,

Karsonova²,

Логинова³

et al. 2022

Preprint

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A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

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Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

Kudryavtsev

¹

,

Arsentieva

²

,

Korobova

³

et al. 2022

Viruses

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Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

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Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children

Cited by 3 publications

References 83 publications

Predicting the Kinetic Coordination of Immune Response Dynamics in SARS-CoV-2 Infection: Implications for Disease Pathogenesis

Predicting the Kinetic Coordination of Immune Response Dynamics in SARS-CoV-2 Infection: Implications for Disease Pathogenesis

Predicting the Cross-Coordinated Immune Response Dynamics in Sars-Cov-2 Infection: Implications for Disease Pathogenesis

Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

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