Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children, 2022, Buonsenso et al

[SNT Gatchaman]

Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children
Buonsenso D, Valentini P, De Rose C, Tredicine M, Pereyra Boza MdC, Camponeschi C, Morello R, Zampino G, Brooks AES, Rende M, Ria F, Sanguinetti M, Delogu G, Sali M, Di Sante G, on behalf of the Gemelli-Pediatric COVID-19 Team.

Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated.

Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9).

Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively).

Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026).

Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.

Link | PDF

Post about a smaller study a year earlier by the same team:
https://www.s4me.info/threads/news-...e-cfs-2020-to-2021.14074/page-212#post-343924

 

[Amw66]

Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children
Buonsenso D, Valentini P, De Rose C, Tredicine M, Pereyra Boza MdC, Camponeschi C, Morello R, Zampino G, Brooks AES, Rende M, Ria F, Sanguinetti M, Delogu G, Sali M, Di Sante G, on behalf of the Gemelli-Pediatric COVID-19 Team.

Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated.

Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9).

Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively).

Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026).

Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.

Link | PDF

Perhaps the latest Phair/ Davis theory playing out ?

 

[SNT Gatchaman]

More specifically, one of the most interesting results of our study concerned the regulatory T cells. As shown in Figure 1B, the regulatory compartment of Long COVID children was more similar to those with early-stage acute infection than those that fully recovered from disease. This finding deserves attention since the expansion of naïve Tregs could be an attempt to restore the balance in the Treg pool in the face of both inflammation and tissue damage, which is supported by emerging evidence of a dual role for Tregs in suppressing immune responses and promoting tissue repair, while the persistently expanded effector T lymphocytes suggest that in some children the immune system is still activated by some persistent stimuli.

Interestingly, although analyzed in only a minority of patients, we also found that some children with persistent Long COVID, analyzed during different time points, have a declining number of total and natural Tregs and of naïve and switched B lymphocytes that produces IgM and IgG. These data further reinforce the hypothesis that some patients remain in an active immune activation status rather than switching to an adaptive post-acute phase. [...] these findings are in line with adult data but, more importantly, with a growing body of knowledge that Long COVID patients may present persistent viral antigens that may subtly stimulate the immune system.