Restoration of dendritic cell homeostasis and Type I/Type III interferon levels in convalescent COVID-19 individuals

Abstract

Background Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity. Results In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNβ) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15–30 to Days 61–90 and plateau thereafter. Similarly, the levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15–30 to Days 61–90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs. Conclusion Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.

Elucidating systemic immune responses to acute and convalescent SARS‐CoV‐2 infection in children and elderly individuals

“…monocytes, intermediate, and nonclassical monocytes, the activation markers sCD14, CRP, sCD163, and stissue factor, DC subsets plasmacytoid dendritic cell, myeloid dendritic cell, and IFNα, IFNβ, IFNλ1, IFNλ2, and IFNλ3, and neutrophil granular proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), and proteinase-3, and memory B cell subsets in convalescent COVID-19 individuals. [24][25][26][27][28] Our current study reveals that elderly individuals are associated with an enhanced immune and inflammatory response compared to children even during convalescence suggesting that the elderly might be prone to long-term sequelae from COVID-19. These findings will have ramifications in terms of the severity and incidence of long COVID-19 in the elderly compared to children.…”

“…Our study also extends the findings to the stage of convalescence. We have previously shown that convalescent adults are characterized by alterations in alterations in lymphocyte counts, neutrophil counts, NL ratio, monocyte counts, memory T cell subset frequencies, common γ‐chain cytokines, frequencies of classical monocytes, intermediate, and nonclassical monocytes, the activation markers sCD14, CRP, sCD163, and stissue factor, DC subsets plasmacytoid dendritic cell, myeloid dendritic cell, and IFNα, IFNβ, IFNλ1, IFNλ2, and IFNλ3, and neutrophil granular proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), and proteinase‐3, and memory B cell subsets in convalescent COVID‐19 individuals 24–28 . Our current study reveals that elderly individuals are associated with an enhanced immune and inflammatory response compared to children even during convalescence suggesting that the elderly might be prone to long‐term sequelae from COVID‐19.…”

IRF7: role and regulation in immunity and autoimmunity

“…reported that IRF7-deficient patients are prone to severe respiratory viral infections, with influenza and COVID-19, due to impaired type I and III IFN expression in both pDCs and respiratory epithelial cells ( 133 – 135 ). Patients with severe COVID-19 at early time points show decreased levels of type I and III IFN ( 136 ). TLR3- and TLR7-dependent production of IFN-I by pDCs and respiratory epithelial cells is essential for host defense against SARS-CoV-2 ( 137 ).…”

“…On the one hand, IRF7 is protective against viral infection. Campbell TM et al reported that IRF7-deficient patients are prone to severe respiratory viral infections, with influenza and COVID-19, due to impaired type I and III IFN expression in both pDCs and respiratory epithelial cells (133)(134)(135). Patients with severe COVID-19 at early time points show decreased levels of type I and III IFN (136).…”