Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

Abstract

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.

Impaired immune response drives age-dependent severity of COVID-19

“…The markedly lower risk of children developing severe COVID-19 on the other hand correlates with an increased basal expression level of the pattern-recognition receptors (PRRs) MDA5 and RIG-I, leading to a stronger innate antiviral immune response upon SARS-CoV-2 infection compared with adults ( Loske et al, 2021 ; Yoshida et al, 2021 ). In agreement, an early type I IFN response in immune cells was associated with the containment of virus dissemination preventing viral pneumonia ( Pekayvaz et al, 2022 ). However, despite its important endogenous role and several clinical trials demonstrating therapeutic efficacy ( Sodeifian et al, 2022 ), the use of type I IFNs as antiviral treatment has some limitations, mainly due to their ability to augment disease at late time points after infection ( Wang et al, 2020 ).…”

Impaired immune response drives age-dependent severity of COVID-19

“…The markedly lower risk of children to develop severe COVID-19 on the other hand correlates with an increased basal expression level of the pattern-recognition receptors (PRRs) MDA5 and RIG-I leading to a stronger innate antiviral immune response upon SARS-CoV-2 infection compared with adults 16, 17 . In agreement, an early type I IFN response in immune cells was associated with the containment of virus dissemination preventing viral pneumonia 18 . However, despite its important endogenous role, type I IFNs have limited therapeutic potential due to their ability to augment disease late during infection 19 .…”

Longitudinal home self-collection of capillary blood usinghomeRNA correlates interferon and innate viral defense pathways with SARS-CoV-2 viral clearance

“…To date, transcriptional profiling of the immune response, especially in longitudinal studies, is heavily focused on hospital-acquired samples and controlled human challenge studies ( 23-25 ), oftentimes from patients with moderate-to-severe symptoms or requiring oxygen support ( 26 ). When mild outpatient cases are evaluated, single time-point samples are collected through initial clinic visit or resource-intensive mobile phlebotomy ( 27 ) and longitudinal studies are oftentimes limited to infrequent sampling timepoints ( 28, 29 ). One study in outpatients with asymptomatic to moderate SARS-CoV-2 collected blood for RNA-seq at days 0 and 5 post-enrollment, which was at a median of 5 days post symptom onset ( 28 ).…”