Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Chandran, Aneesh; Rosenheim, Joshua; Nageswaran, Gayathri; Swadling, Leo; Pollara, Gabriele; Rk, Gupta; Burton, Alice R.; Guerra-Assunção, José Afonso; Woolston, Anne-Marie; Ronel, Tahel; Pade, Corinna; Gibbons, Joseph M.; Estrada, Blanca Sanz-Magallon Duque De; Massy, Marc Robert de; Whelan, Matthew; Semper, Amanda; Brooks, Tim; Altmann, Daniel M.; Boyton, Rosemary J.; Captur, Gabriella; Manisty, Charlotte; Treibel, Thomas A.; Moon, James; Tomlinson, Gillian S.; Maini, Mala K.; Chain, Benjamin M.; Noursadeghi, Mahdad

doi:10.1016/j.xcrm.2022.100557

Cited by 45 publications

(59 citation statements)

References 47 publications

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“…This is due to the increasing uptake of the vaccination campaign that made more difficult the enrolment of unvaccinated individuals. However, the results are robust and in agreement with the recent findings generated in a larger cohort (42). Secondly, SARS-CoV-2 infections included in this study were likely caused by the Alpha variant, dominant between February and June 2021.…”

Section: Discussionsupporting

confidence: 92%

“…After 7-20 days (T1), IFN-α quickly disappeared. This data agrees with the type I IFN response detected by a blood transcriptome analysis in a cohort of subjects recently exposed to SARS-CoV-2 ( 42 ). We extended the analysis to a large panel of soluble factors identifying other cytokines/chemokines upregulated (IP-10, IL-1ra, MCP-1) or downregulated (IL-9, IL-1β, RANTES, MIP-1β) at the earliest stage of infection in household contacts with a positive swab.…”

Section: Discussionsupporting

confidence: 89%

“…This acquired knowledge can be useful for new diagnostic tools or therapy interventions. However, there is a lack of longitudinal studies on the combined analysis of innate immunity, serological and T-cell specific responses against SARS-CoV-2 in the same patient population during the first epidemic wave ( 42 ). Therefore, in this study, we characterized the innate and adaptive immune responses in individuals early exposed to SARS-CoV-2, who have presented an asymptomatic or mild COVID-19, correlating the results with the outcome of the nasopharyngeal swab.…”

Section: Introductionmentioning

confidence: 99%

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Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave

et al. 2022

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ObjectiveTo better define the immunopathogenesis of COVID-19, the present study aims to characterize the early immune responses to SARS-CoV-2 infection in household contacts of COVID-19 cases. In particular, innate, T- and B-cell specific responses were evaluated over time.MethodsHousehold contacts of COVID-19 cases screened for SARS−CoV−2 infection by nasopharyngeal swab for surveillance purposes were enrolled (T0, n=42). Of these, 28 subjects returned for a follow-up test (T1). The innate response was assessed by detecting a panel of soluble factors by multiplex-technology in plasma samples. Cell-mediated response was evaluated by measuring interferon (IFN)-γ levels by ELISA in plasma harvested from whole-blood stimulated with SARS−CoV−2 peptide pools, including spike (S), nucleocapsid (N) and membrane (M) proteins. The serological response was assessed by quantifying anti-Receptor-Binding-Domain (RBD), anti-Nucleocapsid (N), whole virus indirect immunofluorescence, and neutralizing antibodies.ResultsAt T0, higher levels of plasmatic IFN-α, IL-1ra, MCP-1 and IP-10, and lower levels of IL-1β, IL-9, MIP-1β and RANTES were observed in subjects with positive swab compared to individuals with a negative one (p<0.05). Plasmatic IFN-α was the only cytokine detectable in subjects with positive SARS-CoV-2 swabs with high accuracy for swab score positivity (0.93, p<0.0001). Among subjects with positive swabs, significant negative correlations were found among the RT-PCR cycle threshold values reported for genes S and N and IFN-α or IP-10 levels. At T0, the IFN-γ T-cell specific response was detected in 50% (5/10) of subjects with positive swab, while anti-RBD/anti-N antibodies showed a positivity rate of 10% (1/10). At T1, the IFN-γ T-cell specific response was detected in most of the confirmed-infection subjects (77.8%, 7/9), whereas the serological response was still observed in a minority of them (44.4%, 4/9). Overall, the swab test showed a moderate concordance with the T-cell response (78.6%, k=0.467), and a scarce concordance with the serological one (72.9%, k=0.194).ConclusionsPlasmatic IFN-α and the IFN-γ T-cell specific response appear early even in the absence of seroconversion, and show a greater positivity rate than the serological response in household contacts with positive swab.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave

et al. 2022

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“…It is also important to emphasise that given the observational nature of our study, the sequential spread of Omicron BA.1 and BA.2 in the United Kingdom, and the rapid expansion of third-dose vaccination in December 2021, it was not possible to determine whether differences we observed between Delta and the BA.1 and BA.2 VOCs were attributable to intrinsic differences between these variants, or waning of immune protection afforded by vaccination. The reported shift in COVID-19 symptoms between Delta and Omicron sub-variants may be driven by intrinsic differences in the biology of the virus itself, leading to modified host responses; mutations in the Spike protein of SARS-CoV-2 VOCs may directly impact on symptom profiles through changes in viral tropism (2, 3, 32, 33), However, detailed data on differences in the host response to different VOC in vaccinated, non-hospitalised adults are currently lacking, but are likely to involve an interplay between localised mucosal innate and early T-cell interferon-mediated systemic responses (2, 34, 35). Further studies to determine the mechanisms by which different and emerging VOCs affect the host response are urgently required, and will be a necessary counterpart to clinical studies in the assessment of future VOCs.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history

Townsley

Carr

Russell

et al. 2022

Preprint

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Introduction The impact of COVID-19 vaccination on disease in the community has been limited, as a result of both SARS-CoV-2 Variants of Concern that partially escape vaccine-induced immunity. We sought to characterise symptoms and viral loads over the course of COVID-19 infection in otherwise-healthy vaccinated adults, representative of the general population, to assess whether current self-isolation guidance remains justified. Methods In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral kinetics between infections caused by VOCs Delta and Omicron (sub-variants BA.1 and BA.2) and investigated applicability of UK NHS isolation guidelines to these newer VOCs. Results 373 infection episodes were reported among 349 participants. Across VOCs, symptom duration was similar, however symptom profiles differed significantly among infections caused by Delta, Omicron BA.1 and BA.2. Anosmia was reported in <10% of participants with BA.1 and BA.2, compared to 42% with Delta infection, coryza fatigue and myalgia predominated. Most notably, viral load trajectories and peaks did not differ between Delta, BA.1 and BA.2, irrespective of symptom severity, VOC or vaccination status. Conclusion COVID-19 isolation guidance should not differ based on symptom severity or febrile illness and must remain under review as new SARS-CoV-2 VOCs emerge and population immunity changes. Our study emphasises the ongoing transmission risk of Omicron sub-variants in vaccinated adults with mild symptoms that may extend beyond current isolation periods.

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“…However, limited studies have investigated the factors contributing to robust T cell immune responses during COVID-19. An integrative research reports that type I interferon response does not correlate with the antiviral T cell responses ( 14 ). In contrast, another combinatorial study reported a temporary increase of IFN-β and IP10/CXCL10 levels associated with a dominant SARS-CoV-2-specific CD4 T cell response ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

Binayke

Zaheer

Dandotiya

et al. 2022

Preprint

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The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell response during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-4, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients who got infected with ancestral virus. We observed the induction of anti-RBD and SARS-CoV-2 neutralizing antibodies together with antigen-specific T cell responses as early as 0-4 days post-infection. T cell responses were largely preserved against the delta and omicron variants as compared to the ancestral strain. We determined innate immune responses at an early (days 0-4 post-COVID-19 positivity) time point of active infection in response to TLR 3/7/8 mediated activation. Interestingly, the innate immune response exhibited by the elevated levels of IL-6, IL-1β, and IL-23 correlated with a robust SARS-CoV-2-specific Th1 response at the later time point (14-16 days post covid positivity). To further understand the association of metabolic pathways induced upon active COVID-19 infection with innate and T cell response, metabolomic profiling was performed. As compared to healthy individuals, COVID-19 patients displayed a distinct metabolic signature with an enrichment of pyroglutamate, itaconate, and azelaic acid, which correlated with the SARS-CoV-2-induced innate and T cells response. Our observations reveal mechanisms and potential interventional approaches that may assist in COVID-19 therapeutics and vaccine adjuvant strategies.

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Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

Cited by 45 publications

References 47 publications

Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave

Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave

COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

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