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Front Immunol . Evaluating the Immune Response in Treatment-Naive Hospitalised Patients With Influenza and COVID-19

tetano

Editor, Senior Moderator
Front Immunol


. 2022 May 19;13:853265.
doi: 10.3389/fimmu.2022.853265. eCollection 2022.
Evaluating the Immune Response in Treatment-Naive Hospitalised Patients With Influenza and COVID-19


Jelmer Legebeke[SUP] 1 2 [/SUP], Jenny Lord[SUP] 1 [/SUP], Rebekah Penrice-Randal[SUP] 3 [/SUP], Andres F Vallejo[SUP] 4 [/SUP], Stephen Poole[SUP] 2 4 [/SUP], Nathan J Brendish[SUP] 2 4 [/SUP], Xiaofeng Dong[SUP] 3 [/SUP], Catherine Hartley[SUP] 3 [/SUP], John W Holloway[SUP] 1 2 [/SUP], Jane S Lucas[SUP] 2 4 [/SUP], Anthony P Williams[SUP] 5 [/SUP], Gabrielle Wheway[SUP] 1 [/SUP], Fabio Strazzeri[SUP] 6 [/SUP], Aaron Gardner[SUP] 6 [/SUP], James P R Schofield[SUP] 6 [/SUP], Paul J Skipp[SUP] 6 7 [/SUP], Julian A Hiscox[SUP] 3 8 9 [/SUP], Marta E Polak[SUP] 4 10 [/SUP], Tristan W Clark[SUP] 2 4 [/SUP], Diana Baralle[SUP] 1 2 [/SUP]



Affiliations

Abstract

The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body's immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abundances and cellular composition to better understand the natural immune response associated with COVID-19, compared to another viral infection being influenza, and identify a prognostic signature of COVID-19 patient outcome. Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of 88 patients infected with influenza and a cohort of 80 patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines. Gene transcript abundances, enriched pathways and cellular composition were compared between cohorts using RNA-seq. A genetic signature between COVID-19 survivors and non-survivors was assessed as a prognostic predictor of COVID-19 outcome. Contrasting immune responses were detected with an innate response elevated in influenza and an adaptive response elevated in COVID-19. Additionally ribosomal, mitochondrial oxidative stress and interferon signalling pathways differentiated the cohorts. An adaptive immune response was associated with COVID-19 survival, while an inflammatory response predicted death. A prognostic transcript signature, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, was able to stratify COVID-19 patients likely to survive or die. This study provides a unique insight into the immune responses of treatment naïve patients with influenza or COVID-19. The comparison of immune response between COVID-19 survivors and non-survivors enables prognostication of COVID-19 patients and may suggest potential therapeutic strategies to improve survival.

Keywords: COVID-19; adaptive; blood; immune response; influenza; innate; survival; transcriptome.
 
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