PROSAIC-19 [COVID-19]
Research type
Research Study
Full title
Prospective longitudinal assessment in a COVID-19 infected cohort
IRAS ID
282739
Contact name
Peter Kelleher
Contact email
Sponsor organisation
Imperial College London and Imperial College Healthcare NHS Trust
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary:
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is a new rapidly spreading infectious disease with no proven treatment options. The virus causes a spectrum of disease ranging from mild cold-like symptoms to severe lung compromise requiring ventilatory support. Guidance from Public Health England identifies several groups that are at risk of severe disease including the elderly and individuals with chronic lung disease. The mechanisms driving severity of disease in these groups of individuals infected with COVID-19 are however poorly understood. We urgently need to understand the reasons for susceptibility to severe infection in these large groups of individuals to facilitate rapid development of novel effective targeted therapies.
Summary of Results
The aim of the study was to understand how SAR-COV-2 infection cause severe lung damage in patients with COVID-19. We recruited a cohort of patients admitted to Critical Unit who need ventilation and then followed over then a year. We investigated if there were are any changes in the immune system in patients who got recovered after infection or those have lung disease. We found that recovery from both acute infection and severe lung disease was linked to decreases in inflammation mediated by neutrophils (frontline cell of the immune system which normally respond rapidly to infection). Inflammatory responses persisted in those with lung fibrosis (scars) up to a year after infection. Our findings provide a basis for targeted treatments to prevent long terms complication of COVID-19. Sci Transl Med. 2022 Nov 16;14(671):eabo5795.
The rapid adoption of SARS-CoV-2 vaccines during the study allowed the investigators to obtain permission to study immune responses in healthy volunteers with and without a previous history of SARS-CoV-2 infection. Findings from the study enabled first description of how previous infection with SARS-CoV-2 boosted antibody and T cell mediated immune after mRNA vaccination. Lancet. 2021 Mar 27;397(10280):1178-1181. Data obtained from healthy volunteers were used to compared SARS-CoV-2 vaccine responses in transplant cohorts (renal and lung) Lancet. 2021 Oct 23;398(10310):1482-1484. Am J Respir Crit Care Med. 2022 Jun 15;205(12):1476-1479. and in patient receiving immunosuppressive treatment for autoimmune diseases Ann Rheum Dis2021 Oct;80(10):1322-1329.Lay summary of study results:
The aim of the PROSAIC study was to understand how SAR-COV-2 infection causes severe lung damage in patients with COVID-19. We recruited participants with severe and mild COVID-19 and healthcare staff without a history of SARS-COV-2 infection. Study participants with COVID-19 infection were then followed for up for a year. We investigated if there were any changes in the immune system in patients who recovered after infection or those who continued to have lung disease. Recovery from both mild lung infection and severe lung disease was linked to decreases in inflammation mediated by neutrophils (frontline cell of the immune system, which normally respond rapidly to infection). Inflammatory responses persisted in those with lung fibrosis (scars), up to a year after infection. Our findings provide a basis for targeted treatments to prevent long terms complication of COVID-19.
The rapid adoption of SARS-CoV-2 vaccines during the study allowed the investigators to obtain permission to study immune responses in healthy volunteers with and without a previous history of SARS-CoV-2 infection. Findings from the study enabled first description of how previous infection with SARS-CoV-2 boosted antibody and T cell mediated immune after SAR-CoV-2 mRNA vaccination. Vaccine responses using mRNA technology (Pfizer vaccine) and adenoviral vector (Oxford Astra Zeneca vaccine) obtained from healthy volunteers were used to compared SARS-CoV-2 vaccine responses in transplant cohorts (renal, lung and heart) and in patients receiving immunosuppressive treatment for autoimmune diseases in a number of studies published between 2021 and 2024. Our work informed UK government choice of vaccines for general population and immune suppressed patient groups in 2022.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
20/SC/0208
Date of REC Opinion
11 May 2020
REC opinion
Favourable Opinion