COVID-19 hyperinflammation syndrome (COV-HI): rapid cohort study [COVID-19]

• Research type

  Research Study

• Full title

  COVID-19 hyperinflammation syndrome (COV-HI): protocol for a rapidly executed cohort study

• IRAS ID

  282626

• Contact name

  Jessica Manson

• Contact email

  jessica.manson@nhs.net

• Sponsor organisation

  University College London Hospital

• Duration of Study in the UK

  0 years, 3 months, 0 days

• Research summary

  Summary of Research
  Summary of ResearchBased on emerging experience and trials from countries affected early by the COVID-19 (COV19) pandemic, there is evidence that a subgroup of severely affected people develop a hyperinflammatory (HI) syndrome (COV-HI). Trials are in progress of cytokine inhibition and other immune modulation to treat COV-HI. This proposal aims to use a rapidly executed cohort study to characterise the clinical phenotypes of COV-HI in patients in the UK through an established and nimble network of clinicians and scientists with broad experience of identifying and treating HI. The aim is to confirm the COV-HI clinical phenotype and using routine data to try to infer the inflexion point where COV-HI emerges. This would enable refinement of the proposed treatment algorithm and translates to routine clinical practice to improve the outlook for COV-HI.

  Summary of Results
  Background A subset of patients with severe COVID-19 develop an exaggerated, or hyperinflammatory, response to the SARS CoV2 virus which we suspected might contribute the risk of dying. This study explored the specific characteristics of COVID-19-associated hyperinflammation (COV-HI), and its associations with the need for intensive care and the risk of dying and survival.

  Methods
  We enrolled and collected data on consecutive inpatients (aged ≥18 years) admitted to University College London Hospitals and Newcastle upon Tyne Hospitals in the UK COVID-19 during the first wave of the pandemic. Demographic data, laboratory tests, and clinical status were recorded from the day of admission until death or discharge, with a minimum follow-up time of 28 days. We defined COV-HI by using laboratory markers of inflammatory response tested in blood (a C-reactive protein concentration greater than 150 mg/L or doubling within 24 h from greater than 50 mg/L, or a ferritin concentration greater than 1500 μg/L). Respiratory support was categorised as oxygen only, non-invasive ventilation, and intubation. Initial and repeated measures of hyperinflammation were evaluated in relation to the next-day risk of death or need for escalation of respiratory support (as a combined endpoint), using a multi-level logistic regression model.

  Findings
  We included 269 patients admitted to one of the study hospitals between March 1 and March 31, 2020, among whom 178 (66%) were eligible for escalation of respiratory support and 91 (34%) patients were not eligible. Of the whole cohort, 90 (33%) patients met the COV-HI criteria at admission. Despite having a younger median age and lower co-morbidities, a higher proportion of patients with COV-HI on admission died during follow-up (36 [40%] of 90 patients) compared with the patients without COV-HI on admission (46 [26%] of 179). Among the 178 patients who were eligible for full respiratory support, 65 (37%) met the definition for COV-HI at admission, and 67 (74%) of the 90 patients whose respiratory care was escalated met the criteria by the day of escalation. Meeting the COV-HI criteria was significantly associated with the risk of next-day escalation of respiratory support or death (hazard ratio 2·24 [95% CI 1·62–2·87]) after adjustment for age, sex, and comorbidity.

  Interpretation
  Associations between elevated inflammatory markers, escalation of respiratory support, and survival in people with COVID-19 indicate the existence of a high-risk inflammatory phenotype. This data helped support the idea of using drugs that modulate the immune response to the virus as treatments

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  20/YH/0138

• Date of REC Opinion

  15 Apr 2020

• REC opinion

  Further Information Favourable Opinion