the cascade study - measures of complement activation and inflammation in patients with covid-19

Conditions: Coronavirus

Summary: covid-19 is a new disease and therefore it is still not clear exactly how the virus affects the body and why people are affected so differently. it causes infection in the lungs and the virus can then attack blood vessels in the lungs and other organs to spark off an inflammatory process that can make a person very ill. it also can cause damage within tiny blood vessels that makes a person's blood thicken up and stop flow in vital organs. the investigators believe complement (which is a chemical in the body which can be harmful in excess) orchestrates the inflammation and thickening of the blood that can make a person sick. the investigators now need to know which of these complement chemicals are elevated in covid-19 and compare to healthy volunteers, and assess whether the levels are higher in people with severe lung disease. the investigators believe that if levels are increased there are special treatments that can counteract them and potentially be an effective treatment for covid-19. in this study the investigators will measure different parts of the inflammation process to better understand what may be causing severe disease and to see if there may be benefits from a new treatment to reduce inflammation

this study is an observational cross-sectional and cohort study to assess whether there is evidence of increased complement activation and/or ltb4 levels and other parameters of inflammation and a pro-coagulative state in adult patients hospitalised with covid-19 compared to healthy controls and also whether these measures differ with increasing severity of respiratory failure. blood samples (serum and plasma) will be obtained from each participant at the time of recruitment into the trial, to assess the profile of complement activation, cytokines/ chemokines, leukotrienes (specifically leukotriene b4) and markers of coagulation and inflammation in patients with covid-19. participants within the cohort study will be recruited at the point of admission or as close to it as possible. baseline sampling will be performed at time of recruitment. there will be up to 2 additional sampling points (with not more than one sample per day) if there is any worsening of the participants respiratory failure (i.e. deteriorating from mild to moderate or moderate to severe disease). patients just admitted to hospital will be asked to consent for both the case control and the cohort study data will be collected at baseline for all participants and then again at each further sampling point for the participants within the cohort study. patient status will be measured at 14 days from the last point of sampling.

Eligibility criteria:
inclusion criteria: - 1. adults ≥18 years old requiring hospital admission for covid-19 2. covid-19 confirmed by either\*: * a positive swab (using rt-pcr) * or based on a high level of clinical probability confirmed by the presence of typical symptoms and compatible radiological findings on imaging with no alternative cause for these findings identified by the treating physician. exclusion criteria: * 1. renal replacement therapy on itu 2. significant trauma (including an acute fracture or significant head injury) 3. massive transfusion of blood products 4. confirmed bacteraemia with pathogenic organism on blood cultures or other severe bacterial infections (including abscess/empyema) which persist despite broad-spectrum antibiotics and are thought to be significantly contributing to the patient's symptoms and clinical state. recruitment will not be delayed however pending a negative culture.