The COVID-19 pandemic has had broad-reaching implications worldwide and presented a challenge to the medical establishment. Despite discovering more about the virus constantly, much is still not known. One example is the broad impact the virus has on the body, despite supposedly being a respiratory virus (affecting the lungs and breathing system). Some COVID-19 patients have reported symptoms affecting systems such as the brain or joints. Whilst the exact cause of this remains unknown, one theory suggests this is due to autoimmunity, where the body mistakes certain parts of itself as a threat and attacks it. Common examples of autoimmune diseases are rheumatoid arthritis and type 1 diabetes.
To investigate this possible link between COVID-19 and autoimmunity. This study will look at a database which collects information from general practice appointments. Using this database, patients will be split into those who were infected with COVID-19 and those who were not, between the months of January 2020 and June 2021. It will then check if any selected patients developed autoimmune diseases within this time period. The chances of developing autoimmune diseases between the two groups (patients with COVID-19 and without) will then be compared. This investigation will be repeated for smaller groups with people split based on factors such as sex and age, to see if the probability of developing autoimmune diseases changes. The results of this study will add to evidence regarding the link between COVID-19 and the development of autoimmune diseases which could direct future treatment and help recovery.
The primary aim is to investigate if an association exists between COVID-19 and the risk of developing common autoimmune diseases. A secondary aim is to assess which autoimmune diseases (AID) has the strongest association with COVID-19. This is due to case-reports where patients with a COVID-19 diagnosis have developed AID, however, thus far no large-scale retrospective cohort study has assessed this on a population level. (1, 2)
A retrospective cohort study will be conducted from January 31st 2020 to June 30th 2021. Participants will be selected from primary care data using clinical (SNOMED-CT) codes. All eligible participants with a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 will form the exposed group for the primary analysis. This group will be compared to matched controls with regards to the development of selected AID.
The primary outcome will consist of a composite measure of the incidence of common AID in the exposed group compared to the unexposed. The secondary outcome will be the incidence rates of individual AID.
For the primary analysis, the crude incidence rates for the primary and secondary outcomes will be calculated for the exposed and unexposed groups. Further analysis will be done using a Cox proportional hazards models to estimate the adjusted hazard ratio for the outcomes between the two groups. Participants will be matched on relevant covariates during extraction and analysis.
The sensitivity analysis will include both confirmed and ‘suspected’ COVID-19 diagnosis as the ’exposed’ group. Subgroup analyses will be stratified by sex, age, and ethnic groups
This study may demonstrate that the persistent sequalae of COVID-19 are due to an autoimmune reaction. This allows further trials centred around the implementation of AID treatments for patients suffering from long COVID. Thus, aiding the reduction of long COVID disease burden and improving patient quality of life.
A composite measure of the incidence of any of the following autoimmune diseases during the study follow-up period: type 1 diabetes mellitus (T1DM), myasthenia gravis, autoimmune thyroiditis, systemic lupus erythematosus (SLE), Sjogren’s syndrome, vitiligo, rheumatoid arthritis (RA), psoriasis, pernicious anaemia, inflammatory bowel disease (IBD) and celiac disease.
The individual incidence of the aforementioned autoimmune diseases during the study time period
Anuradhaa Subramanian - Chief Investigator - University of Birmingham
Umer Syed - Corresponding Applicant - University of Birmingham
Krishna Gokhale - Collaborator - University of Birmingham
Shamil Haroon - Collaborator - University of Birmingham
Anuradhaa Subramanian - Collaborator - University of Birmingham