Acute and long-term health outcomes for people who survived COVID-19: matched cohort analyses using UK primary and secondary care data

Date of ISAC Approval: 
10/11/2020
Lay Summary: 
At the time of writing (18th June 2020), over 8 million people have been diagnosed with COVID-19 worldwide – the vast majority of whom (around 99%) are likely to survive the disease. While most people with COVID-19 will have only mild symptoms, some people have very severe symptoms that require hospitalisation. Based upon the symptoms of COVID-19, and the experience of survivors of previous similar infectious lung diseases such as SARS, it is possible that survivors of both mild and severe COVID-19 may have a greater burden of long-term health problems. Given that the recorded number of people in the UK who have had or currently have COVID-19 is over 300 000, there is a need to assess the health of people who survive COVID-19 in the UK. Our study will investigate mortality and the burden of health problems in people who: (a) are admitted to hospital due to COVID-19 (i.e. have severe disease) and then survive, and (b) have COVID-19 but are not admitted to hospital (i.e. have milder disease), and then compare each to a group made up of people with no previous record of having COVID-19. We will also look at whether the occurrence of health problems is different based upon a person’s age, ethnicity, sex and any chronic illnesses and/or drug treatment that they had before having COVID-19. As well as helping individual patients and their carers, this information will also help the NHS plan and allocate resources appropriately in order to help people who have survived COVID-19.
Technical Summary: 
There have been over 8 million cases worldwide of COVID-19 due to SARS-CoV-2 infection. With a case-fatality of around 1%, the number of people who survive is set to increase substantially as the pandemic progresses. It is currently not known what the short- or long-term effects of SARS-CoV-2 infection are on those who survive, but clinical features of the condition and existing evidence from the SARS (SARS-CoV-1) pandemic suggest the potential for a range of debilitating post-viral conditions. As over 300 000 have had or currently have COVID-19 (based upon UK Government Pillar 1 test results) and this figure is likely to rise, there is an urgent need to assess and to quantify short and long-term health for people in the UK who survive COVID-19. This information will assist patients and their carers and will inform NHS health service planning. Using two study populations - (a) people who have been admitted to hospital due to COVID-19 (i.e. have severe disease) and (b) people who have COVID-19 but are not admitted to hospital (i.e. have milder disease) - we plan to perform a matched cohort study in which the unexposed are people with no record of COVID-19.We will measure frequency of mortality and a range of key respiratory, neurological, cardiovascular, renal, hepatic, mental health and autoimmune outcomes. Analysis will be performed during the 3-month period after index date and at 4 subsequent time points (6 months,1 year, 3 years and 5 years after index date), and at each timepoint we will look at whether effects differ by age, ethnicity, sex, prior chronic illness and prior drug treatment. Each individual will be matched by age, sex, general practice and charlson comorbidiy index to individuals with no record of having COVID-19, and the time-to-first event for each outcome will be compared between groups. We will also use multivariable ordinal logistic and linear regression to analyse the effect of previous COVID-19 on frailty in survivors >=65 years of age.
Health Outcomes to be Measured: 
1. Mortality: all-cause and cause-specific (with specific-causes being those related to the other outcomes in this list, plus any additional causes listed in the ONS record for people who die following recovery from COVID-19 during the study period) 2. Multimorbidity and healthcare utilisation: Hospital (re)admission, GP consultation frequency, multimorbidity 3. Respiratory conditions: pulmonary fibrosis, pulmonary hypertension, pulmonary embolism, obstructive lung disease 4. Cardiovascular disease: venous thromboembolism, stroke, myocardial infarction, heart failure, major arrhythmias 5. Adverse renal outcomes: acute kidney injury, chronic kidney disease (incident and progression of), dialysis onset, proteinuria 6. Adverse hepatic outcomes: acute liver injury, chronic liver disease 7. Myalgic Encephalomyelitis/Chronic fatigue syndrome/ (ME/CFS), fibromyalgia 8. Neurological/cognitive conditions: anosmia, Guillian Barré syndrome, peripheral neuropathy, acute cognitive impairment (e.g deliruium), chronic mild cognitive impairment, dementia, seizures, epilepsy 9. Mental health conditions: PTSD, depression, sleep disorders, suicide (attempt and completed), anxiety-related disorders, self-harm, alcohol abuse 10. Autoimmune conditions: rheumatoid arthritis 11. Frailty (for survivors aged >=65 years)
Collaborators: 

Kevin Wing - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Amy Mulick - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Caroline Minassian - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Catherine Houlihan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Charlotte Warren-Gash - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Eliana Lacerda - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Helena Carreira - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Jeremy Brown - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kathleen Mudie - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ketaki Bhate - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kevin Wing - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Luigi Palla - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Luis Nacul - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Patrick Bidulka - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Rohini Mathur - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sharon Cadogan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Sinead Langan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )

Linkages: 
2011 Rural-Urban Classification at LSOA level;HES Admitted;ONS;Patient IMD;Pregnancy Register