Background
Post-COVID condition health consequences
Terminology and clinical definitions
Core Outcome Set definition and relevance
Core Outcome Sets for COVID-19 and post-COVID-19 condition
Outcome area | Outcome domain (per COMET taxonomy) | Outcome |
---|---|---|
Death | 1. Mortality/survival | All-cause mortality |
Physiological/clinical | 2. Blood and lymphatic system outcomes | Sustained prothrombotic changes |
Anaemia | ||
Thrombocytopenia | ||
Neutrophil to lymphocyte ratio changes | ||
Changes in inflammatory markers | ||
Changes in serum creatine kinase (CK) | ||
Changes in lactate dehydrogenase (LDH) | ||
Changes in glutamic-pyruvic transaminase (GPT) | ||
Electrolytes changes | ||
3. Cardiac outcomes | Angina pectoris | |
Acute coronary disease | ||
Heart rhythm issues | ||
Heart failure | ||
Palpitations | ||
Chest tightness | ||
Newly diagnosed hypertension | ||
Myocardial fibrosis | ||
Myo- or pericarditis | ||
Changes in cardiovascular fitness | ||
Signal variations in the electrocardiogram (ECG) | ||
High blood pressure | ||
4. Endocrine outcomes | Diabetes mellitus | |
Worsening control of existing diabetes (T1/T2) | ||
Diabetic ketoacidosis | ||
Hyperlipidaemia | ||
Subacute thyroiditis | ||
Hyperthyroidism | ||
Hypothalamic-pituitary-adrenal axis suppression | ||
5. Ear and labyrinth outcomes | Tinnitus | |
Hearing problems | ||
6. Eye outcomes | Visual disturbance | |
Red eyes/eye irritation | ||
Conjunctivitis | ||
Dry eye disease | ||
Sicca syndrome | ||
7. Gastrointestinal outcomes | Nausea or vomiting | |
Diarrhoea | ||
Gastritis | ||
Dyspepsia | ||
Gastro-oesophageal reflux disease (GORD) | ||
Dysphagia | ||
Bloody stool | ||
Enrichment of opportunistic organisms and depletion of beneficial commensals | ||
Post-infectious irritable bowel syndrome | ||
Constipation | ||
8. General outcomes | Fatigue | |
Fever | ||
Malaise | ||
Weakness | ||
New daytime sweating | ||
New night sweats | ||
Flushing | ||
Loss of appetite | ||
Hair loss | ||
Unspecified pain | ||
Sleep disorder | ||
Chest pain | ||
Breathlessness | ||
Sleep apnea | ||
Voice change | ||
Abdominal pain | ||
Faints | ||
Limb oedema | ||
Dry mouth | ||
Dental issues | ||
9. Hepatobiliary outcomes | Chronic liver disease | |
Liver function test changes | ||
10. Immune system outcomes | Hyperinflammatory state-induced SARS-CoV-2 | |
Post-MIS-C: coronary artery aneurysm, neurologic (headache, encephalopathy, stroke and seizure) complications | ||
11. Infection and infestation outcomes | Prolonged viral faecal shedding | |
Tuberculosis | ||
12. Metabolism and nutrition outcomes | Unintentional weight loss | |
Unintentional weight gain | ||
New-onset bone demineralisation | ||
Unintentional change in body constitution | ||
13. Musculoskeletal and connective tissue outcomes | Myalgia | |
Arthralgia | ||
Limb pain—upper or lower | ||
Muscle atrophy | ||
Changes in neuromuscular performance during resistance exercise | ||
Dorsal/low back pain | ||
14. Outcomes relating to neoplasms: benign, malignant, and unspecified (including cysts and polyps) | Worsening of pre-existing cancer/neoplasm | |
15. Nervous system outcomes | Dizziness | |
Headache | ||
Stroke | ||
Autonomic dysfunction | ||
Tremors | ||
Seizures | ||
Taste disturbance | ||
Smell disturbance | ||
Bradykinesia | ||
Dysmetria | ||
Speech difficulty/dysarthria | ||
Numbness | ||
Guillain-Barré syndrome | ||
Abnormal reflex status | ||
Trigeminal neuralgia | ||
Neuralgia/neuropathy | ||
Frontal release signs | ||
Parkinsonism | ||
Problems with balance | ||
Encephalitis | ||
Brain physiology changes | ||
Restless legs | ||
Abnormal muscle tone | ||
16. Renal and urinary outcomes | New-onset bladder incontinence | |
Acute kidney injury | ||
Chronic kidney disease | ||
Urinary tract infections | ||
Problems passing urine | ||
Microhaematuria | ||
Renal function tests change | ||
COVID-19-associated nephropathy (COVAN) | ||
17. Reproductive system and breast outcomes | Dysmenorrhea | |
Erectile dysfunction | ||
Semen/sperm changes | ||
Infertility | ||
18. Psychiatric outcomes | Depression | |
Anxiety | ||
Post-traumatic stress disorder (PTSD) | ||
Acute stress discorder | ||
Mood change | ||
Obsessive-Compulsive Disorder (OCD) | ||
Behaviour change | ||
Thoughts of self-harm/suicide | ||
Risk to self and/or others | ||
Psychosis | ||
Traumatic bereavement | ||
Substance abuse | ||
Smoking habit | ||
Hallucinations | ||
19. Respiratory, thoracic, and mediastinal outcomes | Sore throat | |
Sneezing | ||
New-onset Chronic obstructive pulmonary disease (COPD) | ||
Excessive sputum expectoration | ||
Nasal congestion | ||
Catarrh | ||
Wheezing | ||
Cough | ||
Lung fibrosis | ||
Pleurisy | ||
Pleural effusion | ||
Pain on breathing | ||
Pulmonary function abnormalities | ||
Hypoxaemia | ||
Respiratory failure | ||
Respiratory disease | ||
Bronchiectasis | ||
Asthma | ||
20. Skin and subcutaneous tissue outcomes | Ulcers | |
Skin rash | ||
21. Vascular outcomes | Thromboembolism | |
Venous thrombosis | ||
Pulmonary and systemic vascular disease | ||
22. Congenital, familial, and genetic outcomes | ||
23. Pregnancy and puerperium and perinatal outcomes, including breastfeeding and weaning | ||
Life impact | 24. Physical functioning | Post-exertional malaise |
Impaired mobility | ||
Walking/gait abnormality | ||
Problems with usual activities | ||
25. Social functioning | COVID-related relationship issues | |
26. Role functioning | Functioning | |
Work/occupational function changes | ||
27. Emotional functioning/well-being | Demoralisation symptoms | |
Coping issues | ||
Low mood | ||
Burnout | ||
Perceived stigma/discrimination | ||
Worry about infecting others | ||
Worry about invasion of privacy | ||
Need for accurate information from the government | ||
Fear of no full recovery | ||
28. Cognitive functioning | Confusion | |
Concentration impairment | ||
Memory impairment | ||
29. Global quality of life | Reduced quality of life | |
Reduction in health-related quality of life scores | ||
30. Perceived health status | Illness perceptions | |
31. Delivery of care | Lack of information/uncertain prognosis | |
Difficulty accessing and navigating services | ||
Difficulty being taken seriously/achieving a diagnosis | ||
Variation in standards (e.g. inconsistent criteria for seeing, investigating, and referring patients) | ||
Variable quality of the therapeutic relationship | ||
32. Personal circumstances | Self-care ability | |
COVID-related life issues such as debt, unemployment, and family relationships | ||
Personal finances difficulties | ||
Resource use | 33. Economic | Health economic |
34. Hospital | Post-intensive care syndrome | |
35. Need for further intervention | Hospital readmission | |
Further healthcare contact | ||
Lung transplantation | ||
Oxygen dependence | ||
RRT requirement | ||
Need for regular medical check-ups after discharge | ||
Need for psychiatric service | ||
36. Societal/carer burden | Care dependency | |
Carer burden | ||
Adverse events | 37. Adverse events/effects | Vaccination adverse effects |
Adverse effects of prednisolone |
Considerations and limitations within vulnerable populations
Considerations and limitations within low-middle income settings
Limitations to existing research
Issue | Potential mitigation strategies | |
---|---|---|
1. | The definition of the post-COVID-19 condition. | A few initiatives were launched, including a WHO working group aiming to provide a clinical case definition of the post-COVID-19 condition. |
2. | Pathophysiological mechanisms still lacking. | A WHO working group has been set up to outline plausible hypotheses regarding the underlying immunological and physiological mechanisms of post-COVID condition. Multinational studies aimed to dissect the underling mechanisms of the post-COVID-19 condition should be lunched by multilateral organisations and universities. |
3. | Rapidly emerging data. | Core Outcome Set (COS) should be developed keeping the balance between speed and quality. Acute COVID-19 COS initiatives [41] may be used as an example of efficient management and rapid development. Involve principle investigators from ongoing studies to investigate the possible additional sources of data and allow for the dissemination of the COS upon development. Close interaction and collaboration with the WHO to ensure global geographical coverage and worldwide applicability of the COS. |
4. | Target population and scope: ● Hospitalised cohorts may be potentially different to those studies investigating non-hospitalised patients. ● Criteria for hospitalisation vary substantially within hospitals and countries (i.e. hospitalised patients are different). ● The need for a separate Post-COVID-19 condition COS development for children has not been established. | Despite the focus of COVID-19 research on adults, all age and severity (during acute phase) groups (including asymptomatic individuals) should be included (approaches to patient routing differ within and between the countries and criteria for hospital admission vary). It is imperative to develop COS for children and their carers as the post-COVID-19 condition may potentially have a detrimental life-long effect on child health. A single COS aiming at clinical as well as research settings may be developed. |
5. | What to measure? ● There is a need to define which data should be assessed in the trials and in clinical practice. | Ongoing systematic reviews may assist with the development of a list of candidate outcomes for the evaluation as part of a Core Outcome Set. Patient engagement should drive the agenda to ensure that patient-important outcomes are captured. This can be achieved by survey/Delphi process and consensus meetings. Post-COVID-19 condition COS development is a priority. |
6. | How to measure the Post-COVID-19 condition? ● Existing “validated” tools (e.g. quality of life instruments) have not been validated in COVID-19, and study participants are often asked about their experience pre-COVID retrospectively, which may lead to selection and recall bias. ● New measurement instruments may need to be developed if no adequate instruments exist for prioritised Core Outcome Domains. | Measurement instruments used in the studies should be systematically reviewed and assessed for validity/truth, discrimination ability, and feasibility. |