Three class latent class model for symptoms among patients with Long Covid.

‘Long Covid’ was defined as either (a) presence of any symptom included in the WHO case definition of post COVID condition at least 12 weeks after the initial COVID-19 diagnosis, or (b) a symptom included in the secondary outcome of the study by Subramanian et al. (Nat Med 2022, doi: 10.1038/s41591-022-01909-w, S3 Table), for comparison with that study. For (a), symptoms in the 3 months after the WHO symptom were used in the latent class analysis; for (b) symptom records at any time were used. Cluster descriptions for (a): Class 1 (50.8%): Anxiety / depression (26%), Fatigue / asthenia (19%), Abdominal pain (17%), Headache (13%), Nausea / vomiting (12%), Joint pain (11%), Diarrhoea (10%), Constipation (10%). Class 2 (35.2%): Shortness of breath (67%), Cough (34%), Fatigue / asthenia (28%), Chest pain (20%), Anxiety / depression (17%), Wheezing (13%). Class 3 (13.9%): Shortness of breath (64%), Anxiety / depression (49%), Nausea / vomiting (47%), Cough (42%), Chest pain (37%), Fatigue / asthenia (34%), Abdominal pain (34%), Constipation (28%), Diarrhoea (25%), Purpura / rash (24%), Wheezing (24%), Palpitations / tachycardia (22%), Chills and fever (21%), Headache (18%), Limb swelling (17%), Presyncope / dizziness (16%), Phlegm (16%), Gastric reflux (14%), Weight loss (14%), Paraesthesia (13%), Joint pain (13%), Bloating (12%), Allergies / angioedema (11%). Cluster descriptions for (b): Class 1 (68.8%): Anxiety / depression (17%), Purpura / rash (15%), Fatigue / asthenia (12%), Nausea / vomiting (10%), Shortness of breath (10%). Class 2 (19.0%): Shortness of breath (74%), Cough (56%), Chest pain (29%), Fatigue / asthenia (27%), Wheezing (27%), Anxiety / depression (21%), Phlegm (16%). Class 3 (12.3%): Shortness of breath (53%), Nausea / vomiting (53%), Anxiety / depression (50%), Fatigue / asthenia (47%), Abdominal pain (43%), Cough (41%), Diarrhoea (32%), Constipation (31%), Chest pain (30%), Purpura / rash (29%), Headache (26%), Chills and fever (24%), Presyncope / dizziness (22%), Palpitations / tachycardia (21%), Paraesthesia (20%), Joint pain (18%), Weight loss (18%), Limb swelling (18%), Gastric reflux (18%), Bloating (15%), Wheezing (14%), Phlegm (12%). (PDF)</p

Read terms for viral or respiratory illnesses.

BackgroundLong Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.AimsTo compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.MethodsWe used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and ‘Long Covid’ diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.ResultsWe compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.ConclusionsNumerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.</div

CONSORT diagram showing selection of patients in each category.

CONSORT diagram showing selection of patients in each category.</p

Data flow diagram.

BackgroundLong Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.AimsTo compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.MethodsWe used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and ‘Long Covid’ diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.ResultsWe compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.ConclusionsNumerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.</div

Association of symptoms with prior suspected or confirmed COVID-19, or prior viral or respiratory illness.

Hazard ratios for association of symptoms with previous infection after 12 weeks, by case category. Hazard ratios were adjusted for age, sex, age/sex interaction, number of consultations in the year before the index date, number of symptom days 1–3 months before the index date, recording of the specific symptom 1–3 months before the index date, ethnicity, smoking, body mass index and a generated propensity score for acquiring COVID-19 infection, with the baseline hazard function stratified by general practice.</p

Hazard ratios by level of adjustment.

Association of symptoms with previous COVID infection after 12 weeks, by level of adjustment. ‘Fully adjusted hazard ratios’ were adjusted for age, sex, age/sex interaction, number of consultations in the year before the index date, number of symptom days 1–3 months before the index date, recording of the specific symptom 1–3 months before the index date, ethnicity, smoking, body mass index and a generated propensity score for acquiring COVID-19 infection, and stratified by general practice. (PDF)</p

Hazard ratios for all 89 symptoms.

Association of symptoms with previous COVID infection after 12 weeks. Hazard ratios were adjusted for age, sex, age/sex interaction, number of consultations in the year before the index date, number of symptom days 1–3 months before the index date, recording of the specific symptom 1–3 months before the index date, ethnicity, smoking, body mass index and a generated propensity score for acquiring COVID-19 infection, and stratified by general practice. (PDF)</p

Factors associated with Long Covid as defined by WHO symptoms or GP diagnosis of confirmed or suspected Long Covid.

Factors associated with Long Covid as defined by WHO symptoms or GP diagnosis of confirmed or suspected Long Covid.</p

Hazard ratios by sex.

Association of symptoms with previous infection after 12 weeks, by sex. Hazard ratios were adjusted for age, sex, age/sex interaction, number of consultations in the year before the index date, number of symptom days 1–3 months before the index date, recording of the specific symptom 1–3 months before the index date, ethnicity, smoking, body mass index and a generated propensity score for acquiring COVID-19 infection, and stratified by general practice. (PDF)</p

Association of symptoms with prior COVID-19 infection by source of symptom data.

Hazard ratios for association of symptoms with previous COVID infection after 12 weeks, by source of symptom data (free text or structured data). Hazard ratios were adjusted for age, sex, age/sex interaction, number of consultations in the year before the index date, number of symptom days 1–3 months before the index date, recording of the specific symptom 1–3 months before the index date, ethnicity, smoking, body mass index and a generated propensity score for acquiring COVID-19 infection, with the baseline hazard function stratified by general practice.</p