Covid-19 does not look like what you are looking for: Clustering symptoms by nation and multi-morbidities reveal substantial differences to the classical symptom triad
Authors: Kadirvelu Balasundaram , Burcea Gabriel , Quint Jennifer K , Costelloe Ceire E , Faisal A. Aldo 
Published: April 2021

ABSTRACTCOVID-19 is by convention characterised by a triad of symptoms: cough, fever and loss of taste/smell. The aim of this study was to examine clustering of COVID-19 symptoms based on underlying chronic disease and geographical location. Using a large global symptom survey of 78,299 responders in 190 different countries, we examined symptom profiles in relation to geolocation (grouped by country) and underlying chronic disease (single, co- or multi-morbidities) associated with a positive COVID-19 test result using statistical and machine learning methods to group populations by underlying disease, countries, and symptoms. Taking the responses of 7980 responders with a COVID-19 positive test in the top 5 contributing countries, we find that the most frequently reported symptoms differ across the globe: For example, fatigue 4108(51.5%), headache 3640(45.6%) and loss of smell and taste 3563(44.6%) are the most reported symptoms globally. However, symptom patterns differ by continent; India reported a significantly lower proportion of headache (22.8% vs 45.6%, p<0.05) and itchy eyes (7.0% vs. 15.3%, p<0.05) than other countries, as does Pakistan (33.6% vs 45.6%, p<0.05 and 8.6% vs 15.3%, p<0.05). Mexico and Brazil report significantly less of these symptoms. As with geographic location, we find people differed in their reported symptoms, if they suffered from specific underlying diseases. For example, COVID-19 positive responders with asthma or other lung disease were more likely to report shortness of breath as a symptom, compared with COVID-19 positive responders who had no underlying disease (25.3% vs. 13.7%, p<0.05, and 24.2 vs.13.7%, p<0.05). Responders with no underlying chronic diseases were more likely to report loss of smell and tastes as a symptom (46%), compared with the responders with type 1 diabetes (21.3%), Type 2 diabetes (33.5%) lung disease (29.3%), or hypertension (37.8%). Global symptom ranking differs markedly from the well-known and commonly described symptoms for COVID-19, which are based on a few localised studies. None of the five countries studied in depth recorded cough or temperature as the most common symptoms. The most common symptoms reported were fatigue and loss of smell and taste. Amongst responders from Brazil cough was the second most frequently reported symptom, after fatigue. Moreover, we find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities. These factors uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.Executive SummaryEvidence before this workAn early meta-analysis of epidemiological variation in COVID-19 inside and outside China studied patient characteristics including, gender, age, fatality rate, and symptoms of fever, cough, shortness of breath and diarrhoea in COVID-19 patients. They found that important symptom differences existed in patients in China compared to other countries and recommended that clinical symptoms of COVID-19 should not be generalized to fever, shortness of breath and cough only, but other symptoms such as diarrhoea are also shown to be prevalent in patients with COVID-19.Added value of this workWe find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities.Implications of the evidenceThese factors, uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.