Clustering Covid symptoms by nation and multi-morbidities reveal substantial differences to classical symptoms

  

View ORCID ProfileBalasundaram Kadirvelu,  View ORCID ProfileGabriel Burcea,  View ORCID ProfileJennifer Quint,  View ORCID ProfileCeire E Costelloe,  View ORCID ProfileAldo A. Faisal

doi: https://doi.org/10.1101/2021.04.02.21254818

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.04.02.21254818v1.full.pdf

Abstract

COVID-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.

Competing Interest Statement

Dr. Quint reports grants from MRC, grants from GSK, grants and personal fees from AZ, grants and personal fees from BI, grants and personal fees from Chiesi, grants from The Health Foundation , grants from Bayer, grants from Asthma UK, outside the submitted work; .

Funding Statement

We thank Your.MD, Matteo Berlucchi and his team, for sharing their data with the public freely. We acknowledge funding to AAF (UKRI Turing AI Fellowship), CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, British Lung Foundation, IQVIA, Chiesi AZ, Insmed and Asthma UK. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the North West London NIHR Applied Research Collaboration. The funders had no role in study design or writing. All authors had full access to all the data in the study. The writing committee had sole responsibility for the decision to submit for publication.

https://www.medrxiv.org/content/10.1101/2021.04.02.21254818v1