Long COVID prevalence and risk factors in adults residing in middle- and high-income countries…, 2025, Hermans+

Long COVID prevalence and risk factors in adults residing in middle- and high-income countries: secondary analysis of the multinational Anti-Coronavirus Therapies ACT trials
Lucas Etienne Hermans, Sean Wasserman, Lizhen Xu, John Eikelboom

BACKGROUND
During the recent COVID-19 pandemic, reports of long-term persistence or recurrence of symptoms after SARS-CoV-2 infection emerged, which are now collectively referred to as ‘long COVID’. Most descriptions of long COVID originate from patients residing in high-income countries. We set out to characterise long COVID in a large-scale clinical trial that was conducted in low-middle, high-middle and high-income countries.

METHODS
The Anti-Coronavirus Therapies trials enrolled 6528 adult patients with symptomatic COVID-19 in Argentina, Brazil, Canada, Colombia, Ecuador, Egypt, India, Nepal, Pakistan, Philippines, Russia, Saudi Arabia, South Africa and the United Arab Emirates. Long COVID was defined as the presence of patient-reported symptoms at 180 days after enrolment. Multivariable logistic regression was used to evaluate associations of baseline characteristics with long COVID.

RESULTS
Of 4697 included participants, 1181 (25.1%) reported long COVID symptoms. The most frequently reported symptoms were sleeping disorders (n=601; 12.8%), joint pain (n=461; 9.8%), fatigue (n=410; 8.7%) and headaches (n=382; 8.1%). Long COVID prevalence was higher in participants from lower middle-income compared with high-income countries (29.8% (850/2854) vs 14.4% (102/706); adjusted OR (aOR) 1.53 (1.10 to 2.14); p=0.012). Prevalence also varied between participants of different ethnic backgrounds and was highest (36.1% (775/2145)) for patients of Arab/North African ethnicity. Patients requiring inpatient admission were at increased risk of long COVID (aOR: 2.04 (1.63 to 2.54); p<0.001). Other independent predictors of long COVID were male sex, older age and hypertension. Vaccination, prior lung disease, smoking and diabetes mellitus conferred protective effects.

CONCLUSION
Symptoms of long COVID are reported in a quarter of cases of symptomatic COVID-19 in this study and were significantly more prevalent in participants from countries with lower income status and in patients of Arab/North African ethnicity. Research to further assess the health burden posed by long COVID in low-and middle-income countries is urgently needed.

Link | PDF (BMJ Global Health) [Open Access]

 

It looks as though the Long Covid here has a lot to do with severe acute disease - with the predictors of persisting symptoms being male sex, older age and hypertension. That would be consistent for poorer quality medical care during the acute infection, as might be expected in a comparison of less wealthy and more wealthy countries.

(Edit - see my post below, the abstract is misleading, persisting symptoms were more commonly reported by females, although the effect was not very large. )

Prior lung disease, smoking and diabetes protective against Long Covid? That's a bit weird. Perhaps they did have a requirement for new onset of symptoms? That might mean that people who had some breathlessness before the infectionwould not qualify for Long Covid, even if they became more breathless.

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It's a shame this study doesn't look to be very relevant to ME/CFS-type Long Covid, as it would be really interesting to get some idea about differences in prevalence by country.

 

That makes it sound as if being male made it more likely that people met the Long Covid definition. But, it didn't.

51.6% of the people with Long covid were male; 63.1% of the people without Long Covid were male.

 

Age
The effect of age was statistically significant very small. The mean age of the people with Long Covid was 48.0, the mean age of the people without Long covid was 45.2.

Ethnicity
There's a really big difference.
For Arab/North African: 65.6% of the people with Long Covid were Arab/North African; only 39% of the people without Long Covid were Arab/North African
For South Asian: 9.6% of the people with Long Covid were South Asian; 24.1% of the people with Long Covid were South Asian
A South Asian person had an adjusted odds ratio of getting Long covid of just 0.18 compared to an Arab/North African.

So, there was a relationship with the country income level, although ethnicity also had an impact. The authors note the differences could be environmental or genetic, but there may also be cultural and linguistic effects on symptom reporting rates.

I'd also possibly add regional variation in sex differences in study participation and symptom reporting to that list. I didn't see the percentages of males from each country or ethnicity reported.

 

Vaccination
There was a big difference, vaccination does appear to be protective, and it makes sense that it would be. Vaccinated people would be less likely to have a severe illness leaving tissue damage. But, vaccination is surely correlated with a good health systems, and personal wealth, so I don't think they should be saying that vaccination definitely is protective.

Prior lung disease
It's true that prior lung disease was associated with not having Long Covid, but the numbers were fairly small. There could be some gender effect, or what I mentioned before - if you were breathless before getting Covid, being breathless afterwards probably was not counted as a Long Covid symptom.

Smoking
The so-called protective effect of smoking was pretty marginal I think, and might just be the result of not enough adjustment for things like sex differences in smoking rates.

Diabetes mellitus
The so-called protective effect of diabetes is also very debatable. An association of diabetes with an increased risk of Long Covid (OR=1.07, with the 95% Confidence limits crossing 1) changed to an association of diabetes with a decreased Risk of Long Covid after adjustment (aOR of 0.74).

There is also the complication that to be included in the outpatient trial you had to have a risk factor for severe disease - be male, have diabetes etc. So, there was probably a higher percentage of people with diabetes in the outpatient trial than in the inpatient trial. And people in the inpatient trial had a much greater risk of "Long covid".

[QUOTE="for inclusion in outpatient trial" ]Patients above 30 years of age were eligible, and those below 70 years had to have at least one additional risk factor for disease progression, including male sex, body mass index of at least 30 kg/m², chronic cardiovascular, respiratory, or renal disease, active cancer or diabetes.[/QUOTE]

 

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This is an interesting study because it was undertaken simultaneously in a diverse set of countries. I would like to understand the differences by ethnicity - was there a difference in how males and females reponded? Was there a difference in how the symptom descriptions were understood? Is there a real difference in Long covid prevalence by ethnicity? I don't think we have seen much epidemiology coming out of South Asia yet.

The treatments were not found to be useful for acute Covid-19, and neither did they help protect against Long Covid.
Aspirin can thin the blood and reduces pain and swelling
Colchicine is said to reduce inflammation and the build-up of uric acid
Rivaroxaban is an anti-clotting medicine