Sex Differences in [LC] Prevalence Over One year After the Acute Phase, and Related Risk Factors. The GINA-COVID Cohort Study, 2026, Alvarez-Pedrerol+

[forestglip]

Sex Differences in Long COVID Prevalence Over One year After the Acute Phase, and Related Risk Factors. The GINA-COVID Cohort Study

Spoiler: Authors

Alvarez-Pedrerol, Mar; Polo-Alonso, Sara; Ramos, Rafel; Martí-Lluch, Ruth; Pinsach-Abuin, Mel·lina; Dégano, Irene; Elosua, Roberto; Subirana, Isaac; Hernáez, Álvaro; Selga, Elisabet; Puigdecanet, Eulàlia; Pruneda-Paz, Josefina; Solà-Richarte, Clàudia; Puigmulé, Marta; Pérez, Alexandra; Nogués, Xavier; Masclans, Joan Ramon; Güerri-Fernández, Roberto; Cubero-Gallego, Héctor; Tizon-Marcos, Helena; Vaquerizo, Beatriz; Brugada, Ramon; Camps-Vilaró, Anna; Marrugat, Jaume

Background
This 1-year cohort study aimed to track long COVID prevalence, identify associated risk factors, and assess its association with hospitalization.

Methods
The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months. Hospitalization data were collected from the Catalan Health System. We performed descriptive statistics and logistic regression models stratified by sex to identify factors associated with long COVID, using multiple imputation for missing values and model selection via stepwise regression based on the Akaike Information Criterion.

Results
Significant sex differences appeared, with females showing a two-fold higher risk of developing long COVID compared to males (OR=1.95; 95% CI, 1.68– 2.29).

Females reported higher prevalence and a greater number of persistent symptoms, with fatigue being the most common in both sexes (36% in females, 26% in males at 3 months). The recovery rate at 12 months was lower in females (23% vs. 34%, p< 0.001).

Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48– 0.84), whereas COVID-19 severity was the most influential risk factor in males (OR=2.34; 95% CI, 1.79– 3.08).

Despite these differences, the trajectory of persistent symptoms over time was similar between the sexes. Importantly, long COVID did not increase hospital admissions.

Conclusion
Findings underscore the importance of sex-specific approaches in managing long COVID and suggest further investigation into hypertension’s protective role in females and disease severity’s impact in males.

Web | DOI | PDF | International Journal of Women's Health | Open Access

 

[forestglip]

Hypertension emerged as the most significant protective factor for long COVID in females (OR=0.64; 95% CI, 0.48– 0.84)

From paper:

Hypertension has been consistently reported as a risk factor for poor prognosis in COVID-19,17 and it was associated with long COVID in few studies,27,28 thus, not consistent with our results.

However, Ozawa et al43 also found that females with hypertension were less likely to develop long COVID than those without (OR: 0.51 (0.27–0.98)). These authors explored the use of drugs for hypertension and found that Calcium channel blocker administration was associated with reduced persistent symptoms such as alopecia, memory loss and sleeping disorders, which are prevalent symptoms in females from our study, and less prevalent in males.

 

[Utsikt]

However, Ozawa et al43 also found that females with hypertension were less likely to develop long COVID than those without (OR: 0.51 (0.27–0.98)). These authors explored the use of drugs for hypertension and found that Calcium channel blocker administration was associated with reduced persistent symptoms such as alopecia, memory loss and sleeping disorders, which are prevalent symptoms in females from our study, and less prevalent in males.

Isn’t one of the hypothesised mechanisms of LDN that it «opens up» the calcium channels? Something related to TRPM3, I think. Perhaps it’s different channels?

 

[ScoutB]

Do we have any idea if hypertension is protective against ME/CFS? Seems [potentially] interesting both because it pours some cold water on the idea that we are just broadly unhealthy, and because it could maybe help us figure out if blood flow/pooling issues are upstream or downstream of other problems? (assuming our anecdotes on here of blood flow/fluid problems pan out as real patterns).

I’m biased because, before I fell ill, doctors used to tell me I could stand to eat more salt, since my blood pressure was on the low end.

 

[Murph]

If we accept that many human characteristics are distributed on a curve and we merely pathologise the end-point of that curve, we could maybe wonder if the EDS phenotype (associated with low blood pressure and me/cfs) is a risk factor for LC and its inverse is protective?

related:

A long time ago I did a Twitter poll asking normal, random people the following pair of questions:

Can you sit on the floor happily in the sort of restaurant where they make you do that?

A: Yes. B: No.
Are you goddam robust, never catch cold, do lots of exercise?

1: Yes. 2: No.

My hypothesis was A2>A1 & B1>B2.

That was borne out. Among people who can sit on the floor easily, most people said NO, they are not goddam robust. Among poeple who can't sit on the floor easily, being robust was the more popular answer. I don't have a p-value on it but it was suggestive !!

 

[Trish]

If we accept that many human characteristics are distributed on a curve and we merely pathologise the end-point of that curve, we could maybe wonder if the EDS phenotype (associated with low blood pressure and me/cfs) is a risk factor for LC and its inverse is protective?

related:

A long time ago I did a Twitter poll asking normal, random people the following pair of questions:

Can you sit on the floor happily in the sort of restaurant where they make you do that?

A: Yes. B: No.
Are you goddam robust, never catch cold, do lots of exercise?

1: Yes. 2: No.

My hypothesis was A2>A1 & B1>B2.

That was borne out. Among people who can sit on the floor easily, most people said NO, they are not goddam robust. Among poeple who can't sit on the floor easily, being robust was the more popular answer. I don't have a p-value on it but it was suggestive !!

I wonder whether that would be influenced by gender. More females than males have bendy joints, maybe more males than females like to claim they are robust and keep fit, ie aren't weak.

Do you have numbers?

 

[Murph]

I wonder whether that would be influenced by gender. More females than males have bendy joints, maybe more males than females like to claim they are robust and keep fit, ie aren't weak.

Do you have numbers?

not by gender, but numbers at the link: Twitter poll asking normal, random people the following pair of questions:

 

[Hutan]

Barcelona team

The GINA-COVID cohort study included 2698 COVID-19 patients from Spain, who reported persistent symptoms spontaneously mentioned in an open questionnaire one year after infection. We recorded symptom onset, duration, and recovery rates at 12 months.

That description in the abstract is a bit ambiguous. For a while I thought that all the participants had Long COVID because they all 'reported persistent symptoms' in a questionnaire one year after infection. However, they actually just completed the questionnaire, they responded to the question of whether they had persistent symptoms.

The analysis included a total of 2698 participants (of whom 54% were females), who met the study criteria and completed the 1-year follow-up questionnaire. Among them, more than half of the participants (1531 participants, of whom 62% were females) reported persistent symptoms and were classified as long COVID cases (Figure 1).

Recruitment was conducted across both hospital and primary care settings (Barcelona’s Hospital del Mar, Girona’s Hospital Dr. Josep Trueta, Vic’s Hospital Consortium, and in primary health centers in Girona province), with approximately half of the participants recruited from each. This approach ensured representation of a broad spectrum of disease severity, although the inclusion of hospital-based participants may have increased the proportion of severe COVID-19 cases, while most primary care participants experienced non-severe infections.

Blood pressure measure

Data on age, sex, height, weight, and blood pressure were collected during hospitalization or at outpatient clinic at inclusion

I'm wondering if the fact that blood pressure was collected during hospitalisation for the severe Covid-19 cases and at a clinic some time later for the mild cases might have had some impact on the blood pressure measure. As in, the people in the midst of a severe infection will have a high BP. And these cases might be most likely to feel pretty rubbish for a little while, but to recover once they are over the acute illness.

Whereas other people who have a mild infection might not have high blood pressure, especially if they don't get to the GP until they are well over the acute illness and are worried about persisting fatigue and other symptoms.

 

[Jonathan Edwards]

If we accept that many human characteristics are distributed on a curve and we merely pathologise the end-point of that curve, we could maybe wonder if the EDS phenotype (associated with low blood pressure and me/cfs) is a risk factor for LC and its inverse is protective?

The EDS phenotype is not associated with ME/CFS as far as we know. I don't think either is associated with low BP either.

Joint mobility will be associated with ME/CFS because women are more mobile than men, but equating joint mobility with 'EDS' is fatuous. It is a bit like saying ME/CFS is associated with being shorter, since women are shorter.

 

[Jonathan Edwards]

I suspect that studies of 'Long Covid' based on questionnaires like this are pretty meaningless. There are all sorts of confounding reasons why hypertension might have a negative association.

 

[Hutan]

Females with long COVID were younger and less likely to have hypertension, while males were also younger and more likely to have had a severe COVID-19 illness in comparison with those without long COVID. Non-linear age patterns were examined, but no statistically significant results were identified. Males with long COVID also had higher levels of total and LDL cholesterol, and higher glomerular filtration rate.

It's sounding as though the males' version of long COVID was more likely to be the effects of a severe COVID infection. That would fit with cholesterol and BMI issues. And the females who had high blood pressure would be more likely to have had a severe COVID infection, and so not have ME/CFS.

Interesting to note that the women with long COVID weren't more likely to have cholesterol issues.

Recovery

For both males and females with long COVID, those who recovered from the persistent symptoms, exhibited lower rates of severe COVID-19 (Table 2). No other factors were associated with recovery, except for history of thrombosis in females, which was only present in long COVID females who did not recover.

A history of thrombosis made no difference to the likelihood of females getting Long COVID.


It's pretty hard to get really useful findings when different sorts of long COVID are not separated out. I don't think this thing of hypertension being protective against Long COVID is solid enough for us to think about it much.