Females are significantly more likely to suffer from long COVID than males

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A new study published today in the journal Current Medical Research and Opinion reveals that females are “significantly” more likely to suffer from long COVID than males and will experience substantially different symptoms.

Long COVID is a syndrome in which complications persist more than four weeks after the initial infection of COVID-19, sometimes for many months.

Researchers from the Johnson & Johnson Office of the Chief Medical Officer Health of Women Team, who carried out the analysis of data from around 1.3 million patients, observed that females with long COVID are presenting with a variety of symptoms including ear, nose, and throat issues; mood, neurological, skin, gastrointestinal and rheumatological disorders; as well as fatigue.

Male patients, however, were more likely to experience endocrine disorders such as diabetes and kidney disorders.

“Knowledge about fundamental sex differences underpinning the clinical manifestations, disease progression, and health outcomes of COVID-19 is crucial for the identification and rational design of effective therapies and public health interventions that are inclusive of and sensitive to the potential differential treatment needs of both sexes,” the authors explain.

“Differences in immune system function between females and males could be an important driver of sex differences in long COVID syndrome. Females mount more rapid and robust innate and adaptive immune responses, which can protect them from initial infection and severity. However, this same difference can render females more vulnerable to prolonged autoimmune-related diseases.”

As part of the review, researchers restricted their search of academic papers to those published between December 2019–August 2020 for COVID-19 and to January 2020–June 2021 for long COVID syndrome. The total sample size spanning articles reviewed amounted to 1,393,355 unique individuals.

While the number of participants sounds large, only 35 of the 640,634 total articles in the literature provided sex disaggregated data in sufficient details about symptoms and sequalae of COVID-19 disease to understand how females and males experience the disease differently.

When looking at the early onset of COVID-19, findings show that female patients were far more likely to experience mood disorders such as depression, ear, nose, and throat symptoms, musculoskeletal pain, and respiratory symptoms. Male patients, on the other hand, were more likely to suffer from renal disorders—those that affect the kidneys.

The authors note that this synthesis of the available literature is among the few to break down the specific health conditions that occur as a result of COVID-related illness by sex. Plenty of studies have examined sex differences in hospitalization, ICU admission, ventilation support, and mortality. But the research on the specific conditions that are caused by the virus, and its long-term damage to the body, have been understudied when it comes to sex.

“Sex differences in outcomes have been reported during previous coronavirus outbreaks,” authors add. “Therefore, differences in outcomes between females and males infected with SARS-CoV-2 could have been anticipated. Unfortunately, most studies did not evaluate or report granular data by sex, which limited sex-specific clinical insights that may be impacting treatment.”

Ideally, sex disaggregated data should be made available even if it was not the researcher’s primary objective, so other interested researchers can use the data to explore important differences between the sexes.

The paper also notes complicating factors worthy of additional study. Notably, women may be at greater risk of exposure to the virus in certain professions, such as nursing and education. Further, “there may be disparities in access to care based on gender that could affect the natural history of the disease, leading to more complications and sequela.”

The latter serves as a rallying cry: Availability of sex disaggregated data and intentional analysis is imperative if we are to ensure that disparate outcomes in disease course are addressed. No research is complete unless the data is made available to people who want to answer the question: Do sex and gender matter?


The American Center for Disease Control (CDC) and the British NICE have identified symptoms that could persist for weeks or even months after recovery from COVID-19. How long these symptoms could endure for, possible risk factors for their persistence and the predisposing patient features are all aspects to be further elucidated [6, 7, 8,[17]]. Our study reveals that:

1. The most common symptoms characterizing long COVID were both physical and psychological.
2. Females had a 3-fold higher risk of being diagnosed with long COVID.
3. Severity of disease and time to virological resolution were not associated with long COVID.

The high incidence of long COVID within our cohort was similar to that previously reported: more than half of patients reported symptoms lasting more than 2 months after symptom onset [[4],[5],[16],[18],[19]]. Some symptoms are also commonly seen in other viral illnesses and both psychical and psychological sequelae have been described in MERS and SARS [[12],23, 24, 25, 26, 27, 28, 29].
Literature data are not equivocal about the association between females and long COVID: some preliminary studies have shown an increased prevalence of fatigue [[24]] or other symptoms among women [[1],[5],[13],[16]], while in other studies no gender association was found [[4],18, 19, 20].

Differences in ethnicity, living country and possibly socio-economic status might explain such contrasting results. Hormones may play a role in perpetuating the hyperinflammatory status of the acute phase even after recovery [[30],[31]] and a stronger IgG antibodies production in females in the early phase of disease has been reported; this could turn out in a more favourable outcome in women [[32]], but might play a role as well in perpetuating disease manifestations. Furthermore, we might hypothesise that women are in general more attentive to their body and related distress.

Advanced age was associated with ongoing fatigue and musculoskeletal pain, or impairment in pulmonary functions, reflecting a decline in organ function and a slower ability to recover [[1],[16]]. As far as our finding that reported a weak association between obesity and long COVID is concerned, this was not confirmed in a previous study that however focused on persisting fatigue solely [[24]].

Increased inflammation, defective adaptative immune responses, endothelial dysfunction and coagulation-related disorders are all phenomena that have been well described in obesity and might represent a plausible explanation to the link we observed between high BMI and long COVID [[33]]. Finally, the relationship between smoking and long COVID has not been previously explored; the most frequent symptom reported by smokers was however shortness of breath, which possibly reflects an underlying pulmonary dysfunction.

We were expecting to find an association between severity of disease and residual symptoms, as reported by previous studies [[1]]. However, long COVID has been previously described also in not hospitalised patients diagnosed with a mild, self-limiting disease [[6],16, 17, 18,[24]].

Our study has some limitations: a possible selection bias due to losses to follow-up; the limited sample size for patients with severe disease and females; the lack in validated tools to assess dyspnoea and fatigue and in information about the presence of the symptoms before the onset of acute infection. The possible association between female gender and long COVID should be confirmed in larger populations and by means of a longer follow-up. The evaluation of our patients at six months still needs to be completed and this will certainly allow us to collect further data and build stronger evidence.

In conclusion, in our setting long COVID was a frequent long-term complication of COVID-19 and was diagnosed more frequently in women than in men. It was also commonly seen in patients who recovered from a mild disease form. Follow-up outpatient services are therefore needed in order to manage this syndrome and to better understand the possible association between symptoms and residual organ impairment, and their impact on patient quality of life.

reference link : https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00629-7/fulltext


More information: Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review, Current Medical Research and Opinion (2022). DOI: 10.1080/03007995.2022.2081454

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