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This is a new literature review updated on may 2022. In case some essential information is missing, please contact us at: rafael@hcuge.ch.

Sexual dimorphism in COVID-19: potential clinical and public health implications 

Bechmann N, Barthel A, Schedl A, Herzig S, Varga Z, Gebhard C, Mayr M, Hantel C, Beuschlein F, Wolfrum C, Perakakis N, Poston L, Andoniadou CL, Siow R, Gainetdinov RR, Dotan A, Shoenfeld Y, Mingrone G, Bornstein SR. Lancet Diabetes Endocrinol. 2022 Jan 31:S2213-8587(21)00346-6. doi: 10.1016/S2213-8587(21)00346-6. Epub ahead of print. PMID: 35114136; PMCID: PMC8803381.

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. Due to its role in the severity and progression of SARS-CoV-2 infections, authors argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. Several studies have suggested that women are more at risk of developing long COVID. In women, cardiovascular risk factors, pre-existing mental illness, and self-reported domestic stress increased the risk of long COVID. Besides female sex, number of symptoms in the first week, BMI, and increasing age were found to be predictors for long COVID. For long COVID in particular, as well as for any other symptoms reported to the physician, it is important to consider that there might also be sex-related differences in how symptoms are perceived and reported, which might affect outcomes of studies. 

Increasing evidence suggests that autoantibodies, whose concentrations exhibit also sex-specific differences, play a crucial role in the extended multi-organ illness in patients with long COVID. Pre-existing asthma, which is more prevalent in women than in men, has been reported to further increase the risk of developing long COVID. Further characterization of predictors for long COVID, such as sex and comorbidities, might help to identify patients at high risk of developing long COVID and allow early intervention to address their individual needs and improve outcomes.

Link to study: Sexual dimorphism in COVID-19: potential clinical and public health implications

Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study

Righi E, Mirandola M, Mazzaferri F, Dossi G, Razzaboni E, Zaffagnini A, Ivaldi F, Visentin A, Lambertenghi L, Arena C, Micheletto C, Gibellini D, Tacconelli E.. J Infect. 2022 Feb 10:S0163-4453(22)00065-2. doi: 10.1016/j.jinf.2022.02.003. Epub ahead of print. PMID: 35150765; PMCID: PMC8828388.

Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed in this study from Verona, Italy. Overall, 465 patients (54% males, 51% hospitalised) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalisation and ICU stay vs. non-hospitalised status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress. Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing.

Link to study: Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study

Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients

Chan Sui Ko A, Candellier A, Mercier M, Joseph C, Schmit JL, Lanoix JP, Andrejak C. Int J Infect Dis. 2022 Mar 5;118:220-223. doi: 10.1016/j.ijid.2022.03.006. Epub ahead of print. PMID: 35257903; PMCID: PMC8896858.

Link to study : Number of initial symptoms is more related to long COVID-19 than acute severity of infection: a prospective cohort of hospitalized patients