Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review

Abstract

Objective

We conducted literature reviews to uncover differential effects of sex on sequelae from coronavirus disease 2019 (COVID-19) and on long COVID syndrome.

Methods

Two authors independently searched OvidSP in Embase, Medline, Biosis, and Derwent Drug File. Publications reporting original, sex-disaggregated data for sequelae of COVID-19 (published before August 2020) and long COVID syndrome (published before June 2021) were included in the reviews. The association between COVID-19 sequelae (i.e. lasting <4 weeks after symptom onset) and sex, and between long COVID syndrome (i.e. lasting >4 weeks after symptom onset) and sex, was determined by odds ratio (OR) and 95% confidence interval (CI) (statistical significance defined by 95% CI not including 1).

Results

Of 4346 publications identified, 23 and 12 met eligibility criteria for COVID-19 sequelae and long COVID syndrome, respectively. COVID-19 sequelae in the categories of psychiatric/mood (OR = 1.80; 95% CI: 1.35–2.41), ENT (OR = 1.42; 95% CI: 1.39–1.46), musculoskeletal (OR = 1.15; 95% CI: 1.14–1.16), and respiratory (OR = 1.09; 95% CI: 1.08–1.11) were significantly more likely among females (vs. males), whereas renal sequelae (OR = 0.83; 95% CI: 0.75–0.93) were significantly more likely among males. The likelihood of having long COVID syndrome was significantly greater among females (OR = 1.22; 95% CI: 1.13–1.32), with the odds of ENT (OR = 2.28; 95% CI: 1.94–2.67), GI (OR = 1.60; 95% CI: 1.04–2.44), psychiatric/mood (OR = 1.58; 95% CI: 1.37–1.82), neurological (OR = 1.30; 95% CI: 1.03–1.63), dermatological (OR = 1.29; 95% CI: 1.05–1.58), and other (OR = 1.36; 95% CI: 1.25–1.49) disorders significantly higher among females and the odds of endocrine (OR = 0.75; 95% CI: 0.69–0.81) and renal disorders (OR = 0.74; 95% CI: 0.64–0.86) significantly higher among males.

Conclusions

Sex-disaggregated differences for COVID-19 sequelae and long COVID syndrome were observed. Few COVID-19 studies report sex-disaggregated data, underscoring the need for further sex-based research/reporting of COVID-19 disease.

Keywords:

• COVID-19
• long COVID syndrome
• sex
• female

Transparency

Declaration of funding

This work was supported by funding from Johnson & Johnson, New Brunswick, NJ, USA.

Declaration of financial/other relationships

Shirley V. Sylvester, Carly O’Keefe, Rada Rusu, and Susan Nicholson are employees of Johnson and Johnson and some hold company equity. Some of the contributions to this work by Biankha Chan and Martha Bellows were done while they were employed by Johnson & Johnson. All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors had access to the study data and made the final decision about where to present these data. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

SVS, SN, MB, CO, BC, and RR were involved in the conception, design, analysis and interpretation of the data. All authors were involved in drafting of the paper or revising it critically for intellectual content; the final approval of the version to be published; and, agree to be accountable for all aspects of the work. All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors.

Acknowledgements

The authors acknowledge Sandra Norris, PharmD, of the Norris Communications Group, LLC for medical writing assistance and Ellen Baum, PhD (Janssen Global Services, LLC), for additional editorial support. The authors thank Dr. Serena Venturelli and associates from Bergamo and Milan, Italy, for providing sex-disaggregated data on dermatological complications and on rheumatologic complications of long COVID syndrome, which were combined in their primary report⁵⁴. The authors also thank Alan Fisher, DrPH, an independent consultant, for his assistance in screening articles and Marsha Wilcox, EdD, ScD for her input into the initial design of the review.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary material.