Vaccine against COVID-19 (mRNA)

Additional information

Men are at increased risk of worse outcome and mortality from COVID-19 compared to women. The sex difference is largest in the middle- and older age groups [1-6]. Generally, men have higher morbidity and mortality from lower respiratory tract infections [6, 7]. Possible explanations for these sex differences may be a combination of sex and gender factors. For example; the immunostimulatory effect of female sex hormones, higher levels of circulating ACE2 in women, and more women tend to follow hygiene and disease-preventive routines [1-3, 6, 8]. Other factors may also influence such as health-seeking behavior, smoking, obesity [9]. So far, among published studies on pharmacological treatment in COVID-19 (including antiviral, antimalarial, and immune system modulating drugs), sex-specific analyses are rarely reported [10].

Pharmacokinetics and dosing

No pharmacokinetics studies of the active ingredients in mRNA-based vaccines against COVID-19 have been performed. This is in line with Note for guidance on preclinical pharmacological and toxicological testing of vaccines (CPMP/SWP/465/95) [11].

Effects

Generally about vaccines

Women generally develop stronger innate and adaptive immune responses, express higher antibody levels, and greater T-cell activation, compared to men. These sex differences are observed in response to a variety of vaccines, including vaccines against influenza, yellow fever, rubella, measles, mumps, hepatitis A and B, herpes simplex 2, rabies, dengue and smallpox [12, 13]. However, the mechanisms behind these sex differences in response to vaccines are unknown and may differ based on the recipient’s age, type of vaccine, and type of protective immune responses elicited [12].

Specific for vaccines against COVID-19 (mRNA)

The pivotal studies, on which registration of the vaccines was based, report that men and women have similar efficacy of mRNA vaccines against COVID-19 [14, 15]. The efficacy of Comirnaty was evaluated in a multinational, placebo-controlled, observer-blind trial including persons 16-91 years of age (19 075 men, 18 631 women; median age 52 years). Vaccine efficacy was measured as first COVID-19 occurrence from seven days after the second dose. Subgroup analyses showed similar efficacy in men and women (96.4% in men, 93.7% in women) [14]. Furthermore, the efficacy of Spikevax was evaluated in a phase 3 randomized, observer-blind, placebo-controlled trial including adults (18-95 years) at high risk for SARS-CoV-2 infection or its complications (15 985 men, 14 366 women; mean age 51.4 years). Vaccine efficacy was measured as COVID-19 cases 17 days after the second dose. Subgroup analyses showed similar efficacy in men and women (95.4% in men, 93.1% in women) [15].

Some studies indicate that mRNA vaccination generates greater antibody response in women compared to men while other studies indicate no sex differences in antibody response [16, 17].

Adverse effects

Generally about vaccines

Women generally have higher rates of adverse events including pain, fever, and inflammation to vaccines. These sex differences are observed in response to a variety of vaccines, including vaccines against influenza, yellow fever, and hepatitis B [12, 13]. However, information about adverse events is often self-reported and may thus reflect a gender difference, in which women are more likely to report adverse events [12, 18-21].

Specific for vaccines against COVID-19 (mRNA)

According to the pivotal clinical trials for Comirnaty, no clinically meaningful differences in adverse events were observed in men and women (sex-divided data not shown) [22]. No sex-divided data on adverse events from Spikevax have been reported by the pharmaceutical company [23].

Among reports of suspected adverse reactions for the two vaccines Comirnaty and Spikevax registered in the European database EudraVigilance, the majority of individual cases are women [24]. The most common adverse events reported are the same for both vaccines and same in both men and women: fever, fatigue, pain at the injection site, headache, dizziness, numbness, extremity pain, muscle pain, joint pain [24]. Safety data show that inflammation of the heart (myocarditis) or membrane (pericarditis) can occur in very rare cases following vaccination with Spikevax or Comirnaty. The cases primarily occurred within 14 days after vaccination, more often after the second dose and in younger adult men [25, 26]. This has been confirmed in a large cohort study (11 515 016 men, 11 607 506 women) based on data from registers in Northern Europe, the prevalence of myocarditis was higher after the second dose and higher in younger men. The risk of myocarditis was higher after vaccination with two doses of Spikevax than two doses of Comirnaty (on average 18.4 vs 5.6 number of excess events in 28 days per 100 000 vaccinees [27]. In general, the population prevalence of myocarditis is higher in men than women [28] The risk of myocarditis is higher after infections [29, 30].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).