Vaccine against COVID-19 (adenovirus vector)

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 adenovirus vector 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 (adenovirus vector)

According to data in the manufacturer’s approval documents in the EMA application, the vaccine efficacy of two doses of Vaxzevria were similar in men and women (54.5% in men, 66.7% in women). Vaccine efficacy was measured as incidence of first SARS-CoV-2 virologically-confirmed COVID-19 occurring more than 15 days after the second dose [14]. Furthermore, immune response after a single dose of Vaxzevria was analyzed in a phase 1/2, single-blind RCT in adults. Cellular immune response and total IgG antibody responses were similar in men and women (25 men, 19 women) [15-18].

The efficacy of a single dose of JCOVDEN was evaluated in a phase 3 pivotal trial including persons 18-100 years of age (24 053 men, 19 722 women; median age 52 years). Subgroup analyses of the primary endpoint, prevent occurrence of moderate to severe/critical COVID-19, showed similar efficacy in men and women (68.8% in men, 63.4% in women) [19, 20].

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, 21-24].

Specific for vaccines against COVID-19 (adenovirus vector)

A few very rare cases of unusual thrombosis associated with thrombocytopenia have been reported in people vaccinated with Vaxzevria. Although the majority of cases are women younger than 60 years [18], the EMA have not yet highlighted any specific risk factors, such as patient’s sex, age, or previous medical history of clotting disorders, because the number of cases are too few for robust estimates to be made [25]. EMA continuous to monitor the safety of Vaxzevria [26]. Similar very rare events have been reported for JCOVDEN. The majority of cases were in women and in persons younger than 60 years of age [27].

Among reports of suspected adverse reactions for Vaxzevria and JCOVDEN registered in the European database EudraVigilance, the majority of individual cases are women [28]. The most common suspected adverse events reported are the same for the both vaccines and the same for men and women: fever, fatigue, pain at the injection site, headache, dizziness, numbness, muscle pain, myalgia [28].

Results from the main phase 3 clinical trial [20] show that women reported local and systemic solicited adverse events (AE) more frequently than men after a single dose of JCOVDEN (local AE: 54.5% vs. 46.2%, systemic: 59.9% vs. 50.7%). No sex difference was observed in the placebo group [29]. Sex-divided data on adverse events from pivotal studies of Vaxzevria have not yet been published by the original manufacturer [17].

Reproductive health issues

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