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Gender Disparities in Self-Reported COVID-19 Symptoms in Young Adults

Objective: Young adults constitute a significant proportion of COVID-19 cases but generally experience a milder disease. Our study’s goal was to characterize symptoms of disease in a cohort of young adults and to examine possible gender-associated disparities in clinical manifestations. Study Design and Setting: The study is a retrospective survey study. The study questionnaire was sent to all post-COVID-19 IDF personnel between June and September 2020. Univariate and multivariable analysis adjusting for differences in baseline characteristics were employed in the statistical analysis. J Psychiatry Psychiatric Disord 2021; 5 (6): 203-217 DOI: 10.26502/jppd.2572-519X0146 Journal of Psychiatry and Psychiatric Disorders 204 Results: 3247 questionnaires were sent. A total of 792 questionnaires were included in the analysis. The average age was 24.2Y/O and 21Y/O for males and females, respectively. Only 3 participants were hospitalized. Approximately 97% of participants reported at least one COVID-19 symptom, only 45.8% reported fever above 38.0oC. Female participants reported significantly more symptoms. Most of these differences were maintained in the multivariable analysis. Females also reported increased use of medications. Conclusions: Our findings show a high percentage of symptomatic infection with COVID-19 and suggest young generally healthy female patients experience symptoms of increased severity and duration compared to males.


Introduction
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It was first identified in Wuhan, China on December 2019 and has since spread globally to pandemic proportions [2]. At the time of diagnosis, up to 40% of infected individuals are asymptomatic or pre-symptomatic but potentially contagious to others [3]. Particularly, younger individuals have been found to have an increased rate of asymptomatic infection. Interestingly, several published reports show asymptomatic and pre-symptomatic patients were found in groups of military service members [4,5]. While increasing age and comorbidities are important risk factors for higher morbidity and mortality in COVID-19 patients leading to a devastating number of deaths due to the pandemic, young adults generally experience a milder disease course [6]. Publicly available online data Few reports have been published regarding genderbased differentiating factors in COVID-19 [7,8].
Some studies reported on increased morbidity and mortality in males compared to females [9][10][11][12], at least some of these differences may be gender as well as age dependent [13]. Israeli Defense Force (IDF) service members are in the 18  infection [14]. The aim of the present study is to characterize symptoms of disease in a cohort of generally healthy young adults an examine genderassociated disparities in the clinical manifestations of COVID-19 in patients with a mild clinical course.

Study population and sample selection
In this retrospective cross-sectional survey study, we included all post-COVID-19 IDF service members between 30 June 2020 and 30 September 2020. Data was received from a dedicated IDF COVID-19 center.
In all cases, diagnosis of COVID-19 was performed with SARS-CoV-2 PCR testing from nasopharyngeal swabs. Criteria for SARS-CoV-2 PCR testing was either (a) close contact with known COVID-19 patient + one respiratory symptom, (b) at least two respiratory symptoms (c) dysgeusia and/or anosmia. Some testing was performed at the primary care physician's discretion or when a cluster of cases was found in the unit -even if close contact has not been established. Recovery from COVID-19 was defined as either two consecutively negative SARS-CoV-2 PCR testing or after at least ten days had elapsed since the first positive or borderline positive SARS-CoV-2 PCR test with at least 3 consecutive days with no defining symptoms such as fever, dyspnea or cough.

Research tool and survey administration
An online questionnaire form was sent via text message to the study population. The study questionnaire was written in Hebrew, the participants native language, and contained a description of the study design, aims, and required the recipients informed consent to proceed. The questionnaire was anonymous and no personally identifiable information was collected from study participants, other than last 4 digits of personal ID number to allow for detection of duplicate submissions. All parts of the questionnaire were required for questionnaire submission, thus eliminating missing data.
The questionnaire allowed for data collection of age, military service status (recruits and enlisted personnel in compulsory service status, versus military career officers as well as non-commissioned and warrant officers), smoking habits, presence of chronic illnesses. Participants were required to report whether they suffered from each one of the presented symptoms and rate the duration and its perceived severity on a scale of 1 (mildest) to 5 (most severe).
cough, nasal congestion, shortness of breath, sore throat, diarrhea, stomach pain, nausea and/or vomiting, impaired sense of smell and impaired sense of taste. An English version of the questionnaire is available in the article's supplementary material.

Statistical analysis
Categorical variables were presented with frequencies and percent and continuous/ordinal variables were presented with mean (SD) [median, range]. The association between gender and categorical variables was determined using Chi-square test (or Fisher's exact test).

For continuous/ordinal variable the T-test or
Wilcoxon rank-sum test was used. Prevalence ratios were presented along 95% confidence intervals (95%CI). Multivariable log-binomial regressions were performed (for the probability of having a symptoms as well as for the probability of having specific symptom), with age (continuous), rank (Officer/not officer), type of service (compulsory or military career) and chronic disease (yes/no) as potential confounding factors. Adjusted prevalence ratio were presented as well with 95%CI.
The analyses were performed using SAS 9.4 software.
P<0.05 was considered significant. We conducted a multivariable log-binomial regression analysis adjusting for age, military service type (compulsory vs. military career), officer rank vs. other ranks (including warrant and non-commissioned officers), and presence of any chronic illness as possible confounding factors.

Ethical considerations
The institutional review board of the IDF approved the study (protocol number 2094-2020). All participants were asked to anonymously participate in the study by answering an online questionnaire with their informed consent.

General
Overall, the study questionnaire was sent to 3247 patients who recovered from COVID-19 infection.     (Figures 2A and 2B).
Interestingly, there were no significant differences in the presence or fever, highest measured temperature, and cough between genders (Tables 3A and 3B). The multivariate analysis (as shown in Table 1) showed significant differences between males and females when comparing symptoms of any severity, as well as symptoms of significant severity (graded 4-5 on a scale of 1-5) (Tables 3A, 3B). Specifically, differences in any severity of sore throat, and high severity (grade 4-5) stomachache were not statistically significant in the multivariate analysis.

Medical therapy
Overall, 37.4% received medical treatment. One participant didn't answer the question regarding medical therapy and was excluded from this analysis.
Seven participants specified that they used vitamin C, vitamin D or other vitamin supplements or responded they used medications but did not further specify.
Overall, 289 participants (36.5%) reported on medical treatment. Older participants (>31y) used significantly more medications than the younger age groups (P=0.005). We observed a higher prevalence of medication use in females compared to males (P=0.0146). Specifically, analgetic and/or antipyretic medications were used significantly more by females (P>0.001). These results are shown in Table 3.

Conclusions
Our