1. Characteristics of included studies.
| Study | Study design | Country/Setting | Data collection methods | Intervention(s) description | COVID‐19 definition | Inclusion criteria | Exclusion criteria | Confounders (variables, how measured) | Confounder adjustment | Analysis method | Outcomes of interest | Total participants (n) | Participants HC user (n) | Participants non‐HC user (n) |
| Seeland 2020 | Retrospetive database cohort | Derived from electronic health records of multiple healthcare organizations across 17 countries | Data collected from electronic health records in the TriNetX RealWorld database. Stratified by age: pre‐menopausal cohort (15 to 49 years) and post‐menopausal (> 50 years). Only pre‐menopausal cohort reported here | Hormone use: estradiol and combined hormonal contraception (unclear how many people were using estradiol only). Hormone use was identified via RxNorm codes 4083 (estradiol), 4124 (ethinyl estradiol), progestins VA:HS800, and systemic contraceptives VA:HS200 | COVID‐19 patients were identified via the ICD‐10 code U07.1 or the presence of a SARS‐CoV‐2‐related RNA diagnosis | Pre‐menopausal women ages 15 to 49 who were COVID positive in the last 7 months (n = 18,892) | Those without gender information | TriNetX analytics tools were used to assess baseline characteristics including "demographics, diagnoses, procedures, and medication" No information on exactly which variables were collected or how they were measured | Cohorts were balanced 1:1 using propensity score matching, using a nearest neighbor greedy matching algorithm with a caliper of 0.25 times the standard deviation | A logistic regression analysis was performed for the combined outcome variable "death" incorporating the propensity score matching | Mortality | n = 18,892 | n = 2078 | n = 16,814 |
| Mujumdar 2020 | Retrospective database cohort | Tertiary medical center in the US | Chart review from tertiary medical center electronic health record from 28 March 28 to 27 April 2020 | Hormonal contraception including LNG IUD, POP, CHC, injectable progestin reported in medical chart (patients not contacted to confirm contraceptive use) | Patients who tested positive for SARS‐CoV‐2 | Reproductive age women ages 12 to 49 who tested COVID positive | Pregnancy | Uncertain | "Multivariable logistic regression was used to control for differences at baseline" | Logistic regression | Hospitalization Intubation |
n = 123 COVID positive patients | n = 44 | n = 79 |
| Costeira 2021 | Prospective cohort study | Users of the application in the UK | Self‐reported data from users input to COVID Symptom Study Smartphone Application Data obtained between 7 May 7 to 15 June 2020 exposures, outcomes, and covariates were ascertained following quality control with purpose‐built scripts | Combined oral contraceptive use (self‐report) | Subjects with predicted COVID‐19 probability of > 50% considered COVID positive; model incorporated age, sex, anosmia, persistent cough, severe fatigue, and skipped meals | Female app users 20 to 45 years with BMI between 18 to 35 kg/m2 85% were pre‐menopausal | Use of estrogen for gender transitioning | Age, BMI, smoking status ‐ self‐reported | Binomial generalized mixed models | Binomial generalized mixed models with with a log‐odds/logit link function used for association Age: continuous fixed effect BMI: continuous fixed effect Smoker: categorical fixed effect ‐ never, ex, and current sensitivity analyses performed to match the mean and median age of cases and controls for the exposure variables in subsets of users in 5‐year age bins | Hospitalization | n = 295,689 | n = 64,253 | n = 231,436 |
| Chima 2021 | Case series | 41 healthcare organizations participating in TriNetX ‐ data for 8 patients in the US | Derived from TriNet X EHR | Combined hormonal contraception Case definition: pulmonary embolism: defined using any ICD‐10 root diagnostic code; medications 30 days before and after acute PE diagnosis and COVID diagnosis |
COVID‐19 patients were identified via the ICD‐10code U07.1. Assumed that the day the diagnostic code was entered for billing was the day the diagnosis was made | Pediatric patients < 18 years old with PE and COVID positive. PE diagnosed concurrently or within 30 days of COVID diagnosis | _ | Age, BMI, race, ethnicity, lab results, medications | None, descriptive only | Descriptive | Pulmonary embolism | n = 6 girls | n = 1 | n = 5 |
| Hameed 2021 | Case series | Multicenter multinational study ‐ 10 tertiary care centers in Pakistan, Egypt, Singapore, and the US | Data collected retrospectively from COVID‐19 registries and medical records | "Oral contraception" CVT case definition: "Diagnosis of CVT was confirmed by at least one of the following imaging studies according to the established criteria: magnetic resonance (MR) imaging, MR venography (MRV), computed tomography (CT), CT venography, or cerebral venography" |
COVID‐19 infection, confirmed either by reverse transcriptase‐polymerase chain reaction assay of a nasopharyngeal swab or serum antibody testing for CO‐VID‐19 | "Patients aged 18 years or above with recent COVID‐19 infection, confirmed either by reverse transcriptase‐polymerase chain reaction assay of a nasopharyngeal swab or serum antibody testing for CO‐VID‐19" | Patients with recent trauma or those on anticoagulation | "Risk factors, clinical features, laboratory findings, imaging findings, COVID‐19‐related information"; of note, OCP user also antiphospholipid antibody + | None, descriptive only | Descriptive: frequencies and corellations | Cerebral venous thrombosis | n = 7 women with CVT | n = 1 patient using "oral contraceptive" | n = 6 |
BMI: body mass index; CVT: cerebral venous thrombosis; CHC: combined hormonal contraception; HC: hormonal contraception; ICD‐10: International Classification of Diseases 10th Revision; LNG IUD: levonorgestrel intrauterine device; OCP: oral contraception pill; PE: pulmonary embolism; POP: progestogen‐only pill.