Table 1

Summary of findings on the risk of mortality, hospitalisation, venous thromboembolism, and intubation among COVID-19 patients in tertiary care settings using combined hormonal contraception compared with those using no form of hormonal contraception

Outcomes*Anticipated absolute effects† (95% CI)Relative effect
(95% CI)		Number of participants
(studies)		Certainty of the evidence
(GRADE)		Comments
Risk with no hormonal contraceptionRisk with combined hormonal contraception
Mortality5 per 1000 5 per 1000
(2 to 11)		 OR 1.00
(0.41 to 2.40)		18 892
(1 observational study)		⊕⊝⊝⊝
Very lowद
Hospitalisation7 per 1000d 5 per 1000
(4 to 6)**		 OR 0.79
(0.64 to 0.97)		295 689
(1 observational study)		⊕⊝⊝⊝
Very low¶††‡‡		CHC use may reduce hospitalisation slightly. COVID-19 positivity not confirmed through testing; women were using a mobile phone application to track COVID-19 symptoms. Restricted to patients with BMI <35 kg/m2
Venous thromboembolism1 of 6 paediatric COVID-19 patients with pulmonary embolism had reportedly been using combined hormonal contraception. 1 of 7 reproductive-aged female COVID-19 patients with cerebral venous thromboembolism was using ‘oral contraceptive pills’. This patient also had positive anti-phospholipid antibodies13
(2 observational studies)		⊕⊝⊝⊝
Very low§§¶¶		2 case series were included with 13 total patients, describing VTE in COVID-19 patients. Neither case study ascertained active use of hormonal contraception at time of the outcomei
Intubation1 of 6 people who were not using hormonal contraception required intubation compared with 1 of 1 person reportedly using oral contraceptive pills7
(1 observational study)		⊕⊝⊝⊝
Very low§§***		Case series of 7 reproductive-aged women, all of whom were COVID-19-positive and developed cerebral VTE

  • GRADE Working Group grades of evidence

  • High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.

  • Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

  • Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.

  • Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

  • *The outcomes of arterial thromboembolism and ARDS were not measured and are not included in this table.

  • †The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

  • ‡Downgraded for serious risk of bias given no ascertainment of combined hormonal contraception exposure and no information on variables used for propensity score matching, increasing risk of residual confounding.

  • §Downgraded for indirectness given no ascertainment of combined hormonal contraception use during time of outcome.

  • ¶Downgraded for imprecision given results reported in only 1 study.

  • **Overall 1889 of 295 689 total patients were hospitalised for an absolute risk of 6.4 per 1000 total. Hospitalisations were not reported separately for those using combined hormonal contraception (n=64 253) vs those not using contraception (n=231 436). Anticipated absolute effects were estimated by applying the adjusted relative effect estimate to determine the expected number of intervention and control patients who were hospitalised.

  • ††Downgraded for serious risk of bias due to risk of selection bias and all data are self-reported by users.

  • ‡‡Downgraded for indirectness as users of the application were not confirmed to be COVID-19-positive, but were tracking symptoms given concern for possible COVID-19 positivity.

  • §§Downgraded 2 levels for risk of bias as case series are likely to be subject to significant bias.

  • ¶¶Downgraded for imprecision for small sample sizes.

  • ***Downgraded 2 levels for imprecision given small sample size and results reported in only 1 study.

  • ARDS, acute respiratory distress syndrome; BMI, body mass index; CHC, combined hormonal contraception; VTE, venous thromboembolism.