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We thank Carbillon and coworkers for their perspectives on the optimal dose of chloroquine in pregnancy. The novel use of chloroquine phosphate and hydroxychloroquine in the management of coronavirus disease 2019 (COVID-19) is an area of evolving research. Our rationale for high-dose chloroquine was based, at the time, on expert consensus from the Chinese Ministry of Health and data from the interim analysis of a study by the Health Commission of Guangdong province, China, which supported the use of a twice-daily 500-mg regimen in the clinical management of COVID-19.¹

However, important findings from a subsequent double-masked, randomized phase IIb clinical trial from Brazil (ClinicalTrials.gov number, NCT 04323527) of adults with severe COVID-19 have since demonstrated that high-dose chloroquine is associated with greater toxicity and mortality from QTc prolongation.² Although these results are not generalizable across the COVID-19 disease spectrum, we now caution against the use of high-dose regimens and advise providers to consult their institutional protocols when considering these drugs as a treatment option in pregnancy.

Rancourt and colleagues astutely highlight the influence of body mass index (BMI) on disease outcomes. Although anthropometric data of pregnant women with COVID-19 were not available during the initial stages of the pandemic, obesity is now a well-recognized risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.³ Cohort studies of nonpregnant adults with COVID-19 and a BMI >35 kg/m² have demonstrated a higher risk for admission to critical care and the need for invasive mechanical ventilation. Similar trends are observed in pregnancy; our recent systematic review of 637 pregnant women with laboratory-confirmed SARS-CoV-2 infection demonstrated a 40% prevalence of obesity and diabetes mellitus among COVID-19–related maternal mortalities reported between December 2019 and May 2020.⁴ Prospective data from the United Kingdom Obstetric Surveillance System in addition reveal that overweight and obese pregnant women with COVID-19 were at least twice as likely to require admission to hospital when compared with those with a BMI <25 kg/m².⁵

It is believed that obesity attenuates cardiorespiratory reserves and amplifies circulating serum interleukin-6 levels; the latter, by instigating a cytokine storm, results in a significantly elevated risk of severe disease and mortality from COVID-19.^{3 , 4} Pregnant women who are obese and battling COVID-19 would therefore find themselves between Scylla and Charybdis, where gravid physiology and disease pathology collide to encourage progression to critical illness.