Customize your JAMA Network experience by selecting one or more topics from the list below.
To the Editor We read with interest the article by Villar and colleagues1 and wish to comment on the potential association between COVID-19 infection and higher rates of preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome. SARS-CoV-2 infection induces a state of renin-angiotensin system hyperactivity with elevated levels of angiotensin II (Ang II), interleukin 6 (IL-6), and plasminogen activator inhibitor 1.2,3 This proinflammatory state can potentially lead to acute respiratory distress syndrome, cytokine storm, and autoimmunity.2 Elevated Ang II levels in COVID-19 have been reported to induce pyroptosis, an inflammasome-initiated lytic form of programmed cell death that may further contribute to the COVID-19 cytokine storm. Via the exposure of autoantigens, pyroptosis may also lead to the development of multiple autoantibodies.4 Numerous studies have shown that preeclampsia is a pregnancy-induced autoimmune disease in which key features of the disease result from a pyroptosis-induced Ang II type 1 receptor autoantibodies (AT1-AA) correlating significantly with IL-6 and systolic blood pressure.4 This condition could be aggravated in the presence of the Ang II-augmenting ACE D allele,2 which has been reported to be associated with increased mortality in COVID-19.2 We believe that the possibility of Ang II-induced pyroptosis in pregnant women with COVID-19 infection could mediate persistent proinflammatory Ang II effects and induce preeclampsia via AT1-AA. It would be desirable to evaluate the presence of AT1-AA in pregnant women with COVID-19 infection as lipoxin A4 (LXA4), deficient in individuals with preeclampsia, has been shown to modulate caspase-1 and inhibit AT1-AA.4 Low-dose acetylsalicylic acid5 and increasing bioactive lipid intake (arachidonic acid, 20:4 n-6; eicosapentaenoic acid, 20:5 n-3; and docosahexaenoic acid, 22:6 n-3) may result in the formation of increased amounts of endogenous LXA4, thus offering a treatment option for a potentially lethal complication. Drug design research using LXA4 as a lead compound might result in novel treatment modalities in preeclampsia and other autoimmune diseases.
Corresponding Author: Konstantinos I. Papadopoulos, MD, PhD, THAI StemLife, 566/3 THAI StemLife Building, Soi Ramkhamhaeng 39 (Thepleela 1), Prachauthit Road, Wangthonglang, Bangkok 10310, Thailand (firstname.lastname@example.org).
Published Online: August 16, 2021. doi:10.1001/jamapediatrics.2021.2613
Conflict of Interest Disclosures: None reported.
Papadopoulos KI, Manipalviratn S, Aw T. Further Observations on Pregnancy Complications and COVID-19 Infection. JAMA Pediatr. 2021;175(11):1185. doi:10.1001/jamapediatrics.2021.2613
Monkeypox Resource Center