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Comment & Response
August 16, 2021

Further Observations on Pregnancy Complications and COVID-19 Infection

Author Affiliations
  • 1THAI StemLife, Bangkok, Thailand
  • 2Jetanin Institute for Assisted Reproduction, Bangkok, Thailand
  • 3Department of Laboratory Medicine, Changi General Hospital, Singapore
JAMA Pediatr. 2021;175(11):1185. doi:10.1001/jamapediatrics.2021.2613

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.

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Article Information

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 (kostas@thaistemlife.co.th).

Published Online: August 16, 2021. doi:10.1001/jamapediatrics.2021.2613

Conflict of Interest Disclosures: None reported.

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