Histopathological examination of the placenta after delivery in pregnant women with COVID-19

Year 2022, Volume: 5 Issue: 3, 868 - 874, 30.05.2022

Fatih Taş Fikri Erdemci Fırat Aşır Mustafa Maraşlı Engin Deveci

https://doi.org/10.32322/jhsm.1100731

Cited By: 1

Abstract

Introduction: COVID-19 is a viral disease generated by a new coronavirus named SARS-CoV-2. The consequences of this virus on the human placenta and the newborn are still unclear. IL-6 can disturb the placenta's immunological homeostasis and be employed as an inflammatory marker for the poor prognosis of COVID-19 infection. Bax has some features like being a key protein regulating apoptotic mechanisms and plays an important role in both maintaining dynamic balance and integrity in the placenta as in many tissues. This study aims to indicate the impact of COVID-19 on inflammation and apoptotic pathways in the placenta by using IL-6 and Bax antibodies.
Material and Method: COVID-19 positive (n:10) and COVID-19 negative (n:10) normotensive placentas were included. Haematoxylin-eosin staining and immunohistochemical staining (IL-6 and Bax antibodies) were applied. Statistical data of immunohistochemical (IL-6 and Bax expression) staining results were assessed by analyzing the H-score. Biochemical parameters were recorded. Group means were analyzed with a nonparametric Kruskal Wallis Test.
Results: In the COVID-19 group, increased syncytial knots, fibrin deposition, inflammation, fibrinoid necrosis, neutrophil accumulation were observed. The COVID-19 group had considerably higher levels of IL-6 and Bax expression than the control group. Furthermore, COVID-19 patients had statistically lower WBC and higher CRP values than normotensive patients.
Conclusion: COVID-19 has been linked to placental inflammation and trophoblast cell damage, both of which can result in major maternal and fetal problems during pregnancy. We found intense IL-6 expression in the placentas of pregnant women with COVID-19 infection. A rise in IL-6 levels triggers CRP production, and this increase is linked to the severity of COVID-19 as a risk factor. Also, we suggested that COVID-19 infection triggers the apoptotic process in placental tissue by increasing the expression of the proapoptotic Bax protein. It is clinically very significant to follow up COVID-19 positive pregnancies for maternal and fetal health. During this follow-up, IL-6 and Bax expression levels in the placenta, together with histopathological findings and serum CRP levels, can guide the evaluation of the prognosis, severity and response to treatment of the disease.

Keywords

COVID-19, placenta, IL-6, inflammation, Bax, apoptosis

Supporting Institution

Siirt University

Project Number

2020- SİÜTIP -037

Thanks

This research received specific grant from Siirt University Scientific Research Center with protocol number 2020- SİÜTIP -037. We kindly thank to Siirt University for their financial aid to conduct this study.

References

• Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed 2020; 91: 157-60.
• Eastin C, Eastin T. Clinical characteristics of coronavirus disease 2019 in China. J Emerg Med 2020; 58: 711-2.
• Özüdoğru O, Bolatli G, Tas F. Investigation of revers-transcriptase polymerase chain reaction values of patients with COVID-19 findings in lung computed tomography results. J Teknology Laboratorium 2020; 9: 41-8.
• Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395: 809-15.
• Shoenfeld Y. Corona (COVID-19) time musings: our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev 2020; 19: 102538.
• Turner PJ, Ansotegui IJ, Campbell DE, et al. COVID-19 vaccine-associated anaphylaxis: A statement of the World Allergy Organization Anaphylaxis Committee. World Allergy Organization Journal 2021; 14: 100517.
• Koblinsky M, Chowdhury ME, Moran A, Ronsmans C. Maternal morbidity and disability and their consequences: neglected agenda in maternal health. J Health Popul Nutr 2012; 30: 124-30.
• Golden TN, Simmons RA. Maternal and neonatal response to COVID-19. Am J Physiol Endocrinol Metab 2020; 319: 315-9.
• Hromadnikova I, Kotlabova K, Ondrackova M, et al. Expression profile of C19MC microRNAs in placental tissue in pregnancy-related complications. DNA Cell Biol 2015; 34: 437-57.
• Baergen RN, Heller DS. Placental pathology in COVID-19 positive mothers: preliminary findings. Pediatr Dev Pathol 2020; 23: 177-80.
• Chen S, Huang B, Luo DJ, et al. Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases. Zhonghua bing li xue za zhi= Chinese J Pathol 2020; 49: 418-23.
• Cemgil Arikan D, Aral M, Coskun A, Ozer A. Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia, and their relation with severity of disease and fetal birth weight. J Matern Fetal Neonatal Med 2012; 25: 1569-73.
• Li A, Yang S, Zhang J, Qiao R. Establishment of reference intervals for complete blood count parameters during normal pregnancy in Beijing. J Clin Lab Anal 2017; 31: e22150.
• Sharma A, Satyam A, Sharma JB. Leptin, IL-10 and inflammatory markers (TNF-alpha, IL-6 and IL-8) in pre-eclamptic, normotensive pregnant and healthy non-pregnant women. Am J Reprod Immunol 2007; 58: 21-30.
• Popko K, Gorska E, Stelmaszczyk-Emmel A, et al. Proinflammatory cytokines Il-6 and TNF-α and the development of inflammation in obese subjects. Eur J Med Res 2010; 15: 120-2.
• Stinson LF, Payne MS, Keelan JA. Placental and intra-amniotic inflammation are associated with altered fetal immune responses at birth. Placenta 2019; 85: 15-23.
• Granger JP, Alexander BT, Llinas MT, Bennett WA, Khalil RA. Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation 2002; 9: 147-60.
• Hsiao EY, Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun 2011; 25: 604-15.
• Chen X, Zhao B, Qu Y, et al. Detectable serum severe acute respiratory syndrome coronavirus 2 viral load (RNAemia) ıs closely correlated with drastically elevated interleukin 6 level in critically ıll patients with coronavirus disease 2019. Clin Infect Dis 2020; 71: 1937-42.
• Herold T, Jurinovic V, Arnreich C, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. MedRxiv 2020; doi.org/10.1101/2020.04.01.20047381.
• Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID‐19: a single center experience. J Med Virol 2020; 92: 814-8.
• Peña-Blanco A, García-Sáez AJ. Bax, Bak and beyond-mitochondrial performance in apoptosis. Febs J 2018; 285: 416-31.
• Cil N, Kabukçu C. Effect of vitamin D application on the endometrium. Pamukkale Med J 2021; 14: 175-83.
• Fan J, Yu S, Cui Y, et al. Bcl-2/Bax protein and mRNA expression in yak (Bos grunniens) placentomes. Theriogenology 2017; 104: 23-9.
• Karakoç Z, Topaloğlu U, Ketani MA. Immunohistochemical distribution of ghrelin, obestatin, and leptin hormones in the abomasum of hair goat. Eurasian J Vet Sci 2019; 35: 204-9.
• Curtin WM, Krauss S, Metlay LA, Katzman PJ. Pathologic examination of the placenta and observed practice. Obstet Gynecol 2007; 109: 35-41.
• Lema G, Mremi A, Amsi P, et al. Placental pathology and maternal factors associated with stillbirth: An institutional based case-control study in Northern Tanzania. PLoS One 2020; 15: e0243455.
• Roescher AM, Hitzert MM, Timmer A, Verhagen EA, Erwich JJH, Bos AF. Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth. Early Human Development 2011; 87: 315-9.
• Mullins E, Evans D, Viner RM, O'brien P, Morris E. Coronavirus in pregnancy and delivery: rapid review. Ultrasound Obstet Gynecol 2020; 55: 586-92.
• Schwartz DA, Graham AL. Potential maternal and ınfant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus ınfections. Viruses 2020; 12: 194.
• Di Mascio D, Khalil A, Saccone G, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2020; 2: 100107.
• Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental pathology in COVID-19. Am J Clin Pathol 2020; 154: 23-32.
• Lamouroux A, Attie-Bitach T, Martinovic J, Leruez-Ville M, Ville Y. Evidence for and against vertical transmission for severe acute respiratory syndrome coronavirus 2. Am J Obstet Gynecol 2020; 223: 91-4.
• Ng WF, Wong SF, Lam A, et al. The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation. Pathology 2006; 38: 210-8.
• Hosier H, Farhadian SF, Morotti RA, et al. SARS-CoV-2 infection of the placenta. J Clin Invest 2020; 130: 4947-53.
• Risvanli A, Godekmerdan A. The effects of post-mating administration of anti-IL-10 and anti-TGFß on conception rates in mice. Int J Fertil Steril 2015; 9: 65-70.
• Lash GE, Ernerudh J. Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage. Jf Reproduct Immunol 2015; 108: 83-9.
• Zenclussen AC, Blois S, Stumpo R, et al. Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface. Cytokine 2003; 24: 150-60.
• Zinovkin RA, Grebenchikov OA. Transcription factor Nrf2 as a potential therapeutic target for prevention of cytokine storm in COVID-19 patients. Biochemistry (Mosc) 2020; 85: 833-7.
• Liu JKH. The history of monoclonal antibody development-progress, remaining challenges and future innovations. Annals of Medicine and Surgery 2014; 3: 113-6.
• Aziz M, Haghbin H, Abu Sitta E, et al. Efficacy of tocilizumab in COVID-19: a systematic review and meta-analysis. J Med Virol 2021; 93: 1620-30.
• Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130: 2620-9.
• Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents 2020; 55: 105954.
• Gao YD, Ding M, Dong X, et al. Risk factors for severe and critically ill COVID-19 patients: a review. Allergy 2021; 76: 428-55.
• Mazzoni A, Salvati L, Maggi L, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest 2020; 130: 4694-703.
• Chen CH, Lin SW, Shen CF, Hsieh KS, Cheng CM. Biomarkers during COVID-19: mechanisms of change and ımplications for patient outcomes. Diagnostics 2022; 12: 509.
• Saito J, Yakuwa N, Kaneko K, et al. Tocilizumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk and infant serum. Rheumatology (Oxford) 2019; 58: 1505-7.
• Tanase A, Manea A, Scurtu AD, et al. The “Invisible Enemy” SARS-CoV-2: viral spread and drug treatment. Medicina 2022; 58: 261.
• Seyit M, Avci E, Yilmaz A, Senol H, Ozen M, Oskay A. Predictive values of coagulation parameters to monitor COVID-19 patients. Int J Clin Practice 2022: 8436248.
• Gokalp-Ozkorkmaz E, Asir F, Basaran SO, et al. Examination of Bcl-2 and Bax protein levels for determining the apoptotic changes in placentas with gestational diabetes and preeclampsia. Proceedings 2018; 2: 1548.
• Mohammad Seyedhassani S, Houshmand M, Mehdi Kalantar S, et al. BAX pro-apoptotic gene alterations in repeated pregnancy loss. Arch Med Sci 2011; 7: 117-22.
• Mutlu P, Mirici A, Gönlügür U, et al. Evaluating the clinical, radiological, microbiological, biochemical parameters and the treatment response in COVID-19 pneumonia. J Health Sci Med 2022; 5: 544-51.