key: cord-0725205-g73s1qy6 authors: Boyraz, Baris; James, Kaitlyn; Hornick, Jason L.; Roberts, Drucilla J. title: Placental pathology from COVID-19 recovered (non-acute) patients date: 2022-04-09 journal: Hum Pathol DOI: 10.1016/j.humpath.2022.04.005 sha: 3aeca3d3753b45dabba5f5cb78f68e3f64ffafb0 doc_id: 725205 cord_uid: g73s1qy6 Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has been well described. However, whether the characteristic placental pathology persists after the acute phase of the infection is less clear. We retrospectively identified 67 COVID-19 recovered pregnant patients who had placental pathology available. After reviewing the gross and histopathology we categorized the findings and studied the placentas for evidence of chronic infection by immunohistochemistry for the Spike protein of the virus. We found these placentas showed significantly increased prevalence of maternal and fetal vascular malperfusion when compared to a control group of placentas examined for the sole indication of maternal GBS colonization. None of the COVID-19 recovered placentas showed expression of the viral protein, therefore we found no evidence of persistent infection of the placenta in women with a history of COVID-19 during their pregnancy... We conclude that recovery from a SARS-CoV-2 infection during pregnancy puts the pregnancy at risk for specific pathology. Abstract: 25 Placental pathology can identify characteristic features of specific infectious pathogens. 26 The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has 27 been well described. However, whether the characteristic placental pathology persists after the 28 acute phase of the infection is less clear. We retrospectively identified 67 COVID-19 recovered 29 pregnant patients who had placental pathology available. After reviewing the gross and 30 histopathology we categorized the findings and studied the placentas for evidence of chronic 31 infection by immunohistochemistry for the Spike protein of the virus. We found these placentas 32 showed significantly increased prevalence of maternal and fetal vascular malperfusion when 33 compared to a control group of placentas examined for the sole indication of maternal GBS 34 colonization. None of the COVID-19 recovered placentas showed expression of the viral protein, 35 therefore we found no evidence of persistent infection of the placenta in women with a history of 36 COVID-19 during their pregnancy... We conclude that recovery from a SARS-CoV-2 infection 37 during pregnancy puts the pregnancy at risk for specific pathology. CoV-2 test to delivery ranged from 14 to 230 (mean 87.9) days (see Table 1 ). 38 had a negative The placentas weighed from 117 to 760 (mean 427.1) grams (see Table 2 infectious pathologic findings, 7 (10.4%) other thrombotic findings and 4 (6.0%) anatomic defects. The findings were compared to those observed in the cohort with maternal GBS colonization (see 111 Table 3 ), and the statistically significant differences included higher rates of maternal vascular 112 malperfusion (p: <0.001). A trend towards statistical significance was observed in fetal vascular 113 malperfusion (p=0.051), but no statistical significance was found for infectious, inflammatory, or 114 other thrombotic findings between the two groups. In order to answer these questions, we identified a cohort of 67 patients who 124 were COVID-19 recovered (>14 days after a positive test with a negative test after or cleared with 125 time-based criteria) and herein, we report the pregnancy outcomes, detailed histopathologic 126 findings from placental pathology and immunohistochemistry for viral proteins. Since the placenta is an organ known to be a site for acute SARS-CoV-2 infection, we In our cohort, we identified that maternal vascular malperfusion to be significantly more We believe our study has unique strengths. Our manuscript describes 67 cases all with 168 antepartum and outcome data, all studied for viral protein expression, all examined by experienced 169 placental pathologists following Amsterdam criteria (8), and reviewed by an internationally 170 respected placental pathologist (DJR). Our study is the largest study of COVID-19 recovered 171 placentas and the only one that examined for the presence of the virus in the placenta. In summary, we studied 67 cases of COVID-19 recovered patients' placentas and found no 173 placentas with SARS-CoV-2 placentitis or evidence for viral infection by immunohistochemistry, 174 suggesting that persistent infection does not occur post-clearing of the acute infection. We 175 describe, though, that exposure to SARS-CoV-2 during pregnancy is associated with increased SARS-CoV-2 (n=67) Age; range; mean ± SD (years) 16-42; 30.3 ± 5.8 Time from positive SARS-CoV-2 test to delivery; range; mean ± SD (days) Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings Pregnancy and 184 postpartum outcomes in a universally tested population for SARS-CoV-2 in Histopathologic Findings in the 187 Placentas of Pregnant Women With COVID-19 COVID-19 as an 189 independent risk factor for subclinical placental dysfunction Defining Severe Acute Respiratory Syndrome Coronavirus 2 192 (SARS-CoV-2) Placentitis: A Report of 7 Cases with Confirmatory In Situ Hybridization, Distinct 193 Histomorphologic Features, and Evidence of Complement Deposition Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With 197 Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe 198 Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants A standardized definition of placental infection by SARS-CoV-2, a 203 consensus statement from the National Institutes of Health Child Health and Human Development SARS-CoV-2 Placental Infection Workshop Histologic and Immunohistochemical Evaluation of 65 Placentas From Women With Polymerase Chain 208 Reaction-Proven Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Amsterdam Placental Workshop Group Consensus Statement SARS-CoV-2 and Placental Pathology: Malperfusion Patterns Are Dependent on Timing of 217 Infection During Pregnancy Placental Pathology Findings during and after SARS-CoV-2 Infection: Features of Villitis and 220 Malperfusion Coronavirus disease 2019 infection and placental 223 histopathology in women delivering at term Histopathologic evaluation of placentas after diagnosis of maternal severe acute 226 respiratory syndrome coronavirus 2 infection A structured review of placental morphology and histopathological lesions 229 associated with SARS-CoV-2 infection Maternal vascular malperfusion of the placental bed Fetal vascular malperfusion, an update SARS-CoV-2 placentitis associated with B.1.617.2 (Delta) variant and fetal distress 236 or demise Royal College of Physicians of Ireland FoPatIoOaG. Covid Placentitis: Statement from the RCPI 241 Faculty of Pathology and the Institute of Obstetricians and Gynaecologists Online SARS-CoV-2 can infect the placenta and is not associated with 246 specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers SD -standard deviation Table 2: Placental findings from COVID-19 recovered patients. Placental pathologic category COVID-19 recovered, Nonacute SARS-CoV-2 (n=67) >90%: 1 (1.5) Abbreviations: CHI -chronic histiocytic intervillositis, FVM -fetal vascular malperfusion, IVTintervillous thrombus, MVM -maternal vascular malperfusion, n -number Reference values for singleton and twin placental weights Comparison of placenta findings from COVID-19 recovered patients with patients with GBS infection. COVID-19 recovered, nonacute SARS-CoV-2 (n=67) Abbreviations: FVM -fetal vascular malperfusion, GBS -Group b streptococcal, MVM -maternal vascular malperfusion