The Memphis Pandemic Health Informatics System (MEMPHI-SYS)-Creating a Metropolitan COVID-19 Data Registry Linked Directly to Community Testing to Enhance Population Health Surveillance.

The current coronavirus disease (COVID-19) pandemic has placed unprecedented strain on underfunded public health resources in the Southeastern United States. The Memphis, TN, metropolitan region has lacked infrastructure for health data exchange.This manuscript describes a multidisciplinary initiative to create a community-focused COVID-19 data registry, the Memphis Pandemic Health Informatics System (MEMPHI-SYS). MEMPHI-SYS leverages test result data updated directly from community-based testing sites, as well as a full complement of public health data sets and knowledge-based informatics. It has been guided by relationships with community stakeholders and is managed alongside the largest publicly funded community-based COVID-19 testing response in the Mid-South. MEMPHI-SYS has supported interactive Web-based analytic resources and informs federally funded COVID-19 outreach directed toward neighborhoods most in need of pandemic support.MEMPHI-SYS provides an instructive case study of how to collaboratively establish the technical scaffolding and human relationships necessary for data-driven, health equity-focused pandemic surveillance, and policy interventions.

History Repeating-How Pandemics Collide with Health Disparities in the United States.

Across the United States, public health responses to the COVID-19 pandemic have fallen short. COVID-19 has exacerbated longstanding public health shortfalls in disadvantaged communities. Was this predestined? Understanding where we are today requires reflection on our longer journey. Disparities cataloged during COVID-19 reflect the same unequal host exposure and susceptibility risks that shaped previous pandemics. In this review, we provide historical context to better understand current events and to showcase forgotten lessons which may motivate future action to protect our most vulnerable citizens.

Defining Radiation Treatment Interruption Rates During the COVID-19 Pandemic: Findings From an Academic Center in an Underserved Urban Setting.

PURPOSE: Our purpose was to characterize radiation treatment interruption (RTI) rates and their potential association with sociodemographic variables in an urban population before and during the COVID-19 pandemic. METHODS AND MATERIALS: Electronic health records were retrospectively reviewed for patients treated between January 1, 2015, and February 28, 2021. Major and minor RTI were defined as ≥5 and 2 to 4 unplanned cancellations, respectively. RTI was compared across demographic and clinical factors and whether treatment started before or after COVID-19 onset (March 15, 2020) using multivariate logistic regression analysis. RESULTS: Of 2240 study cohort patients, 1938 started treatment before COVID-19 and 302 started after. Patient census fell 36% over the year after COVID-19 onset. RTI rates remained stable or trended downward, although subtle shifts in association with social and treatment factors were observed on univariate and multivariate analysis. Interaction of treatment timing with risk factors was modest and limited to treatment length and minor RTI. Despite the stability of cohort-level findings showing limited associations with race, geospatial mapping demonstrated a discrete geographic shift in elevated RTI toward Black, underinsured patients living in inner urban communities. Affected neighborhoods could not be predicted quantitatively by local COVID-19 transmission activity or social vulnerability indices. CONCLUSIONS: This is the first United States institutional report to describe radiation therapy referral volume and interruption patterns during the year after pandemic onset. Patient referral volumes did not fully recover from an initial steep decline, but local RTI rates and associated risk factors remained mostly stable. Geospatial mapping suggested migration of RTI risk toward marginalized, minority-majority urban ZIP codes, which could not otherwise be predicted by neighborhood-level social vulnerability or pandemic activity. These findings signal that detailed localization of highest-risk communities could help focus radiation therapy access improvement strategies during and after public health emergencies. However, this will require replication to validate and broaden relevance to other settings.

Epidemiology and Clinical Features of COVID-19 among 4,015 Neonates in Iran: Results of the National Study from the Iranian Maternal and Neonatal Network.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on pregnant women and neonates in Iran. This retrospective study describes the national experience among neonates having suspected and confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection following hospital admission to examine the epidemiology, demographic, and clinical features. STUDY DESIGN: All nationwide cases of suspected and confirmed neonatal SARS-CoV-2 infection were drawn from the Iranian Maternal and Neonatal Network (IMaN) between February 2020 and February 2021. IMaN registers demographic, maternal, and neonatal health data throughout Iran. Statistical analysis of demographic, epidemiological, and clinical data were performed. RESULTS: There were 4,015 liveborn neonates having suspected or confirmed SARS-CoV-2 infection that fulfilled the study inclusion criteria identified in the IMaN registry from 187 hospitals throughout Iran. There were 1,392 (34.6%) neonates that were preterm, including 304 (7.6%) less than 32 weeks' gestation. Among the 2,567 newborns admitted to the hospital immediately after birth, the most common clinical problems were respiratory distress (1,095 cases; 42.6%), sepsis-like syndrome (355; 13.8%), and cyanosis (300 cases; 11.6%). Of 683 neonates transferred from another hospital, the most frequent problems were respiratory distress (388; 56.8%), sepsis-like syndrome (152; 22.2%), and cyanosis (134; 19.6%). Among 765 neonates discharged home after birth and subsequently admitted to the hospital, sepsis-like syndrome (244 cases; 31.8%), fever (210; 27.4%), and respiratory distress (185; 24.1%) were most frequent. A total of 2,331 (58%) of neonates required respiratory care, with 2,044 surviving and 287 having a neonatal death. Approximately 55% of surviving neonates received respiratory support, compared with 97% of neonates who expired. Laboratory abnormalities included elevations of white blood cell count, creatine phosphokinase, liver enzymes, and C-reactive protein. CONCLUSION: This report adds the national experience of Iran to the list of reports from multiple countries describing their experience with COVID-19 in neonates, demonstrating that newborns are not exempt from COVID-19-morbidity and mortality. KEY POINTS: · Most common clinical problem was respiratory distress.. · Sepsis-like syndrome was also frequently present.. · A total of 58% of all neonates required respiratory care..

SARS-CoV-2 placentitis, stillbirth, and maternal COVID-19 vaccination: clinical-pathologic correlations.

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death.

Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.

The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.

SARS-CoV-2 Placentitis, Stillbirth and Maternal COVID-19 Vaccination: Clinical-Pathological Correlations

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology findings present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect greater than 75% of the placenta, effectively rendering the placenta incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunological basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathological aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis and perinatal death.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury.

CONTEXT.­: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.­: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.­: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.­: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.­: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

Impact of the COVID-19 Pandemic on Canadian Radiation Oncology Practices.

PURPOSE: To survey Canadian radiation oncology (RO) practice leaders to determine the effect of the COVID-19 pandemic on radiation services and patient and staff issues in the early phase of the pandemic and 1 year later. METHODS AND MATERIALS: The RO leader (department or division head) from every Canadian cancer center with radiation services was identified. Two surveys were circulated to the identified leader via email from the Canadian Association of Radiation Oncology central office, using the SurveyMonkey survey tool: the first closed in June 2020 and the second (expanded) survey in June 2021, representing 2 points in time of the COVID-19 pandemic. Questions included patient volume, service interruptions and delays, and changes in scheduling and telemedicine use. Additional questions were included in the follow-up survey to determine further effects on disease presentation, volume, vaccination and access, and personnel issues. RESULTS: Telemedicine was widely adopted early in the pandemic and continued to be a common technique to communicate and connect with patients. Although many centers were deferring or delaying certain disease sites early in the pandemic, this was not as prevalent 1 year later. Reduced cancer screening and patients presenting with more advanced disease were concerns documented in the 2021 survey. A high level of concern regarding stress among health care professionals was identified. CONCLUSIONS: Canadian RO centers have faced numerous challenges during the COVID-19 pandemic but continued to provide timely and essential cancer care for patients with cancer. Future evaluation of RO center practices will be important to continue to document and address the effect of the COVID-19 pandemic on issues relevant to RO leaders, patients, and staff.

Demographic Factors Associated With Successful Telehealth Visits in Inflammatory Bowel Disease Patients.

BACKGROUND: This study evaluated synchronous audiovisual telehealth and audio-only visits for patients with inflammatory bowel disease (IBD) to determine frequency of successful telehealth visits and determine what factors increase the likelihood of completion. METHODS: Data were collected from March to July 2020 in a tertiary care adult IBD clinic that was transitioned to a fully telehealth model. A protocol for telehealth was implemented. A retrospective analysis was performed using electronic medical record (EMR) data. All patients were scheduled for video telehealth. If this failed, providers attempted to conduct the visit as audio only. RESULTS: Between March and July 2020, 2571 telehealth visits were scheduled for adult patients with IBD. Of these, 2498 (99%) were successfully completed by video or phone. Sixty percent were female, and the median age was 41 years. Eighty six percent of the population was white, 8% black, 2% other, and 4% were missing. Seventy-five percent had commercial insurance, 15% had Medicare, 5% had Medicaid, and 5% had other insurance. No significant factors were found for an attempted but completely failed visit. Using a multivariate logistic regression model, increasing age (odds ratio, 1.80; 95% CI, 1.55-2.08; P < 0.05), noncommercial insurance status (odds ratio, 1.89; 95% CI, 1.61-2.21; P < 0.05), and black race (odds ratio, 2.07; 95% CI, 1.38-3.08; P < 0.05) increased the likelihood of a video encounter failure. CONCLUSIONS: There is a high success rate for telehealth within an IBD population with defined clinic protocols. Certain patient characteristics such as age, race, and health insurance type increase the risk of failure of a video visit.

Variable Effect of the COVID-19 Pandemic on Radiation Oncology Practices in the United States.

PURPOSE: Early in the pandemic, the American Society for Radiation Oncology surveyed physician leaders at radiation oncology practices in the United States to understand how the field was responding to the outbreak of COVID-19. METHODS AND MATERIALS: Surveys were repeated at multiple points during the pandemic, with a response rate of 43% in April 2020 and 23% in January 2021. To our knowledge, this is the only longitudinal COVID-19 practice survey in oncology in the United States. RESULTS: The surveys indicate that patient access to essential radiation oncology services in the United States has been preserved throughout the COVID-19 pandemic. Safety protocols were universally adopted, telehealth was widely adopted and remains in use, and most clinics no longer deferred or postponed radiation treatments as of early 2021. Late-stage disease presentation, treatment interruptions, shortages of personal protective equipment, and vaccination barriers were reported significantly more at community-based practices than at academic practices, and rural practices appear to have faced increased obstacles. CONCLUSIONS: Our findings provide unique insights into the initial longitudinal effect of the COVID-19 pandemic on the delivery of radiation therapy in the United States. Downstream lessons in service adaptation and improvement can potentially be guided by formal concepts of resilience, which have been broadly embraced across the US economy.

Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy.

Stillbirth is a recently recognized complication of COVID-19 in pregnant women. Other congenitally transmitted infections from viruses, bacteria and parasites can cause stillbirth by infecting fetal organs following transplacental transmission of the agent from the maternal bloodstream. However, recent research on pregnant women with COVID-19 having stillbirths indicates that there is another mechanism of stillbirth that can occur in placentas infected with SARS-CoV-2. In these cases, viral infection of the placenta results in SARS-CoV-2 placentitis, a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, in some cases together with placental hemorrhage, thrombohematomas and villitis, result in severe and diffuse placental parenchymal destruction. This pathology can involve greater than one-half of the placental volume, averaging 77% in the largest study of 68 cases, effectively rendering the placenta incapable of performing its function of oxygenating the fetus. This destructive placental process can lead to stillbirth and neonatal death via malperfusion and placental insufficiency which is independent of fetal infection. Fetal autopsies show no evidence that direct infection of fetal organs is contributory. Because all mothers examined have been unvaccinated, maternal vaccination may prevent viremia and consequent placental infection.

Hofbauer Cells and COVID-19 in Pregnancy.

CONTEXT.­: SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. OBJECTIVE.­: To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. DESIGN.­: Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. RESULTS.­: Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. CONCLUSIONS.­: SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

Meta-analysis of the frequency of intrauterine growth restriction and preterm premature rupture of the membranes in pregnant women with COVID-19

The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pregnancy has yet to be determined. Some studies indicate that SARSCoV- 2 infection may be associated with a higher risk of adverse outcomes in pregnant women. Here, we performed a meta-analysis to estimate the frequency of intrauterine growth restriction (IUGR) and preterm premature rupture of the membranes (PPROM) in pregnant women with Coronavirus disease-2019 (COVID-19). A comprehensive search was performed in various databases, such as PubMed, Scopus, SciELO, MedRxiv, and Web of Science, to find all relevant studies published before 10 February 2021. Cross-sectional and consecutive case series reporting the pregnancy outcomes of COVID-19 were included. A total of 24 studies, including 8 studies on IUGR and 16 studies on PPROM, were selected. Pooled data showed that the frequencies of IUGR and PPROM in pregnant women with COVID-19 were 2.6% and 9.9%, respectively. Analyses stratified by ethnicity showed that the frequencies of IUGR in Asian and Caucasian COVID-19-infected pregnant women were 2.9% and 2.0%, respectively. Moreover, the frequencies of PPROM in Asian and Caucasian COVID-19-infected pregnant women were 10.2% and 5.8%, respectively. This meta-analysis showed that the frequencies of IUGR and PPROM in COVID-19-infected pregnant women were 2.6% and 9.9%, respectively. However, well-designed, large-scale and multicenter clinical studies are required to improve and validate these results.

A meta-analysis for the risk and prevalence of preeclampsia among pregnant women with COVID-19

Preeclampsia and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are both life-threatening disorders when they occur during pregnancy. They are similarly characterized by systemic immune activation and have a deleterious effect on maternal endothelial cells. During the coronavirus disease-2019 (COVID-19) pandemic, there were reports of preeclampsia or a preeclampsia-like syndrome occurring in pregnant women with SARS-CoV-2 infection. We performed a meta-analysis to estimate the risk and prevalence of preeclampsia and SARS-CoV-2 infection in pregnant women. A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure to identify all relevant studies published up to February 29, 2020. All studies that reported the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection were selected. A total of 10 case-control studies and 15 case series met our inclusion criteria. Pooled data revealed no significant difference between infected pregnant women and uninfected pregnant women for the risk of preeclampsia [odds ratio (OR)=1.676, 95% confidence interval (CI) 0.679-4.139, p=0.236]. The stratified analysis revealed significant risk in the infected Asian pregnant women (OR=2.637, 95% CI 1.030-6.747, p=0.043), but not Caucasian. The prevalence of preeclampsia was 8.2% (95% CI 0.057-0.117) in infected pregnant women with COVID-19 in the overall population. Its prevalence was highest in North America (10.7%), followed by Asian (7.9%), Caucasian (6.7%), European (4.9%), and West Asian (2.6%) infected pregnant women. Our pooled data showed that the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection was 8.2%. However, there was no increased risk of occurrence of preeclampsia among pregnant women with SARS-CoV-2 infection.

From ARDS to pulmonary fibrosis: the next phase of the COVID-19 pandemic?

While the coronavirus disease 19 (COVID-19) pandemic has transformed the medical and scientific communites since it was first reported in late 2019, we are only beginning to understand the chronic health burdens associated with this disease. Although COVID-19 is a multi-systemic disease, the lungs are the primary source of infection and injury, resulting in pneumonia and, in severe cases, acute respiratory distress syndrome (ARDS). Given that pulmonary fibrosis is a well-recognized sequela of ARDS, many have questioned whether COVID-19 survivors will face long-term pulmonary consequences. This review is aimed at integrating our understanding of the pathophysiologic mechanisms underlying fibroproliferative ARDS with our current knowledge of the pulmonary consequences of COVID-19 disease.

Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19.

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together-chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.