Placental SARS-CoV-2 distribution correlates with level of tissue oxygenation in COVID-19-associated necrotizing histiocytic intervillositis/perivillous fibrin deposition.

INTRODUCTION: Recent evidence supports the - rare - occurrence of vertical transplacental SARS-CoV-2 transmission. We previously determined that placental expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, and associated viral cell entry regulators is upregulated by hypoxia. In the present study, we utilized a clinically relevant model of SARS-CoV-2-associated chronic histiocytic intervillositis/massive perivillous fibrin deposition (CHIV/MPFVD) to test the hypothesis that placental hypoxia may facilitate placental SARS-CoV-2 infection. METHODS: We performed a comparative immunohistochemical and/or RNAscope in-situ hybridization analysis of carbonic anhydrase IX (CAIX, hypoxia marker), ACE2 and SARS-CoV-2 expression in free-floating versus fibrin-encased chorionic villi in a 20-weeks' gestation placenta with SARS-CoV-2-associated CHIV/MPVFD. RESULTS: The levels of CAIX and ACE2 immunoreactivity were significantly higher in trophoblastic cells of fibrin-encased villi than in those of free-floating villi, consistent with hypoxia-induced ACE2 upregulation. SARS-CoV-2 showed a similar preferential localization to trophoblastic cells of fibrin-encased villi. DISCUSSION: The localization of SARS-CoV-2 to hypoxic, fibrin-encased villi in this placenta with CHIV/MPVFD suggests placental infection and, therefore, transplacental SARS-CoV-2 transmission may be promoted by hypoxic conditions, mediated by ACE2 and similar hypoxia-sensitive viral cell entry mechanisms. Understanding of a causative link between placental hypoxia and SARS-CoV-2 transmittability may potentially lead to the development of alternative strategies for prevention of intrauterine COVID-19 transmission.

Clinicopathologic correlations of COVID-19-related cutaneous manifestations with special emphasis on histopathologic patterns.

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.

Eruptions and related clinical course among 296 hospitalized adults with confirmed COVID-19.

BACKGROUND: Limited information exists on mucocutaneous disease and its relation to course of COVID-19. OBJECTIVE: To estimate prevalence of mucocutaneous findings, characterize morphologic patterns, and describe relationship to course in hospitalized adults with COVID-19. METHODS: Prospective cohort study at 2 tertiary hospitals (Northwell Health) between May 11, 2020 and June 15, 2020. RESULTS: Among 296 hospitalized adults with COVID-19, 35 (11.8%) had at least 1 disease-related eruption. Patterns included ulcer (13/35, 37.1%), purpura (9/35, 25.7%), necrosis (5/35, 14.3%), nonspecific erythema (4/35, 11.4%), morbilliform eruption (4/35, 11.4%), pernio-like lesions (4/35, 11.4%), and vesicles (1/35, 2.9%). Patterns also showed anatomic site specificity. A greater proportion of patients with mucocutaneous findings used mechanical ventilation (61% vs 30%), used vasopressors (77% vs 33%), initiated dialysis (31% vs 9%), had thrombosis (17% vs 11%), and had in-hospital mortality (34% vs 12%) compared with those without mucocutaneous findings. Patients with mucocutaneous disease were more likely to use mechanical ventilation (adjusted prevalence ratio, 1.98; 95% confidence interval, 1.37-2.86); P < .001). Differences for other outcomes were attenuated after covariate adjustment and did not reach statistical significance. LIMITATIONS: Skin biopsies were not performed. CONCLUSIONS: Distinct mucocutaneous patterns were identified in hospitalized adults with COVID-19. Mucocutaneous disease may be linked to more severe clinical course.

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2.

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

Covid-19 and kidney injury: Pathophysiology and molecular mechanisms.

The novel coronavirus (SARS-CoV-2) has turned into a life-threatening pandemic disease (Covid-19). About 5% of patients with Covid-19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS-CoV-2-driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid-19 is necessary to develop management strategies and design effective therapies.