Placental Dysmaturity within a Large Cohort of SARS-CoV-2-Positive Pregnant Women

Background. From 25 February 2020 to 30 June 2021, experienced perinatal pathologists examined 975 placentas, macroscopically and microscopically, of SARS-CoV-2- positive mothers enrolled in a national prospective study, adopting the Amsterdam Consensus Statement protocol. The main results included the absence of specific pathological findings for SARS- CoV-2 infections, even though a high proportion of placentas showed signs of inflammation, including chorioamnionitis, funisitis, villitis, chronic histiocytic intervillositis, and fibrin deposition. In this further analysis, we focused our attention on placental maturity in SARS-CoV-2 infection as, according to recent literature, this feature has scarcely been considered. Method(s): All the maternal and placental data were collected by an online database system. Placental maturation was evaluated in 975 placentas from SARS-CoV-2 positive pregnant women according to the onset of maternal infection. Gestational age (GA) at the time of infection included placentas less than 14 weeks up to 41, but pathological analyses were carried out at delivery, in the third trimester. Parenchymal maturation was classified as follows: consistent with GA, immature, dysmature (also known as delayed villous maturation), and hypermature (or accelerated villous maturation). Incidence of maternal diabetes was also calculated as may affect placental maturation. Result(s): Among 975 placentas, 29 cases were missing (data not inserted by pathologists). On the whole, placental maturation was consistent with GA in 686 cases, immature in 77, hypermature in 48, and dysmature in 135. According to the gestational age at which SARS-CoV-2 infection was diagnosed, the results were as follows: - < 14 weeks: 27 placentas consistent with GA, 2 immature, 4 hypermature, 5 dysmature - 14-27 weeks: 95 placentas consistent with GA, 10 immature, 6 hypermature, 22 dysmature - >=28 weeks: 559 placentas consistent with GA, 65 immature, 38 hypermature, 107 dysmature Incidence of maternal diabetes was quite low in any kind of placental maturation, as reported below: - Immature: 1 / 77 (1.3%) - Consistent with GA: 8/686 (1.2%) - Hypermature: 2/48 (4.2%) - Dysmature: 4/135 (3%) Conclusion(s): In our population, 260/975 cases (26.7%) presented abnormal placental maturation, and among them, about a half (135/260), showed dysmaturity. According to maternal GA at onset of infection, anomalous development was mainly diagnosed after 28 weeks. Incidence of maternal diabetes was very low and unlikely correlated with the histological findings. If SARS-CoV-2 infection plays a role in determining placental abnormal maturation, or instead, if this anomaly may be a permissive feature to the virus, has yet to be investigated.

Acute respiratory distress syndrome in CoViD-19: correlations between clinical and histopathologic patterns

Background and Aim: We conducted a multidisciplinary study to investigate the correlations between clinical-laboratory-imaging data and histopathologic pulmonary patterns in patients died from severe CoViD-19. Materials and Methods: We analyzed lung autoptic tissue from consecutive CoViD-19 patients between February 29 and June 30, 2020. We considered three samples for each pulmonary lobe per patient. The pre-specified histopathological patterns were: exudative diffuse alveolar damage (DAD), proliferative DAD, organizing pneumonia, acute fibrinous organizing pneumonia, interstitial pneumonia, bronchopneumonia, arteriolar thrombi, intracapillary megakaryocytes, and areas of normal lung. Hierarchical cluster analysis was performed. Results: Among 92 autopsies, 48 patients had complete clinical data. Four clusters were identified. Length-of-stay in ICU and in hospital (p<0.0001), days on mechanical ventilation (p<0.0001), days on positive pressure airway (p<0.0001), mean positive endexpiratory pressure PEEP (p=0.007), PEEP x days on mechanical ventilation (p=0.003), PEEP x days on positive pressure airway (p=0.003), worst serum albumin (p=0.017), interleukin 6 (p=0.047), and kidney SOFA (p=0.001) differed between clusters. The cluster characterized by prevalence of exudative-proliferative DAD and lung megakaryocytosis had the greater difference from the others. Conclusions: Our research sheds light on the correlations between clinical-laboratory-imaging pictures and histopathologic findings, with clues on the impact of therapeutic strategies on lung tissues.

SARS-CoV-2 in the knee joint: a cadaver study

OBJECTIVES: Despite the considerable research efforts being made to learn more about COVID-19, little is known about the presence of SARS-CoV-2 genetic material in biological fluids other than respiratory droplets, blood, and feces. The aim of this post-mortem study was to assess the presence of SARS-CoV-2 RNA in the knee synovial fluid, synovial tissue, and bone tissue of COVID-19 patients in order to discover whether the joint is a possible route of transmission during orthopaedic surgical procedures, and clarify the possible role of SARS-CoV-2 as a directly arthritogenic virus. METHODS: Post-mortem synovial fluid, synovial tissue and bone tissue samples were collected from the knees of five patients who died of COVID-19 in our hospital between September and October 2020, and analysed for the presence of SARS-CoV-2 using a commercial real-time polymerase chain reaction (RT-PCR) panel. Quantitative RT-PCR was used to test post-mortem nasopharyngeal swabs of all of the patients. RESULTS: No SARS-CoV-2 RNA was detected in any of the knee samples, despite the positivity of the throat swab. CONCLUSIONS: Our findings indicate that SARS-CoV-2 was not detected in knee synovial fluid, synovial membrane or bone. This makes it unlikely that these are potential sources of contagion, and suggests that SARS-CoV-2 is not directly arthritogenic.

No evidence of SARS-CoV-2 in the knee joint: A cadaver study

Background: Despite the considerable research efforts being made to learn more about COVID-19, little is known about the presence of SARS-CoV-2 genetic material in biological fluids other than respiratory droplets, blood, and feces 1,2. In particular, little is known about the presence of SARS-CoV-2 in the joints either post mortem 3 or in vivo 4. To the best of our knowledge, only Lopéz-Gonzalez et al.5 have published a description of acute arthritides occurring during hospitalisation due to COVID-19, and they did not find any SARS-CoV-2 genetic material in the patients' synovial fluid samples. Objectives: The aim of this post mortem study was to assess the presence of SARS-CoV-2 RNA in the knee synovial fluid, synovial tissue, and bone tissue of COVID-19 patients in order to discover whether the joint is a possible route of transmission during orthopaedic surgical procedures, and clarify the possible role of SARS-CoV-2 as a directly arthritogenic virus. Methods: Post mortem synovial fluid, synovial tissue and bone tissue samples were collected from the knees of five patients who died of COVID-19 in our hospital between September and October 2020, and analysed for the presence of SARS-CoV-2 using a commercial real-time polymerase chain reaction (RT-PCR) panel. Quantitative RT-PCR was used to test post mortem nasopharyngeal swabs of all of the patients. Results: No SARS-CoV-2 RNA was detected in any of the knee samples, despite the positivity of the throat swab. Conclusion: Our findings indicate that SARS-CoV-2 was not detected in knee synovial fluid, synovial membrane or bone. Therefore, our results suggest that all healthcare professionals performing surgical procedures on the joints of COVID-19 patients are exposed to a risk of contagion due to exposure to respiratory droplets, blood and body fluids, but not to direct exposure to joint-or bone-related tissues. Furthermore, given that some case reports of arthritis in COVID-19 patients 5-8 show that it is possible that COVID-19 patients display viral-mediated arthralgias and arthritis, the absence of the virus in the knee highlighted by our study suggests that it is unlikely that SARS-CoV-2 has a direct inflammatory action on the joint, but it could induce an inflammation-related reaction, manifesting as a reactive arthritis 9.

Liver infection and COVID-19: the electron microscopy proof and revision of the literature.

OBJECTIVE: COVID-19, the newly emerging infectious disease, has been associated with acute liver injury, often related to progression to severe pneumonia. The association between moderate-severe liver injury and more severe clinical course of COVID-19 has suggested that liver injury is prevalent in severe than in mild cases of COVID-19, while no difference in liver involvement has been reported between survivors and non-survivors. The spectrum of liver involvement during COVID-19 ranges from an asymptomatic elevation of liver enzymes to severe hepatitis. Only rarely, cases with acute hepatitis have been reported in the absence of respiratory symptoms. Both epithelial and biliary cells possess the angiotensin-converting enzyme-2 receptors that SARS-CoV-2 uses to be internalized. However, to our knowledge, no ultrastructural identification of the virus in liver cells has been reported to date. Here we provide evidence of SARS-CoV-2 in the liver of two patients, a 34-year-old woman and a 60-year-old man with COVID-19. PATIENTS AND METHODS: We investigated two patients with COVID-19 showing several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. In both patients, we performed histological and ultrastructural examinations by liver biopsy. After two months, both patients were free of symptoms, and the SARS-CoV-2 infection had resolved. RESULTS: Liver biopsy histological and ultrastructural examination showed liver injury and several virions within cytoplasmic vacuoles of cholangiocytes and in endothelial cells of hepatic sinusoids. CONCLUSIONS: Although most studies in COVID-19 have been focused on the lungs, recently, cholestatic liver pathology has been introduced in the spectrum of pathological changes related to COVID-19. To the best of our knowledge, those presented in this paper are the first images of hepatic SARS-CoV-2 infected liver cells. Our findings suggest a role for cholangiocytes and biliary structures in the COVID-19.

Hypoalbuminemia in COVID-19: assessing the hypothesis for underlying pulmonary capillary leakage.

BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.