Association of apolipoprotein E4 to the number of cerebral microbleeds in patients recovered from COVID-19

Background: COVID-19 has been associated with cerebral microbleeds (CMB). Previously, an association of ApoE4 with COVID-19 severity and CMBs in autopsy was found. In this study, we investigated if carrying the Apoe4 allele relates to the number of CMBs in magnetic resonance imaging (MRI) in patients recovered from COVID-19. Material(s) and Method(s): Adult patients recovered from COVID-19 and a control group without a history of COVID-19 was recruited. Exclusion criteria were major neurologic disease, developmental disability or pregnancy. The participants underwent brain MRI 6 months after infection, and a blinded neuroradiologist analyzed the findings. ApoE was genotyped using a microarray. Statistical analysis was performed using the statistical software R. A negative binomial model was chosen based on the distribution of CMBs. Result(s): Of the 216 subjects that underwent MRI, 168 consented to genetic testing, additionally 2 patients were excluded due to extensive CMBs and 1 due to diffuse axonal injury. We included 113 COVID-19 patients (49 ICU-treated, 29 ward-treated and 35 home-isolated) and 52 controls. The most prevalent comorbidities were hypertension, asthma and diabetes. CMBs was found in 47 subjects, with the number of CMBs ranging from 0 to 26. The ApoeE4 allele was carried by 37%, equally distributed among the groups. After adjustment, age (aRR = 1.06, p = 0.007) and COVID-19 (aRR = 2.59, p = 0.038) were independently associated with CMBs. The ApoE4 allele (aRR = 2.16, p = 0.07, CI = 0.94-5.10) was not significant. Conclusion(s): Age and previous COVID-19, but not possession of the ApoeE4 allele, were independently associated with the number of CMBs.

GENE ANALYSIS REVEALED THE USEFULNESS OF TRIPLE THERAPY WITH BARICITINIB, RITUXIMAB AND TACROLIMS FOR ANTI-MDA5 ANTIBODY POSITIVE DERMATOMYOSITIS (MDA5-DM)

BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.

Barotrauma in a Previously Healthy and Young COVID-19 Patient: an Autopsy Case Report

Introduction/Objective Since the emergence of a novel SARS-CoV-2 virus caused coronavirus disease 2019 (COVID-19), a great number of autopsy studies have been published. However, histopathologic studies focused on pulmonary barotrauma are very rare. Here we report an autopsy confined to the lungs on a young COVID-19 patient. Methods/Case Report The patient was a 37-year-old male, non-smoker, with no significant past medical history, and a body mass index of 24.1, who presented with shortness of breath and cough. A computerized tomography (CT) showed features of atypical pneumonia. The main abnormal laboratory data included elevated partial thromboplastin time, fibrinogen, and D-Dimer. The patient had been on mechanical ventilation for 35 days, and was complicated by recurrent pneumothoraces, hypotension, and worsening hypoxia. An autopsy limited to the lungs was performed after the patient expired. Grossly, the lungs showed increased weight, adhesions on visceral pleural surface, patchy consolidation and dilated subpleural cysts. Histological examination revealed cystically dilated/remodeled airspaces with extensive coagulative necrosis, focal alveolar hemorrhage and edema, focal confluent fibrosis, and subpleural blebs. Fresh fibrinous thrombi were seen in small- and medium-sized vessels. Viral cytopathic changes or significant inflammation were not observed. The findings in the lungs were consistent with barotrauma in COVID-19. Results (if a Case Study enter NA) NA. Conclusion This case demonstrates various histopathologic changes of the lungs in a previously healthy and young COVID-19 patient with prolonged hospital course of mechanical ventilation. The features of diffuse alveolar damage with inflammation usually seen in the early stage of barotrauma are not identified. Our findings in the lungs may represent the histopathologic characteristics of the later stage of barotrauma in COVID-19.

Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Sequence of actions for visualization of soft tissue hemorrhages/hematomas in elderly patients infected with SARS-CoV-2.

Aim. To determine ultrasound, computed tomography and angiographic image characteristics for soft tissue hemorrhages/hematomas, the sequence of using imaging methods in patients infected with SARS-CoV-2, to study the morphology of changes in soft tissues, to determine the essence of the concept and to develop treatment tactics for this complication of COVID-19. Material and methods. During 4 months of treatment of elderly patients (+60) infected with SARS-CoV-2, 40 patients were identified with soft tissue hemorrhages/hematomas, of which 26 (65%) patients with large hematomas (>10 cm in size and > 1000 ml in volume). The analysis of clinical and laboratory parameters, methods of instrumental diagnostics (ultrasound - 26 patients, CT - 10 patients, angiography - 9 patients, punctures - 6 patients) was carried out;autopsy material was studied in 11 cases. Results. Image characteristics of hemorrhages/hematomas of soft tissue density were obtained using modern instrumental methods, and the sequence of application of visualization methods was determined. A tactic for managing a patient with stopped and ongoing bleeding has been developed. The morphological substrate of hemorrhagic complications in a new viral infection was studied. All patients were treated with conservative and minimally invasive procedures (embolization, puncture with pressure bandage). 15 patients (57.7%) recovered, 11 patients (42.3%) died from the progression of COVID-19 complications. Conclusion. Comprehensive clinical and laboratory sequential instrumental diagnosis of soft tissue hemorrhages in COVID-19. Treatment should be conservative and significantly invasive. The use of the term "soft tissue hematoma" in SARS-CoV-2 infected patients is not a natural quality of the normal pathological process and should not be observed from our point of view.Copyright © 2022 Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.

The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

The application experience of focused ultrasound heart examination in patients with COVID-19 in Prone-position.

Aim of the study. To study the experience of using focused transthoracic echocardiography in patients with COVID-19 in prone position (fEchoPr) in intensive care units (ICU). Materials and methods. The retrospective observational study included 53 patients (period from 15 April to 31 December 2020). Inclusion criteria: confirmed diagnosis of COVID-19, availability of fEchoPr data, outcome certainty (discharge/death). We analyzed electronic medical records. The fEchoPr was performed in patients in the prone position with a bolster under the left side of the chest and left arm raised ('swimmer's position'). We assessed the systolic function of the right ventricle (RV) (tricuspid annular plane systolic excursion (TAPSE)), RV size, RV/LV ratio, systolic function of the left ventricle (LV) (left ventricular outflow tract velocity time integral. (LVOT VTI)), and pulmonary hypertension (PH) (tricuspid regurgitation peak gradient (PGTR). Depending on the results, the patients were divided into 2 groups: informative (+fEchoPr) and non-informative (-fEchoPr) examinations. Results. There was no statistically significant difference in the groups (+fEcho n = 35 vs -fEcho n = 18) by age (65.6 +/- 15.3 vs 60.2 +/- 15.8, p > 0.05), by gender (male: 23 (65.7%) vs 14 (77.8%), p > 0.05), by body mass index (31.3 +/- 5.3 kg/m2 vs 29.5 +/- 5.4 kg/m2, p > 0.05), by mechanical ventilation support (24 (68.6%) vs 17 (94.4%), p = 0.074), by NEWS scale indicators (6.9 +/- 3.7 vs 8.5 +/- 3.5 points), by mortality (82.8% vs 94.4%, p > 0.05). Correlation analysis revealed a moderate inverse relationship between being on mechanical ventilation and the informative value of the study (Spearman's r = -0.30 at p = 0.033). In the +fEchoPr group, the correct measurement of TAPSE and RV/LV was carried out in 100%: a decrease in RV systolic function was recorded in 5 patients (14%), expansion of the RV in 13 patients (37%). Signs of PH were detected in 11 patients (31%), PGTR could not be measured in 10 patients (28%). LV systolic dysfunction was detected in 7 patients (20%). No pathology was detected in 16 patients (46%). One patient was diagnosed with infective endocarditis of native mitral valve, which was later confirmed by autopsy. Conclusion. In 66% of cases, fEchoPr examinations were informative, especially in terms of assessing the state of the right heart. fEchoPr examination is an affordable, valid and reproducible method to assess and monitor the state of the heart in ICU patients.Copyright © 2021 VIDAR Publishing House. All Rights Reserved.

Macerated stillbirth

Stillbirth is defined as the birth of a viable baby without signs of life. They account for more than 2.5 million intrauterine deaths per year worldwide and are associated with a number of risk factors, the most important of which are maternal and placental factors. Autopsy provides information that may be of use in determining time since death, gestational age of the fetus, mode of death, cause of fetal demise, and the likelihood of recurrence. The format of the autopsy is guided by parental consent, but even when consent is limited, valuable information may be obtained by careful consideration of antemortem test results, imaging, and genetic testing. Where there is a delay between death and delivery, fetuses are affected by maceration, which may increase the technical complexity of the autopsy and impart a number of artefactual changes, which should not be misinterpreted as genuine pathology. The most common pathologies encountered at autopsy are placental abnormalities, changes related to maternal disorders, malformations, and central nervous system pathology. © Springer Nature Switzerland AG 2022. All rights reserved.

Leading Pathogens Involved in Co-Infection and Super-Infection with COVID-19: Forensic Medicine Considerations after a Systematic Review and Meta-Analysis.

The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis, treatment and prognosis of the disease. This is also a challenge for forensic pathologists, who may come across cases where the presence of co-infection or over-infection is suspected or confirmed, and it is important that they take this into account when determining the cause of death. The aim of this systematic review is to analyse the prevalence of each specific pathogen co-infecting or over-infecting patients with SARS-CoV-2 infection. In total, 575 studies were selected from the Scopus and Pub-Med online databases and 8 studies were included in a meta-analysis. Male gender, advanced age and nursing home care are risk factors associated with the development of co-infection, whereas age, tachypnoea, hypoxaemia and bacterial infection are predictors of mortality. Overall, however, having a SARS-CoV-2 infection does not represent a real risk for the development of co-infections/super-infections.

Cilia impairment in bronchial epithelial cells detected in autopsy material of SARS-CoV-2-infected patient.

Recent studies indicate that cilia impairment, accompanied by the axonema loss and the basal body misorientation, is a common pathological feature of SARS-CoV-2-infected bronchial epithelial cells. However, these data were obtained using either cultured cells, or animal models, while in human postmortem material, cilia impairment has not been described yet. Here, we present direct observation of cilia impairment in SARS-CoV-2-infected bronchial epithelial cells using transmission electron microscopy of the autopsy material. We were able to observe only single infected cells with cilia impairment in one of twelve examined specimens, while the large number of desquamated bronchial epithelial cells with undisturbed ciliary layer was visible in the bronchial lumens. Thus, it seems that in the lungs of infected patients, the majority of bronchial cells do not die as a direct result of infection, which may explain the rarity of this finding in the autopsy material.

Morphologic Findings in the Cerebral Cortex in COVID-19: Association of Microglial Changes with Clinical and Demographic Variables.

Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = -0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node.

AIMS: The identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this disease; however, only a limited number of case series have focused on lymphoid or haematopoietic tissues. METHODS: BM and lymph node (LN) specimens were obtained from adult autopsies performed between 1 April 2020 and 1 June 2020, for which the decedent had tested positive for SARS-CoV-2. Tissue sections (H&E, CD3, CD20, CD21, CD138, CD163, MUM1, kappa/lambda light chains in situ hybridisation) were examined by two haematopathologists, who recorded morphological features in a blinded fashion. Haemophagocytic lymphohistiocytosis (HLH) was assessed based on HLH 2004 criteria. RESULTS: The BM demonstrated a haemophagocytic pattern in 9 out of 25 patients (36%). The HLH pattern was associated with longer hospitalisation, BM plasmacytosis, LN follicular hyperplasia and lower aspartate aminotransferase (AST), as well as ferritin at demise. LN examination showed increased plasmacytoid cells in 20 of 25 patients (80%). This pattern was associated with a low absolute monocyte count at diagnosis, lower white cell count and lower absolute neutrophil count at demise, and lower ferritin and AST at demise. CONCLUSIONS: Autopsy results demonstrate distinct morphological patterns in BM, with or without haemophagocytic macrophages, and in LN, with or without increased plasmacytoid cells. Since only a minority of patients met diagnostic criteria for HLH, the observed BM haemophagocytic macrophages may be more indicative of an overall inflammatory state.

A fatal case of paediatric post-traumatic pyomyositis.

A 6-year-old girl was brought to the emergency department with a history of an accidental fall a few days earlier. She presented with a fever, cough and constipation. Sars-CoV-2 infection being suspected, she was transferred to a paediatric facility for Covid-positive patients. During the diagnostic process, the clinical picture suddenly deteriorated with the development of bradycardia, tachypnea and altered sensorium. Despite cardiopulmonary resuscitation attempts, the child died about 16 hours after admission to the emergency department. A judicial forensic autopsy was performed that concluded that her death was due to multiple acute pulmonary, cardiac and renal infarctions secondary to septic thromboembolism in the course of post-traumatic bacterial necrotizing pyomyositis of the right ileo-psoas muscle.

Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.

Diffuse Alveolar Damage in COVID-19 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the cause of the recent pandemic, with deaths worldwide. Diffuse alveolar damage (DAD) was a universal finding in these COVID-19-related deaths. We present here a case of a COVID-19 infected pregnant woman dying from DAD, confirmed on histopathologic examination of the lungs on autopsy. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Lung pathology

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

Clinical and laboratory manifestations and pathological anatomical picture of a severe course of a new coronavirus infection COVID-19 with a fatal outcome

Aim - to study the clinical and laboratory manifestations of a severe course of COVID-19 in a lethal outcome with an assessment of the pathomorphological picture based on autopsy material. Material and methods. A retrospective analysis of demographic, clinical and laboratory parameters, as well as the results of a pathoanatomical study of 54 patients with severe COVID-19 who died in the intensive care unit, was carried out. Results. Among the patients included in the study, women and men were equally divided. The mean age was 73.1+/-1.86 years (median 73 years). An increase in body temperature above 38 degreeS was observed in 81.5% of cases, weakness - in 70.4%, dry cough - in 46.3%, a feeling of lack of air - in 46.3%, muscle pain - in 40.7%. The volume of lung damage by the type of bilateral polysegmental pneumonia with areas of compaction of the type of "frosted glasses" and consolidation was more than 75.0% and was determined in 68.5% of patients. Concomitant diseases were detected in 94.4% of patients. It was found that all patients had a pronounced systemic inflammatory response, as evidenced by an increase in the level of C-reactive protein and procalcitonin in all patients. A decrease in albumin levels was observed in 88.9% of cases. A hypercoagulable shift with intravascular coagulation was noted. Morphological studies revealed damage to the lungs, liver, kidneys and pancreas with the development of thrombovascular changes. Conclusion. A severe course of COVID-19 with a fatal outcome was observed in older patients with clinical, radiological and laboratory manifestations of a systemic inflammatory response, which was accompanied by damage to various organs and systems.Copyright © Authors, 2022.

Analysis of deaths during the first wave of a new coronavirus infection - COVID-19

The aim - study the main causes and factors that led to the death of patients with pneumonia from a new coronavirus infection (COVID-19) in a hospital setting. Material and methods. Analysis of 84 case histories with fatal outcomes, as well as postmortem examination of 6 deceased patients. Results and discussion. Comparative analysis of overall mortality rates by nosology among the population for the period 2019-2020 (n=33 537;36 299) shows that in 2020 the number of patients who died from respiratory diseases increased 2.1 times or 106%, from infectious and parasitic diseases - 1.3 times or 30.8%. The first case of infection with a new coronavirus infection (COVID-19) among citizens of the Republic of Tajikistan was registered on April 30, 2020, it was then that a quarantine restrictions was announced in the country. The peak of infection in Tajikistan fell in mid-May and the first ten days of June 2020, when from 80 to 210 patients were registered per day. In Tajikistan, since January 10, 2021, no cases of COVID-19 have been officially registered. As of January 30, 2021, the number of people infected with COVID-19 in the country was 13 308, of which 13 218 (99.3%) people were cured, 90 (0.68%) people died. The number of cases of pneumonia in the first 10 months of 2020 compared to 2019 increased from 12 802 to 18 504 people, or by 5702, and the number of deaths - from 129 to 291, that is, 2.3 times or 125.6%. At the same time, 10 606 cases of COVID-19 associated with pneumonia were registered in Tajikistan during this period, which amounted to 57.3% of the total number of cases. An analysis of the history of the deceased showed that in 4.3% of cases the age of the deceased was from 30 to 39 years, in 30.4% - from 40 to 60 years and in 65.3% - over 61 years. Conclusion. The analysis of deaths among the population of Tajikistan shows that in 2020 there was an increase in the mortality rate, the incidence of seasonal pneumonia and the number of patients with COVID-19 associated with pneumonia.Copyright © 2021 Sovero Press Publishing House. All rights reserved.

Virological Investigation in Synanthropic Rodents in North Italy

Intro: Several rodents, including mice and the brown rat, are synanthropic animals usually found in rural and urban environments in contact with other animals and humans. Rodents are natural reservoirs of infectious agents and could harbour a plethora of zoonotic pathogens of public health importance. Taking advantage of a parallel study on presence and distribution of Hantaviruses, we aimed to investigate the occurrence in mice of other viruses with zoonotic or economic impact. Method(s): From May to July 2022, 41 mice (Mus domesticus) were captured and killed by using baited snap traps in 13 selected cattle, goat and poultry farms located in the Piedmont region. Gut and lung samples were homogenised and tested by PCR methods for pan-Coronavirus (CoV) and SARS-CoV-2, pan-Pestivirus, Mammalian orthoreoviruses, Canine Distemper virus (CDV), Flaviviruses, Influenza A (IAV) and D (IDV) viruses. Finding(s): All captured animals did not present at necropsy lesions related to infectious diseases. Virological investigations detected the presence of CoV in six mice. By sequencing Rodent CoVs was identified in two samples (four more pending). Mammalian orthoreovirus was detected in nine animals and typing and characterization are in progress. One mouse, captured in a bovine farm, tested slightly positive for IDV and confirmation of positivity is in progress by complete sequencing with NGS approach. All samples were negative for Flaviviruses, IAV, CDV, pan-Pestivirus and SARS-CoV-2. Conclusion(s): Rodents are well adapted to a wide range of habitats, including peri-urban and rural environments, where they benefit from human activities. These results, although preliminary, underline the importance of enhancing surveillance in rodents in anthropized areas to better assess the presence of zoonotic agents and the potential risk of transmission.Copyright © 2023

Covid-19, HLA, and race common link: A novel hypothesis.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accountable for the coronavirus disease 2019 (Covid-19) prompted a catastrophic pandemic striking millions of people with diverse presentations, from asymptomatic to severe, potentially lethal disease requiring unprecedented levels of specialized care and extraordinary resources that have overwhelmed healthcare systems around the world. In this detailed communication we postulating a novel hypothesis, based on the viral replication and transplantation immunology. This based on reviewing published journal articles and text book chapters to account for variable mortality and degrees of morbidity among various race and origins. Homo sapiens evolution over millions of years, for that the matter the origin of any biologic form of life form initiated by microorganisms. The entire body of a human has several millions of bacterial and viral genomes incorporated over millions of years. Perhaps the answer or a clue lies how compatible a foreign genomic sequence fits into three billion copies of human genome.