Bronchopneumonia with interstitial pneumonia in beef feedlot cattle: Characterization and laboratory investigation.

Bronchopneumonia with interstitial pneumonia (BIP) has been considered a variant of acute interstitial pneumonia (AIP) rather than a distinct disease. This study compared 18 BIP, 24 bronchopneumonia (BP), and 13 AIP cases in feedlot beef cattle. Grossly, BIP cases typically had cranioventral lung lesions of similar morphology and extent as BP cases, but the caudodorsal lung appeared overinflated, bulged on section, and had interlobular edema and emphysema. Gross diagnosis of BIP had 83% sensitivity and 73% specificity relative to histopathology. Histologic lesions of BIP in cranioventral areas were of chronic BP, while caudodorsal lesions included alveolar and bronchiolar damage and inflammation, interstitial hypercellularity, and multifocal hemorrhages. In BIP cases, cranioventral lung lesions were more chronic than caudodorsal lesions. Histologic scores and microbiology data were comparable in cranioventral lung of BIP versus BP cases and caudodorsal lung of BIP versus AIP cases, with differences reflecting a more chronic disease involving less virulent bacteria in BIP versus BP. Mycoplasma bovis infection was similarly frequent among groups, and a viral cause of BIP was not identified. Lesion morphology and similar blood cytokine concentrations among groups argued against sepsis as a cause of lung injury. Surfactant dysfunction was identified in BIP and BP, and was only partially the result of protein exudation. These and other findings establish BIP as a distinct condition in which chronic cranioventral BP precedes acute caudodorsal interstitial lung disease, supporting a role of chronic inflammation in heightened sensitivity to 3-methylindole or another lung toxicant.

SARS-CoV-2 viral replication persists in the human lung for several weeks after onset of symptomatic severe COVID-19 and is associated with attenuated pulmonary immunity and variant-specific clinical sequalae (preprint)

The immunopathogenesis of severe COVID-19 is incompletely understood. In contradistinction to the upper respiratory tract where replicating (culturable) SARS-CoV-2 is recoverable approximately ~ 4 to 8 days after symptom onset, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (the human lung). We undertook lung tissue sampling (needle biopsy), within ~2 hours of death, in 42 mechanically ventilated decedents during the Beta and Delta waves. Lung biopsy cores underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, immunohistochemistry and cell-based flow cytometry of deconstructed tissue. 38% (16/42) of patients had culturable virus in the lung (persisting for up to 4 weeks after symptom onset). This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced pulmonary pro-inflammatory response and variant-specific increased rates of bacterial bronchopneumonia and accelerated death. These findings question existing paradigms and suggest that in a subset of patients, concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response. Our findings have potential implications for the design of therapeutic interventional strategies and clinical management of severe COVID-19 disease.

Delayed Surgical Management of Acute Type A Aortic Dissection in a Patient with Recent COVID-19 Infection and Post-COVID-19 Bronchopneumonia-Case Report and Review of Literature.

Ever since it was first described in 1760, acute type A aortic dissection has created difficulties in its management. The recent COVID-19 pandemic revealed that extrapulmonary manifestations of this condition may occur, and recent reports suggested that aortic dissection may be amongst them since it shares a common physiopathology, that is, hyper-inflammatory syndrome. Cardiac surgery with cardiopulmonary bypass in the setting of COVID-19-positive patients carries a high risk of postoperative respiratory failure. While the vast majority accept that management of type A aortic dissection requires urgent surgery and central aortic therapy, there are some reports that advocate for delaying surgery. In this situation, the risk of aortic rupture must be balanced with the possible benefits of delaying urgent surgery. We present a case of acute type A dissection with COVID-19-associated bronchopneumonia successfully managed after delaying surgery for 6 days.

Mortality due to respiratory infections: an alert study before COVID-19 pandemic.

Objective: Respiratory tract infections remain a common problem in clinical practice with high morbidity and mortality worldwide. In Portugal, pneumonia was the third leading death cause in 2018. Due to COVID-19 pandemic, there is a growing concern about the burden of respiratory diseases and preventable risk factors. The present study started before the pandemic and its aim was to determine the occurrence of pneumonia/bronchopneumonia in a postmortem series and to characterize its circumstantial context. Methods: A retrospective anatomopathological study was performed on cases with acute pneumonia/bronchopneumonia at the Medicolegal Portuguese Institute (2011-2017). Results: In an autopsy series of 737 patients, 521 were male and 675 presented comorbidities. The mean age was 63.87 ± 19.8 years. The most common acquisition site was community (65.1%), as natural death (65.5%). Concerning the manner of death, most cases (48.0%) were sudden deaths, followed by accidents (29.2%). A statistically significant association was observed between the medicolegal etiology and the place of infection acquisition, with higher prevalence of natural obitus (91.0%) in community-acquired pneumonia/bronchopneumonia versus higher prevalence of violent obitus in hospital-acquired pneumonia/bronchopneumonia (82.1%) (p < 0.001). Conclusions: Forensic anatomopathological postmortem data may contribute to better understand community and hospital pulmonary infections.

Role of chest radiography in the diagnosis of pulmonary tuberculosis during nCovid19 pandemic.

Pulmonary tuberculosis and nCovid 19 share many common risk factors. nCovid19 may increase the risk to develop pulmonary tuberculosis. Pulmonary tuberculosis may precede, co-exist or follow nCovid19. Careful evaluation of chest radiography is useful to differentiate tuberculosis from nCovid19 bronchopneumonia. Symptoms of tuberculosis may be mistaken for long covid. A normal chest x ray in the absence of sputum production may help to rule out tuberculosis in such cases. All patients with nCovid19 bronchopneumonia should undergo a careful chest x ray evaluation for any lesions suggestive of tuberculosis. All patients with chest radiological abnormality should undergo sputum examination to rule tuberculosis as atypical radiological manifestations may be more common in patients with nCovid19. Symptoms, signs, clinical features and chest radiographic features of Pulmonary tuberculosis and nCovid19 bronchopneumonia may overlap in some cases. Correlation of chest radiographic findings with epidemiologic history, clinical presentation, and RT-PCR test results or in later stages antibody titres will help in confirming or excluding the diagnosis in suspected cases of nCovid19. In pulmonary tuberculosis definitive diagnosis should be established by bacteriological confirmation. Molecular diagnostic tools should be used to confirm or exclude tuberculosis in suspect cases as the results are rapid, accurate and reliable.

Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation (preprint)

COVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guerin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung SCV2 viral load and bronchopneumonia. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits immunoglobulin-producing plasma cells to the lung suggesting accelerated antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

The omicron (B.1.1.529) SARS-CoV-2 variant of concern does not readily infect Syrian hamsters (preprint)

The emergence of SARS-CoV-2 variants of concern (VoCs) has exacerbated the COVID-19 pandemic. End of November 2021, a new SARS-CoV-2 variant namely the omicron (B.1.1.529) emerged. Since this omicron variant is heavily mutated in the spike protein, WHO classified this variant as the 5th variant of concern (VoC). We previously demonstrated that the other SARS-CoV-2 VoCs replicate efficiently in Syrian hamsters, alike also the ancestral strains. We here wanted to explore the infectivity of the omicron variant in comparison to the ancestral D614G strain. Strikingly, in hamsters that had been infected with the omicron variant, a 3 log10 lower viral RNA load was detected in the lungs as compared to animals infected with D614G and no infectious virus was detectable in this organ. Moreover, histopathological examination of the lungs from omicron-infecetd hamsters revealed no signs of peri-bronchial inflammation or bronchopneumonia. Further experiments are needed to determine whether the omicron VoC replicates possibly more efficiently in the upper respiratory tract of hamsters than in their lungs.

Outpatient COVID-19 Pneumonia In Elderly Patients In Kazakhstan (preprint)

COVID pneumonia is difficult to manage in elderly patients over 65 years of age.The aim of the study was to determine the clinical features of the course of COVID pneumonia in a cohort of patients over 65 years old.Materials and methods: We observed patients with community-acquired pneumonia, of whom PCR positive for COVID were 33 patients, mean age 67.6 ± 12 years, men – 11, women – 22; 16 patients had no confirmed virus (COVID PCR negative), mean age 65.5 ± 8.2 years, 7 women and 9 men.Examination results: in the group of COVID patients, the disease more often proceeded according to the type of bilateral polysegmental pneumonia according to CT data, with severe monocytosis, с thrombocytosis and transient increase in creatinine, which required the appointment of intensive anticoagulant therapy. Arterial hypertension was observed in the majority of people. In the control group (PCR - ), pneumonia proceeded predominantly as bronchopneumonia, saturation indices were approximately the same in both groups. COVID patients had significantly higher levels of monocytes, blood platelets, CRP, creatinine levels, including arterial hypertension was more common. Conclusion: COVID pneumonia in elderly patients proceeds as multisegmented bilateral pneumonia with moderate disseminated intravascular coagulation syndrome, which is well controlled due to complex therapy with anticoagulants and antibiotics.

ACE2 Expression in Lungs of Severe COVID-19 Infection: A Study on Minimally Invasive Post- mortem Tissue Samples (preprint)

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Utility of CDC Screening Guidelines and Autopsy Findings in Identifying Decedents Who Die of SARS-CoV-2 Infection.

ABSTRACT: We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all "checklist-positive" decedents. Additional "checklist-negative" decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19-associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19-related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.

The Spectrum of Histopathologic Findings in Lungs of Patients With Fatal Coronavirus Disease 2019 (COVID-19) Infection.

CONTEXT.­: Respiratory failure appears to be the ultimate mechanism of death in most patients with severe coronavirus disease 2019 (COVID-19) infection. Studies of postmortem COVID-19 lungs largely report diffuse alveolar damage and capillary fibrin thrombi, but we have also observed other patterns. OBJECTIVE.­: To report demographic and radiographic features along with macroscopic, microscopic, and microbiologic postmortem lung findings in patients with COVID-19 infections. DESIGN.­: Patients with confirmed COVID-19 infection and postmortem examination (March 2020-May 2020) were included. Clinical findings were abstracted from medical records. Lungs were microscopically reviewed independently by 4 thoracic pathologists. Imaging studies were reviewed by a thoracic radiologist. RESULTS.­: Eight patients (7 men, 87.5%; median age, 79 years; range, 69-96 years) died within a median of 17 days (range, 6-100 days) from onset of symptoms. The median lung weight was 1220 g (range, 960-1760 g); consolidations were found in 5 patients (62.5%) and gross thromboemboli were noted in 1 patient (12.5%). Histologically, all patients had acute bronchopneumonia; 6 patients (75%) also had diffuse alveolar damage. Two patients (25%) had aspiration pneumonia in addition. Thromboemboli, usually scattered and rare, were identified in 5 patients (62.5%) in small vessels and in 2 of these patients also in pulmonary arteries. Four patients (50%) had perivascular chronic inflammation. Postmortem bacterial lung cultures were positive in 4 patients (50%). Imaging studies (available in 4 patients) were typical (n = 2, 50%), indeterminate (n = 1, 25%), or negative (n = 1, 25%) for COVID-19 infection. CONCLUSIONS.­: Our study shows that patients infected with COVID-19 not only have diffuse alveolar damage but also commonly have acute bronchopneumonia and aspiration pneumonia. These findings are important for management of these patients.

Particularities of the Evolution of SARS-CoV-2 Infection in Children (preprint)

IntroductionSARS-CoV-2 virus infection was first reported in China in late 2019 and has spread rapidly around the world. There is little information about the peculiarities of COVID-19 infection in children because the number of infected children was small, around 2% of all diseases.MethodsIn this retrospective study, we recruited 143 children infected with SARS-CoV-2 between March and October 2020, in Sibiu, Romania. RT-PCR tests, serum SARS-CoV-2 IgG/ IgM antibodies, lung radiography, biochemical and hematological tests were performed during the hospitalization.ResultsOf the 143 children selected in the study, 47.0% were male and 53% were female. At admission, all children tested positive for SARS-CoV-2, collecting nasopharyngeal exudate.Clinical manifestations included: cough in 75.52% of cases, fever in 55.94% of cases, nasal obstruction in 50.34% of cases, rhinorrhea in 38.46% of cases, muscle pain in 26.57% of cases, fatigue in 17.48% of cases, diarrhea and headache in 14.68% of cases. In 21 children (14,68%), the number of leukocytes was increased. In 38 cases (26,57%), the lung radiograph showed changes similar to bronchopneumonia, and the other cases did not have pulmonary changes. The persistence of the virus in the body of infected children is above the average reported in studies performed in adults, the virus being identified in the respiratory tract between 16 and 34 days. IgG class antibodies in patients' serum appeared between the 4th day of hospitalization and up to a maximum of 25 days, with a mean of 16.5 days.ConclusionThe persistence of the virus in the body of infected children is above the average reported in studies performed in adults, the virus being identified in the respiratory tract between 16 and 34 days. IgG class antibodies in patients' serum appeared within a mean of 16.5 days. All children were treated with symptomatic support without complications.

The study of Mycoplasma pneumonia infection among children with respiratory tract infection in hospital in Chengdu from 2014 to 2020 (preprint)

Aim: The hospitalized children with Mycoplasma pneumonia  (M. pneumonia) infection caused by respiratory tract infection in Chengdu were studied and analysis of the epidemiological characteristics was carried out to provide a theoretical basis for clinical diagnosis and treatment.Method: 22882 hospitalized children with respiratory tract infections between January 2014 and December 2020 were collected M. pneumonia IgM antibody was detected by indirect immunofluorescence method and passive agglutination method. Demographic characteristics, clinical diagnose and laboratory data of these children were analyzed.retrospectively.. Result : The 4213 specimens with M. pneumonia were tested positive, the total positive rate was18.41%(18.30% in male and 22.72% in female). Higher positive rates were found in female children,Look from the statistical analysis results, the consistency between the two sets of data is low（ｘ2=198.078、P＜0.01）. The results of different age patients with contrast different M. pneumonia infection degree were statistically significant（F=162.7532、P＜0.01）,there was higher M. pneumonia positive rate in Preschoolers and school-age children ,33.98% and 32.98%, respectively.The incidence rate of M. pneumonia in 2017 and 2019 was significantly higher than average （F=538.95, P＜0.01)The difference of incidence rate of M. pneumonia was not significant in different months in 2014, 2015 and 2020 (P>0.05). But the probability of M .pneumonia infection patients was much higher from April to May and September to October in2016,2017,2018 and 2019（P＜0.05）. There was no correlation about M. pneumonia infection with temperature and humidity( P＞0.05)，there was negative correlation with PM2.5（R=0.09362, P<0.01）and PM10.（R=0.1185, P<0.01）.There was no difference about constituent ratio of case of M. pneumonia infection between 2014 and 2019 (F=32.34,P>0.05).The  Common respiratory diseases of M. pneumonia infection, bronchopneumonia accounts for the highest proportion,followed the exacerbation of asthma and severe pneumonia.There was significantly difference about constituent ratio of case of M. pneumonia infection between in 2020 and in other years (F=159.35,P<0.01) .The Common respiratory diseases of M. pneumonia infection, bronchopneumonia accounts for the highest proportion,followed the acute bronchitis and exacerbation of asthma.Conclusion:The distribution and epidemiological trend of M. pneumonia in patients with respiratory tract infection showed the risk of inflammation was connected with the gender, age, year and month, no relationship with temperature and humidity in Chengdu,.Higher M. pneumonia positive rate was shown in the children with bronchial pneumonia and exacerbation of asthma.The prevention measures which controlled the COVID-19 disease had effectively controlled the infection rate of M. pneumonia.

Clinico-pathological features in fatal Covid-19 Infection: A Preliminary Experience of a Tertiary Care Centre in North India using Post-Mortem Minimally Invasive Tissue Biopsies (preprint)

Background: The Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than a 8.5million cases. Covid-19 infection primarily involves the lung with the severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single-center study we present the histopathological examination of 37 patients who died with complications of Covid-19. Methods: This was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken with the help of surface landmarking/ultrasonography guidance from lung, heart, liver, and kidneys; after obtaining ethical consent. The biopsy samples were then stained with haematoxylin and eosin stain. Immunohistochemistry (IHC) was performed using CD61 and CD163 in all lung cores. SARS-CoV-2 virus was detected using IHC with primary antibodies in selected samples. Details regarding demographics, clinical parameters, hospital course, treatment details, and laboratory investigations were also collected for clinical correlation. Results: A total of 37 patients underwent post-mortem minimally invasive tissue sampling. Mean age of the patients was 48.7years and 59.5% of them were males. Respiratory failure was the most common complication seen in 97.3%. Lung histopathology showed acute lung injury and diffuse alveolar damage in 78% of patients. Associated bronchopneumonia was seen in 37.5% of patients and scattered microthrombi were visualized in 21% of patients. Immunostaining with CD61 and CD163 highlighted megakaryocytes and increased macrophages in all samples. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of the renal biopsies but none of them showed evidence of microvascular thrombosis. 71% of the liver tissue cores showed evidence of Kupfer cell hyperplasia. 27.5% had evidence of submassive hepatic necrosis and 14% had features of acute on chronic liver failure. All the heart biopsies showed non-specific features such as hypertrophy with nucleomegaly with no evidence of myocardial necrosis in any of the samples. Conclusions The most common finding in this cohort is the diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase of DAD. Microvascular thrombi were rarely identified in the lung, liver and kidney. Substantial hepatocyte necrosis, hepatocyte degeneration, Kupffer cell hypertrophy, micro, and macrovesicular steatosis unrelated to microvascular thrombi suggests that liver might be a primary target of Covid-19. This study highlights the importance of MITS/B in better understanding the pathological changes associated with Covid-19.

Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia.

Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades. The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents. Bilateral diffuse alveolar damage (DAD) was found in all patients. Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients. A key finding was the presence of thrombotic/thromboembolic vascular occlusions. We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%). Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage. All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%). Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis. The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events. Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death.

Curbing the AI-induced enthusiasm in diagnosing COVID-19 on chest X-Rays: the present and the near-future (preprint)

In the current context of COVID-19 pandemic, a rapid and accessible screening tool based on image processing of chest X-rays (CXRs) using machine learning (ML) approaches would be much needed. Initially, we intended to create and validate an ML software solution able to discriminate on the basis of the CXR between SARS-CoV-2-induced bronchopneumonia and other bronchopneumonia etiologies. A systematic search of PubMed, Scopus and arXiv databases using the following search terms ["artificial intelligence" OR "deep learning" OR "neural networks"], AND ["COVID-19" OR "SARS-CoV-2"] AND ["chest X-ray" OR "CXR" OR "X-ray"] found 14 recent studies. Most of them declared to be able to confidently identify COVID-19 based on CXRs using deep neural networks. Firstly, weaknesses of artificial intelligence (AI) solutions were analyzed, tackling the issues with datasets (from both medical and technical points of view) and the vulnerability of used algorithms. Then, arguments were provided for why our study design is stronger and more realistic than the previously quoted papers, balancing the possible false expectations with facts. The authors consider that the potential of AI use in COVID-19 diagnosis on CXR is real. However, scientific community should be careful in interpreting statements, results and conclusions regarding AI use in imaging. It is therefore necessary to adopt standards for research and publication of data, because it seems that in the recent months scientific reality suffered manipulations and distortions. Also, a call for responsible approaches to the imaging methods in COVID-19 is raised. It seems mandatory to follow some rigorous approaches in order to provide with adequate results in daily routine. In addition, the authors intended to raise public awareness about the quality of AI protocols and algorithms and to encourage public sharing of as many CXR images with common quality standards.

STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters (preprint)

Introductory paragraphSince the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Chest CT imaging characteristics of COVID-19 pneumonia in preschool children: a retrospective study (preprint)

Background: Recently, the World Health Organization has declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern. So far, however, limited data are available for children. Therefore, we aimed to investigate the clinical and chest CT imaging characteristics of COVID-19 in preschool children.Methods: From January 26, 2020 to February 20, 2020, the clinical and initial chest CT imaging data of eight preschool children with laboratory-confirmed COVID-19 from two hospitals were retrospectively collected. The chest CT imaging characteristics, including the distribution, shape, and density of lesions, and the pleural effusion, pleural changes, and enlarged lymph nodes were evaluated. Results: Two cases (25%) were classified as mild type, and they showed no obvious abnormal CT findings or minimal pleural thickening on the right side. Five cases (62.5%) were classified as moderate type. Among these patients, one case showed consolidation located in the subpleural region of the right upper lobe, with thickening in the adjacent pleura; one case showed multiple consolidation and ground-glass opacities with blurry margins; one case displayed bronchial pneumonia-like changes in the left upper lobe; and two cases displayed asthmatic bronchitis-like changes. One case (12.5%) was classified as critical type and showed bronchial pneumonia-like changes in the bilateral lungs, presenting blurred and messy bilateral lung markings and multiple patchy shadows scattered along the lung markings with blurry margins.Conclusions: The chest CT findings of COVID-19 in preschool children are atypical and various. Accurate diagnosis requires a comprehensive evaluation of epidemiological, clinical, laboratory and CT imaging data. 

Pathological Study of the 2019 Novel Coronavirus Disease (COVID-19) through Post-Mortem Core Biopsies (preprint)

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.