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.

What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?

Pulmonary damage in SARS-CoV-2 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis. In addition, nosocomial bacterial superinfections and ventilator-induced lung injury (VILI) are likely to occur. The SARS-CoV-2 Omicron variant have manifested itself as a more diffusive virus which mainly affects the upper airways, such as the nose and pharynx. The mechanism leading to a lung injury with a complex clinical course for the Omicron SARS-CoV-2 variant remains unclear. A key question is whether the organ damage is due to direct organ targeting of the virus or downstream effects such as an altered immune response. An immune escape process of Omicron variant is being studied, which could lead to prolonged viral shedding and increase hospitalization times in patients with comorbidities, with an increased risk of pulmonary co-infections/superinfections and organ damage. This brief commentary reports the current knowledge on the Omicron variant and provides some useful suggestions to the scientific community.

The State of Play on COVID-19 Vaccination in Pregnant and Breastfeeding Women: Recommendations, Legal Protection, Ethical Issues and Controversies in Italy.

To date, extensive research has been conducted on vaccination against COVID-19 during pregnancy to verify the safety and efficacy of the vaccines, despite the fact that pregnant women were excluded from the initial clinical trials. The ever-increasing number of scientific publications has confirmed the absence of biological mechanisms associating mRNA vaccines with adverse effects in pregnancy and breastfeeding, although few studies have been carried out on their effect on fertility. While the Italian legal system provides for maternity protection measures and indemnity for vaccination damages pursuant to law no. 210/1992, it is not exempt from controversy. This contribution describes the state of play on COVID-19 vaccination in pregnant and lactating women, including: current recommendations for pregnant and lactating women; ethical issues related to vaccination hesitancy among pregnant women; the legislative paradox whereby sanctions may be imposed on women in certain professional categories who refuse vaccination because they are pregnant; and the possible legal consequences in the event of harm to the unborn child due to vaccination. All of this is considered in accordance with the principles of medical ethics, taking into account the national legislation.

Multiple sites of thrombosis without thrombocytopenia after a second dose of Pfizer-BioNTech COVID-19 vaccine.

In the current international scientific panorama, rare cases of venous thrombotic complications following mRNA vaccine administration have been reported, consisting mainly of cerebral sinus thromboses and acute venous thromboembolism. The present paper describes the case of a 75-year-old woman in good health who developed cerebral venous thrombosis, deep venous thrombosis, and bilateral pulmonary emboli after receiving a second dose of Pfizer-BioNTech COVID-19 vaccine. A series of laboratory tests performed during hospitalization yielded interesting results, allowing us to exclude thrombophilic risk factors and to certify the absence of thrombocytopenia in the patient. Although COVID-19 vaccination is the most important tool in stopping the pandemic, pharmacovigilance is crucial for detecting potential multisystem thrombotic events, even for mRNA vaccines.

The Network of Services for COVID-19 Vaccination in Persons With Mental Disorders: The Italian Social Health System, Its Organization, and Bioethical Issues.

The adoption of restrictive measures aimed at curtailing the spread of SARS-CoV2 has had a harmful impact on socio-affective relationships, while limiting the scope of interventions and activities to promote social inclusion, with considerable negative repercussions for patients with mental disorders. Vaccination has been and will continue to be a valid tool to overcome the barriers of social isolation and to protect the health of this category of patients. In this paper we present an overview of the Italian network of social and healthcare services for COVID-19 vaccination among patients with mental disorders. Some aspects of medical ethics are discussed in order to share good practices for improving the health of this vulnerable group of people. We then consider the measures implemented by the health system in Italy to deal with the phenomenon of vaccine hesitancy before addressing the issue of autonomy and restricted access to vaccination points. Finally, we illustrate some of the perspectives already adopted by the Italian system, which may be useful to the global scientific community.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

COVID-19 Pulmonary Pathology, Ventilator-Induced Lung Injury (VILI), or Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)? Healthcare Considerations Arising From an Autopsy Case and Miny-Review.

Acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) is a serious complication that requires early recognition. Autopsy reports or biopsies of the lungs in patients with COVID-19 revealed diffuse alveolar damage (DAD) at different stages; the fibrotic phase is usually associated with long-standing severe disease. Care management of hospitalized patients is not easy, given that the risk of incurring a ventilator-induced lung injury (VILI) is high. Additionally, if the patient develops nosocomial infections, sepsis-induced ARDS should be considered in the study of the pathophysiological processes. We present an autopsy case of a hospitalized patient whose death was linked to COVID-19 infection, with the histopathological pattern of advanced pulmonary fibrosis. After prolonged use of non-invasive and invasive ventilation, the patient developed polymicrobial superinfection oh the lungs. After analyzing the individual's clinical history and pulmonary anatomopathological findings, we consider healthcare issues that should lead to an improvement in diagnosis and to more adequate standards of care management among health professionals.

Informed Consent and Protection of Personal Data in Genetic Research on COVID-19.

The particular characteristics of COVID-19 demand the careful biomedical study of samples from patients who have shown different symptomatology, in order to understand the genetic foundations of its phenotypic expression. Research on genetic material from COVID-19 patients is indispensable for understanding the biological bases for its varied clinical manifestations. The issue of "informed consent" constitutes the crux of the problem in regulating research biobanks, because it concerns the relationship between the person and the parts separated from the body. There are several consensus models that can be adopted, varying from quite restricted models of specific informed consent to forms that allow very broad authorization (open consent). Our current understanding of COVID-19 is incomplete. Thus, we cannot plan, with precision, the research to be conducted on biological samples that have been, or will be, collected from patients infected by the novel coronavirus. Therefore, we suggest utilizing the "participation pact" between researchers and donors, based on a new form of participation in research, which offers a choice based on the principles of solidarity and reciprocity, which represent the communication of "values". In the last part of this paper, the general data protection regulation concerning the matter is discussed. The treatment of personal data must be performed with explicit goals, and donors must be provided with a clear, transparent explanation of the methods, goals and time of storage. The data must not be provided to unauthorized subjects. In conclusion, open informed consent forms will be necessary for research on individual patients and on populations.

Electromyoneurography and laboratory findings in a case of Guillain-Barré syndrome after second dose of Pfizer COVID-19 vaccine.

Guillain-Barre syndrome (GBS) is an acute immune-mediated disease of the peripheral nerves and nerve roots (polyradiculoneuropathy) that is usually elicited by various infections. We present a case of GBS after receiving the second dose of Pfizer-COVID 19 vaccine. Diagnosis was made after performing an accurate clinical examination, electromyoneurography and laboratory tests. In particular, anti-ganglioside antibodies have tested positive. During this pandemic with ongoing worldwide mass vaccination campaign, it is critically important for clinicians to rapidly recognize neurological complications or other side effects associated with COVID-19 vaccination.

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1ß, IL-6, IL-15 and TNF-α.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1ß, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1ß in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Legal and Ethical Issues Regarding Minors in the Italian Coronavirus Flu Emergency.

On February 21, 2020, Italy became one of the countries hit by an epidemic of the new coronavirus that causes "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). Even a month before that, however, the Italian government began issuing a series of decrees and ordinances aimed at the containment of the virus in Italy, the first of them on January 25, 2020. The COVID 19 infection has been faced as an epidemic through measures to enforce a high degree of isolation. These regulations hold for minors, as well, with consequent difficulties for this age group. While at the moment young people appear to be the least vulnerable to the severe complications of COVID 19, the psychological problems that may be brought on by pandemic-related restrictions should be taken into serious consideration.

Histopathology of COVID-19 pneumonia in two non-oncological, non-hospitalised cases as a reliable diagnostic benchmark.

In lung cancer patients infected with COVID-19, pathological features are not easy to distinguish. This report presents detailed histopathological findings in two non-neoplastic subjects whose out-of-hospital deaths were caused by COVID-19 infection. These 'pure' cases differ in the time of presentation of symptoms, the phase of lung anatomopathological patterns (acute lung injury versus diffuse alveolar damage) and the mechanism of death. The results provide a valid diagnostic benchmark for evaluating the evolution of COVID-19 pneumonia.

SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns.

"Severe acute respiratory syndrome" (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.