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.

The COVID-19 Epidemic and the Prison System in Italy.

On March 7 and 8, 2020, revolts erupted in numerous Italian prisons after the announcement of regulations to contain the spread of COVID-19 in prisons. On April 2, 2020, the first prisoner died of COVID-19, and as of April 9, 58 prisoners and 178 penitentiary police officers have tested positive for the virus. The situation in Italy is made all the more dramatic because of endemic overcrowding: As of April 3, 2020, there were 56,830 prisoners in institutions meant for a maximum of 47,000 people, that is, an occupancy level of 121.75%. The Ministry of Justice and that of Health have established two strategies to limit the spread of COVID-19 in prisons: progressive isolation from the external world and adoption of practices to identify possible cases and to treat infected subjects. The legislation has significantly reduced individual rights in order to protect public health, but in the prison context, the limitations imposed do not guarantee the achievement of the goal of the entire legislation, which is to interrupt the chain of transmission of contagion. A prison cannot be entirely cut off, because its operations depend on people who come and go daily, The effects of these strategy are discussed critically.

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.

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 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.

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.

Regulation of Biobanks in Italy.

In Italy, a biobank is "a non-profit organization that must be officially recognized by the appropriate healthcare authority in the member states and must guarantee the treatment, distribution and conservation of biological material according to standards of quality and professionalism," but must not conserve material already regulated by specific laws, as is the case for organs for transplants, blood for transfusions, as well as embryos and gametes for medically assisted reproduction. The concept of biobank includes not only biological samples, but also the related database of clinical and personal information, from which the subject's lifestyle can be deduced. Unfortunately, at the moment, Italian law does not offer specific itineraries for achieving this legal status.

The COVID-19 Epidemic and the Prison System in Italy.

The Italian Ministry of Justice and that of Health have established two strategies to limit the spread of COVID-19 in prisons: progressive isolation from the external world and adoption of practices to identify possible cases and to treat infected subjects. After the announcement of regulations revolts erupted in numerous Italian prisons. The motivations and effects of these strategy are discussed critically into the search for a balance between the right to health and other rights of prisoners in Italian prisons with the problem of an occupancy level of 121.75%.

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.