Myocardial Infarction Following COVID-19 Vaccine Administration: Post Hoc, Ergo Propter Hoc?

Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50-76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events.

Death after the Administration of COVID-19 Vaccines Approved by EMA: Has a Causal Relationship Been Demonstrated?

More than eight billion doses of COVID-19 vaccines have been administered globally so far and 44.29% of people are fully vaccinated. Pre-authorization clinical trials were carried out and the safety of vaccines is still continuously monitored through post-commercialization surveillance. However, some people are afraid of vaccine side effects, claiming they could lead to death, and hesitate to get vaccinated. Herein, a literature review of COVID-19-vaccine-related deaths has been carried out according to the PRISMA standards to understand if there is a causal relationship between vaccination and death and to highlight the real extent of such events. There have been 55 cases of death after COVID-19 vaccination reported and a causal relationship has been excluded in 17 cases. In the remaining cases, the causal link between the vaccine and the death was not specified (8) or considered possible (15), probable (1), or very probable/demonstrated (14). The causes of deaths among these cases were: vaccine-induced immune thrombotic thrombocytopenia (VITT) (32), myocarditis (3), ADEM (1), myocardial infarction (1), and rhabdomyolysis (1). In such cases, the demonstration of a causal relationship is not obvious, and more studies, especially with post-mortem investigations, are needed to deepen understanding of the possible pathophysiological mechanisms of fatal vaccine side effects. In any event, given the scarcity of fatal cases, the benefits of vaccination outweigh the risks and the scientific community needs to be cohesive in asserting that vaccination is fundamental to containing the spread of SARS-CoV-2.

Not Only COVID-19: Prevalence and Management of Latent Mycobacterium Tuberculosis Infection in Three Penitentiary Facilities in Southern Italy.

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons.

Myocardial Pathology in COVID-19-Associated Cardiac Injury: A Systematic Review.

Coronavirus disease 2019 (COVID-19) can potentially affect all organs owing to the ubiquitous diffusion of the angiotensin-converting enzyme II (ACE2) receptor-binding protein. Indeed, the SARS-CoV-2 virus is capable of causing heart disease. This systematic review can offer a new perspective on the potential consequences of COVID-19 through an analysis of the current literature on cardiac involvement. This systematic review, conducted from March 2020 to July 2021, searched the current literature for postmortem findings in patients who were positive for SARS-CoV-2 by combining and meshing the terms "COVID-19", "postmortem", "autopsy", and "heart" in titles, abstracts, and keywords. The PubMed database was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sixteen papers met the inclusion criteria (case reports and series, original research, only English-written). A total of 209 patients were found (mean age (interquartile range (IQR)), 60.17 years (IQR, 54.75-70.75 years); 122 men (58.37%, ratio of men to women of 1:0.7%)). Each patient tested positive for SARS-CoV-2. Death was mainly the result of respiratory failure. The second most common cause of death was acute heart failure. Few patients specifically died of myocarditis. Variables such as pathological findings, immunohistochemical data, and previous clinical assessments were analyzed. Main cardiac pathological findings were cardiac dilatation, necrosis, lymphocytic infiltration of the myocardium, and small coronary vessel microthrombosis. Immunohistochemical analyses revealed an inflammatory state dominated by the constant presence of CD3+ and CD8+ cytotoxic lymphocytes and CD68+ macrophages. COVID-19 leads to a systemic inflammatory response and a constant prothrombotic state. The results of our systematic review suggest that SARS-CoV-2 was able to cause irreversible changes in several organs, including the heart; this is reflected by the increased cardiac risk in patients who survive COVID-19. Postmortem analysis (including autopsy, histologic, and immunohistochemical examination) is an indispensable tool to better understand pathological changes caused by emerging diseases such as COVID-19. Our results may provide more information on the involvement of the heart in COVID-19 patients.

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy.

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.

SARS-CoV-2 and the brain: A review of the current knowledge on neuropathology in COVID-19.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the new coronavirus responsible for the pandemic disease in the last year, is able to affect the central nervous system (CNS). Compared with its well-known pulmonary tropism and respiratory complications, little has been studied about SARS-CoV-2 neurotropism and pathogenesis of its neurological manifestations, but also about postmortem histopathological findings in the CNS of patients who died from COVID-19 (coronavirus disease 2019). We present a systematic review, carried out according to the Preferred Reporting Items for Systematic Review standards, of the neuropathological features of COVID-19. We found 21 scientific papers, the majority of which refer to postmortem examinations; the total amount of cases is 197. Hypoxic changes are the most frequently reported alteration of brain tissue, followed by ischemic and hemorrhagic lesions and reactive astrogliosis and microgliosis. These findings do not seem to be specific to SARS-CoV-2 infection, they are more likely because of systemic inflammation and coagulopathy caused by COVID-19. More studies are needed to confirm this hypothesis and to detect other possible alterations of neural tissue. Brain examination of patients dead from COVID-19 should be included in a protocol of standardized criteria to perform autopsies on these subjects.

Autopsy findings in COVID-19-related deaths: a literature review.

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements.