key: cord-318492-uu1p1rgi authors: Mansueto, Gelsomina title: COVID-19: Brief Check Point Through The Pathologist's Eye (autopsy archive) date: 2020-08-28 journal: Pathol Res Pract DOI: 10.1016/j.prp.2020.153195 sha: doc_id: 318492 cord_uid: uu1p1rgi During the COVID-19 pandemic many deaths have been caused, especially of patients with cardiovascular comorbidities and old age. Many questions have been asked and few simple answers have been given. The autopsy data are few and the aspects often observed are pulmonary diffuse alveolar damage (DAD), myocarditis, acute myocardial infarction (AMI), and disseminated intravascular coagulation (DIC); these aspects are not only in COVID-19 but also in other viral infections and associated sepsis. We must not lose sight of the fact that coronavirus with its pathological organ changes have already been described in the years preceding the pandemic. A few but long months have passed since the "unknown" and "doubtful" beginning of the pandemic induced by novel SARS-CoV-2 coronavirus (Severe Acute Respiratory Syndrome Coronavirus), named CoV-19. Many things have been said about this RNA virus which is responsible of acute respiratory distress syndrome (ARDS), cardiovascular and multiple organ failure till death. The same has been said about the structure of the virus and its ability to interfere with ACE2 receptor, with the heme synthesis, and with the immune system (1, 2, 3, 4, 5, 6) During the pandemic many deaths have been caused, especially of patients with cardiovascular comorbidities and old age (7, 8, 9) . The research has developed quantitative and qualitative serological tests, but the only reliable test was the nasopharyngeal swab that detects the virus when it is in replication phase; various therapies have been tried without a unique protocol or vaccine (10, 11, 12, 13) . Few autopsies were carried out for fear that the virulent agent could spread even more and for purely organizational reasons of the Italian autopsy rooms often not up to standard for infectious diseases. Many questions have been asked and few simple answers have been given. In this brief summary, I would like to induce the reader's reflection to the fact that coronavirus appears already before the pandemic in many texts of medical doctrine and that the pathological findings related to lung and multi-organ damage are described similar to those induced by other viral pathogens both from the same or different family. The autopsy pathologists can confirm that many deaths are due to complications from viral infections especially in subjects with comorbidities and they can also confirm that the aspects often observed are diffuse alveolar damage (DAD), cardiac damage from myocarditis or acute myocardial infarction (AMI), or even disseminated intra-vascular coagulation (DIC); these findings are also present in sepsis associated with various viral infections. (14, 15, 16, 17, 18, 19, 20) . My observation wants to induce the reader to focus on the common histopathological findings that are present in various viral infections, through the clarification of some salient points. The SARS-CoV-2 is an RNA virus of the coronaviridiae family, that infect epithelial cells of the upper respiratory tract, pulmonary pneumocytes and different epithelial cells types, endothelial cells of arteries and veins, smooth muscle cells, and immune cells The main mechanisms of interaction between SARS-CoV-2 and host are represented by the binding with angiotensin-converting enzyme 2 receptors (ACE2), the inhibition of heme synthesis through competition for the binding of porphyrin to iron, the interference in the native immune response which trigger the expression and activation of anti-viral mediators, recruitment of inflammatory cells, and the dysregulation of host DNA replication with transcription anomalies with triggering of the apoptotic pathways. The dysregulation of major homeostatic cell systems is responsible for primary lung injury with interstitial pneumonia and DAD, and is responsible for secondary heart and multi-organ damage and hyperagulability occurring mainly in the comorbid population (1, 2, 3, 4, 5, 6, 18, 21, 22) . Lung histopathology in CoV-19 disease is characterized by interstitial pneumonia, DAD, oedema, haemorrhage, multinucleated cells, exfoliation associated with or without viral inclusions and associated with reactive aspect of rehash as alveolar epithelial hyperplasia, fibrosis and emphysema. These aspects are described in books as well as in scientific articles and are frequent autoptic findings from direct alveolar demage by viruses, atypical agents and associated with functional vascular and cardiac imbalance (17, 19, 20, 23) . The microscopic observation provides a large spectrum of pathological findings that are not different or peculiar in many viral disease. In acute myocarditis which can be associated with SARS CoV-2, histology is characterized by lymphomonocytic infiltrate, interstitial oedema, myocytolisys, as observed in myocarditis which is associated with other etiological agents according to Dallas Criteria (24) . It is cause of sudden cardiac death (18, 25) , (Fig.2) . In AMI contraction band necrosis, areas of coagulative necrosis, edema and inflammatory infiltrate are the most characteristic aspect of hypoxia and of response within the timeframe from the beginning of the damage to the attempted resolution. Also, in this case the damage is common to many conditions including myocarditis by different viral agents and therefore not peculiar to the CoV-19 infection (26, 27) (Fig.2) . Finally, platelet and fibrin aggregation with micro-thrombotic J o u r n a l P r e -p r o o f events and diffuse vascular occlusion are responsible of poor prognosis to death in DIC entity. As resumed in table 2, many different viral and non-viral agents can be induce DIC (18, 26, 28, 29) , (Tab.2) (Fig.1,3) . Since other etiological agents may also be implicated in etiopathogenesis such as bacteria, it cannot be excluded that these pathologies may be determined by the superposition of the latter. Also in this case the differential diagnosis with identification of the agent is not easy since there is often no evidence of the virus in the myocardium and the morphological changes are the indirect result of the damage caused which manifests itself as inflammatory infiltrate in myocarditis, with necrosis in IMA and with increased state of coagulability and thrombosis in DIC. In the diagnosis of SARS-CoV-2 infection in cases with suspected clinical history and symptoms, the detection of the viral genome with PCR from the upper respiratory tract are currently the most valid. The test is primarily used to detect SARS-CoV-2 and to distinguish it from other viral agents responsible for similar types of pneumonia. In a correct differential diagnosis, first instance laboratory investigations must be accompanied above all to establish the patient's status as well as more specific laboratory investigations aimed at assessing the patient's pre-existing and recent status with the aim of excluding autoimmune, neoplastic or cardiovascular diseases. Regarding therapy, the respiratory support is considered for patients with hypoxemia, and there is no evidence to support a specific drug treatment and antiviral therapies against SARS-CoV-2 have a range of variability. However, the number of antivirals was reduced especially considering the side effects and drug interactions. There have been no changes in the use of corticosteroids, and the treatment plan only considers severe and critical cases. The immunotherapy is described as a therapeutic option (30, 31) . It is clear that both in cases of exclusive pulmonary involvement and in cases with multi-organ dysfunction, treatment must aim at improving the symptoms especially in the population with comorbidities, while active prevention must aim at safeguarding populations especially with comorbidities with the aim of controlling the possible complications that are the real responsible for the deaths. Only what is unknown is not understandable. Infections induced by viruses belonging to the SARS family have already been described although today we have called the new virus as SARS CoV-2 and a disease as COVID-19. In truth, for the first time we found ourselves in a pandemic and this scared us. The lack of autopsy findings did not allow us to evaluate with greater serenity what was happening and to understand that the specific pulmonary histological pictures and the secondary multiorgan damage in the patients with comorbidities were very similar to those already observed for other viral infections. Early knowledge of the changes in the organs would have speeded up the therapeutic approach by targeting complications rather than the viral agent as such. Infact pulmonary pathology with systemic complication can currently be considered not very different from those caused by other viruses which can lead to systemic failure with worsening up to death. Deaths are currently reduced due to early diagnosis in subjects at risk and for the use of generic antiviral and symptomatic therapies, however non-specific directed towards SARS-CoV-2, and diagnoses have increased thanks to the use of nasopharyngeal swabs that highlighted the presence of the virus even in younger asymptomatic subjects. This shows that although Sars-CoV-2 has high virulence, it behaves like other viruses, that in the population the symptoms occur in subjects often with comorbidities and that deaths are due to complications in the same way as it happens for other viral agents. Finally, the therapy for complications in the different cases has proved effective. Not applicable. The images from the forensic autopsy archive of Mansueto Gelsomina MD, PhD. Not applicable. The images from the forensic autopsy archive of doctor Mansueto. 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Areas of coagulative necrosis of the myocardium as initial hypoxic damage. a. HIV (E&E stain x20). b. Coronavirus (E&E stain x20)