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• Pathologists in the era of COVID-19: back to autopsy.
  Franca Di Nuovo, Monica Onorati and Marta Nicola
  Published on: 8 November 2020
• Hic est locus ubi mors gaudet succurrere vitae
  Arianna Giorgetti, Raffaele Giorgetti
  Published on: 4 May 2020
• COVID-19 infection: "high risk to an individual but a low risk to the community"?
  Arnaldo Carbone, Vincenzo Arena
  Published on: 20 April 2020

• Published on: 8 November 2020

  Pathologists in the era of COVID-19: back to autopsy.

  • Franca Di Nuovo, Pathologist Asst Rhodense, Garbagnate Milanese, Italy
  • Other Contributors:
    • Monica Onorati, Pathologist
    • Marta Nicola, Pathologist

  Dear Editor,
  before COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness,...

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  Dear Editor,
  before COVID-19, in the era of targeted therapies, pathologists played a cornerstone role in providing information especially about cancer diagnoses.1 Therefore, scientific community felt that autopsies were out-dated. Now, in this emerging reality, we are assisting to the transformation of the pathologist’s role: instead of proceeding to the “future” of molecular diagnosis we are going back to the “past” of our “noir” connotation. This negative meaning was linked, in the popular culture, to frequent post-mortem examinations performed by pathologist forgetting the paramount value of this medical procedure in explaining pathogenetic mechanisms of all diseases.2 During COVID-19 pandemia, Italian Hospitals changed their usual health department strategy. Hospital Governments strengthened intensive care units and lung units and decreased surgical activities. Pathologists’ role shifted from microscopic diagnosis back to the original mortuary role, setting aside optical microscope, the principal pathologist’s tool, and leaving space to necropsy activity with management of dead bodies by mortuary staff and pathologists in the perspective of threat of transmission of SARS-CoV-2.2 For this reason, Government has promptly implemented extraordinary and detailed measures to restrict viral spread from this source.3 In Italy, pathologists fill in death certificate, a legal instrument and a permanent record of an individual’s death, that requires accuracy, promptness, and completeness and therefore they must take care of this delicate and sad situation having contact with infectious dead bodies. As well as other sanitary staff working with SARS-CoV-2 infected people, pathologists must wear personal protective equipment, like a clean protective outer garment, disposable gloves, a disposable surgical mask and appropriate eye protection. Since SARS-CoV-2 has been categorized as a hazard group 3 pathogen, autopsies of suspected COVID-19 deceased have been centralized in specific Hospitals with adequate autopsy rooms (equipped with negative pressure).4 As it happened in past with the explanation of pathogenetic mechanisms of several diseases, results of COVID-19 autopsies are thought to elucidate the biological bases of this new infectious disease. The aim of this report is to underline that the pandemia of COVID-19 represents a step back to past for pathologists, confirming the gold standard role of post-mortem examination in the progress of medicine and health care, as it happened till the seventies of the 20th century. The occurrence of an emerging, new pathology like COVID-19 restored the dignity of autopsies that will remain an essential tool to learn physiopathological mechanisms of diseases.

  References
  1. Masood S. The changing role of pathologists from morphologists to molecular pathologists in the era of precision medicine. Breast J 2020;26(1):27-34. doi: 10.1111/tbj.13728. Epub
  2. Diebold J. Clinical autopsy—its role in modern medicine. Praxis (Bern 1994) 2007;96(43):1667-71.
  3. Regione Lombardia Nota Direzione Generale Welfare 12/03/2020“Emergenza da COVID-19. Indicazioni in materia di attività funebre”
  4. Hanley B, Lucas SB, Youd E, Swift B, Osborn M.Autopsy in suspected COVID-19 cases. J Clin Pathol 2020 doi: 10.1136/jclinpath-2020-206522. [Epub ahead of print]

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  Conflict of Interest:
  None declared.

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• Published on: 4 May 2020

  Hic est locus ubi mors gaudet succurrere vitae

  • Arianna Giorgetti, MD, Resident in Legal Medicine University of Bologna, Department of Medical and Surgical Sciences, Unit of Legal Medicine, Via Irnerio 49, Bologna, Italy.
  • Other Contributors:
    • Raffaele Giorgetti, Full Professor in Legal Medicine

  In the last few months, starting from the late 2019 in the area of Wuhan, China, an enormous increase in the number of infections due to SARS-coronavirus-2 (SARS-CoV-2) has been witnessed worldwide.[1-2] So far, 16 April 2020, the Situation report of the World Health Organization (WHO) has reported 1,914,916 confirmed cases and 123,010 deaths, of which 84,607 in the European Region.[2] This data could be itself sufficient to testify the importance of the on-going pandemic, which is further confirmed by the uncertainties regarding the possibility of gaining a natural or vaccine-mediated lifelong immunity. It is a matter of fact that, until the discovery of a vaccination, and maybe beyond that, it is likely that the world will have to deal with the virus and its long-time consequences for years. This necessarily imply that measures to deal with SARS-CoV-2 in all aspects, from life until death and post-mortem examination, have to be figured out and put in place.
  A growing issue regards the distinction between “died from” and died with” SARS-CoV-2, which would be fundamental in order to gain knowledge on several issues including lethality of the virus, trend of death rate, and to compare data from different countries and regions (e.g. higher SARS-CoV-2 death rate per 1,000 infections are reported for Italy, UK and Belgium, while it is very low in Germany, Turkey and South Korea.[3] A complete post-mortem examination is probably an irreplaceable mean of distinguishing bet...

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  In the last few months, starting from the late 2019 in the area of Wuhan, China, an enormous increase in the number of infections due to SARS-coronavirus-2 (SARS-CoV-2) has been witnessed worldwide.[1-2] So far, 16 April 2020, the Situation report of the World Health Organization (WHO) has reported 1,914,916 confirmed cases and 123,010 deaths, of which 84,607 in the European Region.[2] This data could be itself sufficient to testify the importance of the on-going pandemic, which is further confirmed by the uncertainties regarding the possibility of gaining a natural or vaccine-mediated lifelong immunity. It is a matter of fact that, until the discovery of a vaccination, and maybe beyond that, it is likely that the world will have to deal with the virus and its long-time consequences for years. This necessarily imply that measures to deal with SARS-CoV-2 in all aspects, from life until death and post-mortem examination, have to be figured out and put in place.
  A growing issue regards the distinction between “died from” and died with” SARS-CoV-2, which would be fundamental in order to gain knowledge on several issues including lethality of the virus, trend of death rate, and to compare data from different countries and regions (e.g. higher SARS-CoV-2 death rate per 1,000 infections are reported for Italy, UK and Belgium, while it is very low in Germany, Turkey and South Korea.[3] A complete post-mortem examination is probably an irreplaceable mean of distinguishing between these classes of deceased, by providing a multidisciplinary study of all organs and an extensive sampling of tissues, and of lowering the risks of misdiagnosis.
  Legal medicine is the field where “mors gaudet succurrere vitae” (literally, death founds pleasure in helping life), or “the dead can speak to livings”.[4] Post-mortem examinations might suggest a mechanism of health harm, prevent the spread of a novel disease, control medical quality, arise suspicion toward a sign and even hint for a specific treatment and a preventive role of post-mortem examinations has been long declared.[5-7]
  For example, the identification of pulmonary thromboemboli at post-mortem examination of patients who died from SARS, together with occlusions and microthrombosis of lung vessels in SARS-CoV-2 lung dissection and D-dimer elevation in patients now suggest the possibility of a therapeutic role of anticoagulant, heparin and low molecular weight heparin (LMWH) against SARS-CoV-2 infection.[8-11] Data regarding the true mechanism leading to death with SARS-CoV-2 are lacking, and it is unknown if a major role is played by respiratory acute insufficiency, multi-organ failure, cytokine release syndrome or hyper-response of the immune system, by haematological abnormalities, triggered within a disseminated intravascular coagulation (CID) syndrome or by all these mechanisms, in a different time from the contagion.[12-14]
  So far, clinical criteria, e.g. onset of relevant symptoms before the death, have been applied, limiting the postmortem examination to the only collection of tissues (e.g. lung biopsies) and biological fluids to confirm the occurred infection by SARS-CoV-2. [15] Indeed, it is fundamental to limit the risks for health care professionals. [15] However, this could be a bit limitative, since the mere presence of a SARS-CoV-2 in the body does not prove that the deceased actually died because of it, even though a certified infection is surely a strong hint. Additionally, it is not clear whether the sensitivity of swabs might be affected in the post-mortem period, if false negatives could occur, due to a death of SARS-CoV-2 when the host succumbs and the timing of this negativity with respect to the time of death.
  Finally, post-mortem examination of patients affected by SARS-CoV-2, healed and later died might provide an opportunity to ass long-time effects of the virus on lungs, hearts and other tissues.

  For the above-mentioned reason, we would like to remark the importance of performing post-mortem examinations in this era of SARS-CoV-2 pandemic spread, provided that guidance to limit the risks for workers are respected and appropriate precautions put in place.[16]
  Given the importance of a homogenization process regarding the death numbers due to SARS-CoV-2, borrowing a concept used in forensic toxicology for novel psychoactive substances (the scientific knowledge of which, as in the case of SARS-CoV-2 is still limited),[17] we would also like to suggest the adoption of a shared scale in the evaluation of the role of SARS-CoV-2.
  In the evaluation the following factors are suggested:
  1. Presence and severity of the infection by SARS-CoV-2, as assessed by in vivo data, including swabs, clinical records, radiological imaging, and post-mortem samples, including once again swabs, blood lower respiratory tract or any other sample.[15] When available, in vivo data are useful to assess if the victim has been infected, possessed risk factors for mortality and was suffering from symptoms suggestive of SARS-CoV-2 or not.[18] Post-mortem examinations on the other hand might provide insights on tissues not accessible in livings and multiple samples. [15, 19]
  2. Presence and severity of previous diseases. These could have a role in facilitating the accidental contact between SARS-CoV-2 and the victim, as in the case of a hospitalized person who came in tight contact with an infected patient and acquired the infection in this setting, or of an immune-depressed patient. The latter is not only characterized by a facilitated contagion, in comparison with a healthy subject, but also a different natural history of the SARS-CoV-2 infection, been on one hand less prone to an abnormal physiological response, on the other extremely more exposed to the direct harm caused by the pathogen.
  3. Circumstances of the death. These are of paramount importance, especially for the exclusion of SARS-CoV-2 as a cause of death, as in road traffic fatal accidents, gunshot-wounds, asphyxia, burns etc. It is clear that an external traumatic event, occurred after the contraction of the virus, could break the chain of the even, or better substitute itself, leading to death in an independent manner with respect to CoV-2. Is this the extreme case of an infected asymptomatic patient which is struck by a vehicle or shot to dead by military forces, as recently occurred in Africa due to curfew violation.[20]
  Suicides should be evaluated carefully, since they do not automatically exclude a contribution of SARS-CoV-2, even though in an indirect way. For examples, it has been reported by the news that suicides occurred due to the fear of having infected other people. Circumstances are also fundamental in order to ascertain the risk of contagion, as in the case of people in close contact with patients because co-inhabitants or due to professional setting, as for doctors. A high index of suspect should be always maintained in the latter case, given the likelihood of an infection.[21]
  4. Post-mortem radiology. Especially when in vivo imaging is not disposable, chest X-ray or, even better, post-mortem computerized tomography (PMCT) or a “virtopsy” approach could facilitate the retrieval of typical features of SARS-CoV-2. Of course, the decision to submit a suspected CoV-2 victim to an expensive and time-consuming (considering the pre-scan and post-scan necessities, as to disinfect the room) PMCT should be evaluated case-by-case and is not mandatory. Most importantly, its execution should not negatively impact clinical routine and the necessities of living patients.
  5. Pathologic macroscopic and microscopic findings. Lungs and respiratory airways appear as the primary target of the infection and certainly their analysis should be as accurate as possible. Some data has already been published on persons with certified infection and could be useful to assess a compatibility of cases to the described features. [15, 19, 22-24]. Though, iatrogenic damage due to medications or devices, as in the case of alveolar hyper-insufflation in the course of mechanical ventilation, is possible and should be considered carefully. Moreover, myocardial, liver and multi-organ failure has been described.[23, 25]
  6. Toxicological evaluation. A toxicological screening of common drugs of abuse could be important to exclude acute intoxications. Moreover, in the cases of patients prescribed multiple drugs, an evaluation of concentrations could be useful to assess if levels were within therapeutic ranges or exceeded them, suggesting a potential overdose.
  7. Additional analyses should be performed whenever suggested by circumstantial, clinical or necroscopic data.

  A possible SARS-CoV-2 significance score or CSS could be classified in four-points, in order to provide a fast assessment tool, which could be used in order to help establishing the cause of death for the Judicial Authority, as follows:
  • 0 when SARS-CoV-2 was merely an occasion, but does not upsurge to the role of cause of death. An occasion is classified by its insignificance with respect to the death, exchangeability, ineffectiveness, non-indispensability.[26] An example is that of a old victim, with multiple increasing episodes of acute pulmonary edema due to cardiac chronic decompensation in the last stage, whose conditions are so severe that he succumbed to the mere rhinitis manifestations of SARS-CoV-2 and would have died even in the presence of usually well-tolerated pathogens.
  • 1, i.e. low, when SARS-CoV-2 was present and a causative role cannot be excluded, even though an alternative leading cause of death is likely. An example could be that of a victim with multi-organ failure due to failed transplant, who suffers of multiple opportunistic infections, including low symptomatic SARS-CoV-2.
  • 2, i.e. medium SARS-CoV-2 has likely contributed to death, even if additional factors might have had a prominent role. An example could be that of a victim with past history of haemorrhages and a poor haemostatic balance, who receives LMWH or other similar medications due to massive SARS-CoV-2-induced CID and dies of cranial hemorrhage.
  • 3, i.e. high: SARS-CoV-2 with all probability was the leading cause to death.
  A CSS could remain U= unclassified/unclear, when not enough data is disposable, until the execution of additional analyses, e.g. of swabs or microscopical analysis, or even after that, when the role of SARS-CoV-2 is unclear.
  The so-presented scale tends to over-aestimate the role of SARS-CoV-2, though this seems necessary at this historic moment due to its diffusion and to the lack of knowledge regarding time course, natural history and mechanisms of injury.
  Moreover, CSS should not be intended as a mathematic simplification of the process of post-mortem evaluation, a self-explanatory and sufficient response to a complex issue. Though CSS contains several elements of judgement and could lower the inhomogeneities in forensic evaluation of SARS-CoV-2, it is to be considered as an additional concise tool to be placed side by side with full medico-legal evaluation and discussion.

  Conflict of Interest:
  None declared.

  References
  1. World Health Organization (WHO) Novel Coronavirus (2019-nCoV) SITUATION REPORT - 1 21 January 2020. Available at : https://www.who.int/docs/default-source/coronaviruse/situation-reports/2...

  2. World Health Organization (WHO) Coronavirus disease 2019 (COVID-19) Situation Report – 86. Data as received by WHO from national authorities by 10:00 CET, 15 April 2020
  Available at : https://www.who.int/docs/default-source/coronaviruse/situation-reports/2...

  3. Worldometers.info. Available from: https://www.worldometers.info/coronavirus/#countries Access date: 18 April 2020

  4. New York Times. Learning to Speak for the Dead. Available from: https://www.nytimes.com/2016/06/12/nyregion/new-york-city-agency-teaches... Access date: 18 April 2020

  5. Byard RW. Preventative pathology. Inj Prevent 1999;5:292–3.

  6. Byard RW. Preventive pathology revisited. Forensic Sci Med Pathol 2014;10(2):155-6. doi: 10.1007/s12024-014-9534-y. Epub 2014 Jan 23.

  7. Buschmann CT, Tsokos M, Kleber C. Preventive pathology: the interface of forensic medicine and trauma surgery for pre-hospital trauma management. Forensic Sci Med Pathol 2015;11(2):317-8. doi: 10.1007/s12024-014-9603-2.

  8. Chong PY, Chui P, Ling AE, et al. Analysis of deaths during the severe acute respiratory syndrome (SARS) epidemic in Singapore: challenges in determining a SARS diagnosis. Arch Pathol Lab Med 2004;128(2):195-204.

  9. Fox SE, Aibek A, Harbert JL, et al. Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. medRxiv 2020.04.06.20050575. doi: https://doi.org/10.1101/2020.04.06.20050575

  10. Luo W, Yu H, Gou J, et al. Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia (COVID-19). Preprints 2020, 2020020407.

  11. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020. doi: 10.1111/jth.14821. [Epub ahead of print]

  12. Henderson LA, Canna SW, Schulert GS, et al. On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol 2020. doi: 10.1002/art.41285. [Epub ahead of print]

  13. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020. doi: 10.1111/jth.14817. [Epub ahead of print]

  14. Shi Y, Wang Y, Shao C, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020. doi: 10.1038/s41418-020-0530-3. [Epub ahead of print]

  15. Hanley B, Lucas SB, Youd E, et al. Autopsy in suspected COVID-19 cases. J Clin Pathol 2020. pii: jclinpath-2020-206522. doi: 10.1136/jclinpath-2020-206522.

  16. Osborn M, Lucas S, Stewart R, et al. The Royal College of Pathologists. Briefing on COVID-19 Autopsy practice relating to possible cases of COVID-19 (2019-nCov, novel coronavirus from China 2019/2020). Available from:
  https://www.rcpath.org/uploads/assets/d5e28baf-5789-4b0f-acecfe370eee622... Access date: 18 April 2020

  17. Elliott S, Sedefov R, Evans-Brown M. Assessing the toxicological significance of new psychoactive substances in fatalities. Drug Test Anal 2018;10(1):120-126. doi: 10.1002/dta.2225.

  18. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020. pii: S0091-6749(20)30495-4. doi: 10.1016/j.jaci.2020.04.006. [Epub ahead of print]

  19. Barton LM, Duval EJ, Stroberg E, et al. COVID-19 Autopsies, Oklahoma, USA. Am J Clin Pathol 2020;aqaa062. doi: 10.1093/ajcp/aqaa062

  20. Courthouse News Service. African Man Shot Dead for Breaking Virus Curfew Available from: https://www.courthousenews.com/african-man-shot-dead-for-breaking-virus-... Access date: 18 April 2020

  21. Zhan M, Qin Y, Xue X, et al. Death from Covid-19 of 23 Health Care Workers in China. N Engl J Med 2020. doi: 10.1056/NEJMc2005696. [Epub ahead of print]

  22. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18.
  23. Tian S, Xiong Y, Liu H, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol 2020. doi: 10.1038/s41379-020-0536-x.

  24. Tian S, Hu W, Niu L, et al. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol 2020. pii: S1556-0864(20)30132-5. doi: 10.1016/j.jtho.2020.02.010. [Epub ahead of print]

  25. Yang F, Shi S, Zhu J, et al. Analysis of 92 deceased patients with COVID-19. J Med Virol 2020. doi: 10.1002/jmv.25891. [Epub ahead of print]

  26. Puccini C. Istituzioni di Medicina Legale. Casa Editrice Ambrosiana 2003.

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  Conflict of Interest:
  None declared.

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• Published on: 20 April 2020

  COVID-19 infection: "high risk to an individual but a low risk to the community"?

  • Arnaldo Carbone, Pathologist Area of Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCC
  • Other Contributors:
    • Vincenzo Arena, Pathologist

  Dear Editor,

  given the spread of Covid-19 infection with its serious consequences and given that the phenomenon has taken on partly unexpected epidemic dimensions which have required drastic Italian government restrictive measures to counteract its spread, in Our opinion it is legitimate to think of a reclassification of the risk category to which the pathogen Covid-19 belongs.

  As it is known, Covid-19 is a viral pathogen of relatively recent acquisition in the human species which in its changed forms has presented over time health problems of growing social impact in different parts of the world and currently in Italy.

  The SARS-1 (SARS-CoV, 2002, China) and MERS (2012, Saudi Arabia) forms have relatively little interest in Europe while the SARS-CoV-2 (China, Wuhan, 2019; Covid-19) has importantly spread in Italy.

  So far beta-coronaviruses capable of causing disease in humans have been classified by WHO in the Risk Group (RG) 3: ”viral agent with high individual risk, but with a risk of collective spread assessed as low-moderate”.

  So, the probability of propagation in the community of this virus was assessed as "moderate".

  Also the NIH Guidelines defines the risk groups 3 as “high risk to an individual but a low risk to the community”

  Furthermore, RG3 (NIH and WHO) is defined as to have efficient therapeutic approaches .

  However, the present experience has led us to realize that Covid-19 has a very hig...

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  Dear Editor,

  given the spread of Covid-19 infection with its serious consequences and given that the phenomenon has taken on partly unexpected epidemic dimensions which have required drastic Italian government restrictive measures to counteract its spread, in Our opinion it is legitimate to think of a reclassification of the risk category to which the pathogen Covid-19 belongs.

  As it is known, Covid-19 is a viral pathogen of relatively recent acquisition in the human species which in its changed forms has presented over time health problems of growing social impact in different parts of the world and currently in Italy.

  The SARS-1 (SARS-CoV, 2002, China) and MERS (2012, Saudi Arabia) forms have relatively little interest in Europe while the SARS-CoV-2 (China, Wuhan, 2019; Covid-19) has importantly spread in Italy.

  So far beta-coronaviruses capable of causing disease in humans have been classified by WHO in the Risk Group (RG) 3: ”viral agent with high individual risk, but with a risk of collective spread assessed as low-moderate”.

  So, the probability of propagation in the community of this virus was assessed as "moderate".

  Also the NIH Guidelines defines the risk groups 3 as “high risk to an individual but a low risk to the community”

  Furthermore, RG3 (NIH and WHO) is defined as to have efficient therapeutic approaches .

  However, the present experience has led us to realize that Covid-19 has a very high propagation ability in the community as it spreads very easily from one individual to another, this is also reflected into the containment measures issued urgently by a number of National European governments.

  In addition, for Covid-19 effective and validated therapies are not currently known and there is no vaccine available against it.

  It should also be considered that validated serological diagnostics for Covid-19 infection are currently unavailable.

  It therefore seems necessary to review the classification of the risk associated with Covid-19 infection and with it, it seems necessary to review the consequent safety levels (bio-containment), for laboratories that have to handle potentially infected material (WHO Laboratory biosafety manual, 2004, III edition).

  The topic is of considerable importance as regards the autopsy activity on subjects with Covid-19 infection or with suspected Covid-19 infection.

  This activity, prudently, should be carried out in safe environments and with procedures corresponding to those relating to the safety levels suitable for the biocontainment of RG4 agents, rather than those corresponding to the containment level for RG3.

  Guidelines are urgently needed to help pathologists operate in the safest way, also contributing to harmonizing approach at European level.

  It is proposed to ensure that:

  1. in case of an ascertained death for SARS-CoV-2 (i.e. with a positive test for Covid-19) post-mortem autopsy should be avoided, unless the procedure is performed in environment and in ways appropriate for diagnostic activities at RG4 level;
  2. in each hospitalized patient, molecular assessment (nasopharyngeal swab test) should be performed to determine Covid-19 presence;
  3. when this first test is negative, a second diagnostic test should be carried out in the following 24 hours as recommended by the WHO;
  4. when a person dies (irrespective if hospitalized or not), in the absence of documented molecular verification on Covid-19 presence, a nasopharyngeal swab should be performed just after having ascertained the death with the usual procedures;
  5. in any case, when a documented valid verification on Covid-19 presence in the subject is absent, post-mortem invasive assessments and procedures should be carried out only with the precautions indicated for RG4;
  6. in any case, based on the available medical documentation, in the present Covid-19 epidemic context the pathologist should be free to decide unquestionably whether to perform a complete autopsy or to perform a minimally invasive autopsy on selected areas of the body.

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  Conflict of Interest:
  None declared.

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