key: cord-1005638-2voe4r7f
authors: Kim, Moon-Young; Cheong, Harin; Kim, Hyung-Seok
title: Proposal of the Autopsy Guideline for Infectious Diseases: Preparation for the Post-COVID-19 Era (abridged translation)
date: 2020-08-14
journal: J Korean Med Sci
DOI: 10.3346/jkms.2020.35.e310
sha: 39b29089571b88cb1ea46dfd590dd10455321a8c
doc_id: 1005638
cord_uid: 2voe4r7f

With the rapidly spreading coronavirus disease 2019 (COVID-19) pandemic over the past few months, the world is facing an unprecedented crisis. Innumerable lives have been lost to this novel infectious disease, the nature of which supersedes conventional medical understanding. The COVID-19 pandemic is not just a global health crisis, several aspects of life in the post-COVID-19 era are also being contemplated. Experts in unison are warning that the upcoming changes in all areas of life could potentially be far more drastic than ever experienced in the entire human civilization. The medical community is no exception, and therefore, personnel involved in forensic medicine also need to be adequately prepared for the future. Forensic medicine is a branch of medicine dedicated to one of the most important stages of the human lifecycle and has always been at the forefront in times of unprecedented social change. The autopsy, one of the most important tools of forensic medicine, is also useful to infectious diseases because it identifies the causal relationship between death and infection, reveals medical and epidemiological knowledge, and provides objective evidence for legal disputes. We present new autopsy guidelines in forensic medicine, formulated based on the various infectious diseases that we presently live with and may encounter in the future. In formulation of these guidelines several considerations have been taken into account, namely, the role forensic pathologists should play in the post-COVID-19 era and the necessary preparations as well as the support needed from society to fulfill that role. The present COVID-19 outbreak should be a starting point for formulating improvements in current practices in forensic science, including autopsy biosafety practices and the medicolegal death investigation system.

Despite the development of medical science, as the complexity of our society increases, various microorganisms that have the potential to be infectious agents constantly threaten humanity. Through accumulated mutation, even well-known microorganisms are becoming new species, resulting in stronger transmission or higher number of fatalities. Korea is also in a situation where management is required of both the interior spread and the foreign inflow of various infectious diseases. For examples of the former in Korea, there are respiratorymediated infectious diseases, such as tuberculosis, which is known to be endemic, and bloodmediated infectious diseases, such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS), which need continuous monitoring. 1,2 Numerous foreign infectious diseases are newly emerging as a result of changes in climate and biological distribution due to environmental degradation, and the collapse of interspecies barriers. As international exchange increases, they can flow into other countries at any time. 3 Recently, several respiratory diseases caused by novel viruses, such as severe acute respiratory syndrome ( In a situation where enormous social and economic losses are caused by the periodic outbreak of novel infectious diseases, the national quarantine system requires improvement to cope with the public health crisis. We believe that autopsy can provide the basic data for establishing appropriate quarantine and preventive measures. The autopsy is the most direct approach to a disease or other medical abnormalities. Historically, a wide range of information on pathogenesis, epidemiology, and the natural course of numerous diseases has been collected through autopsy, leading to the development of medicine. Also, the autopsy identifies legal problems related to death and prevents potential disputes, the necessity for which has been recognized across many sectors of society. It should be considered more important in a death related to an infectious disease.

While the clinical environment is ready for infectious diseases under administrative and financial support, the death investigation system in Korea does not seem to be comparable. Although many infectious diseases are diagnosed only postmortem through autopsy, the personnel related to the autopsy are exposed to the risk of infection, due to insufficient clinical information, lack of facilities or equipment for protection, and injury accidents. Therefore, a guideline for the standard autopsy for infectious diseases is stated here, which aims to: 1) provide scientific grounds to establish appropriate plans for the prevention and treatment of infectious diseases, 2) contribute to improving national health by controlling the spread of pathogens within the community, and 3) protect human resources engaged in autopsy-related work from the risk of infection. Several autopsy guidelines, including more recent ones focusing on COVID-19, have been adopted here. [5] [6] [7] [8] [9] Most of them suggest that the principles of handling COVID-19 during autopsy are not different from that of the handling of other infectious diseases. This guideline does not present the current modus operandi, but indicates the way in which we need to operate from now on, and which needs our continuous effort dedicated to forensics, as well as support from the related social systems.

The pathogen of infectious diseases includes various microorganisms, such as bacteria, viruses, fungi, parasites, and even prions. Among various routes of transmission, direct contact of blood or body fluids, and aerosol transfer via droplet or its nuclei are considered as important during the autopsy. Patients with active infection could have symptoms of acute, subacute, or chronic status, which is called clinical disease, or have no apparent symptoms, which is called subclinical or occult disease. Infection by some agents could be inactive for a certain period, which is called latent infection.

The diagnosis of an infectious disease could be considered based on 1) medical history, from the statements of his or her acquaintances or formal medical records; 2) postmortem tests for the detection of microorganisms, such as serologic, genetic, or culture tests using blood, secretion, fluid, or tissue; 3) pathologic findings, using conventional and special stains; and 4) epidemiologic information about the deceased or his or her close contacts, such as the location of residence and workplace, occupation, travel history, and recent whereabouts.

The Infectious Disease Control and Prevention Act of Korea designated some infectious diseases with epidemiologic importance as 'legal infectious diseases.' These diseases were classified into four classes according to their severity, infectiousness, and isolation level (Appendix 1). An emerging infectious disease with the possibility of severe symptoms or rapid transmission is considered an 'emerging infectious disease syndrome' in Class 1. COVID-19, caused by SARS-CoV-2, is an example of this temporary classification, which should be classified properly after the pathogenesis and clinical features are further revealed.

According to the act, a doctor who identified an infectious disease from a living patient or a dead body should report to the regional public health center. The director of the Korea Centers for Disease Control and Prevention (KCDC) may order an autopsy of the deceased who is suspected of having died from an infectious disease, to confirm the final diagnosis. The autopsy process should be conducted by a specialist in infectious disease, human anatomy, pathology, or forensic medicine, in a facility with an adequate level of biosafety.

The KCDC has suggested a revised classification of the risk groups of infectious agents (Appendix 2) in 2016, which is based on the classification for the biology laboratory published by the WHO in 2004. 10 According to this classification, Risk Group 2 includes the pathogens that are unlikely to be a serious hazard, such as HBV and HCV, while Risk Group 3 includes the pathogens that usually cause serious diseases, such as Mycobacterium tuberculosis, SARS-CoV, and HIV. For both groups, effective treatment and preventative measures are available in general.

The Infectious Disease Control and Prevention Act of Korea classifies the safety control measures of the facilities handling high-risk pathogens into four grades (Appendix 3), which correspond to the biosafety levels (BSLs or BLs) suggested by the WHO. They could be applied to all the pathogens identified so far. Registration with the KCDC is required for handling high-risk pathogens of Grade 1 and 2, while permission from the KCDC is required for those of Grade 3 or 4. The classification is as follows:

• Grade 1: facilities that handle high-risk pathogens that are unlikely to cause diseases to healthy adults. • Grade 2: facilities that handle high-risk pathogens that can cause human diseases unlikely to be a serious hazard and for which effective treatment and preventive measures are available. • Grade 3: facilities that handle high-risk pathogens that usually cause serious human diseases and for which effective treatment and preventive measures are available. • Grade 4: facilities that handle high-risk pathogens that usually cause serious human diseases and for which effective treatment and preventive measures are not usually available.

In addition, the same act designates some infectious agents as 'high-risk pathogens' that require special attention from the nation and society, because of the potential of serious risk to public health if used for biological terrorism, or spread to the outside by accident (Appendix 4). Some agents in Risk Group 2, 3, and 4 recommended by the WHO and some causative agents of a recent outbreak, such as SARS-CoV and MERS-CoV, are included in this list. It is anticipated SARS-CoV-2 will be added here in the near future by revision of the act.

Autopsy plays a critical role in 1) determining the situation and specific causes of death, 2) excluding other causes of death when a patient dies during treatment or isolation for a confirmed infection, and 3) evaluating the medical relationships between infection and death if the infection is not a direct cause of death.

Autopsy is able to provide crucial information for 1) the establishment of an appropriate treatment plan based on the pathological mechanisms by confirming the clinical course, symptoms, histology, and prognosis, and 2) scientific evidence to control and prevent the spread of pathogens within the community, by identifying the path of transmission, and the prevalence of the target population.

Since immediately after a particular death, the possibility of legal disputes related to the death are often unclear, and the bereaved family are often confused, the conducting of an autopsy should be decided under careful consideration of the circumstances surrounding the death. Potential legal disputes may be related to the validity and relevance of medical treatment or administrative actions, compensation claims against industrial accident insurance or commercial medical insurance, or professional negligence of a business owner.

Most of the situations are already covered by the criteria for the decision of unnatural deaths suggested by the KSLM (Appendix 5), or the instructions for handling unnatural deaths declared by the Korean National Police Agency (Appendix 6).

Most of the medical history provided before the autopsy by the police is limited to the statements of bereaved families or acquaintances, or concise data from the National Health Insurance Corporation. Obtaining the medical records of the deceased needs an additional effort of the police or the bereaved families. However, the medical information is mandatory in identifying the health status of the deceased, and preparing against the potential risk of infection. The incidence of tuberculosis among autopsy workers is known to be 100-200 times that of the general population, 11 while it has never been investigated in Korea. A smallgroup survey in Korea indicated that the prevalence of tuberculosis and hepatitis B among medical workers was suspected to be very high. 12 Because hepatitis C and AIDS are difficult to cure and have a poor prognosis, serologic tests are performed on all surgical patients to protect medical personnel. But currently in Korea, no particular tests are required to be conducted in the routine for a dead body before the autopsy.

The purpose of the medico-legal autopsy may be divided into a judicial one, to confirm criminal relevance, and an administrative one, to manage public issues related to infectious diseases, accidents, or disasters, while that of the clinical autopsy is usually focused on medical evaluation. In Korea, the legal basis for all forms of autopsy is prepared. For example, in the cases of infectious diseases that are not expected to be related to crime, the autopsy may be conducted by the Minister of Health and Welfare, the mayor, the governor, the Director of the KCDC, or the head of the quarantine office. But in practice, the autopsy is always requested by the police, which inevitably limits its purpose.

Although autopsy rooms are installed at the National Forensic Service (NFS) and its local branches, and some medical schools having forensic or pathology departments, their BSLs are in different situations. For example, the headquarters of the NFS has a special autopsy room of BSL3, while some medical schools have only BSL1 rooms. In principle, if the deceased is known to be a tuberculosis patient, the autopsy should be conducted in the BSL3 autopsy room, because Mycobacterium tuberculosis belongs to Risk Group 3 with SARS-CoV and HIV. 10 But this principle is hard to follow, due to the high prevalence of tuberculosis in Korea, and a lack of medical history, as mentioned above. Each institution is in charge of the management of personal protective equipment (PPE) required for the autopsy, without sharing a standardized protocol.

To assess the risk of infection caused by autopsy, the medical conditions of autopsy personnel should be checked periodically, especially after the autopsy of a high-risk person. 5 Throughout the branches of the NFS and the universities, there are no principles for the list of target pathogens, the method and frequency of surveillance test, and the criteria for subjects who need such monitoring.

To conduct an autopsy, the sequence of procedures should be involved, of 1) transfer from the funeral home, 2) receive the body at the autopsy room, 3) check the identity of the body with the police or bereaved family, 4) perform the autopsy, 5) return the body to the funeral home, and 6) transfer the samples for postmortem test to other departments. The workers who will be involved before and after the autopsy should be guided and trained in the use of PPE and hygiene control, because during the wrapping and transporting processes, there is a possibility of contagion from the deceased. Laboratory personnel dealing with samples taken from the body during the autopsy should be aware of the potential risk of infection in all autopsy samples, and receive the same level of health support as the autopsy personnel. In particular, all laboratories dealing with the initial sample that has not been chemically treated or biologically inactivated, must have BSL2 or higher level of facilities and appropriate PPE. 10 Throughout the autopsy-related facilities in Korea, there is only a low level of safety considerations for these types of personnel who are not directly involved in the autopsy, and the level is insufficient to deal with a body or samples infected by a highrisk pathogen.

All bodies should be considered to be infected by unspecified microorganisms, until they are diagnosed as negative by a medically verified examination, using appropriate samples. The autopsy personnel have the right to be protected from infection by the body, for which the affiliated agencies should make appropriate efforts. Even if an infectious disease is newly diagnosed after the autopsy, the risk of infection to the autopsy personnel should be low level. A 'standard autopsy' for infectious diseases is defined as an autopsy conducted by an agreed procedure for this purpose, which should always be observed, regardless of the prevalence of the infectious disease. For confirmed cases, some conditions could be added for the optimal protection of the autopsy personnel. In contrast, if any of the facilities, personnel, equipment, or procedure did not meet the standard, an autopsy shall be considered as an 'ordinary autopsy'.

The risk of transmission during an autopsy could be assessed according to the infection status of the body ( Table 1) . To conduct an autopsy for a confirmed case, the biosafety levels of the facilities for autopsy and laboratory tests should be equivalent to or higher than that of the pathogen. During the prevalence of a certain infectious disease, all the unknown cases should be regarded at least as suspected cases. However, considering the realistic restrictions, if there were reasonable compensations, such as preliminary tests before the autopsy, adequate ventilation and disinfection of the facilities, or additional use of PPEs, the autopsy could be conducted by substandard protocols. Even for the negative cases that are allowed for the ordinary autopsy, a higher level of protection is recommended, because there is always the possibility of a false-negative. 

Considering the prevalence and biological risks, a list of infectious pathogens should be selected, and periodically evaluated for surveillance. Preliminary tests for these pathogens are recommended. During the prevalence of high-risk pathogens (Appendix 4) or their equivalents, preliminary tests are mandatory for clinically suspected cases to determine the conduct and the coverage of the autopsy. 4 The autopsy can be postponed until the results of the preliminary tests are available. Even for the cases in which the preliminary test was negative, if suspicious findings were found during the autopsy, it is recommended to repeat the test with the autopsy samples. The possibility of false-negatives should always be considered, because the results could be affected by the infection period, sampling methods, status of the samples or bodies, or the characteristics of the test itself.

Place the body in a leak-proof transparent plastic bag with a thickness of 150 μm, and seal it. Do not use pins or clips that can damage the sealing conditions. 13 Put the plastic bag into another opaque body bag, and wipe its outer surface with sodium hypochlorite diluted 1:4 (e.g., 5% sodium hypochlorite 100 mL + water 400 mL mix), and dry. Attach an identification tag to both the body and its bag, respectively, and make sure that they are not lost. Refrigerate the body at 4°C. At the beginning of the autopsy, disinfect the outer and inner surface of the body bag and the skin of the body with 70% alcohol or sodium hypochlorite diluted 1:99 (e.g., 5% sodium hypochlorite 5 mL + water 495 mL mix).

The biosafety standard of the autopsy-related facilities may correspond to the BSL in general, although a little modification is required to reflect the procedure and equipment of the autopsy. The concept of BSL is also adopted in the 'Standards for the installation and operation of facilities handling high-risk pathogens (Ministry of Health and Welfare Notice No. 2019-59)' (Appendix 3) , which the Korean institutes should follow for handling microorganisms with potential biologic risk.

A BSL2 autopsy room is required for the ordinary autopsy, while a BSL3 or higher level is required for the standard autopsy, according to the risk group of the confirmed or suspected pathogen. 10 In an autopsy room that does not meet the above criteria, at least 1) the air inside the autopsy room should not escape to other spaces in the building, 2) the route of exhaust should avoid other intake vent or public spaces, and 3) additional devices or PPEs should be utilized to compensate insufficiently met requirements. Considering the environment of the autopsy room and the prevalence status of the time, the preliminary test of all the requested bodies should be considered for certain pathogens, and be referred to the decision of the conduct and coverage of the autopsy.

Waste generated in all processes related to the body correspond to medical waste. They should be immediately disposed of in a dedicated envelope or containerboard box. In particular, sharp tools, such as injection needles, suture needles, or scalpels, should be discarded in a dedicated plastic container. Waste are sealed, disinfected, and then refrigerated in a dedicated warehouse. They should be transported to a medical waste incinerator within 7 days, and disposed of within 2 days. 

If a surface is contaminated, wipe it with sodium hypochlorite diluted 1:49 (e.g., 5% sodium hypochlorite 10 mL + water 490 mL mix), and leave it for 15-30 minutes, before wiping it again with water. If a metal surface is to be disinfected, wipe it with 70% alcohol (e.g. 100% alcohol 70 mL + water 30 mL mix). If a surface is visibly contaminated by blood and body fluids, wipe it with sodium hypochlorite diluted 1:4 (e.g., 5% sodium hypochlorite 100 mL + water 400 mL mix), and leave it for 10 minutes, before wiping it again with water. The sodium hypochlorite solution should be newly mixed each time. After disinfection is finished, thorough ventilation is required.

Reusable surgical garments (e.g., gown, mask) made of cotton could be included in the alternative list of PPEs. The cotton contaminated with blood or body fluids should be washed with hot water at 70°C or higher. If unavailable, soak them in sodium hypochlorite diluted 1:49 (e.g., 5% sodium hypochlorite 100 mL + water 4,900 mL mix), and leave them for 30 minutes before washing. Handle as gently as possible, to avoid aerosols.

Aiming to protect the whole body of the autopsy personnel, including respiratory tract, eyes, and hands, from the infection, PPE should be selected in consideration of the nature and the infection route of the pathogen, and the expected situation of possible exposure. PPE should in principle be disposable or single-use, but some items (e.g., powered air-purifying respirators (PAPR), goggles, face shields, surgical garments made of cotton, and boots or shoes) may be designed for reuse, which should be disinfected or sterilized according to the manufacturer's instructions. Keep hair from flowing down, and remove personal accessories, like watches, in advance. To prevent unnecessary contamination, each manual of the PPEs, including dressing and undressing orders, should be understood in advance, and properly applied. Once the PPEs are used, they shall be discarded or disinfected, being regarded as contaminated. Hand hygiene shall be carried out before and after dressing or undressing. Damaged or contaminated PPEs should be discarded, without being reused or stored again. Cross-check between the autopsy personnel is recommended of whether the PPEs are worn properly, or not. 

The dressing order of PPE should be as follows: 

The undressing order of PPE should be as follows:

It is recommended to disinfect inner gloves at each step, as during the undressing they may become contaminated. If PPEs are found to be damaged, these cases should be considered as exposure to the pathogen, followed by proper management for the personnel.

All the processes should be supervised by an experienced forensic pathologist. The number of people who participate in the autopsy should be minimized. However, it is recommended that at least two people be present in the autopsy room, in case of an emergency. 8 To prevent cutting injuries, the dissection of each body part should be conducted by only one person at a time. A person who is not directly participating in the autopsy, such as the bereaved family member or police, is restricted from entering the autopsy room. During the prevalence of certain infectious diseases or the autopsy for confirmed cases, the access of trainees, such as medical students or residents, is also restricted. If necessary, observation through a window or a monitor is recommended, in a completely separate space from the autopsy room.

All the autopsy personnel should be cautious with sharp objects, such as scalpels, knives, needles, or bone sections, which can cause cutting injuries. Damaged or contaminated PPEs should be immediately discarded, and replaced with new ones. In the case of exposure to infection source, disinfect the exposed area immediately in a proper way; and if there is medical evidence, start prophylactic treatment.

If the body is suspected to have an airborne disease, the following should be operated with special caution, to prevent aerosols: 1) cutting bone with electronic saws, for which replacement If a full-body suit is not available, surgical cap and long boots can be used to minimize exposed parts. Also, if the suit or gown is not made of waterproof material, the waterproof function of the PPEs can be supplemented with a plastic apron or arm covers; b Although they are not truly cut-proof, work gloves made of cotton may interrupt the movement of blades.

by manual saws or additional use of vacuum inhalers is recommended, 2) opening the containers or centrifugation of samples, 3) body movement during transportation or postural adjustment during autopsy, which may cause spout of oral and nasal contents, 4) incision of the bronchus or lung parenchyma, which may expose the secretion inside, and 5) washing the body with a showerhead, which may spray its body fluids or adhesives together.

For the suspected cases or the unknown/negative cases with suspicious findings in the autopsy, a medically verified test at the time for each pathogen or disease should be requested, with appropriate samples. In these cases, the autopsy personnel and facilities should be managed as if they participated in the autopsy for confirmed cases, until the test result is assured to be negative.

The initial sample, which is not chemically treated nor biologically inactivated, should be handled within the biosafety cabinet installed in the BSL2 laboratory by experienced personnel wearing the PPEs equivalent to that used in the autopsy room. Meanwhile, after chemical treatment or biologic inactivation, the samples can be handled on an ordinary bench. Purified DNA or protein can be handled in the BSL1 laboratory, but the use of a biosafety cabinet or its equivalent is recommended.

To transport the autopsy samples, they should be prepared in the following order: 1) put the samples into the primary container, and seal it, 2) disinfect the outer surface of the primary container with 70% alcohol, and label it with an identification tag, 3) wrap the primary container with an absorbent (e.g., paper towel), 4) put the primary container into the secondary container, and seal it, 5) put the secondary container into the tertiary container and seal it, and then label it with a tag. The personnel who pack or open the containers should wear the PPEs equivalent to that used in the autopsy room or laboratory. Any work that requires contact with the containers, for example, simple transportation in sealed status, requires at least the wearing of gloves.

The affiliated agency should recognize the major infection history of all personnel who participate in autopsy or handle postmortem samples, and take necessary measures to prevent infections. If the standard autopsy was conducted without any damage of PPEs, the risk of infection is generally low. However, if the biologic nature of the pathogen or the epidemiology and pathophysiology of the disease are not fully identified, all the participants should be alert during the expected incubation period, even though they are not obviously exposed, with self-monitoring of the symptoms and the minimizing of face-to-face contacts. All the personnel who have accessed the autopsy room should be recorded: not only the direct participants in the autopsy, but also assistants for the maintenance of the facilities.

Considering the prevalence and biological risk, a list of infectious pathogens should be selected, and periodically evaluated for surveillance. If there is clinical evidence, prophylaxis, like vaccination, is recommended. In particular, each participant in the autopsy of confirmed cases should check whether he or she is already infected with the pathogen or not, so that if he or she is infected during the autopsy, the infection source could be traced. In the case of personnel who participated in the autopsy of a body confirmed to be infected but the standard protocol was followed, there is no possibility of exposure, so only selfmonitoring of the symptoms and the minimizing of face-to-face contacts during the expected incubation period are required. However, if the autopsy procedures failed to meet the standard protocol, or the PPEs were damaged, infection should be suspected. In this case, self-isolation during the expected incubation period, and if available, prophylaxis, is required. The relevant personnel should be tested for the pathogen at the time point when related symptoms are shown, or the isolation period is nearly ended. If a test was requested after the autopsy, but the results are pending, the same actions are required in the interim.

If the autopsy procedures failed to meet the standard protocol, or the PPEs were damaged, the forensic pathologist in charge of the autopsy may consider adjusting the participant members, or discontinuing and delaying the autopsy schedule, to protect the autopsy personnel.

If a test for certain infection was requested after the autopsy, the process and the result should be shared with all the personnel who had, or would have, contact with the body, including the police, the bereaved family, the person who has discovered, reported, inspected, or transported the body, and the funeral staff. They are required to minimize faceto-face contacts, until the test result is confirmed. 

COVID-19 is a respiratory syndrome caused by the infection of SARS-CoV-2, which belongs to the coronavirus family. Currently, in Korea, COVID-19 is regarded as an 'emerging infectious disease syndrome,' which is included in Class 1 legal infectious disease (Appendix 1), and SARS-CoV-2 is considered a high-risk pathogen, which needs 'urgent management' (Appendix 4) . It is known to be transmitted through aerosols, droplets, or direct contact, while the viruses have also been found in tears and feces. 14, 15 The incubation period is up to 14 days, and symptoms were expressed within 12.5 days after exposure in 95% of the infected. According to the studies published so far, the survival period of SARS-CoV-2 is 3 hours in aerosols, 4 hours on copper surfaces, 24 hours on cardboard surfaces, and 2-3 days on plastic or iron surfaces, which indicate that SARS-CoV-2 can survive for a considerable period outside of the host. 16 2) Clinical and pathologic findings SARS-CoV-2 patients show diverse symptoms, ranging from asymptomatic to severe respiratory failure. Major symptoms are fever, fatigue, dry cough, muscle ache, and shortness of breath; and a few cases included sputum, headache, hemoptysis, and diarrhea. Recently, the CDC of the United States and the KCDC added ageusia and anosmia as major symptoms of COVID-19.

The patients are frequently diagnosed with viral pneumonia, regardless of the actual severity of their symptoms. As of yet, there is no specific therapeutic agent or vaccine. Severe patients suffer from respiratory failure, septic shock, and multiple organ failure. The median time to respiratory failure was 8.0 days from symptom onset, while that to mechanical ventilation was 10.5 days.

According to a few reports of autopsy or histopathology test, microscopic findings included diffuse alveolar damage, fibromucinous exudates, inflammatory infiltration in the interstitium or intra-alveolar area, viral cytopathic-like change, and thrombogenic vasculopathy. 17-21

A diagnostic test for SARS-Cov-2 could be considered based on 1) medical history or symptoms, which are mainly fever or respiratory symptoms, and also include headache, abdominal pain, and fatigue, 2) epidemiologic connection, such as temporal, spatial, or geographical relationships with an epidemic region or confirmed patient, and 3) gross pathologic findings of the lungs, such as consolidation, thick exudates, excessive mucus, or other findings suggestive of acute or severe pneumonia, regardless of the clinical symptoms.

The autopsy of confirmed and suspected cases should be conducted at BSL3 or equivalent facilities. For unknown cases, the autopsy could be conducted under BSL3 facilities, but there should be reasonable compensations, such as preliminary tests before the autopsy, adequate ventilation and disinfection of the facilities, or additional use of PPEs. The management of autopsy related facilities follows the standard autopsy protocol as mentioned above. Even though the generation of droplets or aerosols from bodies is unlikely, it is recommended to minimize direct contact with the bodies or postmortem samples, and prevent damage of PPEs. 22 For pathologic study, the respiratory system, including proximal and distal trachea, pulmonary hilum, main and segmental bronchi, pulmonary parenchyma, and other organs, such as the heart, the liver, kidney, spleen, and intestines, could be sampled, according to the purpose of the study. Fix them with 10% formalin for 2-3 days. 25

(1) The autopsy for confirmed cases The management of facilities, environment, and human resources follows the standard autopsy protocol suggested above. The initial samples should be sent to the BSL3 laboratory.

If there is a risk of infection due to damage of PPEs, skin exposure, aerosol-prone manipulation, or cutting injuries, the relevant autopsy personnel and his or her contacts should be provided with proper medical treatment, including disinfection and virus test. Also, for 2 weeks from the exposed time point, which is the expected incubation period of COVID-19, they should be isolated and excluded from the work, even though the initial test result is negative. The affiliated agency should monitor his or her symptoms.

(2) The autopsy for suspected or unknown cases If a virus test for the body is carried out during the autopsy, the participated autopsy personnel should minimize face-to-face contact, until the results are notified.

If the result of the virus test is positive, a postmortem test, such as toxicology (except for alcohol), biochemical, or genetic test should be requested, after the disinfection of the samples by mixing with 100% alcohol for 3 (sample):7 (alcohol) ratios. 24 Then the samples should be transported according to the standard protocol above. The management of the facilities, environments, and human resources generally follows the standard protocol above, while the disinfection process of the autopsy room and related facilities should refer to the KCDC guideline. If an infection is suspected, for example, due to a substandard autopsy procedure or damaged PPEs, the autopsy personnel and their contacts should be provided with proper medical treatment, including disinfection and virus test, with isolation and monitoring for 2 weeks, as mentioned above in section 6)- (1) . When the body is confirmed to be negative for the virus test, the isolation and monitoring could be discontinued.

Since the autopsy personnel are under constant risk of infection, there should be consistent effort for the implementation of the standard autopsy guidelines. First of all, expecting the periodic spread of infectious diseases in the future, the preparation of adequate level of PPEs 13/25 https://jkms.org https://doi.org/10.3346/jkms.2020.35.e310

and BSL of the autopsy related facilities, and the establishment of a health monitoring and surveillance system are required.

To compensate for the problems of the current death investigation system, which is focused on the judicial purpose, in the short term, the range of unnatural death considered as the subject of judicial autopsy should be expanded as wide as possible, in consultation with the police and the prosecution. In the long term, the autopsy request ordered by the directors of the Ministry of Health and Welfare or the KCDC should be encouraged with systemic supports. Also, the Ministry of Health and Welfare or the KCDC should be in charge of the management of biosafety requirements in the autopsy facilities and the arrangement of the qualified human resources and financial support, so that this guideline could be satisfactorily implemented.

Forensic medicine has developed and gradually improved over a long period, despite all the difficulties such as unfavorable environment and systemic constraints. However, in the upcoming post-COVID-19 era, there should be more integrated and organized provision, especially against the risk of infectious diseases. Health authorities and forensic pathologists should work together to improve the autopsy environment and the death investigation system, so that a better national health system can be established in the near future. 

Trends in infectious disease mortality

The Korean Society of Infectious Diseases. Guidelines for Potential Emerging Infectious Diseases in Korea. Seoul: The Korean Society of Infectious Diseases

Republic of Korea

Biosafety considerations for autopsy

Interim guidance for collection and submission of postmortem specimens from deceased persons under investigation (PUI) for COVID-19

Briefing on COVID-19: Autopsy Practice relating to Possible Cases of COVID-19

Guide to forensic pathology practice for death cases related to coronavirus disease 2019 (COVID-19) (Trial draft)

Central Disaster Management Headquarters and Central Disease Control Headquarters. Corona Virus Infection-19 Response Guideline. 7-4th ed. Cheongju: Central Disaster Management Headquarters and Central Disease Control Headquarters

Mycobacterium tuberculosis at autopsy--exposure and protection: an old adversary revisited

Occupational infections of health care personnel in Korea

Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission

Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection

Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

COVID-19 autopsies

WITHDRAWN: mortality of a pregnant patient diagnosed with COVID-19: A case report with clinical, radiological, and histopathological findings

Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases

Death in the course of judicial execution, such as arrest, interrogation, detention, etc

Death at the accommodation for health, welfare, and nursing, etc

1. The term "unnatural death" means a death falling under any of the following whose cause is unclear:A. Death suspicious, or confirmed to be related to a crime B. Accidental death due to natural disaster, traffic accident, safety accident, industrial accident, fire, drowning, etc. C. Suicide, or Death suspected as suicide D. Death in the course of judicial execution, such as arrest, interrogation, detention, etc. E. Death at the accommodation for health, welfare, and nursing F. Death suspected as acute poisoning by drug, pesticide, alcohol, gas, etc. G. Other death with unknown cause 2. The term "unnatural death case" means a case in which one or more bodies that correspond to, or are suspected of unnatural death, are found.

1. The director of an unnatural death case shall apply for a warrant for an autopsy in any of the following cases (referred to as a "priority control case"), unless there are special circumstances: A. Death suspected to be by murder B. Unidentified body, despite the investigation of belongings, fingerprints, etc. at the scene C. Death that is expected to draw social attention, such as collective death, child abuse, etc. D. Severely decomposed body, so hard to identify injuries or cause of death 2. The director of an unnatural death case shall consider a warrant for an autopsy in any of the following cases (referred to as a "autopsy-considered case"), to confirm the relation to a crime: A. Unexpected death of infant or child B. Death in the course of judicial execution, such as arrest, interrogation, detention, etc. C. Death suspected as acute poisoning by drug, pesticide, alcohol, gas, etc. D. Death suspected to be drowning or falling, for which eyewitness or CCTV footage is unavailable E. Body that is carbonized or skeletonized F. Death for which the bereaved family harbors suspicions about the cause G. Death by traffic accident suspicious for the relationship to other crime H. Death of a person with excessive death benefit, compared to his or her property I. Death with disagreement about the cause between the inspection doctor, the investigators, or the director of the case J. Other death for which autopsy is required to confirm its cause or circumstance