Characteristics of indoor and outdoor fatal hypothermia cases in Chiba, Japan.

In forensic medicine, hypothermia is a frequently encountered cause of death, and this characteristic provides public health information to prevent similar deaths in the future. Previous studies revealed regional differences in hypothermia occurrence (indoors or outdoors). However, to our knowledge, no recent studies in Japan have directly compared the characteristics of indoor- and outdoor-onset cases based on forensic autopsy reports. Hence, this study aimed to determine the characteristics and risks of unexpected hypothermia-related death. It included 218 cases from the Chiba Prefecture, Japan, wherein forensic autopsies were performed and hypothermia was diagnosed; these cases were categorized into indoor- and outdoor-onset cases, and their characteristics were examined. The results showed no significant differences between the two groups in relation to the age of onset or residential environment (i.e., the presence or absence of cohabitants). The outdoor-onset group tended to have a higher incidence of dementia. Regarding the causes of hypothermia, the indoor group had more internal causes (p < 0.0001), whereas the outdoor group had more primary and external causes (p < 0.0001 and p = 0.0029, respectively). The indoor group was more undressed than the outdoor group. Atypical antipsychotic components were predominantly detected in the blood in the outdoor group (p = 0.0077). The body mass index tended to be lower in the indoor group than in the outdoor group. Broadening public awareness of the present study findings may aid in developing preventative strategies for hypothermia based on the location of onset.

Autopsy doesn't always tell all: The importance of exhuming skeletal remains of cemetery unidentified decedents.

The process of personal identification differs according to the state of preservation of the corpse, becoming more complicated when dealing with remains altered by taphonomic variables. Since 2015, the staff of the Laboratory of Forensic Anthropology and Odontology (LABANOF) of the University of Milan has been engaged in recovering the skeletons of 36 unknown people from the cemeteries of the city of Milan, to redraw their biological profiles and give them back the possibility of being identified. Of the 36 starting skeletons, 7 have been identified and therefore are not the object of this study, 25 individuals were previously subjected to an autopsy examination and 4 skeletons were studied for the first time in the present work. The post-mortem data of all the individuals who had previously undergone autopsy and had not yet been identified (n = 25) have been retrieved from the archives of the Institute of Forensic Medicine in Milan and allowed for a comparison with those obtained from the new anthropological study of each exhumed skeleton. The authors aim to present the three most interesting cases to better highlight the results that emerged from the comparison. The autopsy information alone lacked important details. In all cases, the anthropological examination proved to be capable of detailing the biological profile of the unknowns even after a long period of inhumation (even more than 20 years). The limitations of instrumental investigations in achieving the goal single-handedly and the importance of recovering the unknown skeletons from cemeteries for identification purposes are discussed.

Molecular autopsy in Chinese sudden cardiac death in the young.

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5-year result (2017-2021) of molecular autopsy services provided for victims of SCDY (age 1-40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016-2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)-causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD-causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at-risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted.

Profile of Mortal Injuries in Vehicular Accidents: An Autopsy-Based Study.

Background It is crucial to analyze the trends of fatal injuries among pedestrians, passengers, motorcycle riders, and drivers of three- and four-wheelers in traffic accidents. Objective To ascertain the trend of fatal injuries to the head, chest, and abdomen across different victim categories in vehicular accidents. Materials and methods An autopsy-based prospective study was carried out in the mortuary of a rural tertiary care hospital. A total of 108 fatal cases of vehicular accidents were taken into consideration. All natural and unnatural deaths, other than those stemming from vehicle crashes, were excluded from this study; only the victims of fatal vehicular accidents were included. Results Males outnumbered female victims by 8.8:1. The age range of 41-60 years was the most affected (38.9%). The greatest number of victims (17, or 15.8%) were male motorcycle riders in the range of 21-40 years. Most vehicular mishaps (61; 56.5%) occurred during the evening. The most frequent injury pattern reported was head injuries (53.4%). Conclusions Motorcycle riders constituted the most severely injured victim category in a vehicular accident. Most mishaps occurred in the dark because of inadequate lighting or bad road conditions in rural areas. Furthermore, the most frequently occurring type of injury was an injury to the head, which may be an outcome of riders' lack of compliance with the mandatory helmet-use policy.

Death following cylindrical battery ingestion associated with toxic manganese levels.

Cases of battery ingestion are well documented in the scientific literature, especially concerning button cell battery ingestion in children. In this instance, the authors present an atypical case of a young man who voluntarily ingested a cylindrical alkaline battery containing manganese. The patient died approximately a week later, despite not exhibiting any specific symptoms. The battery was found in the cecum during the autopsy, showing deterioration at its positive pole. The cecal mucosa exhibited two ulcerations without perforation. Histological analysis revealed intestinal ischemia in the cecum, with no microscopic lesions in other organs. Toxicology reports indicated high levels of manganese in both cardiac and peripheral blood. Considering all the results from the additional analyses, the experts concluded that the death was likely of multifactorial origin, associated with a toxic blood concentration of manganese. To the best of our knowledge, this is the first recorded death following the ingestion of a cylindrical battery, and the first instance of manganese intoxication resulting from the ingestion of an alkaline battery. The authors will present the case and provide a literature review to assess the extent to which the presence of manganese may have contributed to the fatality.

Selective postmortem arterial angiography of head and neck using digital x-ray or computed tomography: A practical and rapid method to identify vascular injuries.

Identification of vascular injuries is crucial for complete postmortem evaluation and understanding of trauma deaths by the Medical Examiner. Some vascular injuries are difficult to evaluate due to challenging anatomic locations, especially in the head and neck. Documenting injuries of the facial and vertebral arteries is challenging and necessitates time-consuming dissections that can create artifacts and disfigurement. In busy medical examiner offices with a significant number of traumatic injuries, finding a creative solution to employ reliable postmortem angiography is desirable. At the Office of the Chief Medical Examiner for the State of Maryland (OCME), we created and effectively implemented a selective angiography procedure using traditional indwelling Foley catheters and water-soluble barium swallow contrast to evaluate arterial injuries using either digital radiography or computed tomography imaging modalities. This technique and imaging interpretation can be performed by a medical examiner or forensic pathology fellow after basic technical training and basic radiology training. This study outlines the technique, methods, and utilization of the procedure and describes the findings of six deaths due to vascular lesions from different injury mechanisms and disease processes and describes the ease of implementation on a broader scale in busy Medical Examiner's offices.

Streptococcal Toxic Shock Syndrome with Multiple Cerebral Infarctions Caused by Streptococcus dysgalactiae subsp. equisimilis: An Autopsy Case Report.

We herein report an autopsy case of streptococcal toxic shock syndrome with disseminated intravascular coagulation and multiple cerebral infarctions induced by Streptococcus dysgalactiae subsp. equisimilis (STSS) in an 84-year-old male. Pathological examination revealed sepsis with hemophagocytosis in the reticular system and intravascular bacteria in multiple organs, originating from bacterial necrotizing fasciitis of the lower extremities. The brain MRI findings showed a DWI-FLAIR mismatch, whereas the pathology was almost normal, thus supporting a hyperacute phase of cerebral infarction. The findings in this case help to elucidate the pathogenesis of STSS and develop appropriate treatment strategies.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles.

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review.

BACKGROUND: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. METHODS: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. RESULTS: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. CONCLUSIONS: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.

Minimally invasive autopsy - endoscopic approach to post-mortem diagnostics.

The noticeable decline in the number of autopsies performed in recent years requires investigation into the causes of the phenomenon and attempts to prevent it. One potential cause of this trend is fear of disfiguring the body. Carrying out autopsies using a minimally invasive method may reduce the decrease in the number of autopsies performed. The first work on the development of the method and its continuation gave promising results. This allows us to start a discussion on attempts to introduce the method. The solution seems especially justified when the alternative is to completely abandon post-mortem examinations using the traditional method. Laparoscopy and thoracoscopy are tools that allow for accurate imaging and analysis of organ changes. Enriching them with additional tests using endoscopic techniques may have a positive impact on the accuracy of autopsy diagnoses. The development of a clear protocol for minimally invasive post-mortem diagnosis requires further research to determine the accuracy of the method.

Immunohistochemical Diagnosis of Amyloid Typing: Utility and Limitations as Determined by Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood. METHODS: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-ß2-microglobulin antibodies in 40 autopsy cases. RESULTS: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis. CONCLUSIONS: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.

Single-camera photogrammetry using a mobile phone for low-cost documentation of corpses.

Photogrammetry is a technique for studying and defining objects' shape, dimension, and position in a three-dimensional space using measurements obtained from two-dimensional photographs. It has gained popularity following the development of computer graphics technologies and has been applied to various branches of medicine. In this study, the authors present a method for low-cost photorealistic documentation of corpses during autopsy using single-camera photogrammetry with a mobile phone. Besides representing the body by demonstrating the injured and non-injured body parts as control, evidencing the body parts on a 3D reconstruction allows easy explanation to nonmedical experts such as lawyers.

Histopathological Investigation of Progressive Encephalomyelitis with Rigidity and Myoclonus: An Autopsy Case Characterized by Oculomotor Dysfunction and Autonomic Failure.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disease associated with the presence of anti-glycine receptor (GlyR) antibodies. We herein report an autopsy case of an 80-year-old man diagnosed with anti-GlyR antibody-positive PERM who presented with symptoms of oculomotor dysfunction and autonomic failure. Despite intensive immunotherapy, the neurological symptoms showed almost no improvement, and the patient succumbed to aspiration pneumonia and bacterial translocation. Postmortem pathology revealed mild inflammatory changes and neuronal loss that were disproportionate to a severe clinical presentation. These results suggest that the clinical symptoms of PERM may result from antibody-mediated GlyR internalization, leading to neuronal disinhibition, rather than a neuroinflammatory signature.

Diagnostic accuracy of post-mortem computed tomography for fractures of the hyoid-larynx complex.

Post-mortem computed tomography (PMCT) is routinely used at many forensic institutions to guide the following autopsy and is especially useful for diagnosing fractures. This systematic review aims to investigate the sensitivity and specificity of a PMCT scan in fracture diagnosis of the hyoid-larynx complex (HLC) compared to traditional autopsy in cases involving traumatic neck injuries. We searched PubMed, SCOPUS and Web of Science and included papers with cases n ≥ 3 published between January 2000 and April 2023 reporting on PMCT and autopsy findings of fractures of the HLC. The search provided 259 results of which 10 were included. Overall sensitivity and specificity were 0.70 [0.59; 0.79] and 0.92 [0.80; 0.97] for hyoid bone fractures and 0.80 [0.62; 0.91] and 0.76 [0.63; 0.85] for the thyroid cartilage. The results show great variation, and a large range between studies. These results indicate that PMCT cannot replace autopsy in cases with HLC fractures. Future larger prospective studies are needed, examining fracture details, scan protocols and different slice thicknesses using uniform reporting.

Sudden cardiac death due to an obstructive large right atrial myxoma.

Sudden cardiac death is a phenomenon that affects more than 200,000 individuals annually in the United States. Among sudden cardiac deaths, only a fractionally small portion is thought to be attributable to intracardiac neoplasms. Though rarely implicated as the primary cause of death, cardiac myxomas are the most common benign neoplasms of the heart and have been known to cause death due to multifactorial embolic events, fatal arrhythmias, and frank obstructive events. In this case, a healthy, asymptomatic young male was found unresponsive in his residence. Examination of the heart at autopsy revealed dilation of the right atrium and a large, hemorrhagic, irregular, and obstructing mass arising from the right atrium, consistent with cardiac myxoma. When unusual cardiac findings are discovered at autopsy, a systematic investigation of the heart, including retaining the organ for cardiac pathology consultation, is mandatory to correctly identify the cause of death.

Forensic Assessment of Alcohol Intoxication in Cases of Fatal Road Traffic Accidents in Lithuania.

Background: There is strong evidence that alcohol consumption is a significant risk factor for fatal road traffic accidents. It is estimated that the number of alcohol-related road accidents remains high in the past few years in Lithuania. This study aims to examine the prevalence of alcohol in blood samples collected from the autopsy results of road traffic accident victims. Materials and methods: A retrospective study of 136 road traffic accident victims was performed in State Forensic Medicine Service of Lithuania in the period of 2013 to 2023. We analyzed blood alcohol concentration (BAC) in relation to sex, age, road user type, place and time of the day at death. Results: 31% of the victims were under influence of alcohol at the time of death, with mean BAC 1.99 ± 0.92‰. The mean BAC was 2.16 ± 0.8‰ in male and 1.18 ± 1.12‰ in female group. By the type of road users, 23% of the pedestrians (mean BAC 2.45 ± 0.71‰), 32% of car drivers (mean BAC 2.13 ± 0.75‰), 41% of vehicle passengers (mean BAC of 1.73 ± 1.19‰), 37% of the motorcycle riders (mean BAC of 1.28 ± 0.53‰), 37% of the cyclists (mean BAC of 1.15 ± 0.75‰) were found to be intoxicated during the time of accident. Highest mean blood alcohol concentration was found during the night time hours (9 p. m. - 5 a. m.) 2.28 ± 0.91, comparing to in afternoon hours (12 p. m. - 5 p. m.) 1.49 ± 0.99, evening hours (5 p. m. - 9 p. m.) 2.10 ± 0.73 and morning hours (5 a. m. - 12 p. m.) 1.94 ± 1.00. The mean BAC in road traffic accidents during summer was 1.48 ± 0.71‰, spring 2.25 ± 0.76‰, autumn 2.12 ± 1‰, winter 2.42 ± 1‰. Conclusions: Alcohol consumption by road users is a significant contributing factor in road traffic accidents and their outcomes in Lithuania.

Deaths during Sexual Activity.

Background: Deaths during sexual activities are rarely identified phenomena in forensic medicine practice. Most often, such deaths are classified as accidents or deaths due to the manifestation of certain diseases during sexual activity. It is important to rule out homicide or suicide as the cause of death when investigating sexual deaths. Determining the cause of death requires a comprehensive assessment of the evidence and circumstances and should not be based solely on autopsy findings. When determining the cause of death, it is necessary to evaluate the circumstances of the discovery, important evidence found near the body, the position of the deceased, the place where the deceased was found, and the characteristics of the environment. Cases: Case 1: A 65-year-old male was clothed in women's underwear and was found hanging in a noose in a bedroom after a house fire. The autopsy revealed a ligature mark on the neck, bruises in neck muscles, tears in carotid arteries, and signs of acute pulmonary distension. The cause of death was determined to be suffocation due to neck compression by a ligature, compounded by significant alcohol intoxication, with additional postmortem burns covering 30% of the body surface area likely occurring after death.Case 2: A 55-year-old naked male was found without external injuries but with a plastic tube inserted into the rectum, causing a 2.5 cm rupture in the ileum. The perforation led to complications, including purulent diffuse peritonitis, intoxication, and acute cardiac and respiratory failure, resulting in death within 3-6 hours after insertion. Concurrent findings included atherosclerotic changes in the heart, internal organ hyperemia and edema, hepatic steatosis, renal cyst, and a lack of ethyl alcohol in blood but 0.17 ‰ presence in urine according to toxicology analysis. Conclusions: A detailed evaluation of all the evidence is very important in the forensic examination of the deceased during sexual activity. Therefore, to determine the cause of death, not only the autopsy data, toxicological and microscopic examinations of the deceased are important, but also the evaluation of all findings at the scene. The most common cause of death of an autoerotic nature is asphyxia, and the most commonly identified group of the dead are men aged around 40 years.

Malaria Tropica: An Autopsy Case Report With a Discussion on the Presence of Malaria in Bulgaria.

Malaria is an infectious disease caused by several types of parasitic plasmodia and transmitted to humans through Anopheles mosquitoes. The disease has long been widespread and has caused a significant number of deaths and decreased life quality from sequelae worldwide. As understanding of the disease increased immensely at the beginning of the 20th century, eradication plans were implemented to decrease disease transmission. This led to the successful eradication of malaria across predominantly industrialized countries, with multiple geographic areas remaining malaria endemic zones to this day. With climate changes and migration, the risk of reintroduction of malaria to malaria-free zones has risen due to relatively easy travel to endemic zones and importation of cases. On the one hand, this is a significant public health risk and, on the other, a challenge to the medical system, as healthcare workers in malaria-free zones are often ill-prepared to recognize, diagnose, and treat malaria cases. Herein, we present an autopsy and histopathology case report of tropical (falciparum) malaria, complicated with blackwater fever (malignant malaria) with prevalent gross and histopathological changes, including hemomelanin deposition in the spline, liver, and bone marrow; visible parasitic forms in the remaining red blood cells; Durk's granulomas, sludge, and petechial hemorrhages in the central nervous system; and hemoglobin casts within the renal tubular structures. We also discuss the history and risk of reintroducing malaria into a malaria-free zone - Bulgaria.

Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls was performed, excluding patients previously treated with glucocorticoids. Several SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity of mineralocorticoids and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls, excluding those that affected adrenal function. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with those in SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with exacerbation of inflammation, differentiation and the presence of dual-ZG/ZF identity cells. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of adrenal axis and the corticosteroid sensitivity.