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Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation.

ABSTRACT: Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.

SUBMITTER: Evert K

PROVIDER: S-EPMC7816067 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE:To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN:Prospective cohort study. SETTING:Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS:The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS:Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS:Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION:Limited sample size. CONCLUSION:The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE:University Medical Center Hamburg-Eppendorf.

Project description:The severe acute respiratory syndrome (SARS)-CoV-2 was identified for the first time in China, in December 2019. Confirmed cases of COVID-19 have been reported around the world; indeed, this infection has been declared a pandemic. Consequently, the scientific community is working hard to gain useful information about the history of this virus, its transmission, diagnosis, clinical features, radiological findings, research and development of candidate therapeutics as well as vaccines. This review aims to analyze the diagnostic techniques used to ascertain the COVID-19 infection, critically reviewing positive points and criticism for forensic implications, obviously including autopsy. Finally, this review proposes a practical workflow to be applied in the management of corpses during this outbreak of the COVID-19 infection, which could be useful in cases of future infectious disease emergencies. Analyzing the diagnostic methods, to date, virus nucleic acid RT-PCR represents the standard method used to ascertain the COVID-19 infection in living subjects and corpses, even if this technique has several criticisms: mainly, the staff should be highly specialized, working in high-throughput settings, able to handle high workloads and aware of health risks and the importance of the results. Thus, IgG/IgM serological tests have been developed, overcoming RT-qPCR duration, costs, and management, not requiring highly trained personnel. Nevertheless, serological tests present problems; the WHO recommends the use of these new point-of-care immunodiagnostic tests only in research settings. Furthermore, nothing has yet been published regarding the possibility of applying these methods during post-mortem investigations. In light of this scenario, in this review, we suggest a flow chart for the pathologist called on to ascertain the cause of death of a subject with historical and clinical findings of COVID-19 status or without any anamnestic, diagnostic, or exposure information. Indeed, the literature data confirmed the analytical vulnerabilities of the kits used for laboratory diagnosis of COVID-19, particularly during postmortem examinations. For these reasons, autopsy remains the gold standard method to ascertain the exact cause of death (from or with COVID-19 infection, or other causes), to consequently provide real data for statistical evaluations and to take necessary measures to contain the risks of the infection. Moreover, performing autopsies could provide information on the pathogenesis of the COVID-19 infection with obvious therapeutic implications.

Project description:Objective: This study aimed to investigate the evolution of radiological findings in the patients with coronavirus disease 2019 (COVID-19) pneumonia with different severities from onset to 1-year follow-up and identify the predictive factors for different pulmonary lesion absorption status in the patients infected with COVID-19. Methods: A retrospective study was performed on the clinical and radiological features of 175 patients with COVID-19 pneumonia hospitalized at three institutions from January 21 to March 20, 2020. All the chest CT scans during hospitalization and follow-ups after discharge were collected. The clinical and radiological features from the chest CT scans both at the peak stage and before discharge from the hospital were used to predict whether the pulmonary lesions would be fully absorbed after discharge by Cox regression. Then, these patients were stratified into two groups with different risks of pulmonary lesion absorption, and an optimal timepoint for the first CT follow-up was selected accordingly. Results: A total of 132 (75.4%) patients were classified into the non-severe group, and 43 (24.6%) patients were classified into the severe group, according to the WHO guidelines. The opacification in both the groups changed from ground-glass opacity (GGO) to consolidation and then from consolidation to GGO. Among the 175 participants, 135 (112 non-severe and 23 severe patients with COVID-19) underwent follow-up CT scans after discharge. Pulmonary residuals could be observed in nearly half of the patients (67/135) with the presentation of opacities and parenchymal bands. The parenchymal bands in nine discharged patients got fully absorbed during the follow-up periods. The age of patient [hazard ratio (HR) = 0.95, 95% CI, 0.95-0.99], level of lactate dehydrogenase (LDH) (HR = 0.99; 95% CI, 0.99-1.00), level of procalcitonin (HR = 8.72; 95% CI, 1.04-73.03), existence of diffuse lesions (HR = 0.28; 95% CI, 0.09-0.92), subpleural distribution of lesions (HR = 2.15; 95% CI, 1.17-3.92), morphology of residuals (linear lesion: HR = 4.58, 95% CI, 1.22-17.11; nodular lesion: HR = 33.07, 95% CI, 3.58-305.74), and pleural traction (HR = 0.41; 95% CI, 0.22-0.78) from the last scan before discharge were independent factors to predict the absorption status of COVID-19-related pulmonary abnormalities after discharge. According to a Kaplan-Meier analysis, the probability of patients of the low-risk group to have pulmonary lesions fully absorbed within 90 days reached 91.7%. Conclusion: The development of COVID-19 lesions followed the trend from GGO to consolidation and then from consolidation to GGO. The CT manifestations and clinical and laboratory variables before discharge could help predict the absorption status of pulmonary lesions after discharge. The parenchymal bands could be fully absorbed in some COVID-19 cases. In this study, a Cox regression analysis indicated that a timepoint of 3 months since onset was optimal for the radiological follow-up of discharged patients.

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Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation.

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