The Black Swan: The Impact of the Highly Improbable

A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression.

This systematic review summarizes the evidence on the earliest patients with COVID-19-HIV co-infection. We searched PubMed, Scopus, Web of Science, Embase, preprint databases, and Google Scholar from December 01, 2019, to June 1, 2020. From an initial 547 publications and 75 reports, 25 studies provided specific information on COVID-19 patients living with HIV. Studies described 252 patients, 80.9% were male, the mean age was 52.7 years, and 98% were on antiretroviral treatment (ART). Co-morbidities in addition to HIV and COVID-19 (multimorbidity) included hypertension (39.3%), obesity or hyperlipidemia (19.3%), chronic obstructive pulmonary disease (18.0%), and diabetes (17.2%). Two-thirds (66.5%) had mild to moderate symptoms, the most common being fever (74.0%) and cough (58.3%). Among patients who died, the majority (90.5%) were over 50 years old, male (85.7%), and had multimorbidity (64.3%). Our findings highlight the importance of identifying co-infections, addressing co-morbidities, and ensuring a secure supply of ART for PLHIV during the COVID-19 pandemic.

/pdf/covid-19-among-people-living-with-hiv-a-systematic-review-4hy64ggfvk.pdf

COVID-19 Among People Living with HIV: A Systematic Review.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.

/pdf/covid-19-famotidine-histamine-mast-cells-and-mechanisms-1bq9couen3.pdf

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated cardiac injury has been postulated secondary to several mechanisms. While tissue diagnosis is limited during the acute illness, postmortem studies can help boost our understanding and guide management. Objective: To report the cardiac tissue autopsy findings in coronavirus disease 2019 (COVID-19) decedents. Evidence Review: Articles published in PubMed and Embase reporting postmortem cardiac pathology of COVID-19 decedents till September 2020. We included adult studies excluding preprints. The Joanna Briggs Institute Critical Appraisal Checklist for Case Reports was used to assess quality. We extracted gross and histology data as well as the incidence of myocarditis, cardiac ischemia, thrombosis, and dilatation. We also looked at the reported cause of death (PROSPERO registration CRD42020190898). Findings: Forty-one relevant studies identified including 316 cases. The deceased were mostly male (62%) and elderly (median age, 75; range, 22-97 years). The most common comorbidities were hypertension (48%) and coronary artery disease (33%). Cardiac pathologies contributed to the death of 15 cases. Besides chronic cardiac pathologies, postmortem examination demonstrated cardiac dilatation (20%), acute ischemia (8%), intracardiac thrombi (2.5%), pericardial effusion (2.5%), and myocarditis (1.5%). SARS-CoV-2 was detected within the myocardium of 47% of studied hearts. Conclusions and Relevance: SARS-CoV-2 can invade the heart, but a minority of cases were found to have myocarditis. Cardiac dilatation, ischemia, mural, and microthrombi were the most frequent findings. The systematic review was limited by the small number of cases and the quality of the studies, and there is a need to standardize the cardiac postmortem protocols.

/pdf/covid-19-and-the-heart-a-systematic-review-of-cardiac-twidshotmz.pdf

COVID-19 and the Heart: A Systematic Review of Cardiac Autopsies

Case details: A case of a 50-year old HIV-positive man is presented, with focus on visualization of post-mortem computed tomography (PMCT) of the lungs, in comparison to a forensic control case. He had been found dead at home, a day after his nasopharyngeal swab had returned positive for SARS-COV-2, three days after the sample had been taken as an outpatient, over five weeks after first exhibiting possible symptoms. 3D-visualization was performed by visually discriminating correlates for aerated, poorly aerated and non-aerated lung regions. The visual side-by-side comparison with a control case shows the deterioration beyond any ”normal” post-mortem finding, however. The PMCT findings in the lungs resemble those of patients with acute respiratory distress syndrome (ARDS), while histologically identified inflammation also shows, in part binuclear, lymphocytes. In addition, acute liver dystrophy and acute tubular necrosis in the kidneys were found. Except coronary artery atherosclerosis, there appeared to be no remarkable pathology of the heart.
Comment: With the pandemic impact of SARS-COV-2, a range of issues unfolds, also for medicolegal investigations into deaths, as we report the first Swiss case with post-mortem CT where death had occurred due to a SARS-COV-2 infection, with features of a severe acute respiratory distress syndrome, as an outpatient. As this pandemic from the view of risk assessment does constitute a black swan, underestimated fat tails as technical reason should be addressed by also analyzing apparent extreme single observations. This case of an outpatient (without hospital or intensive-care treatment) shows a pulmonary progression beyond the typical findings of COVID-19, to a non-specific picture of ARDS, where histologically, in part binuclear lymphocytes were remarked. What appeared to be an initially slow progression with final rapid escalation raises the question whether nasopharyngeal swabs alone or added pulmonary CT might be better for screening high-risk patients. The reported symptoms and relatively late medical consultation in this case appeared to contrast with the extensive pathology, raising the question whether any search for super-spreaders should not just focus on asymptomatic but under-reported symptomatic patients, and whether their prolonged circulation in everyday life would justify measures such as for example more extensive face mask policies. As post-mortem testing for SARS-COV-2 may not be available for every case, PMCT may provide sensitive testing for lung changes related to COVID-19. In order to allow for more precise medicolegal investigations in the context of COVID-19, however, any more specific extra tests may have to be financed by stakeholders in epidemiology, infectious disease or policy.

Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19

We report a case of a contraindicated attachment of a speaking valve to a tracheal tube with an inflated cuff, which rapidly resulted in the patient’s death. The attached one-way valve allowed unrestrained inspiration through the tracheal tube but prevented physiological expiration. The increased pulmonary pressure resulted in alveolar rupture and replaced expiration with a steady release of air into the peribronchial sheaths and the mediastinum, resulting in what is commonly known as the Macklin effect. From the mediastinum, air inflated both pleural cavities, the peritoneum, and the subcutaneous tissue of the entire body. No gas was found in the blood vessels, the brain, the bones, or in the inner organs. The entire air volume was estimated by radiological segmentation to be more than 25 l. This implies continuous inspiration, while expiration turned into an aberrant pulmonary decompression by whole-body gas-enclosure. Death ultimately resulted from asphyxia following bilateral (tension) pneumothorax.

Fatal bilateral pneumothorax and generalized emphysema following contraindicated speaking-valve application.

As it is unclear if and how long DNA evidence can persist on submerged skin, we examined the potential for recovery of touch DNA and blood stain DNA from skin samples immersed in different aquatic environments and temperatures for forensic purposes in this proof-of-concept study. We used pig skin, either smeared with human blood or held firmly for 30 s by two test-persons, before immersing it in either cold, room-temperature or warm water as well as in a stream and a pond for up to seven days prior to DNA testing. The samples were then typed at 16 STR loci. Cold water samples yielded the most promising results, as shown by the recovery of the full set of 16 reproducible STR loci from the touch DNA sample of one test-person after 7 days. For blood stains, we were able to recover all 16 reproducible STRs after 2 days. Room-temperature water and warm water yielded varying results for both blood stain DNA and touch DNA. For pond and stream samples, DNA recovery was possible only within two days. While the pond and stream samples were at relatively cold temperatures, DNA recovery may have been affected by the presence of water insects and snails in the pond and mud in the stream. Our findings show the potential of using immersed samples, particularly those immersed in cold water, as we could detect a complete DNA profile from blood stains and from touch DNA after several days. Our study opens the way for future in-depth studies, examining larger datasets and a wider range of conditions.

Eva Meixner

Papers

Implications for forensic death investigations from first Swiss post-mortem CT in a case of non-hospital treatment with COVID-19

Fatal bilateral pneumothorax and generalized emphysema following contraindicated speaking-valve application.

Persistence and detection of touch DNA and blood stain DNA on pig skin exposed to water

Rapid death following undiagnosed stercoral perforation in a chronic opioid user.