Monday, June 15, 2020

Brain and pulmonary post-mortem findings in a series of COVID-19 cases.   

JUNE 15, 2020

Brain and pulmonary post-mortem findings in a series of COVID-19 cases

By Denise Baez
NEW YORK -- June 15, 2020 -- Post-mortem brain and pulmonary findings from patients with coronavirus disease 2019 (COVID-2019) have been detailed in 2 separate case studies.
The first case series, published in The New England Journal of Medicine, showed hypoxic-ischaemic changes, but no encephalitis, meningitis, strokes, or changes in olfactory bulbs or tracts in the brains of 18 consecutive patients who died up to 32 days after the onset of symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
“Autopsies were performed in a uniform manner with sampling of 10 standard brain areas,” reported Isaac H. Solomon, MD, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues. “Gross inspection showed atherosclerosis in 14 brain specimens but no acute stroke, herniation, or olfactory bulb damage. Microscopic examination showed acute hypoxic injury in the cerebrum and cerebellum in all the patients, with loss of neurons in the cerebral cortex, hippocampus, and cerebellar Purkinje cell layer, but no thrombi or vasculitis. No microscopic abnormalities were observed in the olfactory bulbs or tracts.”
All patients had been treated for COVID-19 at Brigham and Women’s Hospital between April 14 and April 29, 2020. Most (78%) of the patients were male and the median age of all patients was 62 years. The patients had presented a median of 2 days after the onset of symptoms and were hospitalised for a median of 6 days before death. According to a retrospective chart review by neurologists, all patients had a confused state or decreased arousal from sedation for ventilation (61% received mechanical ventilation).
Testing of brain tissue was performed with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for the SARS-CoV-2 nucleocapsid protein, and immunohistochemical analysis was performed to detect SARS-CoV-2 in the same tissue blocks analysed by qRT-PCR.
“The virus was detected at low levels in 6 brain sections obtained from 5 patients; these levels were not consistently related to the interval from the onset of symptoms to death,” the authors reported. “Positive tests may have been due to in situ virions or viral RNA from blood. There was no staining in the neurons, glia, endothelium, or immune cells. Nonspecific staining in the choroid plexus was observed in 8 sections obtained from 7 patients; however, this signal was present in negative control brains and did not correlate with the qRT-PCR results.”
The next case series, published in The Lancet Infectious Diseases, showed that the predominant pattern of lung lesions in patients with COVID-19 patients was diffuse alveolar damage.
Luca Carsana, Papa Giovanni XXIII Hospital, Bergamo, Italy, and colleagues analysed lung tissue samples from 38 patients who died from COVID-19 in 2 hospitals in northern Italy between February 29, 2020, and March 24, 2020.
“To our knowledge, these data represent the first relevant provisional information regarding tissue damage specifically induced by SARS-CoV-2, besides the previously described diffuse alveolar damage, a feature that characterises interstitial pneumonia regardless of infectious agent,” the authors wrote.
A median of 7 tissue blocks were taken from each lung, selecting the most representative areas identified at macroscopic examination. To better characterise the inflammatory infiltrate, immunohistochemical staining was done on the most representative areas of randomly selected cases for inflammatory infiltrate and cellular components, including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67.
Upon macroscopic examination, the lungs of all patients were heavy, congested, and oedematous, with patchy involvement. In all cases, histological examination revealed features corresponding to the exudative and early or intermediate proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).
“Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent,” the authors wrote. “Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.”
The patients had a mean age of 69 years and most (87%) were male. Time spent in the intensive care unit or intermediate medical ward ranged from 1 day to 23 days. At the time of hospitalisation, all patients had clinical and radiological features of interstitial pneumonia. Of the 26 patients with available D-dimer results, all had high values (>10 × the upper reference limit). Mean time from symptom onset to death was 16 days.
SOURCE: The New England Journal of Medicine and The Lancet Infectious Diseases

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