Interesting that the acute hypoxic injury is not large enough to be called stroke, probably because it is diffused throughout the brain and would never show up in a CT or MRI scan. Also that the autopsies of lungs showed lots of alveolar(lungs) capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza. So lots of thrombi in the lungs but not in the brain, something doesn't sound right here. This means that my massive anti-coagulation strategy needs to be immediately applied after diagnosis
Neuropathological Features of Covid-19
To the Editor:
Neurologic symptoms, including headache, altered mental status, and anosmia, occur in many patients with Covid-19.1-3
We report the neuropathological findings from autopsies of 18
consecutive patients with SARS-CoV-2 infection who died in a single
teaching hospital between April 14 and April 29, 2020.
All
the patients had nasopharyngeal swab samples that were positive for
SARS-CoV-2 on qualitative
reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays. The
median age was 62 years (interquartile range, 53 to 75), and 14 patients
(78%) were men. The presenting neurologic symptoms were myalgia (in 3
patients), headache (in 2), and decreased taste (in 1). Coexisting
conditions included diabetes mellitus (in 12 patients), hypertension (in
11), cardiovascular disease (in 5), hyperlipidemia (in 5), chronic
kidney disease (in 4), prior stroke (in 4), dementia (in 4), and treated
anaplastic astrocytoma (in 1) (see Tables S1 and S2 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).
The
patients had presented a median of 2 days (interquartile range, 0 to 5)
after the onset of the first symptoms of SARS-CoV-2 infection and were
hospitalized for a median of 6 days (interquartile range, 2 to 9) before
death (Fig. S1A); 11 received mechanical ventilation. According to a
retrospective chart review by neurologists, all the patients had a
confusional state or decreased arousal from sedation for ventilation.
Brain magnetic resonance imaging, electroencephalographic imaging, and
cerebrospinal fluid examinations were not performed. Cranial computed
tomography without contrast was performed in 3 patients and showed no
acute abnormalities; the tumor resection cavity in the patient with a
known anaplastic astrocytoma was seen.
Table 1. 
Gross Findings and Results of Histologic Analysis to Detect SARS-CoV-2.
Death
occurred 0 to 32 days after the onset of symptoms (median, 8 days;
mean, 10 days). Autopsies were performed in a uniform manner with
sampling of 10 standard brain areas. Specimens were fixed in formalin
and stained with hematoxylin and eosin, as described in the Materials
and Methods section in the Supplementary Appendix.
Gross inspection showed atherosclerosis in 14 brain specimens but no
acute stroke, herniation, or olfactory bulb damage. Residual anaplastic
astrocytoma was seen in the patient who had received a diagnosis of
anaplastic astrocytoma previously (Table 1).
Microscopic examination (Fig. S1B) 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. Rare foci of perivascular lymphocytes were
detected in 2 brain specimens, and focal leptomeningeal inflammation was
detected in 1 brain specimen. No microscopic abnormalities were
observed in the olfactory bulbs or tracts (Fig. S2).
Testing
of brain tissue was performed with quantitative RT-PCR (qRT-PCR) for
the SARS-CoV-2 nucleocapsid protein (techniques are described in the
Materials and Methods section in the Supplementary Appendix).
As shown in Table S3, for 2 patients, all 10 sections were tested, and
for the remaining 16 patients, 2 sections were tested (1 from the
frontal lobe and olfactory nerve and 1 from the medulla). The results
were equivocal (defined as a viral load of <5.0 copies per cubic
millimeter) in 5 of 10 brain sections from 1 patient and in 4 of 10
sections from another patient (Table S3); the remaining 11 sections
obtained from these 2 patients were negative. In 32 sections obtained
from the remaining 16 patients, 3 sections from the medulla and 3
sections from the frontal lobes and olfactory nerves were positive (5.0
to 59.4 copies per cubic millimeter); the results were equivocal in 20
sections and negative in 6 sections. The test results in relation to the
interval between the onset of symptoms and death were inconsistent
(Fig. S1).
Immunohistochemical analysis (as described in the Supplementary Appendix)
was performed to detect SARS-CoV-2 in the same tissue blocks analyzed
by qRT-PCR (in 52 blocks from 18 patients). 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 (Figs. S1 and S3). The tumor blocks
obtained from the patient with anaplastic astrocytoma were not tested by
qRT-PCR or immunohistochemical analysis to detect SARS-CoV-2.
In
conclusion, histopathological examination of brain specimens obtained
from 18 patients who died 0 to 32 days after the onset of symptoms of
Covid-19 showed only hypoxic changes and did not show encephalitis or
other specific brain changes referable to the virus. There was no
cytoplasmic viral staining on immunohistochemical analysis. 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. Positive tests may have been due to in situ
virions or viral RNA from blood.
Erica Normandin, B.A.
Broad Institute, Cambridge, MA
Broad Institute, Cambridge, MA
Shamik Bhattacharyya, M.D.
Brigham and Women’s Hospital, Boston, MA
Brigham and Women’s Hospital, Boston, MA
Shibani S. Mukerji, M.D., Ph.D.
Kiana Keller, B.S.
Massachusetts General Hospital, Boston, MA
Kiana Keller, B.S.
Massachusetts General Hospital, Boston, MA
Ahya S. Ali, M.B., B.S.
Brigham and Women’s Hospital, Boston, MA
Brigham and Women’s Hospital, Boston, MA
Gordon Adams, B.A.
Broad Institute, Cambridge, MA
Broad Institute, Cambridge, MA
Jason L. Hornick, M.D., Ph.D.
Robert F. Padera, Jr., M.D., Ph.D.
Brigham and Women’s Hospital, Boston, MA
Robert F. Padera, Jr., M.D., Ph.D.
Brigham and Women’s Hospital, Boston, MA
Pardis Sabeti, M.D., D.Phil.
Broad Institute, Cambridge, MA
Broad Institute, Cambridge, MA
Supported
by a grant (2U19AI110818, to Ms. Normandin and Dr. Sabeti) from the
National Institutes of Health (NIH), a grant (to Ms. Normandin and Dr.
Sabeti) from the Howard Hughes Medical Institute, and a grant
(K23MH115812, to Dr. Mukerji) from the NIH.
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on June 12, 2020, at NEJM.org.
Dr. Solomon and Ms. Normandin contributed equally to this letter.
No comments:
Post a Comment