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COVID-19



COVID-19


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May 27, 2022


ARE CEREBROSPINAL FLUID SARS-COV-2 ANTIGENS ASSOCIATED WITH CENTRAL NERVOUS
SYSTEM INFLAMMATION IN PATIENTS WITH COVID-19?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid
antigen (N-Ag) was detectable in cerebrospinal fluid (CSF) in most patients
hospitalised with acute coronavirus disease 2019 (COVID-19), despite the absence
of detectable CSF viral RNA, and was correlated with central nervous system
(CNS) immune activation, according to a study published in JAMA Network Open. 

“Furthermore, neurosymptomatic patients had a more pronounced immune activation
profile compared with neuroasymptomatic patients, and patients with COVID-19 had
signs of neuroaxonal injury compared with controls. These observations could not
be attributed to differences in COVID-19 severity, where no differences in CSF
biomarkers were seen in patients with moderate compared with severe disease,”
reported Arvid Edén, MD, University of Gothenburg, Gothenburg, Sweden, and
colleagues. “These results highlight the clinical relevance of neurologic
symptoms and suggest that viral components can contribute to CNS immune
responses without direct viral invasion.”

The study performed from March 1, 2020 to June 30, 2021 involved 44 patients
(median age, 57 years; 68% were male) hospitalised for COVID-19, of whom 26 had
moderate COVID-19 and 18 had severe COVID-19 based on the World Health
Organization Clinical Progression Scale. A total of 10 healthy controls (median
age, 58 years; 50% were male), and 41 patient controls who were
COVID-19-negative without evidence of CNS infection (median age, 59 years; 46%
were male) were also included in the study. 

Of the patients with COVID-19, 23 were neurosymptomatic, mostly with
encephalopathy (n = 21). All CSF samples tested negative for SARS-CoV-2 RNA,
whereas 14 patients (11 of 20 neuroasymptomatic and 3 of 15 neurosymptomatic)
had detectable viral RNA in plasma. The median cycle threshold value for
detectable plasma samples was 36.0 (range, 31.3-38.0). Meanwhile, SARS-CoV-2
N-Ag was detectable in CSF in 31 of 35 patients (89%) with data available and in
none of the 41 controls. The measured CSF N-Ag concentrations were not
significantly different between the groups of patients with COVID-19 according
to neurosymptoms or disease severity after adjustment for CSF sampling day.

On the other hand, patients with COVID-19 had markedly increased CSF neopterin,
β2-microglobulin (β2M), interleukin (IL) 2, IL-6, IL-10, and tumor necrosis
factor α compared with controls. Neurosymptomatic patients had significantly
higher median CSF interferon (IFN)-γ (86 vs 21 fg/mL; P = 0.03) and had a
significantly higher inflammatory biomarker profile using principal component
analysis compared with neuroasymptomatic patients (0.54; 95% confidence interval
[CI], 0.03-1.05; P = 0.04). Age-adjusted median CSF neurofilament light (NfL)
protein concentrations were higher in patients compared with controls (960 vs
618 ng/L; P = 0.002). No differences were seen in any CSF biomarkers in moderate
compared with severe disease.

A close correlation was found between serum and CSF concentrations of SARS-CoV-2
N-Ag (r = 0.84; P < 0.001). Initial analysis also indicated a significant
association between CSF N-Ag and the immune activation markers CSF neopterin,
β2M, and IFN-γ, but after adjusting for CSF sampling day, correlations remained
significant only for CSF neopterin (r = 0.38, P = 0.03) and IFN-γ (r = 0.42;
P = 0.01). 

“Although CSF N-Ag concentrations were not significantly different between
patient groups, patients with COVID-19 had higher concentrations of CSF NfL
compared with controls, and neurosymptomatic patients had a more marked immune
activation biomarker profile, suggesting that the magnitude of the CNS immune
response, possibly triggered by viral components, contributes to the
neuropathogenesis of COVID-19,” the authors remarked. 

The authors further noted that “although confirmatory studies evaluating the
significance of viral antigen detection in CSF are needed, these results suggest
that viral components may contribute to CNS immune responses without direct
viral invasion into the CSF compartment, which could partly explain the apparent
discrepancy between the scarcity of CSF viral RNA detection and the marked CNS
inflammatory response seen in patients with COVID-19 with neurologic symptoms.
The results of this study also highlight the importance of neurologic symptoms,
including encephalopathy.” 

“These findings have important potential implications for clinical treatment of
patients with COVID-19, including the use of antiviral therapies, as well as for
the continued importance of including CSF analyses in future studies of CNS
pathogenesis and treatment strategies,” the authors added.

Source: JAMA Network Open

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THE LANCET ONCOLOGY

Alert


STUDY ASSESSES VACCINE EFFECTIVENESS AGAINST COVID-19 BREAKTHROUGH INFECTIONS IN
PATIENTS WITH CANCER

Findings from a study published in The Lancet Oncology showed that individuals
with cancer had demonstrable, albeit impaired, overall vaccine effectiveness
against breakthrough infections with severe acute respiratory syndrome
coronavirus...read more

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JAMA NETWORK OPEN

Alert


ARE CEREBROSPINAL FLUID SARS-COV-2 ANTIGENS ASSOCIATED WITH CENTRAL NERVOUS
SYSTEM INFLAMMATION IN PATIENTS WITH COVID-19?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid
antigen (N-Ag) was detectable in cerebrospinal fluid (CSF) in most patients
hospitalised with acute coronavirus disease 2019 (COVID-19), despite the absence
of...read more

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3

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CDC; STATE HEALTH AGENCIES

Alert


COVID-19: AN INCREASE OF MORE THAN 181,000 CASES REPORTED IN US

According to CDC's COVID Data Tracker on May 26, 2022 5:37 pm ET, the case count
of COVID-19 in the US stands at 83,590,446* cases, including 1,000,980* deaths,
in 55...read more

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PLOS MEDICINE

News


ASYMPTOMATIC SARS-COV-2 INFECTIONS RESPONSIBLE FOR SPREADING OF COVID-19 LESS
THAN SYMPTOMATIC INFECTIONS

Based on studies published through July 2021, most severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) infections were not persistently
asymptomatic, and asymptomatic infections were less infectious than symptomatic
infections, according...read more

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JOHNS HOPKINS UNIVERSITY CSSE; OUR WORLD IN DATA

Alert


COVID-19: DAILY DASHBOARD

Global case count (as of May 26, 09:20 ET): 527,501,315 confirmed cases;
6,283,594 deaths (1.2%). The following are the 30 countries with the highest
case counts as of May 26,...read more

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