Study points to pathogenic role of impaired anti-SARS-CoV-2 response in cerebrospinal fluid

In a recent study posted on medrex sib* On the preprint server, the researchers used serological methods on a high-throughput system to collect serum and cerebrospinal fluid (CSF) samples from individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). compared. Identify alterations in the SARS-CoV-2 humoral immune response.

Background

One of the emerging long-term effects of the novel coronavirus disease 2019 (COVID-19) pandemic is persistent complications in non-respiratory organ systems such as the nervous system. Acute neurological sequelae of COVID-19 (neuroPASC) include cognitive impairment, poor concentration, persistent headaches and confusion, and even encephalitis, etc.

Studies have hypothesized different pathophysiological mechanisms that explain the symptoms of neuroPASC, including the presence of viral reservoirs, immune dysfunction, hormonal dysregulation, vagal signal impairment, and recurrent neurotrophic infections. Given the role of antibodies in local pathology and as biomarkers of pathogen exposure, humoral signatures can be used to understand the mechanisms behind long-term COVID neurological symptoms.

About research

In this study, we investigated SARS-CoV-2 infection during the first COVID-19 wave in Italy from March to August 2020, with and without acute post-COVID-19 neurological complications. , individuals were recruited.

Inclusion criteria for individuals in the Neuro-PASC group included neurological symptoms or changes in neurological status unexplained by other causes and confirmed by a positive polymerase chain reaction (PCR) test or positive SARS-CoV-2. SARS-CoV-2 infections included immunoglobulin G (IgG) serology, with or without COVID-19 symptoms.

A control group of HCWs who were routinely tested as part of SARS-CoV-2 surveillance and had a positive PCR test for SARS-CoV-2 infection but no neuroPASC symptoms was selected. No patients were vaccinated at the time the study was conducted. At study initiation, SARS-CoV-2 infection was confirmed using a SARS-CoV-2 IgG-positive enzyme-linked immunosorbent assay (ELISA).

Serum samples were obtained from all patients and CSF was obtained from neuroPASC patients only when diagnostic evaluation was required. Neurological outcome was assessed with the Modified Rankin Scale (mRS). An mRS value of less than 2 indicates a good outcome and greater than 2 indicates a poor outcome.

Antibody responses were measured against five SARS-CoV-2 antigens. spike protein, receptor-binding domain (RBD), subunits S1 and S1, and nucleocapsid protein.Responses to four other antibodies coronavirus Three non-coronavirus control antigens were also measured.

Isotype levels, Fc receptor binding, and antigen-specific antibody subclasses were determined. In addition, the team also determined antibody-dependent cellular and neutrophil phagocytosis and antibody-dependent complement deposition, and performed his ELISA to measure antibody-dependent natural killer cell activation.

result

The results revealed a unique fluid profile in patients who exhibited neuroPASC. A neuroPASC patient’s serum sample contained all antibody isotypes and subclasses, but CSF contained concentrated her IgG1 and lacked IgM. These humoral profiles suggest that the anti-SARS-CoV-2 response undergoes brain-specific compartmentalization, with selected antibodies crossing the blood-brain barrier from the serum to her, rather than being synthesized within the spinal cord. Indicated to move to CSF. CSF.

Patients who developed neuroPASC after SARS-CoV-2 infection also showed reduced antibody-dependent complement deposition and antibody-dependent natural killer cell activation, and reduced Fcγ receptor binding.

Patients with NeuroPASC, especially those who demonstrated a poor prognosis (mRS > 2), were tested for other coronaviruses including Human Coronavirus (HCoV) – NetherLand 63 (NL63), HCoV- Hong Kong University 1 (HKU1), HCoV- Organ also showed an antibody response to Culture 43 (OC43), and HCoV-229E. Her other humoral activation to HCoV suggests that immunological imprinting, in which the current immune response is shaped by pre-existing immunity to related viruses, may be a prognostic marker for neuroPASC. increase.

Cumulatively, results indicated a role for inappropriate viral clearance from the brain and neuroinflammation due to reduced CSF immune responses to SARS-CoV-2 in the development of neurological complications during long-lasting COVID .

Conclusion

Overall, the results suggest a different humoral signature in the serum and CSF of patients with neuroPASC, with reduced responses to SARS-CoV-2 but expanded responses to other human coronaviruses, immunologically It shows imprinting.

The authors suggest that long-lasting COVID neurological symptoms may be due to defective clearance of the virus from the brain causing neuroinflammation, and that immunological imprinting may be a prognostic marker for neuroPASC. I believe there is

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .