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J Infect Dis ; 225(6): 965-970, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1740882


Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.

Antibodies, Viral/blood , COVID-19/diagnosis , Immunoglobulin G/blood , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , SARS-CoV-2/isolation & purification , Aged , Antibodies, Neutralizing/blood , Antibody Formation , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/blood , COVID-19/cerebrospinal fluid , COVID-19/complications , Female , Humans , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296424


Pathogenic mitochondrial (mt)DNA molecules can exhibit heteroplasmy in single cells and cause a range of clinical phenotypes, although their contribution to immunity is poorly understood. Here, in mice carrying heteroplasmic C5024T in mt-tRNA Ala – that impairs oxidative phosphorylation – we found a reduced mutation burden in peripheral T and B memory lymphocyte subsets, compared to their naïve counterparts. Furthermore, selection diluting the mutation was induced in vitro by triggering T and B cell antigen receptors. While C5024T dysregulated naïve CD8 + T cell respiration and metabolic remodeling post-activation, these phenotypes were partially ameliorated by selection. Analogous to mice, peripheral blood memory T and B lymphocyte subsets from human MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) patients – carrying heteroplasmic A3243G in mt-tRNA Leu – displayed a reduced mutation burden, compared to naïve cells. In both humans and mice, mtDNA selection was observed in IgG + antigen-specific B cells after SARS-CoV-2 Spike vaccination, illustrating an on-going process in vivo . Taken together, these data illustrate purifying selection of pathogenic mtDNA variants during the oxidative phosphorylation checkpoints of the naïve-memory lymphocyte transition. Highlights In human MELAS patients (A3243G in mt-tRNA Leu ) and a related mouse model (C5024T in mt-tRNA Ala ), T and B memory subsets displayed a reduced mtDNA mutation burden compared to their naïve counterparts. Selection was observed in antigen-specific IgG + B cells after SARS-CoV-2 Spike protein vaccination. T and B cell antigen receptor stimulation triggered purifying selection in vitro , facilitating mechanistic studies of mtDNA selection. Heteroplasmic pathogenic mutations in mtDNA dysregulated metabolic remodeling after lymphocyte activation and reduced macrophage OXPHOS capacity.