Adaptive Immunity Dysregulation Is Associated to the Development of Long Covid
Topics in Antiviral Medicine
; 31(2):115-116, 2023.
Article
in English
| EMBASE | ID: covidwho-2318723
ABSTRACT
Background:
The pathogenetic mechanisms behind the development of long- COVID (LC) are largely unknown. Because both plasma SARS-CoV-2 RNAemia and dysregulated immunity have been correlated with COVID-19 severity, we evaluated whether they are associated with LC. Method(s) We consecutively enrolled unvaccinated hospitalized COVID-19 patients during acute-COVID-19 (T0) in March-October 2020 who either developed LC at a follow-up visit 2-3 months from virologic clearance (T1) or did not. LC was defined as persistence >=2 months after recovery of >=1 symptom anosmia, dysgeusia, fever, gastrointestinal symptoms, dyspnoea, fatigue, musculoskeletal pain, muscle weakness, brain fog. We measured SARS-CoV-2 RNAemia (RT-qPCR, log10(copies/mL)), magnitude (ELISA, AUC) and functionality (pseudovirus neutralization, ID50;Fc-mediated functions, %ADCC) of SARS-CoV-2-specific antibodies, SARS-CoV-2-specific B and CD4-T-cells (Immunophenotype, AIM and ICS assays). Result(s) We enrolled 48 COVID-19 individuals, 38/48 (79.2%) developed LC (LC+) and 10 did not (LC-). LC+ and LC- had similar co-morbidities and symptoms in the acute phase (Fig.1A), and the majority showed a radiologically documented SARS-CoV-2 pneumonia. The SARS-CoV-2 RNAemia did not differ between groups at both time points. The levels of RBD-specific Abs, as well as their functionality, appeared to increase over time in the LC- group but not in the LC+ (Fig.1B-D). Similarly, a trend towards increased RBD-specific B-cells was observed over time in the LC- group but not in LC+ (Fig.1E). B-cell immunophenotyping showed a significant increase over time of classical memory B cells (MBCs) at the expenses of activated MBCs (Fig.1F-G) as well as an IgA class-switching in the LC- group compared to LC+ (Fig.1H-I). Furthermore, LC+ showed a faster decline of SARS-CoV-2-specific (CD69+CD137+) CD4- TEMRA and CD4-TEM (Fig.1L-M). Finally, IFN-gamma-producing TREG of LC- individuals increased over time (Fig.1N). Conclusion(s) Acutely ill, hospitalized COVID-19 patients developing LC feature a dysregulated SARS-CoV-2-specific humoral as well as B- and T-cell response, in both magnitude and functionality, suggesting a link between dysregulated SARS-CoV-2-specific adaptive immunity and LC development. The fine understanding of the factors contributing to such dysregulation in LC patients is strongly needed, that might further inform targeted therapeutic interventions. (Figure Presented).
acutely ill patient; adaptive immunity; adult; anosmia; antibody dependent cellular cytotoxicity; B lymphocyte; clinical article; clouding of consciousness; comorbidity; conference abstract; controlled study; coronavirus disease 2019; dysgeusia; dyspnea; enzyme linked immunosorbent assay; fatigue; female; fever; follow up; gastrointestinal symptom; human; human cell; human tissue; id50; immunoglobulin class switching; immunophenotyping; long COVID; male; memory B lymphocyte; muscle weakness; musculoskeletal pain; nonhuman; regulatory T lymphocyte; RNA blood level; Severe acute respiratory syndrome coronavirus 2; T lymphocyte; CD4 antigen; endogenous compound; gamma interferon; immunoglobulin A
Search on Google
Collection:
Databases of international organizations
Database:
EMBASE
Topics:
Long Covid
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2023
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS