The role of immune activation and antigen persistence in acute and long COVID

Journal of Investigative Medicine, Journal Year: 2023, Volume and Issue: 71(5), P. 545 - 562

Published: March 6, 2023

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited comparable to other upper viral pathogens, portion of individuals develop illness leading substantial morbidity and mortality. Furthermore, an estimated 10%–20% SARS-CoV-2 are followed by post-acute sequelae COVID-19 (PASC), or long COVID. Long COVID is associated with wide variety clinical manifestations including cardiopulmonary complications, persistent fatigue, neurocognitive dysfunction. Severe hyperactivation increased inflammation, which may be underlying in subset individuals. However, immunologic mechanisms driving development still under investigation. Early pandemic, our group others observed immune dysregulation persisted into convalescence after COVID-19. We subsequently cohort experiencing demonstrated SARS-CoV-2-specific CD4 + CD8 T-cell responses antibody affinity patients symptoms. These data suggest symptoms due chronic activation presence antigen. This review summarizes literature date detailing how these observations relate addition, we discuss recent findings support antigen evidence that this phenomenon contributes local systemic inflammation heterogeneous nature seen

Language: Английский

---

Protective role of SARS-CoV-2 anti-S IgG against breakthrough infections among European healthcare workers during pre and post-Omicron surge—ORCHESTRA project

Infection, Journal Year: 2024, Volume and Issue: 52(4), P. 1347 - 1356

Published: Feb. 7, 2024

Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants concern, dropped. Several studies investigated if this was related to decrease humoral response over time; however, issue is still unclear. The aim study understand whether anti-S IgG levels can be used predict breakthrough infection risk and define timing for further booster doses administration.

Language: Английский

---

Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5352 - 5352

Published: March 10, 2023

More than three years ago, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused unforeseen COVID-19 pandemic with millions of deaths. In meantime, SARS-CoV-2 has become endemic and is now part repertoire viruses causing seasonal severe respiratory infections. Due to several factors, among them development immunity through natural infection, vaccination current dominance seemingly less pathogenic strains belonging omicron lineage, situation stabilized. However, challenges remain possible new occurrence highly variants remains a threat. Here we review development, features importance assays measuring neutralizing antibodies (NAbs). particular focus on in vitro infection molecular interaction studying binding receptor domain (RBD) its cognate cellular ACE2. These assays, but not measurement SARS-CoV-2-specific per se, can inform us whether produced by convalescent or vaccinated subjects may protect against thus have potential predict risk becoming newly infected. This information extremely important given fact that considerable number subjects, vulnerable persons, respond poorly production antibodies. Furthermore, these allow determine evaluate virus-neutralizing capacity induced vaccines administration plasma-, immunoglobulin preparations, monoclonal antibodies, ACE2 synthetic compounds be used for therapy assist preclinical evaluation vaccines. Both types relatively quickly adapted emerging virus about magnitude cross-neutralization, which even estimate infected appearing variants. Given paramount discuss their specific features, advantages disadvantages, technical aspects yet fully resolved issues, such as cut-off levels predicting degree vivo protection.

Language: Английский

---

Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 13, 2023

Background Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, poorly understood. We investigated the humoral and cellular immune of hospitalized COVID-19 patients during Delta Omicron infection waves. Methods The corresponding variant respective were identified by whole genome sequencing. Humoral analyzed ELISA a cell culture-based neutralization assay against D614G isolate (wildtype), Alpha, (AY.43) (BA.1 BA.5). Cellular immunity was evaluated an IFN-γ ELISpot assay. Results On level, showed minor response after stimulating PBMCs mutated regions variants. Neutralizing antibody titers Omicron-BA.1 especially BA.5 strongly reduced. Double-vaccinated breakthrough significantly increased neutralizing compared to double-vaccinated uninfected controls (median complete titer (NT 100 ) 640 versus 80, p<0.05). BA.1 NT 160 20 controls, p=0.07) that received booster vaccination 50 p=0.68). For boosted infection, we found no enhancing effect on Conclusion reduced infections. but not Omicron-BA.5 vaccination. Despite those may still be vulnerable for reinfections or other newly emerging concern.

Language: Английский

---

SARS-CoV-2 Vaccine Breakthrough Infections of Omicron and Delta Variants in Healthcare Workers

Vaccines, Journal Year: 2023, Volume and Issue: 11(5), P. 958 - 958

Published: May 7, 2023

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance mitigating the effects COVID-19 pandemic facilities. An observational prospective cohort study was conducted employees with acute infection between October 2021 and February 2022. Serological molecular testing performed to determine viral load, lineage, antibody levels, neutralizing titers. A total 571 (9.7%) experienced during enrolment period, which 81 were included. The majority (n = 79, 97.5%) symptomatic most 75, 92.6%) showed Ct values < 30 RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing titers strongest wildtype, intermediate Delta, lowest Omicron variants. occurred at higher anti-RBD-IgG serum levels (p 0.00001) a trend loads 0.14, median difference 4.3, 95% CI [-2.5-10.5]). For both variants, significantly participants lower 0.02). In conclusion, while clinical course Delta variants predominantly mild moderate our population, waning immune response over time prolonged shedding observed.

Language: Английский

---

SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1247 - 1247

Published: April 23, 2023

Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk breakthrough infections, although no clear cut-off is available. We describe incidence SARS-CoV-2 vaccine infections in COVID-19-free personnel our hospital, according B- T-cell response elicited one month after mRNA third dose vaccination.

Language: Английский

---

Follow-up SARS-CoV-2 serological study of a health care worker cohort following COVID-19 booster vaccination

BMC Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 24, 2024

Abstract Background Studies have shown that Omicron breakthrough infections can occur at higher SARS-CoV-2 antibody levels compared to previous variants. Estimating the magnitude of immunological protection induced from COVID-19 vaccination and infection remains important due varying local pandemic dynamics types programmes, particularly among at-risk populations such as health care workers (HCWs). We analysed a follow-up serological survey HCWs tertiary referral hospital in Germany following onset variant. Methods The was conducted January 2022, one year after surveys 2020 availability boosters including BNT162b2, ChAdOx1-S, mRNA-1273. voluntarily provided blood for serology completed comprehensive questionnaire. analyses were performed using an Immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Antibody reported according HCW demographic occupational characteristics, history, multivariate linear regression used evaluate these associations. Results In 2022 (following fourth wave variant), 1482/1517 (97.7%) tested seropositive, 4.6% December (second wave). Approximately 80% had received three vaccine doses 15% laboratory-confirmed infection. IgG geometric mean titres ranged 335 (95% Confidence Intervals [CI]: 258–434) those vaccinated twice without 2204 CI: 1919–2531) times with Heterologous combinations mRNA-1273 booster significantly associated highest other schemes. There 8-to 10-fold increase 31 who May vaccination. Conclusions Our findings demonstrate importance ongoing strategies context variants despite hybrid immunity infections, HCWs. Where feasible, effective vaccination, mRNA vaccines, appropriate timing administration should be carefully considered.

Language: Английский

---

Kinetics of SARS-CoV-2 Serum Antibodies Through the Alpha, Delta, and Omicron Surges Among Vaccinated Health Care Workers at a Boston Hospital

Open Forum Infectious Diseases, Journal Year: 2023, Volume and Issue: 10(7)

Published: May 17, 2023

Abstract Background Longitudinal serology studies can assist in analyzing the kinetics of antibodies to SARS-CoV-2, helping inform public health decision making. Our study aims characterize circulating antibody trends over 18 months vaccinated participants with and without evidence COVID-19 infection. Methods A cohort care workers employed at Boston Medical Center was followed collect serum samples survey data 6 time points from July 2020 through December 2021 (N = 527). History SARS-CoV-2 infection, vaccination, booster status were confirmed, where possible, electronic medical records. Serum assessed for qualitative semiquantitative detection IgG levels (anti-nucleoprotein [anti-N] anti-spike [anti-S], respectively). Piecewise regression models utilized time. Results Anti-S titers remained above positivity threshold following infection and/or vaccination throughout 18-month follow-up. Among no declined significantly faster initial 90 days after full (β −0.056) March as compared decline observed dose uptake −0.023, P &lt; 0.001). Additionally, prior attenuated anti-S when vaccine (P Lastly, fewer contracted Omicron boosted (12.7%) fully (17.6%). Regardless status, who positive had lower than those did not test positive, but this difference significant. Conclusions These findings provide novel highlight durability hybrid immunity, underlining strong humoral response stimulated by combined vaccination.

Language: Английский

---

CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

mBio, Journal Year: 2023, Volume and Issue: 14(5)

Published: Sept. 1, 2023

Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs policy for booster doses and future designs. Existing studies demonstrate humoral protection, but the role T cells in is still unclear. In this study, we explore antibody cell immune responses associated with Delta variant a well-characterized cohort UK Healthcare Workers (HCWs). We evidence to support CD4+ CD8+ as well antibodies infection. addition, our results suggest potential cross-reactive breakthrough.

Language: Английский

---

CD4+ and CD8+ T cell and antibody correlates of protection against Delta vaccine breakthrough infection: A nested case-control study within the PITCH study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 17, 2023

ABSTRACT T cell correlates of protection against SARS-CoV-2 infection after vaccination (‘vaccine breakthrough’) are incompletely defined, especially the specific contributions CD4+ and CD8+ cells. We studied 279 volunteers in Protective Immunity from Cells Healthcare Workers (PITCH) UK study, including 32 cases (with positive testing two vaccine doses during Delta-dominant era) 247 controls (no test nor anti-nucleocapsid seroconversion this period). 28 days second vaccination, before all breakthroughs occurred, had lower ancestral S- RBD-specific immunoglobulin G titres S1- S2-specific interferon gamma (IFNγ) responses compared with controls. In a subset matched controls, IFNγ tumour necrosis factor to Delta S peptides reduced versus Our findings support protective role for cells breakthrough infection.

Language: Английский

---