Tag: antibody response

PASC (Post Acute Sequelae of COVID-19) is associated with decreased neutralizing antibody titers in both biological sexes and increased ANG-2 and GM-CSF in females

Abstract:

Post-acute sequelae of COVID-19 (PASC) or the continuation of COVID-19 (Coronavirus disease 2019) symptoms past 12 weeks may affect as many as 30% of people recovering from a SARS-CoV-2 (severe acute respiratory coronavirus 2) infection. The mechanisms regulating the development of PASC are currently not known; however, hypotheses include virus reservoirs, pre-existing conditions, microblood clots, immune dysregulation, as well as poor antibody responses. Importantly, virus neutralizing antibodies are essential for COVID-19 recovery and protection from reinfection but there is currently limited information on these immune regulators and associated cytokines in PASC patients. Understanding the key drivers of general and specific symptoms associated with Long COVID and the presence of virus neutralizing antibodies in PASC will aid in the development of therapeutics, diagnostics, and vaccines which currently do not exist.

We designed a cross-sectional study to investigate systemic antibody and cytokine responses during COVID-19 recovery and PASC. In total, 195 participants were recruited in one of four groups: (1) Those who never had COVID-19 (No COVID); (2) Those in acute COVID-19 recovery (Acute Recovery) (4–12 weeks post infection); (3) Those who recovered from COVID-19 (Recovered) (+ 12 weeks from infection); and (4) those who had PASC (PASC) (+ 12 weeks from infection). Participants completed a questionnaire on health history, sex, gender, demographics, experiences with COVID-19 acute and COVID-19 recovery/continuing symptoms. Serum samples collected were evaluated for antibody binding to viral proteins, virus neutralizing antibody titers, and serum cytokine levels using Ella SimplePlex Immunoassay™ panels.

We found participants with PASC reported more pre-existing conditions (e.g. such as hypertension, asthma, and obesity), and PASC symptoms (e.g. fatigue, brain fog, headaches, and shortness of breath) following COVID-19 than COVID-19 Recovered individuals. Importantly, we found PASC individuals to have significantly decreased levels of neutralizing antibodies toward both SARS-CoV-2 and the Omicron BA.1 variant. Sex analysis indicated that female PASC study participants had sustained antibody levels as well as levels of the inflammatory cytokines GM-CSF and ANG-2 over time following COVID-19.

Our study reports people experiencing PASC had lower levels of virus neutralizing antibodies; however, the results are limited by the collection time post-COVID-19 and post-vaccination. Moreover, we found females experiencing PASC had sustained levels of GM-CSF and ANG-2. With lower levels of virus neutralizing antibodies, this data suggests that PASC individuals not only have had a suboptimal antibody response during acute SARS-CoV-2 infection but may also have increased susceptibility to subsequent infections which may exacerbate or prolong current PASC illnesses. We also provide evidence suggesting GM-CSF and ANG-2 to play a role in the sex-bias of PASC. Taken together, our findings maybe important for understanding immune molecular drivers of PASC and PASC subgroups.

Source: Jansen EB, Ostadgavahi AT, Hewins B, Buchanan R, Thivierge BM, Sganzerla Martinez G, Goncin U, Francis ME, Swan CL, Scruten E, Bell J, Darbellay J, Facciuolo A, Falzarano D, Gerdts V, Fenton ME, Hedlin P, Kelvin DJ, Kelvin AA. PASC (Post Acute Sequelae of COVID-19) is associated with decreased neutralizing antibody titers in both biological sexes and increased ANG-2 and GM-CSF in females. Sci Rep. 2024 Apr 29;14(1):9854. doi: 10.1038/s41598-024-60089-4. PMID: 38684819; PMCID: PMC11058778. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058778/ (Full text)

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Abstract:

Background: Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.

Methods: The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.

Results: The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD–CD27–) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.

Conclusions: The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.

Source: Limoges MA, Quenum AJI, Chowdhury MMH, Rexhepi F, Namvarpour M, Akbari SA, Rioux-Perreault C, Nandi M, Lucier JF, Lemaire-Paquette S, Premkumar L, Durocher Y, Cantin A, Lévesque S, Dionne IJ, Menendez A, Ilangumaran S, Allard-Chamard H, Piché A, Ramanathan S. SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition. Front Immunol. 2023 Sep 21;14:1223936. doi: 10.3389/fimmu.2023.1223936. PMID: 37809081; PMCID: PMC10551145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551145/ (Full text)

The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms

Abstract:

Background: The associations between longitudinal dynamics and the breadth of SARS-CoV-2 neutralizing antibody response with various Long COVID (LC) phenotypes prior to vaccination are not known. The capacity of antibodies to cross neutralize a variety of viral variants may be associated with ongoing pathology and persistent symptoms.

Methods: We measured longitudinal neutralizing and cross-neutralizing antibody responses to pre- and post-SARS-CoV-2 Omicron variants in participants infected during the early waves of the COVID-19 pandemic, prior to wide-spread rollout of SARS-CoV-2 vaccines. Cross sectional regression models adjusted for various clinical covariates and longitudinal mixed effects models were used to determine the impact of the breadth and rate of decay of neutralizing responses on the development of Long COVID symptoms in general, as well as LC phenotypes.

Results: We identified several novel relationships between SARS-CoV-2 antibody neutralization and the presence of LC symptoms. Specifically, we show that, although neutralizing antibody responses to the original, infecting strain of SARS-CoV-2 were not associated with LC in cross-sectional analyses, cross-neutralization ID50 levels to the Omicron BA.5 variant approximately 4 months following acute infection was independently and significantly associated with greater odds of LC and with persistent gastrointestinal and neurological symptoms. Longitudinal modeling demonstrated significant associations in the overall levels and rates of decay of neutralization capacity with LC phenotypes. A higher proportion of participants had antibodies capable of neutralizing Omicron BA.5 compared with BA.1 or XBB.1.5 variants.

Conclusions: Our findings suggest that relationships between various immune responses and LC are likely complex but may involve the breadth of antibody neutralization responses.

Source: Buck AM, Deitchman AN, Takahashi S, Lu S, Goldberg SA, Hoh R, Williams MC, Kerbleski M, Deveau TM, Munter SE, Lombardo J, Wrin T, Petropoulos CJ, Durstenfeld MS, Hsue PY, Kelly JD, Greenhouse B, Martin JN, Deeks SG, Peluso MJ, Henrich TJ. The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms. medRxiv [Preprint]. 2023 Mar 31:2023.03.30.23287923. doi: 10.1101/2023.03.30.23287923. PMID: 37034660; PMCID: PMC10081395. https://www.medrxiv.org/content/10.1101/2023.03.30.23287923v1.full-text (Full text)

Immune responsiveness in chronic fatigue syndrome

Abstract:

We have endeavoured to find immunological indications of chronic virus infection in patients with chronic fatigue syndrome (myalgic encephalomyelitis) and to investigate immune responsiveness to viruses in such patients in comparison with normal subjects and patients with muscular dystrophy.

Levels of circulating IgM immune complexes were elevated (above the 95% normal control range) in 10 (17%) of 58 patients with chronic fatigue syndrome, which was not significantly different from the normal controls or from dystrophy controls (by Mann Whitney U test). Levels of IgG complexes were only increased in 10% of patients. Lymphocyte proliferation in response to concanavalin A (Con A), assessed by increase in 3H-thymidine incorporation, did not differ between 14 patients and 18 normal subjects.

The proliferative response to Coxsackie B virus antigen did not differ between chronic fatigue patients and normal subjects when expressed either as an increase in counts or as a stimulation index. Adjustment of the counts in relation to the proliferation response to Con A, as an indication of the overall proliferative response of the cell preparation, did not reveal any hidden difference. IgM antibodies to Coxsackie B viruses were not found in any of 20 patients and in 1 of 20 dystrophy controls.

Significant levels of neutralizing antibodies to Coxsackie B viruses 1-5 were found in 6 out of 19 (32%) patients compared with 4 out of 17 (24%) dystrophy controls, which does not differ from currently expected normal incidence. Antibody titres to other respiratory viruses were also not notably different between the patient and control groups.

In conclusion we can find no evidence for a definable viral aetiology for the chronic fatigue syndrome, neither in terms of a persistent infection nor an altered ability to respond to virus.

Comment in: Immune responsiveness in chronic fatigue syndrome. [Postgrad Med J. 1992]

 

Source: Milton JD, Clements GB, Edwards RH. Immune responsiveness in chronic fatigue syndrome. Postgrad Med J. 1991 Jun;67(788):532-7. http://www.ncbi.nlm.nih.gov/pubmed/1656416

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398884/

 

A comprehensive immunological analysis in chronic fatigue syndrome

Abstract:

A detailed analysis of cell-mediated and antibody-mediated immunity was performed in 20 CDC-defined patients with chronic fatigue syndrome (CFS) and 20 age- and sex-matched healthy controls.

CD3+, CD4+, CD8+, and CD20+ lymphocytes were comparable in two groups. Natural killer cells as defined by CD16, CD56 and CD57 antigens were significantly reduced in CFS. A significant increase in the proportions of CD4+ ICAM 1+ T cells was observed in CFS. Monocytes from CFS displayed increased density (as determined by mean fluorescence channel numbers) of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function associated antigen 1 (LFA-1), but showed decreased enhancing response to recombinant interferon-gamma in vitro.

The lymphocyte DNA synthesis in response to phytohaemoglobulin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was normal but the response to soluble antigens was significantly reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal. In vivo specific antibody response to pneumococcus vaccine was depressed in CFS.

Forty percent of patients showed titres of anti-human herpes virus 6 (anti-HHV-6) antibody higher than that in the controls (greater than or equal to 1/80). These data suggest immunological dysfunction in patients with chronic fatigue syndrome. The significance of these observations is discussed.

 

Source: Gupta S, Vayuvegula B. A comprehensive immunological analysis in chronic fatigue syndrome. Scand J Immunol. 1991 Mar;33(3):319-27. http://www.ncbi.nlm.nih.gov/pubmed/1849315