Cellular and humoral immunity to SARS-CoV-2 infection in multiple sclerosis patients on ocrelizumab and other disease-modifying therapies: a multi-ethnic observational study

Objective: To determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection. Methods: MS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike RBD antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture ELISA; and IL-2 and IFNγ ; ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. Results: Between 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) - 40%; natalizumab - 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 - asymptomatic. Antibody responses were markedly attenuated in OCR compared to other groups (p≤0.0001). T-cell responses (IFNγ) were decreased in S1P (p=0.03), increased in natalizumab (p<0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r=0.45, p=0.0002) and non-OCR (r=0.64, p<0.0001). Immune responses did not differ by race/ethnicity. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. Interpretation: DMTs had differential effects on humoral and cellular immune responses to SARS-CoV-2 infection. Immune responses did not correlate with COVID-19 clinical severity in this relatively young and non-disabled group of MS patients.

Tuberculosis detection in nonhuman primates is enhanced by use of testing algorithms that include an interferon-γ release assay

OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.

The role of Herpesviridae infection in the progression of comorbid somatic pathology

Background. The objective was to study the peculiarities of cellular and humoral immunity in patients with chronic obstructive pulmonary disease (COPD) group B and C, GOLD 2–3, who have signs of metabolic syndrome (MS) and Herpesviridae infection. Materials and methods. Forty-two patients with B and C groups of COPD, GOLD 2–3, associated with MS were examined. Eighteen individuals had COPD combined with MS, and Herpesviridae infection. The average age of patients was 51.3 ± 4.2 years. The comparison group included 24 people with COPD and MS without signs of Herpesviridae infection. All patients underwent determination of herpes simplex virus (HSV) type 1 and cytome­galovirus (CMV) antigens in the blood and saliva, titer of specific immunoglobulin (Ig) G and IgM antibodies to HSV type 1 and CMV, a comprehensive immunological examination with a study of cellular and humoral immunity indexes, cytokine status. Results. The study of the activity of herpes viruses in the blood of patients of the main group did not reveal active replication of HSV type 1 and CMV; in the saliva of 15 individuals (83.3 %), an active replication of HSV type 1 was detected, and in 12 people (66.7%) — of CMV. All patients in the main group had a severe course of Herpesviridae infection with an exacerbation rate of more than 6 times a year. The immunological status of patients of the main group showed immunodeficiency mainly of T-cell immune system and NK-cells, a significant increase in the relative number of T- and B-lymphocytes with early and late markers of activation on the background of autoimmune manifestations and inflammatory changes in peripheral blood. Conclusions. The presence of chronic persistent infection of HSV type 1 and CMV causes a severe course of COPD associated with MS, induces the development of infectious exacerbations of COPD and more significant manifestations of systemic inflammation in atherosclerosis as a morphological substrate of MS.

Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged &lt;12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.

Peculiarities of immunophysiological shifts in adaptation to climatic and geographical conditions of mountains

The functioning of the immune system of people exposed to prolonged exposure to natural factors has been monitored and the main immunity indicators have been studied in practically healthy population of different mountain heights in Chui and Naryn regions. Indicators of specific immunity in the residents of the zone of compensated discomfort is reduced compared with the standards of the zone of relative comfort and refers to the mixed type with suppression of cellular and humoral immunity, apparently, this is associated with the climatic and geographical and environmental characteristics of the region. Key words: adaptation, immune system, T- lymphocytes, B- lymphocytes, immunoglobulins, circulating immune complexes, mountainous conditions.

Guillain-Barré syndrome: diagnosis and treatment guidelines

GuillainBarr syndrome is an acute, rapidly progressive immune-mediated disease of the peripheral nervous system, combining several variants and subtypes with various clinical, pathophysiological and electrophysiological signs. GuillainBarr syndrome usually develops 13 weeks after the viral or bacterial infection, which acts as the trigger triggering autoimmune mechanisms, leading to demyelination and axonal damage. The disease is getting more acute due to the emergence of a new coronavirus infection. Behind the diseases dipathophysiology there is the activation of cellular and humoral immunity with the production of autoantibodies to specific gangliosides and glycolipids and the formation of circulating immune complexes that attack peripheral nerves and roots (the phenomenon of molecular mimicry). The examination of patients requires an integrated approach, including, along with clinical and anamnestic data, the results of laboratory and neurophysiological examination. The treatment of patients with GuillainBarr syndrome is carried out in an intensive care unit and includes both pathogenetic therapy and nonspecific measures aimed to correct dysfunctions of vital organs, prevent complications and provide symptomatic therapy. Currently, the main direction of pathogenetic therapy of this disease is the use of high-dose intravenous immunotherapy with human normal immunoglobulin preparations or high-volume therapeutic plasmapheresis. Taking into account the absence of data about differences in the effectiveness of these methods, the choice of direction is determined taking into account the contraindications and possible development of adverse events, as well as the capabilities of the medical institution (2 tables, bibliography: 15 refs)