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1.
The Journal of Allergy and Clinical Immunology: In Practice ; 11(1):107-115, 2023.
Article in English | ScienceDirect | ID: covidwho-2165477

ABSTRACT

In the past 10 years, we have witnessed major advances in clinical immunology. Newborn screening for severe combined immunodeficiency has become universal in the United States and screening programs are being extended to severe combined immunodeficiency and other inborn errors of immunity globally. Early genetic testing is becoming the norm for many of our patients and allows for informed selection of targeted therapies including biologics repurposed from other specialties. During the COVID-19 pandemic, our understanding of essential immune responses expanded and the discovery of immune gene defects continued. Immunoglobulin products, the backbone of protection for antibody deficiency syndromes, came into use to minimize side effects. New polyclonal and monoclonal antibody products emerged with increasing options to manage respiratory viral agents such as SARS-CoV-2 and respiratory syncytial virus. Against these advances, we still face major challenges. Atypical is becoming typical as phenotypes of distinct genetic disease overlap whereas the clinical spectrum of the same genetic defect widens. Therefore, clinical judgment needs to be paired with repeated deep immune phenotyping and upfront genetic testing, as technologies rapidly evolve, and clinical disease often progresses with age. Managing patients with organ damage resulting from immune dysregulation poses a special major clinical challenge and management often lacks standardization, from autoimmune cytopenias, granulomatous interstitial lung disease, enteropathy, and liver disease to endocrine, rheumatologic, and neurologic complications. Clinical, translational, and basic science networks will continue to advance the field;however, cross-talk and education with practicing allergists/immunologists are essential to keep up with the ever-changing clinical and genetic landscape of inborn errors of immunity.

2.
Psychiatry Res Case Rep ; 1(2): 100074, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2150453

ABSTRACT

"Pediatric acute-onset neuropsychiatric syndrome", or PANS, is a rare syndrome characterized by an acute onset of obsessive-compulsive disorder (OCD), and/or severely restricted food intake accompanied by a variety of neuropsychiatric symptoms. To our knowledge, this is the first case report of twin adolescents with COVID-19-associated PANS. Dizygotic twin sisters in late teens, with abrupt and acute onset of severely restrictive food intake, weight loss, OCD, anxiety with intermittent auditory and visual hallucinations, depression, attention deficit, and sleep disturbances, simultaneously accompanied by milder neurologic symptoms such as hand tremor, tinnitus, dizziness, headache, and weakness of proximal muscles, were applied to child and adolescent psychiatry clinic. The only relevant agent underlying those neuropsychiatric and somatic complaints was COVID-19, and it was validated with laboratory testing, such as positive IgG titers of SARS-CoV-2 and negative biomarkers for other possible bacterial or viral agents. Generalized epileptic anomaly and a vermian/folial atrophy in the cerebellum were detected in further evaluations. Treatment options consisted of psychotropic agents, antibiotics, antiepileptic, and intravenous immunoglobulin transfusion finely treated the neuropsychiatric symptoms. Clinicians should consider SARS-CoV-2 as a potential agent, when a child presents with abrupt onset, dramatic neuropsychiatric symptoms also consisting of PANS, even in asymptomatic patients or with mild respiratory symptoms.

3.
Immunologiya ; 43(5):485-503, 2022.
Article in Russian | EMBASE | ID: covidwho-2164674

ABSTRACT

The development of the COVID-19 pandemic initiated the search for effective drugs for the treatment and prevention of infection. Of particular importance for the fight against the pandemic is the timing of the introduction of drugs into clinical practice. Therefore, countries with developed healthcare systems (EU, USA, Russian Federation, etc.), issue conditional marketing authorizations of drugs for treatment and prevention of COVID-19, based on regulatory requirements for the circulation of medicines in emergency situations. The approval is issued on the basis of limited clinical data, with the condition that the full evaluation of safety and effectiveness will be carried out after the issuance of the authorization in the post-registration period. The COVID-19 pandemic has revolutionized the design and time frame of clinical trials, including phase I, II, and III adaptive trials, which has led to the approval of biologics for the treatment and prevention of COVID-19 in record time in most advanced pharmaceutical countries. At the same time, regulatory/healthcare authorities or international organizations constantly monitor the safety and effectiveness of used drugs and, if necessary, make adjustments (changes to the indications for use, dosage change, drug discontinuation etc.). Since the beginning of the pandemic, in fact, in conditions where the use of medicines was allowed based on very limited data, studies have begun to substantiate the safety and effectiveness of the use of immunoglobulin preparations and monoclonal antibodies for the treatment and prevention of COVID-19. As new data became available, changes were made regarding the indications for use, doses, and other characteristics of preparations of immunoglobulins and monoclonal antibodies for the treatment and prevention of COVID-19. The review presents a critical analysis of the results of evaluation the safety and effectiveness of the use of immunoglobulin preparations and monoclonal antibodies in a pandemic. Copyright © 2022 Meditsina Publishers. All rights reserved.

4.
China Tropical Medicine ; 22(9):816-820, 2022.
Article in Chinese | Scopus | ID: covidwho-2164284

ABSTRACT

Objective To investigate the dynamic changes and clinical significance of specific antibodies in patients with coronavirus disease 2019 (COVID-19). Methods A retrospective study was conducted to collect 141 adult COVID-19 survivors who were followed up in the Eighth Hospital affiliated to Guangzhou Medical University from February 6, 2020, to March 24, 2021. The patients were divided into severe group (severe and critical) and non-severe group (light and ordinary) according to the diagnosis at discharge. The antibody changes of the two groups were compared and analyzed at 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year after discharge. Results After discharge from hospital, the positive rate of IgG in the severe group was 95.00% after 1 week and 100.00% in the following year, in the positive rate of IgG in the non-severe group was 59.50% after 1 week, 90.08% in 6 months and 76.03% in one year. The level of serum IgG in the severe group was significantly higher than that in non-severe group (Z=-2.441, P=0.015). One-year follow-up: the serum IgG in the severe group was significantly higher than that in the non-severe group (Z=-3.410, P=0.001). The serum IgM level of the severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-2.259, P=0.024). The serum IgG and IgM level of the non-severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-7.37, P<0.01;Z=3.850, P<0.01). Conclusion The level of serum protective antibody in COVID-19 patients remained high within 6 months after discharge, and remained stable within 1 year after discharge. The antibody titers in the severe group were significantly higher than those in the non-severe group and lasted for at least one year. COVID-19 survivors receive 1 year of natural immune protection, and patients with critical conditions receive immunity for longer periods of time. © 2022 The authors.

5.
Pediatrics ; 150, 2022.
Article in English | ProQuest Central | ID: covidwho-2162666

ABSTRACT

PURPOSE OF THE STUDY: To evaluate if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could promote the initial development or relapse of Juvenile Dermatomyositis (JDM). The secondary aim was to identify if SARS-CoV-2 played a role in triggering of JDM through induction of interferon-α (IFNα). STUDY POPULATION: This study included 10 patients with new disease onset (n = 6) or relapse (n = 4) of JDM at a single center in France between April 2020 and March 2021. All patients met diagnostic criteria for JDM according to the European Neuro Muscular Centre 2018 dermatomyositis classification criteria. METHODS: This was a cross-sectional analysis of IgG and IgM levels directed against 5 different portions of the SARS-CoV-2 virus in the plasma of 10 patients with new onset or relapse of JDM at the time of diagnosis. The point prevalence of a positive SARS-CoV-2 infection concomitantly among new onset or relapse of JDM was determined using basic data analysis. Descriptive statistical analysis was also performed comparing the level of interferon-α2 (IFNα2) protein among 2 patients with concomitant SARS-CoV-2 infection against median IFNα2 protein levels of 33 JDM patients with active disease followed in the same clinical center. RESULTS: Out of the 10 patients, this study identified 2 (20%) patients with high titers of both IgG and IgM antibodies directed against SARS-CoV-2 proteins. One patient had new onset JDM (P1) and the second patient had relapsing JDM (P2). The clinical presentation at relapse (isolated to skin) in P2 was similar to the lesions observed at diagnosis. Both had an asymptomatic SARS-CoV-2 infection. Two weeks after diagnosis, there was a 150-fold increase in the IFNα2 level in P1 (73 476 fg/mL) and a 9-fold increase in the IFNα2 level in P2 (4612 fg/mL) compared with the median IFNα2 level (491 fg/mL) in 33 patients with active JDM at same clinical center. For P2, following treatment with IVIG and corticosteroids, there was a progressive decrease in IFNα2 level (1466 fg/mL) seen at 10 weeks after symptom onset. CONCLUSIONS: The point prevalence was 20% for a concomitant SARS-CoV-2 infection among the 10 patients with new onset or relapse of JDM at a single clinical center in France. SARS-CoV-2 infection may trigger the development of JDM through induction of IFNα.

6.
Immunity ; 2022.
Article in English | ScienceDirect | ID: covidwho-2149893

ABSTRACT

Summary The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation of all IGHV genes. The IGHV1-69∗20-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-69∗20 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high affinity receptor binding domain interaction. These results demonstrate that single polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.

7.
J Med Virol ; 2022.
Article in English | PubMed | ID: covidwho-2148395

ABSTRACT

Vaccines are critical cost-effective tools to control the COVID-19 pandemic. The heterologous prime-boost vaccination has been used by many countries to overcome supply issues, so the effectiveness and safety of this strategy need to be better clarified. This study aims to verify the effect of heterologous prime-boost COVID-19 vaccination on healthcare professionals from Dante Pazzanese Hospital in Brazil. It was performed serological assays of vaccinated individuals after 2-dose of CoronaVac (Sinovac, n=89) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca, n=166) followed by a BNT162b2 booster (Pfizer-BioNTech, n=255). The serum antibodies anti-S (spike), anti-N (nucleocapsid), and anti-RBD (receptor binding domain) were assessed by enzyme-linked immunosorbent assay. The heterologous booster dose induced a ten-fold higher anti-Spike antibody regardless of the 2-dose of a prime vaccine. It was strikingly observed that BNT162b2 enhanced levels of anti-spike antibodies, even in those individuals who did not previously respond to the 2-dose of CoronaVac. In conclusion, the heterologous scheme of vaccination using mRNA as a booster vaccine efficiently enhanced the antibody response against SARS-CoV-2, especially benefiting those elderly who were seronegative with a virus-inactivated vaccine. This article is protected by copyright. All rights reserved.

8.
Journal of the American Society of Nephrology ; 33:892-893, 2022.
Article in English | EMBASE | ID: covidwho-2124798

ABSTRACT

Background: Presenting features for glomerular disease can be varied, including but not exclusively, acute kidney injury, nephrotic syndrome or haemo-proteinuria. At our regional tertiary centre we conducted a retrospective study to see whether clinical presentations of glomerular diseases had changed during the COVID-19 pandemic. Method(s): In this study, new and repeat native renal biopsies were included from January 2018 to October 2021. Glomerular pathologies of interest included minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis and pauciimmune glomerulonephritis. We looked at three periods of time: prior to the start COVID-19 pandemic in 2018/19;during the COVID-19 pandemic in 2020;and after the introduction of COVID-19 vaccines in 2021. Result(s): 263 biopsies were identified over the 4-year period. IgA nephropathy - n = 13. Lupus nephritis - n = 43. The different classes of lupus nephritis are shown in (see figure 1) Minimal change disease - n = 57. All presented with the nephrotic syndrome. Between 6-25% over the study period presented with AKI (mean 19%) Pauci-immune glomerulonephritis - n = 85. Between 81%-91% over the study period presented with AKI, or AKI on CKD (mean 84%) Membranous glomerulopathy - n = 66. 50%, presented with the nephrotic syndrome. 20% presented with AKI in addition to proteinuria. Conclusion(s): Our analysis has not shown a significant change in clinical presentations of glomerular disease. There has not been an increased propensity in presenting with AKI in minimal change disease or membranous nephropathy. We saw the highest proportion of class IV lupus nephritis in 2021.

9.
Journal of the American Society of Nephrology ; 33:307, 2022.
Article in English | EMBASE | ID: covidwho-2124691

ABSTRACT

Background: Glomerular disease carries a significant burden of morbidity and mortality. There is emerging evidence of the impact of the COVID-19 pandemic and COVID-19 vaccination on glomerular disease. The aim of the study was to retrospectively analyse our experience of the incidence of glomerular disease between 2018 and 2021. Method(s): Native renal biopsy results were reviewed to compare the incidence of glomerular disease prior to the COVID-19 pandemic (2018/19);prior to development of COVID-19 vaccination (2020);and after the introduction of COVID-19 vaccines (2021). Biopsy data from January 2018 to October 2021 were collated from pathology records for all glomerular disease patients in our unit. We focused on the incidence of IgA nephropathy, lupus nephritis, minimal change disease, membranous nephropathy and pauci-immune glomerulonephritis. Result(s): 263 native biopsies were performed;45 biopsies in 2018, 75 in 2019, 65 in 2020 and 78 in the first ten months of 2021. The proportional incidence of each disease is shown in figure 1. The incidence of membranous nephropathy was noted to be higher in 2021, coinciding with the introduction of the COVID-19 vaccine programme in the UK, from an average of 23% of cases between 2018-2020, to 31% in the first ten months of 2021. The overall incidence of glomerular disease, excluding vasculitis, seemed to have fallen during 2020. Conclusion(s): The emergence of COVID-19 does not appear to have caused a significant increase in the overall incidence of glomerular disease in our population. We noted an increase in the incidence of membranous nephropathy following the introduction of the COVID-19 vaccination programme in 2021. The relatively lower incidence in 2020 could be related to limited access to primary health care practitioners and consequent reduction in referrals to secondary care at the time.

10.
Allergy Asthma Immunol Res ; 14(6): 604-652, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2144267

ABSTRACT

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

11.
Front Immunol ; 13: 993720, 2022.
Article in English | MEDLINE | ID: covidwho-2142018

ABSTRACT

Pathogenesis of lung injury in COVID-19 is not completely understood, leaving gaps in understanding how current treatments modulate the course of COVID-19. Neutrophil numbers and activation state in circulation have been found to correlate with COVID-19 severity, and neutrophil extracellular traps (NETs) have been found in the lung parenchyma of patients with acute respiratory distress syndrome (ARDS) in COVID-19. Targeting the pro-inflammatory functions of neutrophils may diminish lung injury in COVID-19 and ARDS. Neutrophils were isolated from peripheral blood of healthy donors, treated ex vivo with dexamethasone, tocilizumab and intravenous immunoglobulin (IVIG) and NET formation, oxidative burst, and phagocytosis were assessed. Plasma from critically ill COVID-19 patients before and after clinical treatment with IVIG and from healthy donors was assessed for neutrophil activation-related proteins. While dexamethasone and tocilizumab did not affect PMA- and nigericin-induced NET production ex vivo, IVIG induced a dose-dependent abrogation of NET production in both activation models. IVIG also reduced PMA-elicited reactive oxygen species production, but did not alter phagocytosis. COVID-19 patients were found to have elevated levels of cell-free DNA, neutrophil elastase and IL-8 as compared to healthy controls. Levels of both cell-free DNA and neutrophil elastase were lower 5 days after 4 days of daily treatment with IVIG. The lack of impact of dexamethasone or tocilizumab on these neutrophil functions suggests that these therapeutic agents may not act through suppression of neutrophil functions, indicating that the door might still be open for the addition of a neutrophil modulator to the COVID-19 therapeutic repertoire.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , Lung Injury , Respiratory Distress Syndrome , Humans , Neutrophils/metabolism , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/pharmacology , COVID-19/drug therapy , Leukocyte Elastase/metabolism , Lung Injury/metabolism , Cell-Free Nucleic Acids/metabolism , Dexamethasone
12.
Infect Drug Resist ; 15: 6695-6701, 2022.
Article in English | MEDLINE | ID: covidwho-2141130

ABSTRACT

Background: "Pneumonia Prevention No.1" belongs to 'traditional Chinese medicine prescription for prevention of viral pneumonia and influenza' was urgently formulated by Notice on Printing the Novel Coronavirus Diagnosis and Treatment Scheme for COVID-19 (Trial Version 3) and Traditional Chinese Medicine Prevention and Treatment Scheme for COVID-19 in Hubei Province (Trial). Because the prescription drug has the bidirectional regulation function of human immune function, moderate improvement of immune function can effectively resist virus invasion, while excessive immune function will produce immune overresponse. Excessive immune response will aggravate the condition of patients with COVID-19, resulting in the death of severe patients. Methods: Twenty medical workers aged 20-60 years old, who had no immune disease, no current disease and healthy physical examination, were selected as participants. The participants took Hubei "Pneumonia Prevention No.1" decoction, one dosage each day, twice a day, for 7 consecutive days. With the before-after control method, blood samples were collected from the median cubital veins before and after medication. Immunoglobulin IgA, IgG and IgM were measured by immunoturbidimetry, and T lymphocyte subsets CD3, CD4, CD8 and CD4/CD8 were measured by flow cytometry. The changes of indexes before and after medication were compared with SPPS 13.0 statistical software. The data were expressed by (mean ± standard deviation). T-test was adopted, and P < 0.05 was considered statistically significant (P < 0.05). Results: The results of this study show that in healthy participants, the immunoglobulin and T lymphocyte subsets did not differ significantly before and after drug administration (P > 0.05). Conclusion: Under normal drug administration circumstances, "Pneumonia Prevention No. 1" had no significant regulating effect on the immune system in a healthy population and did not increase the immune system capacity beyond a reasonable range. It is safe to be used as a prophylactic measure in healthy populations.

13.
Biol Direct ; 17(1): 36, 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2139383

ABSTRACT

BACKGROUND: The major histocompatibility complex (MHC) and the killer cell immunoglobulin-like receptors (KIR) are key regulators of immune responses. The cynomolgus macaque, an Old World monkey species, can be applied as an important preclinical model for studying human diseases, including coronavirus disease 2019 (COVID-19). Several MHC-KIR combinations have been associated with either a poor or good prognosis. Therefore, macaques with a well-characterized immunogenetic profile may improve drug evaluation and speed up vaccine development. At present, a complete overview of the MHC and KIR haplotype organizations in cynomolgus macaques is lacking, and characterization by conventional techniques is hampered by the extensive expansion of the macaque MHC-B region that complicates the discrimination between genes and alleles. METHODS: We assembled complete MHC and KIR genomic regions of cynomolgus macaque using third-generation long-read sequencing approach. We identified functional Mafa-B loci at the transcriptome level using locus-specific amplification in a cohort of 33 Vietnamese cynomolgus macaques. RESULTS: This is the first physical mapping of complete MHC and KIR gene regions in a Vietnamese cynomolgus macaque. Furthermore, we identified four functional Mafa-B loci (B2, B3, B5, and B6) and showed that alleles of the Mafa-I*01, -B*056, -B*034, and -B*001 functional lineages, respectively, are highly frequent in the Vietnamese cynomolgus macaque population. CONCLUSION: The insights into the MHC and KIR haplotype organizations and the level of diversity may refine the selection of animals with specific genetic markers for future medical research.

14.
Transfus Med ; 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2137290

ABSTRACT

OBJECTIVE: Evaluate the safety and effectiveness of convalescent plasma (CP) or hyperimmune immunoglobulin (hIVIG) in severe respiratory disease caused by coronaviruses or influenza, in patients of all ages requiring hospital admission. METHODS: We searched multiple electronic databases for all publications to 12th October 2020, and RCTs only to 28th June 2021. Two reviewers screened, extracted, and analysed data. We used Cochrane ROB (Risk of Bias)1 for RCTs, ROBINS-I for non-RCTs, and GRADE to assess the certainty of the evidence. RESULTS: Data from 30 RCTs and 2 non-RCTs showed no overall difference between groups for all-cause mortality and adverse events in four comparisons. Certainty of the evidence was downgraded for high ROB and imprecision. (1) CP versus standard care (SoC) (20 RCTS, 2 non-RCTs, very-low to moderate-high certainty); (2) CP versus biologically active control (6 RCTs, very-low certainty); (3) hIVIG versus SoC (3 RCTs, very-low certainty); (4) early CP versus deferred CP (1 RCT, very-low certainty). Subgrouping by titre improved precision in one outcome (30-day mortality) for the 'COVID high-titre' category in Comparison 1 (no difference, high certainty) and Comparison 2 (favours CP, very-low certainty). Post hoc analysis suggests a possible benefit of CP in patients testing negative for antibodies at baseline, compared with those testing positive. CONCLUSION: A minimum titre should be established and ensured for a positive biological response to the therapy. Further research on the impact of CP/hIVIG in patients who have not yet produced antibodies to the virus would be useful to target therapies at groups who will potentially benefit the most.

15.
Proc Natl Acad Sci U S A ; 119(48): e2212658119, 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2133966

ABSTRACT

Protein glycosylation is a crucial mediator of biological functions and is tightly regulated in health and disease. However, interrogating complex protein glycoforms is challenging, as current lectin tools are limited by cross-reactivity while mass spectrometry typically requires biochemical purification and isolation of the target protein. Here, we describe a method to identify and characterize a class of nanobodies that can distinguish glycoforms without reactivity to off-target glycoproteins or glycans. We apply this technology to immunoglobulin G (IgG) Fc glycoforms and define nanobodies that specifically recognize either IgG lacking its core-fucose or IgG bearing terminal sialic acid residues. By adapting these tools to standard biochemical methods, we can clinically stratify dengue virus and SARS-CoV-2 infected individuals based on their IgG glycan profile, selectively disrupt IgG-Fcγ receptor binding both in vitro and in vivo, and interrogate the B cell receptor (BCR) glycan structure on living cells. Ultimately, we provide a strategy for the development of reagents to identify and manipulate IgG Fc glycoforms.


Subject(s)
COVID-19 , Single-Domain Antibodies , Humans , Immunoglobulin G/metabolism , SARS-CoV-2 , Immunoglobulin Fc Fragments/metabolism , Polysaccharides/metabolism
16.
Am J Obstet Gynecol MFM ; 5(2): 100796, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2129787

ABSTRACT

BACKGROUND: For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. OBJECTIVE: We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons. STUDY DESIGN: We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test. RESULTS: Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). CONCLUSION: The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.

17.
Revue Medicale Suisse ; 17(723):234, 2021.
Article in French | EMBASE | ID: covidwho-2146894
18.
Multiple Sclerosis Journal ; 28(3 Supplement):365-366, 2022.
Article in English | EMBASE | ID: covidwho-2138913

ABSTRACT

Introduction: People with multiple sclerosis (PwMS) treated with anti-CD20 therapies and fingolimod are less likely to successfully produce a humoral response to COVID-19 vaccines 1 and 2. Objective(s): To measure the humoral and/or cellular response to COVID-19 booster vaccinations in a cohort of PwMS who were previously seronegative after their initial COVID vaccine course. Aim(s): To determine whether there is a benefit of COVID-19 booster vaccinations for people with MS who are known to have had an attenuated response to initial vaccines. Method(s): We studied a cohort of PwMS all of whom were seronegative for anti-SARS-CoV-2 spike protein IgG after the 1st and 2nd COVID-19 vaccines, including PwMS treated with ocrelizumab (n=53), fingolimod (n=15), other DMTs (n=9) and no DMT (n=2). Dried blood spot +/- whole blood samples were obtained from participants at 2-8 weeks after their 3rd (n=79) and 4th (n=40) COVID-19 vaccines. Samples were used to measure anti-SARS-CoV-2 spike protein IgG (ELISA) and T-cell response (IFN-g release assay measured on whole blood). Result(s): Overall 27/79 (34%) who were seronegative after COVID vaccine 2 seroconverted after vaccine 3. Seroconversion rates were 17% for PwMS treated with ocrelizumab, 47% for fingolimod and 100% for other DMTs. A further 2/30 (7%) of those who remained seronegative after vaccine 3 seroconverted after vaccine 4. Anti-SARS-CoV-2 T-cell responses were measurable in 26/40 (65%) after vaccine 3 and 13/19 (68%) after vaccine 4 but were conspicuously absent in people treated with fingolimod. Overall, 75% of participants showed either humoral or cellular response after receiving 4 COVID vaccinations. PwMS with laboratory evidence of prior COVID-19 infection had higher measurable T-cell responses. Conclusion(s): Booster vaccinations for COVID-19 are associated with incremental benefits in measurable immunity in those with attenuated responses to the initial vaccine course. Overall, three quarters of those who were seronegative after COVID vaccines 1 & 2 had a measurable immune response after COVID vaccine 4. This data supports the use of booster vaccinations in pwMS at risk of attenuated vaccine response.

19.
Multiple Sclerosis Journal ; 28(3 Supplement):480-481, 2022.
Article in English | EMBASE | ID: covidwho-2138897

ABSTRACT

Background and goals: The goal of this study was to assess the rate of self-reported side effects, need for medical assistance and hospitalizations after a third COVID-19 vaccination in people with multiple sclerosis (pwMS) with or without disease-modifying treatments. We also wanted to investigate if SARS-CoV2 antibody levels correlate with side effects. Method(s): Participants enrolled in the vaccination trial Nevrovax were invited to complete a questionnaire on side effects after the third dose of SARS-CoV-2 vaccination. SARS-CoV2 antibodies were measured in BAU/mL after 3 weeks or longer after vaccination. The results were linked to data from the Norwegian Immunization Registry. Statistical analyses were performed using SPSS Stastistics version 26. Group comparisons were analyzed using independent samples t-tests and chi-square tests with a significance level of 0.05. Result(s): In total 606 pwMS (77.4% female, mean age 48.3 years) were included in this study. At the time of immunization, 61.7% of all pwMS were treated with anti-CD20 monoclonal antibodies and 19%with sphingosine 1-phosphate receptor modulators. Mean time to follow up from third dose to answering the questionnaire was 29.9 days.586 patients received an mRNAvaccine (257 BNT162b2 and 344 mRNA1273 as dose 3) while 20 received a viral vector vaccine-AZD1222 (One as dose 3). Data on vaccine type of dose 3 was missing in 4 patients. Side effects were reported by 66.2% of all pwMS. Mean age of patients with and without side effects were 47.0and 50.7 years, respectively (p < 0.01). We found a higher rate of side effects among women (68.8%) than men (59.1%) (p=0.047), and a higher rate among those using anti-CD20 therapy (73.3%) (p<0.05). Blood samples of SARS-CoV2 antibodies were obtained in 547 patients. There were no significant difference in antibody levels in patients with side effects (mean 1185 BAU/ mL) and patients without side effects (mean 1174 BAU/mL), p= 0.66. 16 pwMS (2.6%) sought medical help after vaccination. No pwMS needed hospitalization. Conclusion(s): Our results demonstrate that a third dose of SARSCov2 vaccines are safe in pwMS using different DMTs. Rate and severity of side effects vary with both treatment and demographic factors. SARS-CoV2 IgG levels did not correlate with side effects. There were no hospitalizations after vaccination with a 3rd dose.

20.
Multiple Sclerosis Journal ; 28(3 Supplement):336, 2022.
Article in English | EMBASE | ID: covidwho-2138890

ABSTRACT

Introduction: B-cell depletion agents such as ocrelizumab (OCR) are highly effective treatment options for active multiple sclerosis (MS). However, it is known, that B-cell depletion can be associated with a lower antibody response after SARS-CoV-2 immunisation. The individual factors that contribute to the immune response are less understood. Objective, aims and method: Here, we retrospectively analysed single centre, structured clinical routine SARS-CoV-2 spike antibody response data after completion of basic immunization in 42 consecutive included MS patients under OCR therapy who are standardised investigated in our outpatient clinic. In particular, we examined treatment duration, previous immunotherapies, immunoglobulin levels, and lymphocyte subsets includingB-cell and lymphocyte countsas well as time interval between last OCR treatment and SARS-CoV-2 vaccination as influencing factors in patients with and without SARS-CoV-2 spike antibody response. All patients gave written ethical consent. Result(s): 42 MS patients were identified and included (38 RRMS, 4 PPMS patients, 28 females, median age: 42.0 years, median disease duration: 11.2 years), which are treated with OCR (median treatment duration: 2.0 years. 29 patients (69.1 %) and showed no SARS-CoV-2 spike antibody response. Median IgG and IgM levels and B-cell counts were marginally lower in patients without SARS-CoV-2 spike antibody response.The time interval between last OCR administration and first vaccination, however, was significantly longer (median = 2.8 [0.3;5.1] months vs median = 4.0 [2.9;5.7] months [min;max]) in patients with positive SARS-CoV-2 spike antibody response. Antibody response was not associated with age, sex, number of previous immunotherapies and duration of OCR therapy. Further data regarding lymphocyte subsets will be presented during the ECTRIMS congress. Conclusion(s): As an influencing factor the time interval between last OCR dosing and vaccination affects SARS-CoV-2 spike antibody response to vaccination. Our results support previous findings and help to advise patients for the best timepoint of vaccination under B-cell depleting therapies. We identified the time interval between OCR dosing and vaccination date as the main influencing factor after SARS-CoV-2 vaccination. Against expectation, the duration of ocrelizumab therapy and the number of previous therapies do not seem to be an influencing factor.

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