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1.
Brain Behav Immun ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031148

ABSTRACT

BACKGROUND: Although factors associated with the antibody response to the BNT162b2 mRNA COVID-19 vaccine have been reported, psychological factors have not been examined. Depression or anxiety may affect vaccine reactions because these factors influence immune responses. This study aimed to determine whether psychological status at the time of vaccination predicts antibody responses. METHODS: A prospective observational study of the BNT162b2 mRNA COVID-19 vaccine response was carried out among individuals attending for an annual health check-up. Participants included 78 volunteers out of 80 hospital workers in Nagoya, Japan. No participants had been infected with COVID-19 and all gave written informed consent to participate in the study. Blood samples were obtained approximately 28 days after the second dose of the vaccine, and antibody titers of the SARS-CoV-2 spike protein were determined using the SARS-CoV-2 IgG II Quant assay. Participants completed the Japanese version of the hospital anxiety and depression scale (HADS) questionnaire, one day before both vaccinations. Participants also recorded any adverse reactions, such as body temperature and other side effects, every day for two weeks after each dose. The relationships between antibody titers and the predictive factors were analyzed using multiple linear regression analysis, with the antibody titers as the dependent variables, followed by univariate analysis. RESULTS: Multiple linear regression analysis revealed that no or excessive alcohol intake (p = 0.039), poor results from a health check-up (p = 0.011), a longer duration between the second dose and blood collection (p = 0.039), and degree of depressive symptoms (p = 0.041) were significant negative predictors of antibody titers, while body temperature one day after the second dose as a significant positive predictor (p < 0.0005). CONCLUSION: We identified that depressive symptoms just before the second dose of the BNT162b2 mRNA COVID-19 were an independent negative predictor of antibody responses, in addition to other factors. Our results highlight the importance of mental health at the time of vaccination to achieve the higher antibody responses necessary to acquire humoral immunity.

2.
Journal of Personalized Medicine ; 12(8), 2022.
Article in English | Web of Science | ID: covidwho-2023829

ABSTRACT

Mortality and morbidity from influenza and other respiratory viruses are significant causes of concern worldwide. Infections in the respiratory tract are often underappreciated because they tend to be mild and incapacitated. On the other hand, these infections are regarded as a common concern in clinical practice. Antibiotics are used to treat bacterial infections, albeit this is becoming more challenging since many of the more prevalent infection causes have acquired a wide range of antimicrobial resistance. Resistance to frontline treatment medications is constantly rising, necessitating the development of new antiviral agents. Probiotics are one of several medications explored to treat respiratory viral infection (RVI). As a result, certain probiotics effectively prevent gastrointestinal dysbiosis and decrease the likelihood of secondary infections. Various probiotic bacterias and their metabolites have shown immunomodulating and antiviral properties. Unfortunately, the mechanisms by which probiotics are effective in the fight against viral infections are sometimes unclear. This comprehensive review has addressed probiotic strains, dosage regimens, production procedures, delivery systems, and pre-clinical and clinical research. In particular, novel probiotics' fight against RVIs is the impetus for this study. Finally, this review may explore the potential of probiotic bacterias and their metabolites to treat RVIs. It is expected that probiotic-based antiviral research would be benefitted from this review's findings.

3.
Frontiers in Immunology ; 13, 2022.
Article in English | Scopus | ID: covidwho-2022745

ABSTRACT

Influenza vaccines remain the most effective tools to prevent flu and its complications. Trivalent or quadrivalent inactivated influenza vaccines primarily elicit antibodies towards haemagglutinin and neuraminidase. These vaccines fail to induce high protective efficacy, in particular in older adults and immunocompromised individuals and require annual updates to keep up with evolving influenza strains (antigenic drift). Vaccine efficacy declines when there is a mismatch between its content and circulating strains. Current correlates of protection are merely based on serological parameters determined by haemagglutination inhibition or single radial haemolysis assays. However, there is ample evidence showing that these serological correlates of protection can both over- or underestimate the protective efficacy of influenza vaccines. Next-generation universal influenza vaccines that induce cross-reactive cellular immune responses (CD4+ and/or CD8+ T-cell responses) against conserved epitopes may overcome some of the shortcomings of the current inactivated vaccines by eliciting broader protection that lasts for several influenza seasons and potentially enhances pandemic preparedness. Assessment of cellular immune responses in clinical trials that evaluate the immunogenicity of these new generation vaccines is thus of utmost importance. Moreover, studies are needed to examine whether these cross-reactive cellular immune responses can be considered as new or complementary correlates of protection in the evaluation of traditional and next-generation influenza vaccines. An overview of the assays that can be applied to measure cell-mediated immune responses to influenza with their strengths and weaknesses is provided here. Copyright © 2022 Janssens, Joye, Waerlop, Clement, Leroux-Roels and Leroux-Roels.

4.
Front Immunol ; 13:920627, 2022.
Article in English | PubMed | ID: covidwho-2022711

ABSTRACT

BACKGROUND: The pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration. METHODS: Prospective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed. RESULTS: Of 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98;95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03-0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months. CONCLUSION: Patients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.

5.
Clin Infect Dis ; 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-2017792

ABSTRACT

BACKGROUND: Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. METHODS: Seventy-eight residents and 106 staff members, naïve or previously infected with SARS-CoV-2, were recruited in NH in Belgium before immunization with two doses of 30µg BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. RESULTS: SARS-CoV-2 naïve residents had lower Ab responses to BNT162b2 mRNA vaccination than naïve staff. These poor responses involved lower levels of IgG to all spike domains, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naïve resident had detectable neutralizing Ab to the B.1.351 variant. In contrast, SARS-CoV-2 infected residents had high responses to mRNA vaccination, with Ab levels comparable to infected staff. Cluster analysis revealed that poor vaccine responders not only included naïve residents but also naïve staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection naïve residents and in some naïve staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

6.
J Infect Dis ; 2022 Jun 24.
Article in English | MEDLINE | ID: covidwho-2017956

ABSTRACT

The risk of a severe course of SARS-CoV-2 infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those over 40 years of age. After primary SARS-CoV-2 vaccination the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1-specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, mRNA-1273 or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after two mRNA vaccinations or after two ChAdOx1 vaccinations. After two mRNA vaccinations lower antibody concentrations were seen with increasing age.

7.
BMJ : British Medical Journal (Online) ; 378, 2022.
Article in English | ProQuest Central | ID: covidwho-2020004

ABSTRACT

The Food and Drug Administration (FDA) authorised updated boosters from Pfizer BioNTech and from Moderna on 31 August, and an expert advisory committee convened the next day by the Centers for Disease Control and Prevention (CDC) voted 13-1 to recommend their use. A projection shown to the experts estimated that waiting to roll out the new boosters until November, when more human data will be available could have resulted in 9700 more deaths and 137 000 more hospital admissions.1 Canada approves older omicron booster Health Canada on 1 September approved for adults Moderna’s bivalent booster that targets the omicron BA.1 variant. BA.1 disappeared from circulation in May, but Canada’s National Advisory Committee on Immunization said the new booster will generate a significantly more effective neutralising antibody response against BA.4 and BA.5 than the original Moderna vaccine.

8.
The New Microbiologica ; 45(3):181, 2022.
Article in English | ProQuest Central | ID: covidwho-2012948

ABSTRACT

Background. Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nucleocapsid (NCP) IgG, was investigated. Methods. A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnancy and newborn parameters were evaluated in comparison with 200 uninfected controls. Results. Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mounted significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and newborn parameters were not significantly different from those observed in uninfected controls. Conclusion. Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.

9.
NeuroQuantology ; 20(8):7591-7595, 2022.
Article in English | EMBASE | ID: covidwho-2010532

ABSTRACT

The current research aimedto demonstrate the extent such as increase in the rate of immune response to antibodies (IgG, IgM) for people who received the first dose of the Pfizer mRNA vaccine at (1-3) weeks times period and to compare them with people who were not taken for the first dose of the same vaccine and none infected with COVID-19.Also the results appearedsignificant variations in immunoglobulin (IgG) levels (P≤ 0.05) between case (Recipients mRNA vaccination) and control patients, there were. In terms of age and gender, however, there were no significant changes (P≥ 0.05) in immunoglobulin (IgM) levels between case (Recipients mRNA vaccination) and control patients.

10.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009860

ABSTRACT

Allelic diversity of human leukocyte antigen (HLA) class II genes may help maintain humoral immunity against infectious diseases. In this study, we investigated germline genetic variation in classical HLA class II genes and employed a systematic, unbiased approach to explore the relative contribution of this genetic variation in the antibody repertoire to various common pathogens. We leveraged a well-defined cohort of 800 adults representing the general Arab population in which genetic material is shared because of the high frequency of consanguineous unions. By applying a high-throughput method for large-scale antibody profiling to this well-defined cohort, we were able to dissect the overall effect of zygosity for classical HLA class II genes, as well as the effects associated with specific HLA class II alleles, haplotypes and genotypes, on the antimicrobial antibody repertoire breadth and antibody specificity with unprecedented resolution. Our population genetic studies revealed that zygosity of the classical HLA class II genes is a strong predictor of antibody responses to common human pathogens, suggesting that classical HLA class II gene heterozygosity confers a selective advantage. Moreover, we demonstrated that multiple HLA class II alleles can have additive effects on the antibody repertoire to common pathogens. We also identified associations of HLA-DRB1 genotypes with specific antigens. Our findings suggest that HLA class II gene polymorphisms confer specific humoral immunity against common pathogens, which may have contributed to the genetic diversity of HLA class II loci during hominine evolution.

11.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009630

ABSTRACT

Background: Patients with hematologic malignancies have a lower vaccine response and higher rates for SARS CoV-2 morbidity and mortality. We present preliminary data focusing on humoral vaccine responses and correlates with disease subtype and treatment exposure. Methods: We analyzed data from 332 patients with a hematologic malignancy from May 1, 2021 - Jan 31, 2022 who received SARSCoV-2 vaccination and performed a prospective cohort serologic study with the Elecsys®Anti-SARSCoV-2-S test. Patients received homologous or heterologous vaccine combination of BNT162b2, mRNA1273, ChAdOx1 nCoV-19, and/or Ad26.COV2.S. Blood samples were obtained before any vaccination, 2-6 weeks after the second vaccine (2V), before third vaccine (3V), and 2-6 weeks after 3V. Results: The median age was 67 years (range 18-91years) with 41.9% female. At 2V, 11.5% and at 3V, 23.8% received heterologous vaccines. Treatment status at first vaccine dose significantly affected peak 2V antibody response (p < 0.05). Seropositive rate and median antibody titer after 2V for previously untreated patients were higher compared to patients on active therapy or had previously been treated. Treatment naïve (n = 60;seropositivity 85.1%;median titer 1306 U/mL;[Q1-Q3:11.4-> 2499]);first-line (1L) active therapy (n = 127;65.4%;41.25 U/mL;[ < 0.8-592.5]);second-line and beyond (2L+) active therapy (n = 56;60.7%;2.6U/mL;[ < 0.8-154]);previous treatment with 1L (n = 66;64.8%;118 U/mL;[ < 0.8-> 2499]);previous treatment with 2L+ (n = 23;59.1%;4U/mL;[ < 0.8-229.5]). Of 61 patients that were seronegative at 2V, 17 (27.9%) seroconverted after 3V. Anti-CD20 monoclonal antibody (mAb) containing therapy as the most recent treatment from 2V had the greatest impact on humoral response. Exposure to anti-CD20 mAb based regimens or as monotherapy revealed low antibody responses (n = 84;seropositivity 22.6%;median titer < 0.8 U/mL;Q1-Q3 [ < 0.8-< 0.8]). On analysis of indolent B-cell Non-Hodgkin Lymphomas whereby antiCD-20 mAb are often incorporated, treatment proximity to 2V impacted responses: < 3 months (n = 33;22%;< 0.8 U/ mL;[ < 0.8-< 0.8]) vs. 12-24 months (n = 4;60%;228 U/mL;[ < 0.8-232]). In contrast, tyrosine kinase inhibitor (n = 38;100%;858 U/mL;[221-> 2499]), proteosome inhibitor monotherapy (n = 4;100%;median titer 1520 U/mL;[462-> 2499]) were among the subgroups with the highest numerical responses, however, the addition of corticosteroids impacted vaccine response as seen in proteosome inhibitor with corticosteroids (n = 7;85.7%;6.6 U/mL;[1.8-115.2]). Conclusions: The humoral response from our single institution cohort identifies diminished responses depending on treatment status and the type of treatment including the proximity of treatment exposure to receipt of vaccination. Furthermore, vaccine boosters can induce antibody responses in patients who were previously seronegative.

12.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009618

ABSTRACT

Background: Cancer and systemic anti-cancer treatment (SACT) have been identified as possible risk factors for infection and related severe illness associated with SARS-CoV-2 virus as a consequence of immune suppression. The Scottish COVID CAncer iMmunity Prevalence (SCCAMP) study aimed to characterise the incidence and outcomes of SARS-Cov-2 infection in patients undergoing active anticancer treatment during the COVID-19 pandemic and their antibody response following vaccination. Methods: Eligible patients were those attending secondary care for active anti-cancer treatment for a solid tumour. Blood samples were taken for total SARS-CoV-2 antibody assay (Siemens) at baseline and after 1.5, 3, 6 and 12 months. Data on COVID-19 infection, vaccination, cancer type, treatment and outcome (patient death) was obtained from routine electronic health records. Results: The study recruited 766 eligible participants between 28th May 2020 and 31st October 2021. During the study period there were 174 deaths (22%). The median age was 63 years, and 67% were female. Most received cytotoxic chemotherapy (79%), with the remaining 14% receiving immunotherapy and 7% receiving another form of anti-cancer therapy (radiotherapy, other systemic anti-cancer treatment). 48 (6.3%) tested positive for SARS-CoV-2 by PCR during the study period. The overall infection rate matched that of the local adult general population until May 2021, after which population levels appeared higher than the study population. Antibody testing detected additional evidence of infection prior to vaccination, taking the total number to 58 (7.6%). There was no significant difference in SARS-CoV-2 PCR positive test rates based on type of anti-cancer treatment. Mortality rates were similar between those who died within 90 days of a positive SARS-CoV-2 PCR and those with no positive PCR (10.4% vs 10.6%). Death from all causes was lowest among vaccinated patients, and of the patients who had a positive SARS-CoV-2 PCR at any time, all of those who died during the study period were unvaccinated. Multivariate analysis correcting for age, gender, socioeconomic status, Charlson co-morbidity score and number of previous medications revealed that vaccination was associated with a significantly lower infection rate regardless of treatment with chemotherapy or immunotherapy with hazard ratios of 0.307 (95% CI 0.144-0.6548) or 0.314 (95% CI 0.041-2.367) in vaccinated patients respectively. Where antibody data was available, 96.3% of patients successfully raised SARSCoV-2 antibodies at a time point after vaccination. This was unaffected by treatment type. Conclusions: SCCAMP provides real-world evidence that patients with cancer undergoing SACT have a high antibody response and protection from SARS-CoV-2 infection following COVID-19 vaccination.

13.
Therapeutic Advances in Vaccines and Immunotherapy ; 10, 2022.
Article in English | EMBASE | ID: covidwho-2009344

ABSTRACT

While antibodies garner the lion’s share of attention in SARS-CoV-2 immunity, cellular immunity (T cells) may be equally, if not more important, in controlling infection. Both CD8+ and CD4+ T cells are elicited earlier and are associated with milder disease, than antibodies, and T-cell activation appears to be necessary for control of infection. Variants of concern (VOCs) such as Omicron have escaped the neutralizing antibody responses after two mRNA vaccine doses, but T-cell immunity is largely intact. The breadth and patient-specific nature of the latter offers a formidable line of defense that can limit the severity of illness, and are likely to be responsible for most of the protection from natural infection or vaccination against VOCs which have evaded the antibody response. Comprehensive searches for T-cell epitopes, T-cell activation from infection and vaccination of specific patient groups, and elicitation of cellular immunity by various alternative vaccine modalities are here reviewed. Development of vaccines that specifically target T cells is called for, to meet the needs of patient groups for whom cellular immunity is weaker, such as the elderly and the immunosuppressed. While VOCs have not yet fully escaped T-cell immunity elicited by natural infection and vaccines, some early reports of partial escape suggest that future VOCs may achieve the dreaded result, dislodging a substantial proportion of cellular immunity, enough to cause a grave public health burden. A proactive, rather than reactive, solution which identifies and targets immutable sequences in SARS-CoV-2, not just those which are conserved, may be the only recourse humankind has to disarm these future VOCs before they disarm us.

14.
Annals of the Rheumatic Diseases ; 81:1711, 2022.
Article in English | EMBASE | ID: covidwho-2009209

ABSTRACT

Background: We recently reported an attenuate immunogenicity in patients with autoimmune rheumatic diseases. However, the effect of spondyloarthritis (SpA) and its treatment on COVID-19 vaccine immunogenicity remains to be determined for this group of patients. We therefore aimed to evaluate humoral immune responses to inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with SpA (axial spondyloarthritis and psoriatic arthritis) taking DMARDs and commonly used targeted biological therapies, compared with a control group(CG). Objectives: Evaluate immunogenicity and safety of CORONAVAC (Sninovac, Beijing) in Spondyloarthritis (SpA) patients. Methods: Prospective observational cohort patients diagnosed with 194 SpA and 183 CG were vaccinated with CoronaVac in two doses with a 28-days interval. 194 patients completed the study and could be paired with CG for immunogenicity analysis. Blood samples were collected in the days 0, 28 and 69 (D69) to evaluate anti-SARS-CoV-2 IgG seroconversion(SC) and presence of neutralizing antibodies (NAb) in participants with negative IgG and NAb at baseline. Results: Patients and GC were comparable regarding age (p=0.93) and sex (p=1.00). Immunogenicity at D69 showed a moderate/high SC (80.2% vs. 95.7%, p<0.0001) and Nab positivity (61.6% vs. 82.7%, p<0.0001) in SpA but lower than CG. Factors associated with lower immunogenicity were older age (56.8 vs. 51.4;p=0.03318) and higher frequencies of prednisone (25.7% vs 4.2%;p=0.0004), methotrexate (51.4% vs 40.1%, p=0.0016) and TNF inhibitor (TNFi) (62.9% vs 34.5%, p=0.0035). Likewise, prednisone (17.6% vs. 2.8%, p=0.0013) and TNFi (50% vs 33.9%;p=0.0408) were associated with diminished NAb positivity. Sulfasalazine was associated with higher SC rates (8.6% vs. 26.8%, p=0.0246) and NAb positivity (13.2% vs. 29.4%, p=0.0168). The multivariate analysis revealed that older age (p=0.037), prednisone (p=0.001), TNFi (p=0.016), and methotrex-ate(p=0.017) were independently associated with lower SC while prednisone (p=0.006) and TNFi (p=0.027) were also associated with reduced NAb response. Conclusion: Our fnding of an excellent safety and moderate/high SC rate in SpA supports the recommendation of CoronaVac vaccination. The impaired immune response in the minority of patients under immunosuppressive and biological therapy requires novel strategies to enhance antibody response in this subgroup of patients.

15.
Annals of the Rheumatic Diseases ; 81:371-372, 2022.
Article in English | EMBASE | ID: covidwho-2009176

ABSTRACT

Background: The frst vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated infammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identifed leading to specifc vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specifc recommendations are lacking. Objectives: To evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the frst vaccine dose. Methods: We have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their frst vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantifed with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We ftted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confdence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations. Results: Among 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the frst vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, fnally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B). Conclusion: Humoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the frst vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.

16.
Annals of the Rheumatic Diseases ; 81:760, 2022.
Article in English | EMBASE | ID: covidwho-2009136

ABSTRACT

Background: Pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov2/COVID19) determines the life of clinicians and patients since 2 years. Limited information is available on the nature, prognosis, and complications of SARS-Cov2 virus infection in patients with idiopathic infammatory myopathies (IIM). There are also few data on triggered humoral response, side effects and disease course after COVID19 infection or vaccination in IIM. Objectives: The primary goals of the current research were to assess frequency and outcome of COVID-19 disease and to determine the vaccination rate and effect in our IIM cohort. Secondary objectives were to search for risk factors of infection, predictive factors of hospitalization and to assess incidence of vaccination adverse events, complications and post vaccination breakthrough infections. Methods: We retrospectively identifed the confrmed COVID19 positive patients and assessed the symptoms, disease course and outcome on 01/06/2021 then patients were prospectively followed. Incidence and complications of vaccination were determined by questionnaires. Anti-SARS-CoV-2 S enzyme electrochemilu-minescent immunoassay has been used to assess seroconversion, which measures total antibody (IgM and IgG) to the SARS-CoV2 S protein and SARS-CoV2 N protein. Disease activity was determined by physician global activity. Results: A total of 176 patients were screened and 101 participated in the study. By 01/06/2021, the COVID infection rate was 34,7% (mean age: 49.54 years, 72.72% women), which was signifcantly higher than the national prevalence at that time (8.2%). A third of these infections occurred asymptomatically or mild but 20% of the infected patients were hospitalized, one patient died. Longer disease duration (8.67 vs. 17.87 years;p=0.003) and higher incidence of anti-Jo-1 antibody (57% vs. 10% p=0.018) were signifcantly associated with hospitaliza-tion. All of COVID infected patients became seropositive regardless of immu-nosuppressive therapy or symptoms severity. 53,4 % of the patients received anti-COVID19 vaccine, 75,9 % choose the mRNA type. The titer of antibodies against the spike protein induced by vaccines showed high variance, but 72,3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfzer-BioNTech vaccination compared to others (177,1 U/ml vs. 81.1 U/ml;p <001). Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment (94,03 U/ml vs. 165.6 U/ml;p = 0.008). With the follow-up of vaccinated patients, we did not found short term vaccine related major adverse events, but long term data revealed 7, 4 % post vaccination disease relapse. Breakthrough infection was detected in 9.25 % of the vaccinated patients, one cancer associated patient without post vaccination seroconversion died due to COVID pneumonia. All the fatal COVID infections occurred in patients with seron-egativity to anti-SARS-CoV2 S protein. Conclusion: Based on our results, myositis may be associated with an increased risk of infection with SARS-CoV-2. Independent risk factor for hospitalization is anti-Jo1 positivity and longer disease duration. Anti-SARS-CoV2 vaccines are safe, tolerable and strongly recommended for IIM population, but further investigation is required to assess clinical signifcance of post-vaccination disease fare.

17.
Annals of the Rheumatic Diseases ; 81:969-970, 2022.
Article in English | EMBASE | ID: covidwho-2009125

ABSTRACT

Background: Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19 (1). Furthermore, vaccination-induced CD4 and CD8 T-cell responses have been suggested to have a protective role in COVID-19 (2). If T-cell responses are diminished after vaccination in immuno-compromised individuals is not known to date. Objectives: To investigate cellular immunity following mRNA vaccination against COVID-19 in healthy individuals and patients undergoing B-cell depletion therapy. Methods: In this interim analysis of the CoVVac study (NCT04858607), we analyzed T-cell responses in autoimmune patients treated with B-cell depleting therapy (BD, n=41) and age-matched healthy controls (HCs, n=50) 3-4 weeks after the second dose of mRNA vaccination against COVID-19. Therefore, we isolated PBMCs and stimulated them with a peptide pool covering the spike protein in vitro. Reactive CD4 and CD8 T-cells were determined by staining for IFNg, TNFa, IL-2 and GzmB by fow cytometry. Anti-SARS-CoV-2 antibody assays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed to elucidate concomitant B-cell responses. Results: We observed signifcant alterations in anti-SARS-CoV-2 antibody responses in our cohort, the frequency of IFNg+ and IL-2+ CD4 and CD8 T-cells was similar in BD patients and controls. On the other hand, TNFa+ CD4 T-cells were signifcantly enriched in healthy controls versus BD patients (p=0.017) and correlated signifcantly with antibody titres (p=0.003). Similarly, GzmB+ CD8 T-cells were signifcantly diminished in our patient cohort (p<0.001) and also showed a signifcant correlation with antibody titres (p<0.001). Overall, the frequency of GzmB+ CD8 T-cells correlated very well with reactivity of T-cell subsets for other cytokines. This effect, however, is lost in the BD cohort. No difference was observed in the frequency of TNFa+ CD8 T-cells between the groups. Only 21 (42%) healthy individuals and 14 (34%) patients showed reactive T-cells for all the cytokines tested. This observation is mainly explained by a lack of cytokine production of CD8 T-cells in 26 (52%) HCs and 27 (66%) BD patients. In turn, 22 (44%) HCs and 17 (42%) patients didn't show any IL-2 producing CD8 cells. Of note, only 2 (4%) of HCs showed no GzmB+ CD8 T-cells whereas the number increased to 15 (37%) of BD individuals (p<0.001). In contrast, 42 (84%) HCs as well as 32 (78%) of patients showed production of all IFNg, TNFa and IL-2 in CD4 T-cells. Conclusion: Our data suggest that most patients with B-cell depleting therapy are able to mount T-cell responses similar to those of healthy individuals while a minority of these patients did not show complete immunity against SARS CoV-2. Further analyses are needed to better understand a possible link of B-cell depletion therapy and CD8 T-cell responses.

18.
Annals of the Rheumatic Diseases ; 81:1694-1695, 2022.
Article in English | EMBASE | ID: covidwho-2009109

ABSTRACT

Background: Several research groups have recently described a reduced vaccination response to COVID-19 vaccination under methotrexate (MTX) (1,2). The increase in humoral immune response when pausing MTX two weeks after vaccination has already been described for infuenza vaccination (3). However, data regarding MTX-hold during COVID-19 vaccination are still lacking. Objectives: To study the effect of MTX and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods: In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 rheumatic patients on methotrexate therapy, 31 of whom temporarily paused medication without a fxed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication. Results: MTX patients showed a signifcantly lower mean antibody response compared to AIRD patients without immunosuppressive therapy (71.8 % vs 92.4 %, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49;p<0.001). All nine patients with antibody levels below the cutoff were older than 60 years. Patients who held MTX during at least one vaccination showed signifcantly higher mean neutralising antibody levels after second vaccination, compared to patients who continued MTX therapy during both vaccinations (83.1 % vs 61.2 %, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8 % vs 51.9 %, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. Conclusion: MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination signifcantly improves the antibody response in patients over 60 years of age.

19.
Annals of the Rheumatic Diseases ; 81:369-370, 2022.
Article in English | EMBASE | ID: covidwho-2009092

ABSTRACT

Background: An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with rheumatic and musculoskeletal diseases (RMD) (1). We sought to identify clinical factors associated with poor humoral response following primary (two-dose mRNA or single adenoviral vector dose) SARS-COV-2 vaccination in patients with RMD on immunosuppression. Objectives: To identify clinical predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination in RMD patients on immunosuppression. Methods: We included patients ≥18 years old with RMD on immunosuppres-sion who received either two-dose mRNA or single dose Janssen/Johnson and Johnson (J&J) vaccination. Demographics, diagnoses, and therapeutic regimens were collected via participant report;those with prior COVID-19 infection were excluded. One month after vaccination, participants underwent SARS-CoV-2 antibody testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures antibody to the SARS-CoV-2 S-recep-tor binding domain (RBD) protein (ceiling >250U/mL later expanded to >2500U/mL). Associations were evaluated using Fisher's exact and Wilcoxon rank sum tests. Logistic regression analyses were performed to evaluate for clinical factors associated with antibody response. We adapted survival methods to address right-truncation of titers;this methodology was used to calculate medians. Participants provided informed consent electronically and the study was approved by the local Institutional Review Board. Results: We studied 1138 RMD participants on immunosuppression;most were female (93%) and white (91%) (Table 1). One-hundred and ffteen (10%) had anti-RBD response in the negative range at a median (IQR) of 29 days (28-34) following completion of vaccine series. A greater proportion of participants with negative response were non-white, received J&J vaccine, reported use of myco-phenolate, rituximab, or glucocorticoids. Antibody response differed by immuno-suppressive regimen, with those receiving rituximab having poorest response (Figure 1). Use of mycophenolate (aOR 9.92, p=0.001), rituximab (aOR 56.99, p=0.001), glucocorticoids (aOR 2.99, p=0.001) or receipt of J&J (aOR 3.13, p=0.039) were associated with negative antibody response. Conclusion: Use of mycophenolate, glucocorticoids, rituximab and receipt of J&J vaccine were the strongest predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination;these data support use of an additional primary dose in RMD patients.

20.
Annals of the Rheumatic Diseases ; 81:380-381, 2022.
Article in English | EMBASE | ID: covidwho-2009089

ABSTRACT

Background: The spread of COVID-19 pandemic raised the need to perform an additional vaccine dose to overcome the diffusion of the infection and possible life-threatening disease complications. Certain population subsets seem to be at increased risk of developing such complications, such as elderly and/or immu-nocompromised patients. Objectives: To assess the persistence of immunity following SARS-CoV-2 mRNA vaccine and the magnitude of the humoral response after the booster dose in a cohort of patients affected by giant cell arteritis (GCA). Methods: Patients with GCA regularly followed at the Rheumatology Department of the University of Pavia, Italy, who received a booster dose of SARS-CoV-2 mRNA vaccine (BNT162b2 Pfizer/BioNtech or mRNA-1273 Moderna) between October 1st and December 31st, 2021 were included. Humoral response was assessed by measuring SARS-CoV-2 Trimeric S (TSAbs) and Neutralizing (NAbs) antibodies, with a cut-off of 33.8 Binding Antibody Units (BAU)/mL and 1:10 dilution, respectively. Blood samples from each patient were drawn at least 4 months after the second and three weeks after the third vaccine dose. Results: Forty-two patients who received the booster dose of SARS-CoV-2 mRNA vaccine were enrolled. Thirty (71.4%) were females, mean age 73.2±4.7 years, disease duration 58±38 months, 19 (45.2%) had large-vessel vasculitis. Thirty-two (76.2%) were on glucocorticoids (GCs) at a mean dose of 4.9±7.8 mg/day prednisone equivalent, with 7 (16.7%) receiving ≥7.5 mg/day. Eighteen (42.9%) were on methotrexate (MTX) (mean dose 14.2±3.5 mg/week) and 8 (19.0%) were treated with subcutaneous tocilizumab (TCZ) 162 mg/week. SARS-CoV-2 serology was tested prior to the third vaccine dose at an average of 5.4±0.4 months from the former vaccination scheduled: 37 (88.1%) retained TSAbs and 30 (71.4%) NAbs. The median TSAb titre was 134 BAU/mL (IQR 97-292). Four out of 5 patients (80.0%) without TSAbs and 7 out of 12 (58.3%) without NAbs were on both GCs and MTX. Moreover, those on GCs plus MTX had lower pre-third dose TSAb titres as compared to other treatment subgroups (Figure 1A). GC doses ≥7.5 mg/day prednisone equivalents seemed to blunt NAb levels along time: 28.6% patients on GCs ≥7.5 mg/day prednisone equivalents had negative NAbs before the third dose vs. 80.0% of those taking <7.5 mg/day (p=0.007) as well as lower NAb titres (Figure 1B). Data regarding antibody response after the booster dose were available for 35 patients (83.3%). Blood collection occurred at a median of 25 days (IQR 24-32) after the third vaccine dose. All patients developed TSAbs, even those who did not respond to the previous shots. The median TSAb titre rose to 2080 BAU/mL (IQR 2080-2080) (p<0.001), while the median NAb titre increased from 1:10 to 1:320 (p<0.001). One patient (2.9%) treated with prednisone 8.75 mg/day plus MTX 12.5 mg/week did not develop NAbs. NAb levels were lower in patients taking MTX as compared to those who did not (Figure 1C,D), whereas treatment with TCZ or GCs, along with the GC dose, did not affect the magnitude of the antibody response. There were no serious adverse events from the vaccine. However, 3 patients (8.6%) experienced a disease relapse 24±5 days after the booster dose. Conclusion: In our cohort, most patients who seroconverted after the second dose of vaccine retained the humoral immunity, with excellent serocon-version rates following the booster dose. However, GCs, especially at doses ≥7.5 mg/day prednisone equivalents, may contribute to the waning of NAb titres. On the other hand, immunosuppressants like MTX, especially when combined with GCs, might impair the magnitude of the humoral response to the booster dose.

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