Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases

AbstractIntroductionSingle-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.MethodsWe identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.ResultsBaseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.ConclusionThe hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.What is already known about this subject?A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naïve personsA second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce toleranceVaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.What does this study add?Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccineBesides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.How might this impact on clinical practice?Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.

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An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

10.1101/2021.03.09.21253218 ◽

2021 ◽

Author(s):

Sheila F Lumley ◽

Gillian Rodger ◽

Bede Constantinides ◽

Nicholas Sanderson ◽

Kevin K Chau ◽

...

Keyword(s):

Cohort Study ◽

Single Dose ◽

Positive Result ◽

Healthcare Workers ◽

Natural Infection ◽

Natural Immunity ◽

Symptomatic Infection ◽

Gene Target ◽

Adjusted Incidence Rate ◽

Induced Immunity

AbstractBackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.

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Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)

10.21203/rs.3.rs-787293/v1 ◽

2021 ◽

Author(s):

Chandima Jeewandara ◽

Harsha Fernando ◽

Pradeep Pushpakumara ◽

Shyrar Tanussiya ◽

Achala Kamaladasa ◽

...

Keyword(s):

Single Dose ◽

Immune Responses ◽

High Frequency ◽

Ex Vivo ◽

Natural Infection ◽

Receptor Binding Domain ◽

Cell Responses ◽

Blocking Antibodies ◽

With Memory ◽

Dose Vaccine

Abstract As the first dose of Gam-COVID-Vac, is currently used as a single dose vaccine in some countries, we investigated the immunogenicity of this at 4 weeks (327 naïve individuals). 88.7% seroconverted, with significantly lower seroconversion rates in those over 60 years (p = 0.004) and significantly lower than previously seen with AZD1222 (p = 0.018). 82.6% developed ACE2 receptor blocking antibodies, although levels were significantly lower than following natural infection (p = 0.0009) and a single dose of AZD1222 (p < 0.0001). Similar titres of antibodies were observed to the receptor binding domain of WT, B.1.1.7 and B.1.617.2 compared to AZD1222, while the levels for B.1.351 were significantly higher (p = 0.006) for Gam-COVID-Vac. 30% developed ex vivo IFNγ ELISpot responses (significantly lower than AZD1222), and high frequency of CD107a expressing T cells along with memory B cell responses. Although single dose of Gam-COVID-Vac was highly immunogenic, administration of a second dose is likely to be beneficial.

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Physical activity associates with enhanced immunogenicity of an inactivated virus vaccine against SARS-CoV-2 in patients with autoimmune rheumatic diseases

10.21203/rs.3.rs-782398/v1 ◽

2021 ◽

Author(s):

Bruno Gualano ◽

Italo Lemes ◽

Rafael Silva ◽

Ana Pinto ◽

Bruna Mazzolani ◽

...

Keyword(s):

Physical Activity ◽

Rheumatic Diseases ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Active Lifestyle ◽

Physically Active ◽

Autoimmune Rheumatic Diseases ◽

Vaccine Schedule ◽

Vaccine Immunogenicity ◽

Dose Vaccine

Abstract Immunocompromised individuals show lower vaccine immunogenicity, which may be modulated by physical activity. This prospective cohort study within a phase-4 vaccination trial investigated whether physical activity is associated with enhanced immunogenicity of Coronavac (SARS-CoV-2 inactivated vaccine) in patients with autoimmune rheumatic diseases (ARD) (n=898) and non-ARD (n=197) individuals without pre-existing immunogenicity to SARS-CoV-2 after receiving a two-dose vaccine schedule. Seroconversion rates of total anti-SARS-CoV-2 S1/S2 IgG (SC), geometric mean titers of anti-S1/S2 IgG (GMT), factor-increase in GMT (FI-GMT), frequency of neutralizing antibody (NAb), and median neutralizing activity were assessed. After controlling for covariates, active patients (≥150 min/week) exhibited greater SC (OR: 1.4 [95%CI: 1.1-2.0]), GMT (32% [95%CI: 8.8-60) and FI-GMT (33% [95%CI: 9.6-63%]) vs. inactive. Cluster analysis (physical activity/sedentary status) revealed greater GMT (43.0% [95% CI: 11.0-84.0%) and FI-GMT (48.0% [95%CI: 14.0-92.0%]) in active/non-sedentary (≥150 min/week/<8h/day) vs. inactive/sedentary (<150 min/week/>8h/day) ARD. A dose-response was observed, with greater benefits for ≥350 min/week of physical activity (OR: 1.6 [95%CI: 1.1-2.4]; 41% [95%CI: 10-80%]; 35% [95%CI: 4.3-74], for SC, GMT, and FI-GMT, respectively). Greater SC (OR: 9.9 [95%CI: 1.1-89.0]) and GMT (26% [95%CI: 2.2-56.0%]) were observed in active vs. inactive non-ARD. A physically active lifestyle may enhance SARS-CoV-2 vaccine immunogenicity, a finding of particular clinical relevance for immunocompromised individuals.

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Hybrid immunity versus vaccine-induced immunity against SARS-CoV-2 in patients with autoimmune rheumatic diseases

The Lancet Rheumatology ◽

10.1016/s2665-9913(21)00356-8 ◽

2021 ◽

Author(s):

Padmanabha Shenoy ◽

Sakir Ahmed ◽

Aby Paul ◽

Somy Cherian ◽

Rashwith Umesh ◽

...

Keyword(s):

Rheumatic Diseases ◽

Autoimmune Rheumatic Diseases ◽

Induced Immunity

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Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)

10.21203/rs.3.rs-787293/v2 ◽

2021 ◽

Author(s):

Gathsaurie Malavige ◽

Chandima Jeewandara ◽

Harsha Fernando ◽

Pradeep Darshana Pushpakumara ◽

Shyrar Tanussiya ◽

...

Keyword(s):

Single Dose ◽

Immune Responses ◽

High Frequency ◽

Ex Vivo ◽

Natural Infection ◽

Receptor Binding Domain ◽

Cell Responses ◽

Blocking Antibodies ◽

With Memory ◽

Dose Vaccine

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Immunogenicity and safety of routine vaccines in children and adolescents with rheumatic diseases on immunosuppressive treatment — a systematic review

European Journal of Pediatrics ◽

10.1007/s00431-021-04283-w ◽

2021 ◽

Author(s):

Michèle Keller ◽

Laure F. Pittet ◽

Petra Zimmermann

Keyword(s):

Systematic Review ◽

Disease Activity ◽

Children And Adolescents ◽

Rheumatic Diseases ◽

Geometric Mean ◽

Immunosuppressive Treatment ◽

Safety Concerns ◽

Vaccine Responses ◽

Autoimmune Rheumatic Diseases ◽

Increased Risk

AbstractThe immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination, and there is a potential for worsening in disease activity. In this systematic review, we summarise studies that investigated the immunogenicity and safety of routine vaccines in children and adolescents with JARD on immunosuppressive treatment. We identified 37 studies investigating 2571 children and adolescents with JARD on immunosuppressive treatment and 4895 control children. Of the 56 geometric mean antibody titres measured, 19 (34%) were lower, six (11%) higher, and 31 (55%) similar; of the 39 seroprotection rates measured, 10 (26%) were lower, two (5%) higher, and 27 (69%) similar; and of the 27 seroconversion rates measured, nine (33%) were lower, two (8%) higher, and 16 (59%) similar in children with JARD on immunosuppressive treatment compared with control children. However, many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls. Subgroup analysis for different types of immunosuppressive treatments was not feasible, as most studies did not report results by treatment. Severe adverse events were reported in 38 children (33 with juvenile idiopathic arthritis, four with systemic lupus erythematosus, and one in a healthy child); most of them were likely not related to the vaccination (e.g. elective hospitalisation or surgery). A worsening in disease activity was reported in 44 (2%) children with JARD; again, many of them were likely not related to the vaccination. There were no safety concerns with live attenuated vaccines; however, only few studies reported results for this.Conclusion: Vaccination in children with JARD on immunosuppressive treatment is safe and should be promoted, especially since these children are at increased risk for infection. The importance for the completion of vaccination schedules should be stressed. Strategies to compensate for the lower vaccine responses, which are found in approximately one-third of these children, include measuring antibody levels to determine the optimal timing for the administration of additional booster doses. What is Known: • Children with juvenile autoimmune rheumatic diseases (JARDs) are at higher risk for infections, due to their underlying disease and their immunosuppressive treatment. • In children with JARD, the immunogenicity of vaccines might be reduced, and concerns about safety or the potential for worsening in disease activity after vaccination exist. What is New: • Our systematic review shows that vaccines in children with JARDs on immunosuppressive treatment are safe and immunogenic. • There are several limitations of the currently published studies, including random timing of measuring vaccine responses and age differences between children with JARD and control groups. Many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls.

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EVALUATION OF ANTI-DFS70 ANTIBODIES PRE-ABSORPTION PROTOCOL FOR ANA-IIF HEP-2 TESTING IN THE DIAGNOSTIC APPROACH OF SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES

10.26226/morressier.56e174dbd462b8028d88ad4c ◽

2016 ◽

Author(s):

Alexandra Tsirogianni

Keyword(s):

Rheumatic Diseases ◽

Diagnostic Approach ◽

Autoimmune Rheumatic Diseases

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TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0043-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Manal Y. Tayel ◽

Aida Nazir ◽

Ibtessam M. Abdelhamid ◽

Myriam A. S. Helmy ◽

Nadia E. Zaki ◽

...

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lymphoproliferative Disorders ◽

Group Iii ◽

Autoimmune Rheumatic Diseases ◽

Group I ◽

Tnf Α ◽

Ifn Γ ◽

Tgf Β1 ◽

Distribution Frequency

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

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A Study of Varicella Seroprevalence in a Pediatric and Adolescent Population in Florence (Italy). Natural Infection and Vaccination-Acquired Immunization

Vaccines ◽

10.3390/vaccines9020152 ◽

2021 ◽

Vol 9 (2) ◽

pp. 152

Author(s):

Beatrice Zanella ◽

Angela Bechini ◽

Benedetta Bonito ◽

Marco Del Riccio ◽

Alessandra Ninci ◽

...

Keyword(s):

Natural Infection ◽

Age Groups ◽

Varicella Vaccination ◽

Age Group ◽

Disease Notification ◽

Test Elisa ◽

Vaccine Schedule ◽

Almost All ◽

Vaccination Campaigns ◽

Dose Vaccine

Background: Varicella is a well-known infectious disease that can have severe complications, also in young children. The Universal Varicella Vaccination (UVV) program was introduced in Tuscany (Italy) in 2003, with a two-dose vaccine schedule given to children between their 13th and 15th month, and at 5–6 years old, as a monovalent for varicella (V) or tetravalent (measles, mumps, rubella and varicella (MMRV)) formulation. Although varicella notifications have dramatically fallen in the last two decades, varicella disease underreporting remains a challenge. Methods: A qualitative immunoenzymatic test (ELISA) was used to measure the presence of anti-varicella antibodies in 165 sera of subjects aged 1–18 years residing in the province of Florence (Italy). Information regarding the anamnestic and vaccination status (including disease notification) was also collected. Results: Our study showed an overall varicella seropositivity of 75.8% (reaching the maximum at 96.3% in the 15–18 years age group). We found that varicella disease notification had been recorded for only 7/165 subjects; however, since 42/165 recalled having had the disease, we can hypothesize that some of them must have been underreported. Furthermore, our study showed that the presence of antibodies after the varicella vaccination remained over time, lasting up to 12 years. Conclusions: Although varicella seroprevalence is <95% in almost all our age groups (except for the 15–18 years age group), our data are encouraging and reflect the success of the introduction of the UVV program and the vaccination campaigns promoted in the Tuscany region.

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P052 Leflunomide and severe COVID-19 outcome: a cautionary observation from the COVID-19 Scottish Registry of Autoimmune Rheumatic Diseases (SCAR-19)

Rheumatology ◽

10.1093/rheumatology/keab247.049 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Maira Karabayas ◽

James Brock ◽

Gillian Fordyce ◽

Neil Basu

Keyword(s):

Rheumatic Diseases ◽

Clinical Characteristics ◽

National Registry ◽

Favourable Outcome ◽

Non Invasive ◽

Autoimmune Rheumatic Diseases ◽

Non Invasive Ventilation ◽

Pcr Diagnosis ◽

Related Symptom ◽

Disease Modifying

Abstract Background/Aims Leflunomide, a conventional disease modifying drug (csDMARD), is used in a variety of autoimmune rheumatic diseases (ARD) due to its immunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, due to its long half-life, drug washout procedures are often advised in the context of serious infections. Interestingly, Leflunomide is currently being tested as a potential therapy for COVID-19 in the general population. It is unknown whether leflunomide therapy is associated with a poor or favourable outcome among ARD patients infected with COVID-19. Methods A Scottish-wide registry was rapidly developed in March 2020. Clinical characteristics and outcomes of infected cases were collated across all Scottish health boards. Eligible patients included any adult leflunomide treated ARD patients with a confirmed (clinically or PCR) diagnosis of COVID-19. Results Of the 69 cases included in the registry, n = 4 were treated with leflunomide (75% female; mean age 61, SD 4.2). N = 2 were treated with combination baricitinib or hydroxychloroquine respectively, whilst n = 1 received recent corticosteroid therapy (intramuscular Kenalog). Comorbidities observed in this sub-cohort include diabetes mellitus n = 3, hypertension n = 2, cardiovascular disease n = 1, lung disease n = 1 and latent TB n = 1. At presentation, all patients (n = 4) experienced the established COVID-19 related symptom triad of dyspnoea, cough and fever and promptly developed acute respiratory syndrome. Diarrhoea was also recorded in n = 2 and constitutional upset n = 3. All patients suffered a serious COVID-19 disease outcome (defined as a requirement of invasive or non-invasive ventilation (n = 4) and/ or death (n = 2). P052 Table 1:Patient demographics, clinical characteristics and outcomesPatient 1Patient 2Patient 3Patient 4Age58635766SexFemaleFemaleMaleFemaleRheumatic diagnosisRheumatoid arthritisPsoriatic arthritisPsoriatic arthritisRheumatoid ArthritisComorbiditiesDiabetesHypertension Diabetes COPDNilIschaemic heart disease Hypertension Diabetes Latent TBClinical presentationDyspnoea Cough Fever Confusion Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetDyspnoea Cough Fever Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetAdditional csDMARD*NilNilNilHydroxychloroquinebDMARD**/ tsDMARD***BaricitinibNilNilNilSteroid therapyNilNilNilIM KenalogInvasive or non-invasive ventilationYesYesYesYesDeathNoNoYesYes* conventional disease modifying drug,**biologic disease modifying drug,***targeted synthetic disease modifying drug. Conclusion Preliminary data from this Scotland-wide registry has identified only a small number of leflunomide treated ARD patients infected with COVID-19. However, it is concerning that all cases experienced a serious outcome. Given the relatively infrequent prescription of this drug, combining similar national registry data is necessary to ensure this observation is not spurious. If confirmed, leflunomide washout procedures should be encouraged among such patients when they first present with COVID-19. Disclosure M. Karabayas: None. J. Brock: None. G. Fordyce: None. N. Basu: None.

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