Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity.

Patients with autoimmune rheumatic diseases with a previous infection by the SARS-CoV-2 virus have exaggerated responses to a single dose of COVID-19 vaccination as compared to fully vaccinated infection naive patients. The second dose is currently recommended at an extended gap after the infection, but the information available regarding response to the second dose in this subgroup is limited. Patients with AIRDs previously infected with COVID-19, who have received at least one dose of AZD1222/ChAdOx1 (n = 200) were included and stratified based on vaccine doses (V), and infection (I) into I + V, I + V + V, V + I, V + V + I. Anti-RBD (receptor binding domain) antibodies were compared across the four groups. In 49 patients of the I + V + V group (AZD12222), paired sera were compared for antibody levels and neutralization after each vaccine dose. Thirty patients with hybrid immunity after BBV152 and 25 with complete vaccination without infection were included as controls. The highest anti-RBD antibody levels were observed in the V + V + I group (18,219 ± 7702 IU/ml) with statistically similar titers in the I + V + V (10,392 ± 8514 IU/ml) and the I + V (8801 ± 8122 IU/ml). This was confirmed in the 49 paired samples that paradoxically showed a lowering of antibody titers after the second dose [9626 (IQR: 4575-18,785)-5781 (2484-11,906); p < 0.001]. Neutralization of the Delta variant was unaffected but Omicron neutralization was significantly reduced after the second dose [45.7 (5.3-86.53)-35% (7.3-70.9); p = 0.028]. Ancillary analyses showed that only the hybrid immune sera could neutralize the Omicron variant and AZD1222 hybrids performed better than BBV152 hybrids. The second dose of AZD1222 did not boost antibody titers in patients with RD who had COVID-19 previously. In the analysis of paired sera, the second dose led to a statistically significant reduction in antibody titers and also reduced neutralization of the Omicron variant.

Effectiveness of delayed second dose of AZD1222 vaccine in patients with autoimmune rheumatic disease.

There is paucity of data on extended dosing interval between two doses of AZD1222 (AstraZeneca) in patients with Autoimmune Rheumatic Diseases (AIRD). We aimed to study the humoral response and rate of breakthrough infections between the two groups who had received the second dose of vaccine at 4 weeks (Group 1) and 10-14 weeks (Group 2). From established cohort [COVID-19 vaccination cohort from CARE(CVCC)] of vaccinated patients with AIRD, those who had received AZD1222 were included and divided into two groups. Anti-Receptor Binding Domain (RBD) antibodies (IU/ml) were measured 1 month after the second dose. Its predictors and rate of breakthrough infections were studied. Four hundred ninety-five patients with AIRD were included in this study. Group 2 had higher anti-RBD antibody titres [1310.6 (±977.8) and [736 (±864.7), p = 0.0001. On univariate analysis, presence of Diabetes Mellitus; use of Methotrexate, Sulfasalazine, and Mycophenolate Mofetil; and vaccine interval were significantly associated with anti-RBD antibodies. Diabetes Mellitus and vaccine interval were independent predictors on multivariate analysis. Breakthrough infections were higher in Group 1 numerically on survival analysis but the difference was not significant (7.5% and 4.5%; log rank test: p = 0.25). In conclusion, increasing the gap between doses of the AZD1222 vaccine from 4 week to 10-14 weeks was found to be more beneficial in terms of antibody response in patients with AIRD. There was a trend towards higher breakthrough infections in the short interval group, supporting the antibody data. Key Points • There is paucity of data on effectiveness of increased dosing interval from 4-6 to 10-14 weeks for AZD1222 in patients with AIRDs • We observed a better humoral response with increased dosing interval with the interval and Diabetes Mellitus being independent predictors of the anti-RBD antibody levels • Breakthrough infections were numerically higher in the short interval group but the difference wasn't significant.

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort.

INTRODUCTION: To assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections. METHODS: Patients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4-6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8-212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies. RESULTS: We studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection. CONCLUSION: Breakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

Safety of the ChAdOx1 nCoV-19 and the BBV152 vaccines in 724 patients with rheumatic diseases: a post-vaccination cross-sectional survey.

Patients with rheumatic and musculoskeletal (RMD) diseases may be at higher risks for COVID-19 infection. Data on the safety of the adenoviral vector-borne ChAdOx1 nCoV-19 and the heat-inactivated BBV152 Vaccines in this group are limited. 724 patients with RMD who had received at least one dose of either the ChAdOx1 or the BBV152 were audited to find out post-vaccination adverse effect (AE) or disease flares. The AE rates in patients with autoimmune rheumatic disease (AIRD) were compared with those with non-AIRD RMDs. The mean age of the cohort was 59.9 (± 10.43) years with a female (n = 581; 80.24%) majority. 523 (70.8%) had AIRD. The ChAdOx1 and the BBV152 vaccines were received by 624 (86.18%) and 77 (10.63%), respectively. 23 (3.17%) were unaware of which vaccine they had received. 238 (32.87%) of patients had at least one comorbidity. 436 (60.22%) participants [306 (59.64%) of those with AIRD and 130 (61.61%) with other RMDs] had at least one adverse effect (AE). Four patients reported flare of arthritis that resolved within 5 days. No patient had any severe AE or required hospitalization. All AEs were self-limiting. Both the ChAdOx1 and the BBV152 vaccines appear safe in RMDs. AEs do not differ between patients with AIRD or non-AIRD. This information can help negate vaccine hesitancy amongst all stakeholders.

Efficacy of rituximab in resistant palindromic rheumatism: first report in literature.

BACKGROUND: Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data regarding efficacy of RTX in seropositive Palindromic Rheumatism (PR), a forerunner of RA. AIM: To determine the efficacy and safety of RTX treatment in active PR patients exhibiting inadequate response to conventional synthetic DMARDs (csDMARDs). METHODS: The retrospective study, over a period of 3 years, included seropositive (RF ± antiCCP) PR patients with inadequate control of PR (> 4 attacks per months) despite combination csDMARDs and were treated with RTX. All the patients were treated with an initial dose of 500 mg RTX and later with a second infusion after 2 weeks' period in those who did not achieve adequate/ complete disease control. Patients were continued on csDMARDS and retreated with RTX on relapse of symptoms. RESULTS: Thirty-three seropositive PR patients with a mean age of 48.15 ± 14.2 years, mean disease duration of 68.4 ± 68.2 months, mean follow up period of 24.3 ± 10.8 months, were treated with RTX. 88% patients were on combination DMARDS and 79% patients were females. All patient achieved rapid and complete control of palindromic attacks with RTX. Fifteen patients had a relapse after a mean duration of 10.4 ± 5.5 months and needed repeat RTX infusions following which remission was achieved. None of the patients progressed to RA till the end of the follow-up. No serious adverse effects were recorded. CONCLUSION: RTX treatment could be effective in achieving disease control in active palindromic rheumatism not responding to csDMARDs. KEY POINTS: • PR is thought to be a forerunner of RA and rituximab (RTX) has been found to be effective in RA. • Our study supports the hypothesis that B cells play an important role in the pathophysiology of PR and that the combination (RTX+ conventional drugs) can prevent the disease evolution into RA. • This 3-year retrospective study showed that rituximab was found to be effective in those who responded poorly to conventional drugs and remission was achieved in all patients. • Although it is a rare disease, we see palindromic rheumatism patients in India more often. As the symptoms are very debilitating in these patients, in those patients, not controlled on conventional drugs, rituximab offers newer promise in controlling the attacks and prevents further progression to RA.