Correlates of breakthrough Omicron (B.1.1.529) infections in a prospective cohort of vaccinated patients with rheumatic diseases.

BACKGROUND: Data on the effectiveness of SARS-CoV-2 vaccines and the durability of protection against the prevalent Omicron variant are scarce, especially in patients with autoimmune rheumatic diseases (AIRDs). Hence, we prospectively studied Omicron breakthrough infections in patients with AIRDs and attempted to isolate associated risk factors. METHODS: Patients with AIRDs who had completed primary vaccination with either AZD1222 or BBV152 vaccines were included and prospectively followed up from January 2022 onwards for the development of breakthrough Omicron infections. The time interval from the last event [2nd dose of vaccination (V) or past COVID-19 infection (I) whichever was later] to Omicron infection was recorded. Patients were divided based on the events and their order of occurrence into V + V, V + I, I + V, V + I + V, and V + V + I groups. The incidence of breakthrough infections and their predictors were studied with a focus on the vaccine type and hybrid (H) immunity (vaccinated individuals with a history of COVID-19 infection). RESULTS: We included 907 patients with AIRDs (53.5 ± 11.7 years and a male-to-female ratio of 1:5.1), and the majority of patients had received AZD1222 (755, 83.2%). Breakthrough infections were observed in 158 of 907(17.4%) of which 97 (10.4%) were confirmed by RT-PCR. Breakthrough infections were significantly greater in the V versus the H group (15.7% and 3.5%, log-rank test, p = < 0.01). Among the hybrid group, the order of infection and vaccination had no bearing on the risk of breakthrough infections. On multivariate analysis, breakthrough infections were significantly lesser in the H versus the V group [HR: 0.2(0.1-0.4); p = 0.01]. CONCLUSION: The risk of breakthrough Omicron infections in fully vaccinated patients with AIRDs was 17.4% with a significantly lower risk in patients with hybrid immunity.

Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

Boosting Vaccine Response in Autoimmune Rheumatic Disease Patients With Inadequate Seroconversion: An Analysis of the Immunogenicity of Vector-Based and Inactivated Vaccines.

BACKGROUND: An additional dose of COVID-19 vaccine is being offered to vaccinated people, especially those immunocompromised. The most widely available vaccines in India are the adenoviral vector-based AZD1222 (ChAdOx1 nCoV-19) and the heat-inactivated (BBV152). This study investigated the efficacy of both vaccines in patients with autoimmune rheumatic diseases (AIRD). OBJECTIVES:  To compare final anti-SARS-CoV-2 antibody titers, neutralization of pseudovirions by these antibodies, and T cell responses between patients of AIRD who had received the third dose of AZD1222 and BBV152 vaccines. METHODS: Patients with stable AIRD who had completed two doses of COVID-19 vaccination but had a suboptimal response (anti-receptor binding domain (RBD) antibody<212) were randomized (1:1) to receive either AZD1222 or BBV152 as a booster dose. Patients with previous hybrid immunity or those who developed COVID-19 during the trial were excluded. Antibody titers, neutralization of Wuhan and Omicron pseudovirions, and interferon release by T cells (enzyme-linked immunosorbent spot (ELISpot)) in response to the Spike antigen were measured four weeks after this booster dose. RESULTS: 146 were screened, 91 were randomized, and 67 were analyzed per protocol. The third dose improved antibody titers (p<0.001), neutralization of the Wuhan strain (p<0.001), and T cell interferon release (p<0.001) but not neutralization of the Omicron strain (p=0.24). Antibody titers were higher (p<0.005) after ADZ1222 boost (2,414 IU (interquartile range (IQR): 330-10,315)) than BBV1222 (347.7 IU (0.4-973)). Neutralization of the Wuhan stain was better (AZD1222: 76.6%(23.0-95.45) versus BBV152 (32.7% (0-78.9), p=0.03 by ANCOVA). Neutralization of Omicron (0 (0-28.4) vs 0 (0-4.8)) and T cell interferon release (57.0 IU (23.5-95) vs 50.5 IU (13.2-139)) were similar. CONCLUSION: The third dose improved all parameters of immunogenicity in AIRD patients with previous inadequate responses except Omicron neutralization. The vector-based vaccine exhibits notable efficacy, particularly in antibody titers and neutralizing the Wuhan strain. TRIAL REGISTRATION: CTRI/2021/12/038928.

Clinical and psychosocioeconomic impact of COVID-19 pandemic on patients of the Indian Progressive Systemic Sclerosis Registry (IPSSR).

OBJECTIVES: The aim was to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on access to health care among patients with scleroderma and to analyse the economic and psychosocial impacts and the infection prevention measures taken by them during the pandemic. METHODS: A 25-item questionnaire designed to assess the components of the objectives was tele-administered between October 2020 and January 2021 to the patients enrolled in the Indian Progressive Systemic Sclerosis Registry. RESULTS: Of the 428 patients in the registry, 336 took part in the study. A scheduled outpatient visit was missed by 310 (92.3%) patients, and 75 (22.3%) skipped prescription drugs. During the pandemic, 75 (22.3%) had a family member lose a job. Financial difficulties were reported by 155 (46.1%), with 116 (34.5%) patients having to spend an additional INR 4000 (2000-10 000) [USD 54.9 (27.0-137.4)] to continue treatment. Although 35 patients (10.4%) had at least one symptom suggestive of COVID-19, infection was confirmed in only 4. None of them needed hospitalization or had adverse outcomes. Worsening of scleroderma was seen in 133 (39.6%) individuals, with 15 (4.5%) requiring hospitalization. Most (96%) of the patients were aware of infection prevention measures, and 91 (27.1%) had taken unproven prophylactic medications. CONCLUSION: Individuals with scleroderma in India have been affected during the pandemic owing to closure of hospital services, lack of transport, loss of jobs and the additional financial burden. Health-care providers should continue to educate patients to stay on their medications and encourage them to be vaccinated for COVID-19.