Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials.

Background: There is a necessity for an optimal COVID-19 vaccination strategy for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. Thus, we aimed to assess the effects of withholding methotrexate for 2 weeks after each dose of ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation of methotrexate, in terms of post-vaccination antibody titres and disease flare rates. Methods: MIVAC I and II were two parallel, independent, assessor-masked, randomised trials. The trials were done at a single centre (Dr Shenoy's Centre for Arthritis and Rheumatism Excellence; Kochi, India) in people with either rheumatoid arthritis or psoriatic arthritis with stable disease activity, who had been on a fixed dose of methotrexate for the preceding 6 weeks. Those with previous COVID-19 or who were positive for anti-SARS-CoV-2 nucleocapsid antibodies were excluded from the trials. People on high-dose corticosteroids and rituximab were also excluded, whereas other disease-modifying antirheumatic drugs were allowed. In MIVAC I, participants were randomly assigned (1:1) to stop methotrexate treatment for 2 weeks after each vaccine dose or to continue methotrexate treatment. In MIVAC II, participants who had continued methotrexate during the first dose of vaccine were randomly assigned (1:1) to withhold methotrexate for 2 weeks after the second dose of vaccine or to continue to take methotrexate. The treating physician was masked to the group assignments. The primary outcome for both MIVAC I and MIVAC II was the titre (absolute value) of anti-receptor binding domain (RBD) antibody measured 4 weeks after the second dose of vaccine. All analyses were done per protocol. The trials were registered with the Clinical Trials Registry- India, number CTRI/2021/07/034639 (MIVAC I) and CTRI/2021/07/035307 (MIVAC II). Findings: Between July 6 and Dec 15, 2021, participants were recruited to the trials. In MIVAC I, 250 participants were randomly assigned and 158 completed the study as per the protocol (80 in the methotrexate hold group and 78 in the control group; 148 [94%] were women and 10 [6%] were men). The median post-vaccination antibody titres in the methotrexate hold group were significantly higher compared with the control group (2484·0 IU/mL, IQR 1050·0-4388·8 vs 1147·5 IU/mL, 433·5-2360·3; p=0·0014). In MIVAC II, 178 participants were randomly assigned and 157 completed the study per protocol (76 in the methotrexate hold group and 81 in the control group; 135 [86%] were women and 22 [14%] were men). The methotrexate hold group had higher post-vaccination antibody titres compared with the control group (2553·5 IU/ml, IQR 1792·5-4823·8 vs 990·5, 356·1-2252·5; p<0·0001). There were no reports of any serious adverse events during the trial period. Interpretation: Withholding methotrexate after both ChAdOx1 nCov-19 vaccine doses and after only the second dose led to higher anti-RBD antibody titres compared with continuation of methotrexate. However, withholding methotrexate only after the second vaccine dose resulted in a similar humoral response to holding methotrexate after both vaccine doses, without an increased risk of arthritis flares. Hence, interruption of methotrexate during the second dose of ChAdOx1 nCov-19 vaccine appears to be a safe and effective strategy to improve the antibody response in patients with rheumatoid or psoriatic arthritis. Funding: Indian Rheumatology Association.

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.

Molecular phylogenetic study on few morphotypes of a patellogastropod Cellana karachiensis from northern Arabian Sea reveals unexpected genetic diversity.

A group of limpets, Cellana karachiensis, exhibiting phenotypic plasticity were examined from Gujarat coastline India, using molecular phylogeny. Previous examination of the COI genes established the presence of three different haplotypes X, Y and Z, while present study showed three more haplotypes X1, X2 and Z1. Thus, a total of six COI gene haplotypes, having 99.23% to 99.85% sequence similarity, were observed with variations at six sites. Bayesian phylogenetic analysis shows divergence of lineages X-Y, X1-X2 and Z-Z1. Careful observation of nucleotide alterations showed a nonrandom mutation with more A↔G and C↔T transitions between closely related species of the genus Cellana. A stretch of 17 base pair, within COI region, was marked as region with high degree of variability between species of Cellana. Results suggest that this could be the beginning of speciation, with partial or complete reproductive barrier or these are already distinct species in different stages of evolution.

Probing the phylogenetic relationships of a few newly recorded intertidal zoanthids of Gujarat coast (India) with mtDNA COI sequences.

The present study reports the phylogenetic relationship of six zoanthid species belonging to three genera, Isaurus, Palythoa, and Zoanthus identified using systematic computational analysis of mtDNA gene sequences. All six species are first recorded from the coasts of Kathiawar Peninsula, India. Genus: Isaurus is represented by Isaurus tuberculatus, genus Zoanthus is represented by Zoanthus kuroshio and Zoanthus sansibaricus, while genus Palythoa is represented by Palythoa tuberculosa, P. sp. JVK-2006 and Palythoa heliodiscus. Results of the present study revealed that among the various species observed along the coastline, a minimum of 99% sequence divergence and a maximum of 96% sequence divergence were seen. An interspecific divergence of 1-4% and negligible intraspecific divergence was observed. These results not only highlighted the efficiency of the COI gene region in species identification but also demonstrated the genetic variability of zoanthids along the Saurashtra coastline of the west coast of India.

Identification of a group of cryptic marine limpet species, Cellana karachiensis (Mollusca: Patellogastropoda) off Veraval coast, India, using mtDNA COI sequencing.

Present communication reports the phylogenetic relationship between three groups of a marine limpet having different color banding patterns using COI sequencing. Samples were sequenced for mtDNA COI gene using universal primer. Comparative BLAST revealed that all three types were around 99.59% identical with Cellana karachiensis, first record of this species from Indian coasts. Apart from the morphological variations, the mtDNA COI gene analysis revealed around 1% nucleotide variations between these three types. The observed dissimilarity in COI sequences was possibly too little to consider these types as three different species. The derivation of amino acid positions indicated that these types could possibly be a complex of three cryptic species of C. karachiensis. The study proposes that the Oman and Indian populations of C. karachiensis might have derived by allopatric speciation due to geographical isolation. The group of these three cryptic species, sharing same habitat between themselves, possibly showed sympatric speciation.