key: cord-311284-5nxh7ybe authors: Kumar, U.; Goswami, R. P.; Bhadu, D.; Kanjilal, M.; Nagar, S.; Vij, P.; Mittal, D.; Meena, L.; Roy, D. title: COVID-19 in rheumatic diseases: A random cross-sectional telephonic survey date: 2020-08-13 journal: nan DOI: 10.1101/2020.08.09.20170985 sha: doc_id: 311284 cord_uid: 5nxh7ybe Objective. To describe the incidence, clinical course, and predictive factors of coronavirus 2019 (COVID-19) infection in a cohort of rheumatological patients residing in New Delhi (National Capital Region), India. Methods. We performed a cross-sectional, random telephonic survey from 20th April to 20th July 2020 on patients with rheumatic diseases. Patients were interviewed with a predesigned questionnaire. The incidence of COVID-19 in the general population was obtained from open access government data repository. Report of reverse transcriptase polymerase chain reaction report was taken as confirmatory of COVID-19 infection. Results. Among the 900 contacted patients 840 responded (713 with rheumatoid arthritis (RA), 100 with systemic lupus erythematosus (SLE), 20 with spondylarthritis (SpA) and 7 with others; mean age 45 years, mean duration 11.3 years; 86% female). Among them 29 reported flu-like symptoms and four RA patients had confirmed COVID-19 infection. All of them were hospitalized with uneventful recovery. Rheumatological drugs were discontinued during the infectious episode. Disease modifying agents and biologics were equally received by those with or without COVID-19. The incidence of COVID-19 was similar to general Delhi population (0.476% vs 0.519% respectively, p=0.86). Two patients had relapse of rheumatic disease after recovery. After recovery from COVID-19 or Flu-like illness, eight patients (27.6%, 95% confidence interval 14.7-45.7) reported disease flare. Conclusion. Patients with rheumatic diseases in India have similar incidence of COVID-19 infection compared to the community. Relapse of underlying rheumatic disease after recovery is not uncommon and continuation of glucocorticoid through the infection should be considered. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint 4 Declarations: Ethics approval: The study protocol was reviewed and approved by the institutional review board (no. IEC-280/17.4.2020). All authors agree to be accountable for all aspects of the work including accuracy of the data and integrity All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint 5 Introduction: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic which was declared a public health emergency of international concern on January 2020 has posed a special challenge to rheumatologists [1]. Patients with rheumatic are expected to be at an increased risk of severe infection because of inherent immune dysregulation, associated co-morbidities and, use of immunosuppressive drugs. It is well known that viral infections commonly occur among these patients especially respiratory viral infections [2] . Syndrome of cytokine storm and immune mediated systemic thrombosis have emerged as contributors to the disease severity in COrona VIrus Disease (COVID19) [3] . While both conventional (csDMARDs) and targeted disease-modifying antirheumatic drugs (tsDMARDs) increase risk of various infections, some of them are currently being tested as potential therapeutic agent for COVID-19 [4] , such as reports of in-vitro viral inhibition with hydroxychloroquine (HCQ) [5] and potential role of tocilizumab in the virus-related cytokine storm [3] . Also, to contain the epidemic there were widespread "lockdowns" in India, resulting in difficulty in getting access to health care facilities which lead to the initiation of "teleconsultation" services. However, an accurate representation of status of patients with rheumatic diseases, during these difficult times of pandemic is definitely lacking but data on epidemiology of SARS-CoV-2 among these patients is scarce but emerging slowly building up confidence amongst rheumatologists. To address this, we conducted cross-sectional, random telephonic survey from 20 th April to 20 th July 2020 to assess the incidence, and the predictive factors of SARS-CoV-2 infection in a cohort of rheumatological patients residing in Delhi, one of the worst hit regions of India. Patients and methods: The present study was a cross-sectional, random telephonic survey conducted from 20 th April to 20 th July 2020 on patients with rheumatological All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. In certain cases, especially in patients with reported increased disease activity, or those who were COVID19 positive, were contacted multiple times throughout the period to ensure the correct clinical course of both COVID-19 and the underlying rheumatic disease. Statistical methods: Descriptive data was displayed as mean ± standard deviation and categorical data as percentage (fraction). Comparison of means was done with Mann Whitney U test and comparison of proportions with Fisher's exact test or Chi Squared test, as appropriate. Incidence of COVID-19 was expressed as percentage with 95% All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint 7 confidence interval (CI). For comparison of incidences across different diagnostic classes, to correct for family wise error rate, correction of p-value divided by number of pre-defined comparisons was taken as cut-off. All statistical calculations were done using Microsoft Excel Spreadsheets and SPSS ver 20 (IBM Corp.). Description of the cohort: Overall, 900 patients were contacted and 840 patients responded. The mean age was 45 ± 13 years with 54% females (n=456). Detailed demographic and clinical details of the cohort is given in Table 1 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint 8 reported increased joint symptoms. Among the 11 lupus disease flares, one was renal, five haematological, two musculoskeletal and three were cutaneous. Among our patients 29 reported flu-like symptoms but rT-PCR on nasophayngeal swab was done only on six cases (four with RA, one with AS, and one with SLE) among which four tested positive and the rest didn't report to the medical facility. Detailed demographic and clinical features of COVID-19 positive cases is given in Table 2 . None of the patients were on tsDMARDs or monoclonal antibodies. Two had hypertension and one had coronary artery disease as comorbidities. All of them were admitted in Government run medical institutions with fever. None of the patients required intensive care or ventilatory support. All were discharged without any complications. All of these (Figure 1 ). If we consider only the diagnostic class of RA, even then the incidence of COVID-19 was similar between patients with RA and the general Delhi population (0.56% vs 0.519%, difference 0.041%, 95% CI: -0.3012% to 0.9131%, p=0.87). COVID-19: clinically suspected cases All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint 9 Another 25 patients, had flu-like symptoms but were not tested with nasopharyngeal swab. None of these patients reported travel outside India or Delhi or even contact with a known COVID-19 case. Details of these patients are summarized in Table 1 . However, all of them resided within containment zones, which are zones demarcated by the Government as high risk of transmission and have strong restriction of movement. Twenty-one of them had RA, three had SLE and one had AS. Among these patients, seventeen were on methotrexate, eleven were on leflunomide, ten were on hydroxychloroquine, seven were on prednisolone, three on sulfasalazine, two on anti-TNF agents and one each on azathioprine, mycophenolate and rituximab. Only one of these patients was hospitalized and needed supplemental oxygen but made a full recovery. The incidence of Flu-like symptoms in patients with RA was similar to those observed in CTD (2.95%, 21/713 vs 2.8%, 3/107 respectively, p=0.999) and patients with SpA (2.95%, 21/713 vs 5%, 1/20, respectively, p=0.46). Two patients with RA had stopped medications and both of them and four other patients with RA experienced a disease relapse, all of them after the flu-like episode. One patient with SLE also discontinued all her medications following her flu-like episode and developed a renal flare with subnephrotic proteinuria and raised creatinine for which she was instituted on high dose prednisolone and mycophenolate and is still in re-induction therapy. Discussion: This is the first detailed report in a cohort of patients with various rheumatological diagnoses from an area of high transmission and case load from India. We observed a similar incidence of COVID-19 among patients with rheumatological diseases compared to the general population of Delhi. The results were stable even after the sensitivity analyses done to reduce heterogeneity. However, between patients All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. However, among this cohort 17 had suspect symptoms, among which only two were tested. Therefore, the incidence of flu-like symptoms in that cohort was 2%, which is very similar to what was observed among our patients with CTD (2.8%). Regarding the impact of COVID-19 on our patients, we observed unscheduled stoppage of medications in 15.7% (132/840) patients and increased disease activity in 2% (16/840) of patients. One quarter of our patients relapsed after recovery from COVID-19 infection and 28% (7/25) of our other patients with flu-like symptoms relapsed after recovery. Total post infectious rheumatic disease relapse rate was 27.6%, 95% confidence interval 14.7-45.7). A myriad of mechanisms is hypothesized for this kind of reactivation of autoimmune disease after COVID-19 ranging from molecular mimicry, bystander killing, epitope spreading, viral persistence to formation of neutrophil extracellular traps [13] . However, the most plausible explanation is stoppage of immunosuppressive drugs during the infectious episode. Recent evidence suggests that dexamethasone in COVID-19 is actually useful for those on mechanical ventilation or oxygen support and at least not All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . Our study has a few limitations: single-centre cross-sectional survey, less than a 100% response to the telephonic survey and all suspected patients were not confirmed with rt-PCR. However, long-term follow up and detailed diagnostic and therapeutic information and details of flu-like symptoms and COVID-19 natural history over repeated and multiple telephonic conversations with the patients are the strengths of our study. To conclude, we observed that the incidence of COVID-19 infection among patients with rheumatic diseases was similar to the community. The incidences of Flu-like symptoms were similar across different diagnostic classes. DMARDs neither increased risk of the infection nor provided any protection to the same. Since, relapse of disease, especially after stoppage of disease modifying agents, is a concern after this infection, continuation of glucocorticoid through the infection might be a prudent strategy. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint Dry Cough Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study COVID-19: consider cytokine storm syndromes and immunosuppression COVID-19 infection and rheumatoid arthritis: Faraway, so close Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro Ventricular arrhythmia risk due to Hydroxychloroquine-Azithromycin treatment for COVID-19 Coronavrius Outbreak in india Frequency of infection in patients with rheumatoid arthritis compared with controls: A population-based study All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted August 13, 2020. . https://doi.org/10.1101/2020.08.09.20170985 doi: medRxiv preprint All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All of these p-values are above cut-off set after correcting for family wise error rate, i.e., 0.0166, and therefore non-significant