|Year : 2021 | Volume
| Issue : 4 | Page : 441-446
COVID-19 and Rheumatic Diseases in Tamil Nadu – A multicenter retrospective observational study
Sowndhariya V Annamalai1, Sham Santhanam2, Kavitha Mohanasundaram3, Thilagavathy Nambi4, Sriram Sankaran5, Raja Natarajan6, Prithvi Mohandas7
1 Consultant Rheumatologist, MIOT Hospital, Chennai, Tamil Nadu, India
2 Consultant Rheumatologist, Gleneagles Global and Vijaya Hospitals, Chennai, Tamil Nadu, India
3 Associate Professor of Rheumatology, Saveetha Medical College Hospital, Chennai, Tamil Nadu, India
4 Consultant Rheumatologist, SIMS Hospital, Chennai, Tamil Nadu, India
5 Consultant Rheumatologist, Apollo Hospitals, Greams Road, Chennai, Tamil Nadu, India
6 Consultant Rheumatologist, Padmavathy Rheumatic Care Centre and Sri Narayani Hospital and Research Centre, Vellore, Tamil Nadu, India
7 MIOT International Hospital, Chennai, Tamil Nadu, India
|Date of Submission||04-Dec-2020|
|Date of Acceptance||13-May-2021|
|Date of Web Publication||28-Oct-2021|
Dr. Kavitha Mohanasundaram
6 First Street, Shanthi Nagar, Adambakkam, Chennai - 600 088, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aim: To describe the clinical and demographic characteristics of rheumatic disease patients who were diagnosed with COVID-19 infection. To identify the risk factors associated with hospitalization of patients and find out differences if any between patients managed as in-patients and out-patients.
Methods: This was a multi-center retrospective observational study done by the analysis of data collected from six tertiary care centers from April 1, 2020, to October 15, 2020. All consecutive patients with a confirmed diagnosis of rheumatic disease and with a recent history of COVID-19 illness were included in the study.
Results: Our study had a total of 85 patients with 58 managed as inpatients and 27 as outpatients. Six patients needed intensive care management and two patients succumbed to the illness. The majority were females (62/85) and majority (80/85) tested positive by the Reverse transcriptase-polymerase chain reaction method. The common rheumatic disease was rheumatoid arthritis (51.7%) followed by systemic lupus erythematosus (15.2%), psoriatic arthritis (10.5%), and others. Thirty-seven patients were on steroids and 28 were on hydroxychloroquine. There was no statistical difference in the mean dose of disease-modifying drugs between the two groups. Out of hospitalized people, 84.4% were above 40 years. There was a higher prevalence of comorbidities among hospitalized patients which was statistically significant (Chi-square test, P = 0.029). There was a positive correlation between duration of stay and steroid dose (Spearman rank correlation, “r” = 0.232), which was statistically significant (P = 0.03). There was no association between stay duration and other disease-modifying agents.
Conclusion: There was a positive and statistically significant correlation between steroid dose and duration of stay. The prevalence of comorbidities was higher among hospitalized patients. There was no correlation between other immunosuppressive drugs and stay duration nor was there any difference in mean dosages of these drugs between patients treated as in-patients and out-patients.
Keywords: COVID-19, immunosuppressants, inpatients, outpatients, rheumatic disease, severe acute respiratory syndrome-coronavirus 2
|How to cite this article:|
Annamalai SV, Santhanam S, Mohanasundaram K, Nambi T, Sankaran S, Natarajan R, Mohandas P. COVID-19 and Rheumatic Diseases in Tamil Nadu – A multicenter retrospective observational study. Indian J Rheumatol 2021;16:441-6
|How to cite this URL:|
Annamalai SV, Santhanam S, Mohanasundaram K, Nambi T, Sankaran S, Natarajan R, Mohandas P. COVID-19 and Rheumatic Diseases in Tamil Nadu – A multicenter retrospective observational study. Indian J Rheumatol [serial online] 2021 [cited 2022 Jan 24];16:441-6. Available from: https://www.indianjrheumatol.com/text.asp?2021/16/4/441/329489
| Introduction|| |
The COVID-19 infection outbreak was declared as pandemic by the World Health Organization on March 12, 2020. The pandemic had a definitive impact on the rheumatology practice by interrupting scheduled visits, hesitancy to use drugs like biologics and immunosuppressants and concerns with infection outcomes. A multicenter retrospective observational study from China had stated that patients with the autoimmune disease might be at an increased risk of contracting COVID-19 infection. A Spanish registry did not find any difference in mortality whereas, the Brazilian registry found high mortality in patients with rheumatic diseases., Conflicting reports, the uncertainty regarding the factors contributing to the hospitalization and the paucity of data from India made us undertake this study.
We studied the clinical and demographic characteristics of rheumatic disease patients who were diagnosed with COVID-19 infection. We tried to identify the risk factors associated with hospitalization of patients and find out differences, if any, between patients managed as inpatients and outpatients.
| Methods|| |
This was a multi-center retrospective observational study done by the analysis of data collected from six tertiary care centers from April 01, 2020, to October 15, 2020. All consecutive patients with a confirmed diagnosis of rheumatic disease, who were on regular treatment and follow-up, with a recent clinical history of COVID-19 infection were included in the study. Using a structured pro forma, data were retrieved either from the hospital medical records (for patients who were managed as in-patients) or from records collected from patients (for patients who were managed as out-patients) during their follow up outpatient visits. Informed consent was obtained from all the patients and from the relatives of the deceased.
Patient's basic demographic details (age, sex, preexisting rheumatic disease, steroid dosage, anti-rheumatic drugs, comorbidities, and habits) and COVID-19 infection-related details (method by which infection was confirmed, C reactive protein [CRP], D dimer, interleukin-6 [IL-6] levels, computed tomography [CT] chest, treatment details) were collected in an excel sheet. All patients who had confirmed COVID-19 infection by laboratory method reverse transcriptase-polymerase chain reaction (RT-PCR) assay (as per the state health policy) or by antibody assay (done for patients with the typical clinical picture and CT findings, but negative for RT-PCR) were included. The clinical characteristics were analyzed and compared for patients managed as inpatients and outpatients.
For discrete data, ratio/proportion was computed, and mean (standard deviation) or median (interquartile range) was computed for continuous data. For comparison of means of continuous variables (normally distributed), two sample independent “t” test was used and for correlation of two continuous variables, Spearman rank analysis was used. For comparison between two categorical variables, Chi-square test was used. The level of significance was set as P < 0.05. The data were managed and analyzed using IBM SPSS statistics for Windows (version 25, Armonk, New York, USA).
Due approval from the Institutional Ethical Committee was obtained. (MIOTIEC/20/94; 10/11/2020).
| Results|| |
Study population with autoimmune rheumatic diseases
The basic clinical characteristics and demographics of patients with rheumatic disease who suffered from COVID-19 and managed as outpatients and inpatients are shown in [Table 1]. Five among inpatients had lupus nephritis and one had chronic kidney disease. Two patients had interstitial lung disease in inpatient group and one in the outpatient group. All the patients were on immunosuppressive drugs or disease-modifying agents except for one outpatient with antiphospholipid antibody syndrome. There was no statistical difference in the mean dose of disease-modifying drugs between the two groups [Table 1].
|Table 1: Basic clinical characteristics and demographics of patients with autoimmune inflammatory rheumatic diseases managed as outpatients versus in-patients|
Click here to view
Clinical characteristics and outcome of COVID-19 infection
COVID-19 related clinical characteristics of patients with rheumatic diseases managed as inpatients and outpatients are listed in [Table 2]. Six patients needed intensive care unit (ICU) management, one was on home oxygen therapy postrecovery and two died. None of these patients were on ventilator. Majority of the inpatients were treated with steroids and low molecular weight heparin. During the course of illness, hydroxychloroquine (HCQ) was continued for all and low dose steroids was continued for out-patients. For in-patients, all received the higher dose of steroids as a part of the COVID-19 management protocol.
|Table 2: COVID-19-related clinical characteristics (clinical features, diagnosis, treatment, and outcome) of rheumatic disease patients managed as outpatients versus inpatients|
Click here to view
One among the deceased was a patient with central nervous system vasculitis on high dose steroids (60 mg of prednisolone/day) and pulse cyclophosphamide. The other deceased patient in our cohort was a case of rheumatoid arthritis on methotrexate (15 mg/week), HCQ (200 mg/day), and prednisolone (5 mg/day). She had coexisting diabetes and hypertension. Both the patients had progressive lung infiltrates due to COVID and succumbed due to acute respiratory distress syndrome.
Risk factors for inpatients
There was a positive correlation between duration of stay and steroid dose (Spearman rank correlation, “r” =0.232), which was statistically significant (P = 0.03). There was no association between stay duration and other disease-modifying agents. Age, sex, and presenting clinical symptoms had no association with the stay duration except for breathlessness (P = 0.015). Among inpatients there was no association between stay duration and serum CRP, ferritin, IL-6 and D-dimer levels. There was a higher prevalence of comorbidities among inpatients in comparison to outpatients, which was statistically significant (Chi-square test, P = 0.029).
| Discussion|| |
The influence of COVID-19 infection on the underlying rheumatic disease and the course and outcome of COVID-19 in these patients is still debated. Rheumatologists in a way are perplexed whether to continue or with-hold the disease-modifying/immunosuppressive agents during infection. A systematic review on the association between immunosuppressive drugs and COVID-19 infection concluded that there was no definite evidence to say that low dose methotrexate, JAK inhibitors, tumor necrosis factor (TNF) alpha blockers are contraindicated during the infection and low dose prednisolone, tacrolimus may rather have beneficial effect on its course. American College of Rheumatology guidelines says in the context of active COVID-19, regardless of its severity, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped or withheld., In our cohort, 43.5% of patients were on steroids and 33% on HCQ. After documented COVID-19 infection, all the Disease-modifying antirheumatic drugs (DMARDs) were with-held except HCQ.
Goyal et al. reported the impact of COVID-19 on systemic lupus erythematosus (SLE) patients on a multicentrer questionnaire-based survey earlier in May 2020. They had 19 cases with the majority on HCQ (96.2%) and concluded that the use of various immunosuppressants by patients with SLE did not result in the high incidence of COVID-19 or a worse outcome.
A comparative study between outcomes of COVID-19 in patients with and without rheumatic diseases by D'Silva reported a similar rate of mortality (6%) between the two groups but higher rates of mechanical ventilation in people with rheumatic diseases. A preliminary report about the mortality risk of COVID-19 in patients with rheumatic diseases by Marques et al. observed a lethality risk of 9.2% with higher prevalence inactive SLE and recent use of methylprednisolone and cyclophosphamide. In a retrospective matched cohort study from New York, COVID-19 patients with autoimmune disease had no increased risk of ICU outcome, admission, or death. The mortality rate in our study was 2.3%, slightly higher than the state and the national average of 1.49%–1.45% (as on December 3, 2020) respectively.
Rajasingham et al., did a randomized controlled trial to assess the efficacy of HCQ as preexposure prophylaxis in health care workers and HCQ was found not to be effective in comparison to placebo. We had 28 (33%) patients on regular HCQ, when they got infected. One of the deceased patients was on prior HCQ for RA.
C19 Global Rheumatology Alliance (GRA) registry (COVID-19 GRA), concluded that older age, comorbidities like diabetes, hypertension, chronic kidney disease, lung diseases, prednisolone dose more than 10 mg/day increased the risk of hospitalization whereas anti-TNF reduced the risk of hospitalization. Moreover, glucocorticoid use was associated with dose-dependent increase in the risk of bacterial infections as compared with methotrexate use. In our study, steroids were used by 43.5% of the people for their underlying rheumatic disease and we found a positive correlation between the length of stay and the dosage of steroids.
A cross-sectional study conducted in Germany with 104 rheumatic disease patients, stated that more males contracted COVID infection than females and patients with comorbidities were at risk of severe COVID as similar to that of the general population. A Belgian study on the clinical course of COVID-19 in rheumatic diseases was not able to arrive at firm conclusions due to the limited number of patients affected but it reported that all patients with the severe form of infection had at-least one comorbidity.
Majority of the people hospitalized (84.4%) in our cohort were of age above 40 years. Around 10.3% of the hospitalized patients had been treated in intensive care, all of them were above 40 years of age. In our study, the prevalence of diabetes mellitus (29.3% of inpatients vs. 14.8% of outpatients), systemic hypertension (29.3% of in patients vs. 18.5% of outpatients), and obesity was (36.2% of inpatients vs. 7.4% of outpatients) more in inpatients and the difference was statistically significant.
A meta-analysis on the prevalence and outcome of COVID-19 in autoimmune diseases demonstrated that the risk of infection is more in patients with autoimmune diseases than controls, attributed to the use of glucocorticoids, the combination of both conventional and b DMARDS/ts DMARDS, however monotherapy with biologics, especially anti-TNF agents was associated with reduced risks of hospitalization. We were not able to find any association between stay duration and disease-modifying agents or biologics.
Our study has few limitations. It is a retrospective observational study lacking controls such as people without rheumatic diseases infected with COVID-19. The criterion for inpatient management was not uniform with some getting admitted due to fear of illness and not due to disease severity. The protocol for management had few variations depending on individual centers. To the best of our knowledge, there are limited data from India. Our study is one among the very few studies from India reporting the clinical characteristics and outcome of rheumatic disease patients infected with severe acute respiratory syndrome-coronavirus-2.
To conclude, there was a positive and statistically significant correlation between steroid dose and duration of stay. The prevalence of comorbidities was higher among hospitalized patients. There was no correlation between other immunosuppressive drugs and stay duration nor was there any difference in mean dosages of these drugs between patients treated as in-patients and out-patients.
We would like to acknowledge Mr. R. Balasubramaniam, statistician cum lecturer of Annapoorna Medical College, Salem, Tamilnadu and Dr. R. Balaji, Professor of Community Medicine, SRM Medical College, Chennai for the help rendered.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gupta L, Misra DP, Agarwal V, Balan S, Agarwal V. Management of rheumatic diseases in the time of covid-19 pandemic: Perspectives of rheumatology practitioners from India. Ann Rheum Dis 2021;80:e1.
Zhong J, Shen G, Yang H, Huang A. COVID-19 in patients with rheumatic disease in Hubei province, China: A multicentre retrospective observational study. Lancet Rheumatol 2020;2:e557-64.
Sanchez-Piedra C, Diaz-Torne C, Manero J, On behalf of the BIOBADASER study group, et al.
Clinical features and outcomes of COVID-19 in patients with rheumatic diseases treated with biological and synthetic targeted therapies. Ann Rheum Dis 2020;79:988-90.
Marques C, Pinheiro MM, Reis Neto ET, Dantas AT, Ribeiro FM, Melo AKG. COVID-19 in patients with rheumatic diseases: what is the real mortality risk? Ann Rheum Dis. 2020: annrheumdis-2020-218388. doi: 10.1136/annrheumdis-2020-218388.
Roongta R, Ghosh A. Managing rheumatoid arthritis during COVID-19. Clin Rheumatol 2020;39:3237-44.
Russell B, Moss C, George G, Santaolalla A, Cope A, Papa S, et al.
Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience 2020;14:1022.
Holder AA, Wootton JC, Baron AJ, Chambers GK, Fincham JR. The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptic and chymotryptic peptides and the complete sequence. Biochem J 1975;149:757-73.
Goyal M, Patil P, Pathak H, Santhanam S, Goel A, Sharma V, et al.
Impact of COVID-19 pandemic on patients with SLE: results of a large multicentric survey from India. Ann Rheum Dis. 2021;80:e71.
D'Silva KM, Serling-Boyd N, Wallwork R, Hsu T, Fu X, Gravallese EM, et al.
Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: A comparative cohort study from a US 'hot spot'. Ann Rheum Dis 2020;79:1156-62.
Faye AS, Lee KE, Laszkowska M, Kim J, Blackett JW, McKenney AS, et al.
Risk of Adverse Outcomes in Hospitalized Patients with Autoimmune Disease and COVID-19: A Matched Cohort Study From New York City. J Rheumatol. 2021;48:454-62.
Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML, et al.
Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. medRxiv [Preprint]. 2020:2020.09.18.20197327. doi: 10.1101/2020.09.18.20197327. Update in: Clin Infect Dis. 2020 Oct 17.
Gianfrancesco M, Hyrich KL, Al-Adely S, Carmona L, Danila MI, Gossec L, et al.
Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: Data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis 2020;79:859-66.
Schneeweiss S, Setoguchi S, Weinblatt ME, Katz JN, Avorn J, Sax PE, et al.
Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum 2007;56:1754-64.
Hasseli R, Mueller-Ladner U, Schmeiser T, Hoyer BF, Krause A, Lorenz HM, et al.
National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): A valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD. RMD Open 2020;6:e001332.
Pistone A, Tant L, Soyfoo MS. Clinical course of COVID-19 infection in inflammatory rheumatological patients: A monocentric Belgian experience. Rheumatol Adv Pract 2020;4:rkaa055.
Akiyama S, Hamdeh S, Micic D, Sakuraba A. Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis. Ann Rheum Dis. 2020. annrheumdis-2020-218946. doi: 10.1136/annrheumdis-2020-218946.
[Table 1], [Table 2]