A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases
Abhishek Patil, Padmanabha Shenoy, Vikram Haridas, Sharath Kumar, Manisha Daware, Ramya Janardana, Benzeeta Pinto, Ramaswamy Subramaniam, Yogesh Preet Singh, Shweta Singhai, Ramesh Jois, Vikramraj Jain, B G Dharmanand, Chethana Dharmapalaiah, Sangeetha Kn, Vijay K Rao, Vineeta Shobha
doi:10.21203/rs.3.rs-805748/v1
Background We conducted this study to identify the in uence of prolonged use of hydroxychloroquine(HCQ), glucocorticoids (GC) and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs).
Methods This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome.
Results COVID-19 occurred in 314(3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129,219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence ((17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh(Kerala) ) and case fatality (4.1% vs 1.3 % (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was signi cantly higher (p < 0.001) compared to the general population of the corresponding geographic region.
Conclusions Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.
include inability to accurately assess the impact of disease activity on occurrence and outcome of COVID-19. As rheumatologists are not the primary physicians for COVID-19 care, we were not able to access precise information with regards to O2 therapy, hospitalization and ICU care. Also, the testing for COVID-19 in individual patients was as per Govt. of India, Govt. of Karnataka and Govt. of Kerala protocols which have undergone modi cations as the pandemic progressed. Our data may not have captured all asymptomatically infected patients in this analysis. This could have biased the result and might have altered the reported incidence as well as mortality. Also the comparison of incidence and mortality of COVID-19 in AIRD with the general population might have been in uenced by the differential age and sex composition in both the populations.
Conclusions Long term HCQ use had no signi cant impact on COVID-19 occurrence and mortality in AIRD patients while moderate doses of GC increased the risk of infection. AIRD patients who are elderly, male, smokers, hypertensive, diabetic and those with underlying lung disease have a higher risk of contracting COVID-19. The incidence rate is at least 3 fold higher and the case fatality rate is 4.6 times higher than that of the general population in the same geographic region during the same time period. Hence, this group of AIRD regardless of age and other comorbidities, merits rst access to the various protective measures implemented..
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:p>Background\n'
'\n'
'We conducted this study to identify the influence of prolonged use of '
'hydroxychloroquine(HCQ), glucocorticoids (GC) and other immunosuppressants (IS) on occurrence '
'and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs).\n'
'Methods\n'
'\n'
'This was a prospective, multicenter, non-interventional longitudinal study across 15 '
'specialist rheumatology centers. Consecutive AIRD patients on treatment with '
'immunosuppressants were recruited and followed up longitudinally to assess parameters '
'contributing to development of COVID-19 and its outcome.\n'
'Results\n'
'\n'
'COVID-19 occurred in 314(3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR '
'129,219) days. Long term HCQ use had no major impact on the occurrence or the outcome of '
'COVID-19. Glucocorticoids in moderate dose (7.5-20mg/day) conferred higher risk (RR\u2009'
'=\u20091.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) '
'and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk '
'factors such as male sex (RR\u2009=\u20091.51), coexistent diabetes mellitus (RR\u2009=\u2009'
'1.64), pre-existing lung disease (RR\u2009=\u20092.01) and smoking (RR\u2009=\u20093.32) were '
'the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the '
'strongest risk factor being pre-existing lung disease (RR\u2009=\u20096.36, p\u2009=\u2009'
'0.01). Incidence ((17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh(Kerala) ) '
'and case fatality (4.1% vs 1.3 % (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was '
'significantly higher (p\u2009<\u20090.001) compared to the general population of the '
'corresponding geographic region.\n'
'Conclusions\n'
'\n'
'Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD '
'patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease '
'contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is '
'much higher than that in the general population.</jats:p>',
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