Definitions • Septic Shock

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Definitions

• Septic shock: Persisting hypotension despite volume resuscitation, requiring vasopressors to maintain mean artery pressure (MAP) ≥65 mmHg and serum lactate level >2 mmol/L (1). • Renal failure: Doubling of basal Creatinine value or urine output <0.5 ml/kg/h for ≥12h (2) • Heart failure: Gradual or rapid change in heart failure signs and symptoms resulting in a need for urgent therapy (3). • Myocarditis: Myocarditis was diagnosed if serum levels of high-sensitivity cardiac troponin I were above the 99th percentile upper reference limit and compatible abnormalities were shown in electrocardiography and echocardiography. • Encephalopathy: Impaired consciousness as change of consciousness level (somnolence, stupor, and coma) or consciousness content (confusion and delirium) (4). • Thrombosis: Clinically or by imaging diagnosed acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism (5).

References

1. World Health Organization. Clinical management of severe acute respiratory infection when Novel coronavirus (nCoV) infection is suspected: interim guidance. 2020. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection- when-novel-coronavirus-(ncov)-infection-is-suspected.

2. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012;120:c179-84. 10.1159/000339789.

3. Gheorghiade M, Zannad F, Sopko G, et al. Acute heart failure syndromes: current state and framework for future research. Circulation. 2005;112(25):3958-3968.

4. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China [published online ahead of print, 2020 Apr 10]. JAMA Neurol. 2020;77(6):1-9.

5. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-147.

Pablos JL, et al. Ann Rheum Dis 2020; 79:1544–1549. doi: 10.1136/annrheumdis-2020-218296 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Ann Rheum Dis

Table S1. Diagnosis and clinical characteristics of included patients

Diagnosis n Disease duration2 Active disease3 Inflammatory Arthritis 136 10.69 ± 8.08 34.3 RA 65 11.75 ± 7.56 33.3 PsA 35 8.92 ± 6.57 32.4 SpA 36 10.46 ± 9.88 37.8 CTD 92 9.31 ± 8.54 18.1 PMR 24 8.37 ± 8.23 20.0 SLE 16 14.34 ± 10.38 43.8 SS 13 5.46 ± 2.85 15.4 SSc 7 6 .0 ± 6.38 - PAPS 6 11.71 ± 9.57 - Sarcoidosis 5 9.79 ± 5.86 20.0 GCA 4 4.25 ± 5.9 0 Inflammatory myopathy 3 11.91 ± 12.86 0 Other Vasculitis 3 8.0 ± 5.67 0 Other 91 10.69 ± 8.08 16.7 1 Behcet´s, disease, IPAF, Undifferentiated connective tissue disease, Hidradenitis suppurativa, IgG-4 related disease 2 Mean ± SD 3 Proportion of patients with physician reported active rheumatic disease at COVID-19 onset n (%). For inflammatory arthritis, DAS28, BASDAI or DAPSA were used. For CTD, physician narrative impression was considered.

Table S2. Description of evolution of COVID-19 in four main rheumatic disease subgroups.

SpA incl. PsA RA SLE and related Vasculitis, incl. COVID evolution n=71 n=65 CTD n=34 PMR/GCA n=32 No. days before PCR+, m ± SD 7.85 ± 7.41 6.98 ± 5.34 7.29 ± 8.70 5.04 ± 3.13 Radiologically confirmed pneumonia 42 (60.9) 50 (76.9) 20 (60.6) 22 (71.0) Hospitalisation 43 (60.6) 55 (84.6) 23 (67.7) 27 (84.4) Duration of hospital stay, m ± SD 10.34 ± 7.58 12.26 ± 7.99 17.06 ± 10.50 11.29 ± 9.90 Respiratory distress 30 (42.9) 44 (67.7) 18 (52.9) 23 (71.9) ICU admission 1 (1.4) 5 (7.8) 5 (14.7) 4 (12.5) Respiratory category No oxygen was necessary 40 (57.1) 21 (32.8) 16 (47.1) 10 (31.3) Oxygen by nasal cannula 26 (37.1) 36 (56.3) 12 (35.3) 20 (62.5) Oxygen with reservoir 2 (2.9) 0 0 0 Non-invasive ventilation 1 (1.4) 4 (6.3) 3 (8.8) 1 (3.1) Invasive ventilation 1 (1.4) 3 (4.7) 3 (8.8) 1 (3.1) Significant complications 9 (12.7) 24 (38.1) 14 (41.2) 14 (45.2) Myocarditis 1 (1.4) 4 (6.5) 3 (9.1) 3 (9.7) Encephalopathy 1 (1.4) 0 1 (3.0) 1 (3.1) Thrombotic event 1 (1.4) 1 (1.6) 4 (12.1) 0 Kidney failure 7 (9.9) 10 (16.1) 6 (18.2) 6 (18.8) Septic shock 3 (4.2) 4 (6.5) 3 (9.4) 5 (16.1)

SpA incl. PsA RA SLE and related Vasculitis, incl. COVID evolution n=71 n=65 CTD n=34 PMR/GCA n=32 Death 3 (4.2) 18 (28.1) 7 (20.6) 10 (31.3) Days from 1st symptom, m ± SD 54.8 ± 13.9 43.5 ± 20.7 47.85 ± 20.74 36.79 ± 22.85 Severe COVID-19* 10 (14.1) 28 (43.1) 14 (41.2) 17 (53.1) OR (95% CI)† 0.53 (0.24 - 1.18) 1.60 (0.82 -3.11) 2.87 (1.14 - 7.21) 2.76 (1.19 - 6.40) Antivirals Lopinavir/ritonavir 21 (29.6) 29 (44.6) 16 (47.1) 7 (21.9) Remdesivir 0 (0) 1 (1.5) 1 (2.9) 0 (0)

Values in cells represent n (%) unless otherwise indicated. * Death, ICU admission, or serious COVID-19 complication. † From logistic models adjusted for age over 60, male sex, obesity, diabetes, heart failure, and antivirals. All other rheumatic diseases were coded as missing.

Table S3. Risk of poor COVID-19 outcome in four main rheumatic disease subgroups.

SpA incl. PsA RA SLE and related Vasculitis, incl. Factors n=71 n=65 CTD n=34 PMR/GCA n=32 Specific RMD 0.53 (0.24 - 1.18) 1.60 (0.82 - 3.11) 2.87 (1.14 - 7.21) 2.76 (1.19 - 6.40) Age > 60 5.48 (2.70 - 11.14) 3.91 (1.98 - 7.73) 6.97 (3.27 - 14.84) 6.60 (2.98 - 14.60) Male sex 1.85 (1.03 - 3.34) 2.25 (1.28 - 3.96) 2.31 (1.24 - 4.30) 2.25 (1.23 - 4.12) Obesity 1.42 (0.67 - 3.02) 1.27 (0.64 - 2.54) 1.72 (0.78 - 3.78) 1.17 (0.54 - 2.53) Diabetes 0.51 (0.23 - 1.12) 0.72 (0.35 - 1.49) 0.61 (0.27 - 1.36) 0.57 (0.27 - 1.25) CV disease 1.01 (0.48 – 2.13) 1.17 (0.61 - 2.25) 0.91 (0.43 - 1.91) 0.92 (0.45 - 1.86) Antivirals 1.89 (1.04 - 3.40) 2.03 (1.16 - 3.54) 2.94 (1.57 - 5.48) 2.40 (1.29 - 4.45)

Model properties Correctly classified 75.68% 70.24% 74.71% 72.59%

Values in cells represent odds ratio and 95% confidence interval. Abbreviations: CV, cardiovascular; GC, glucocorticoids. Significant associations marked in bold.

Sensitivity analysis (adding GC as covariate)

SpA incl. PsA RA SLE and related Vasculitis, incl. Factors n=71 n=65 CTD n=34 PMR/GCA n=32 Specific RMD 0.48 (0.19 - 1.21) 1.55 (0.65 - 3.70) 3.04 (1.05 - 8.74) 6.37 (1.53 - 26.63) Correctly classified 75.93% 70.24% 74.71% 72.97%

Methods (Tables S2 and S3) Objective To compare the outcome of COVID-19 in people with specific inflammatory rheumatic diseases and people without inflammatory rheumatic diseases, adjusting by risk factors of poor prognosis of COVID-19. Methods We kept the cohort without inflammatory rheumatic diseases as control for all comparisons. The following cohorts were compared: (1) Spondyloarthritis (SpA), including psoriatic arthritis (PsA) (2) Rheumatoid arthritis (RA), including undifferentiated arthritis (3) Systemic lupus erythematosus (SLE) and related connective tissue diseases (CTD), including SLE, antiphospholipid syndrome, and Sjögren’s syndrome (4) Vasculitis: polymyalgia rheumatica with or without giant cell arteritis (PMR/GCA), and other systemic vasculitis. Variables and measurements The primary outcome was ‘severe COVID-19’, a composed variable including death, ICU admission, intratracheal intubation, or serious COVID-19 complications. The explanatory variable was the specific RMD, and all the others, obtained from the best fitted model of previous steps (age over 60, male sex, cardiovascular disease, obesity, diabetes, and antivirals). A sensitivity test adding glucocorticoids as covariate was also run. Statistical analysis Bivariable and multivariable logistic regression models were run with each of the specific diseases as dependent variables and the best model covariates.

Pablos JL, et al. Ann Rheum Dis 2020; 79:1544–1549. doi: 10.1136/annrheumdis-2020-218296