The recent outbreak caused by a novel severe acute respiratory syndrome coronavirus
2 disease 2019 (COVID-19) has spread rapidly worldwide, and it has been declared a
pandemic by the WHO.1 Elder people, male sex and some underlying comorbidities seem
to be risk factors for morbidity and mortality, although an immunosuppressive status
could favour the infection and the development of complications.2 However, as progress
is made in the knowledge of the physiopathology of COVID-19, it has been observed
that severe respiratory forms occur as a result of an hyperinflammatory status and
an excessive production of cytokines.3
In this descriptive retrospective study, we aimed to characterise features related
to severity and mortality in these patients and the influence of immune modulating
drugs on the course of the infection. Patients were included from 25 February 2020
to 8 June 2020 with COVID-19 infection and rheumatic inflammatory diseases from Rheumatology
Department of La Paz University Hospital.
One hundred and twenty-two patients were included. One hundred (82.0%) were confirmed
through nasopharyngeal swabs. Twenty-two patients (18.0%) exhibited compatible symptoms
with compatible lung imaging and/or positive serology. Patients characteristics are
shown in table 1.
Table 1
Patients with COVID-19 characteristics
Demographics
Female sex, n (%)
80 (65.6)
Caucasian ethnicity, n (%)
98 (80.3)
Age (mean±SD),
58.3±16.3
Comorbidity, n (%)
Hypertension
48 (39.3)
Obesity
27 (23.6)
Chronic pulmonary disease
20 (16.4)
Cardiovascular disease
21 (17.2)
Diabetes mellitus
14 (11.5)
Active smokers
7 (5.6)
Treatment with ACE/ARB, n (%)
34 (27.9)
Rheumatic diseases, n (%)
RA
41 (33.6)
SpA
24 (19.7)
SLE
13 (10.7)
PsA
13 (10.7)
Miscellaneous*
31 (25.4)
Duration of rheumatic disease (mean±SD), years
12.2±9.3
Concomitant treatment, n (%)
Hydroxychloroquine
26 (21.3)
Glucocorticoids
48 (39.3)
cDMARDs
80 (65.6)
Methotrexate
54 (44.3)
Sulfasalazine
19 (15.6)
Leflunomide
13 (10.7)
Azathioprine
2 (1.6)
Cyclophosphamide
1 (0.8)
bDMARDs/tsDMARDs
42 (34.4)
Anti-TNF
28 (23.0)
Rituximab
7 (5.7)
Abatacept
3 (2.5)
Tocilizumab
1 (0.8)
Sarilumab†
–
Secukinumab
0 (0.0)
Tofacitinib
1 (0.8)
Baricitinib
1 (0.8)
Symptoms, n (%)
Dry, non-productive cough
84 (74.3)
Fever
74 (64.3)
Dyspnoea
59 (50.0)
Arthromyalgia
42 (36.5)
Anosmia/ageusia
41 (37.5)
Nausea/vomiting
39 (33.9)
Respiratory insufficiency, n (%)
54 (52.5)
Non-invasive oxygen supplementation, n (%)
50 (41.0)
Pneumonia, n (%)
67 (54.9)
Time from disease onset to hospital admission, days (median, IQR)
7.2 (4.1–10.5)
Hospital admission, n (%)
69 (56.6)
ICU admission, n (%)
6 (4.9)
Time of hospital admission, days (median, IQR)
8.0 (5.0–15.2)
COVID-19 specific treatment, n (%)
Hydroxychloroquine
76 (62.3)
Azithromycin
50 (41.0)
Glucocorticoids
8 (6.6)
Lopinavir/ritonavir
6 (4.9)
Anti-IL6
6 (4.9)
Anti-IL1
2 (1.6)
IVIg
3 (2.5)
Recovered patients, n (%)
106 (87.6)
Exitus, n (%)
14 (11.5)
*See online supplementary table S1.
†One patient on double blind clinical trial with sarilumab versus placebo.
ARB, angiotensin-receptor blocker; bDMARDs, biological disease-modifying antirheumatic
drugs; cDMARDs, conventional synthetic disease-modifying antirheumatic drugs; ICU,
intensive care units; IL, interleukin; IVIg, intravenous immunoglobulins; PsA, psoriatic
arthritis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SpA, spondyloarthritis;
TNF, tumour necrosis factor; tsDMARDs, targeted synthetic disease-modifying antirheumatic
drugs.
10.1136/annrheumdis-2020-218054.supp1
Supplementary data
Variables associated with hospital admission in univariate analysis (table 2) were
age (5-year intervals; OR 1.34, 95% CI 1.17-1.55), prednisone dose >5 mg/day (OR 2.55,
95% CI 1.07–5.59), chronic pulmonary disease (OR 5.34, 95% CI 1.47-19.35) and hypertension
(OR 4.06, 95% CI 1.79-9.19). Independent risk factors for hospital admission were
methotrexate (OR 2.06, 95% CI 1.01-5.29) and age (5-year intervals; OR 1.31, 95% CI
1.11-1.48). No association was found with hydroxychloroquine, other conventional disease-modifying
antirheumatic drugs (cDMARDs), targeted synthetic disease-modifying antirheumatic
drugs or biological disease-modifying antirheumatic drugs (bDMARDs) or laboratory
parameters. Methotrexate treatment was not associated with age, sex, glucocorticoids
or subtype of rheumatic disease.
Table 2
Factors associated with hospital admission in patients with COVID-19
Variable
Inpatients(n=69)
Outpatients(n=53)
P value
Demographics
Female sex, n (%)
42 (60.8)
37 (71.1)
0.25
Age (mean±SD)
63.9±15.6
50.5±14.1
<0.01
Comorbidity
Hypertension
36 (52.1)
11 (21.1)
0.01
Obesity
25 (36.2)
17 (32.6)
0.58
Chronic pulmonary disease
17 (24.6)
3 (5.7)
0.01
Cardiovascular disease
15 (21.7)
5 (9.6)
0.08
Diabetes mellitus
11 (15.9)
3 (5.7)
0.09
Active smokers
4 (5.7)
3 (5.7)
1.00
Concomitant treatment, n (%)
Hydroxychloroquine
13 (18.8)
12 (23.0)
0.62
Glucocorticoids
33 (47.8)
14 (26.9)
0.02
Low-dose prednisone (≤5 mg/day)
27 (39.1)
11 (20.7)
0.04
cDMARDs
47 (68.1)
32 (61.5)
0.43
Methotrexate
36 (52.1)
18 (34.6)
0.06
Leflunomide
6 (8.6)
7 (13.4)
0.11
Sulfasalazine
10 (14.4)
9 (17.3)
0.33
Azathioprine
1 (1.4)
–
–
Cyclophosphamide
1 (1.4)
–
–
bDMARDs/tsDMARDs
20 (28.9)
22 (42.3)
0.12
Anti-TNF
9 (13.0)
19 (36.5)
0.04
Rituximab
7 (10.1)
–
0.01
Abatacept
2 (2.8)
1 (1.9)
–
Tocilizumab
–
1 (1.9)
–
Sarilumab*
–
–
–
Secukinumab
–
–
–
Tofacitinib
–
1 (1.9)
0.36
Baricitinib
–
1 (1.9)
0.36
*One patient on double blind clinical trial with sarilumab versus placebo.
bDMARDs, biological disease-modifying antirheumatic drugs; cDMARDs, conventional disease-modifying
antirheumatic drugs; TNF, tumour necrosis factor; tsDMARDs, targeted synthetic disease-modifying
antirheumatic drugs.
Fourteen patients died (11.5%) due to respiratory failure. Nine patients were on cDMARDs
(either in monotherapy or in combination), one was on bDMARD (rituximab) and four
were taking only oral glucocorticoids. Hydroxychloroquine did not show differences
in mortality. On univariate analysis, factors associated with mortality were age (OR
1.60, 95% CI 1.20-2.01), arterial hypertension (OR 12.17, 95% CI 2.58-57.38), pulmonary
disease (OR 5.36, 95% CI 1.60-17.94) and prednisone dose >5 mg/day (OR 5.70, 95% CI
1.63-19.92).
The recent outbreak of COVID-19 represents a source of concern for the management
of patients with inflammatory rheumatic diseases. However, there are some reports
that suggest that treatments typically used for rheumatic diseases might be effective
against COVID-19.4 In our series, there was a high proportion of patients that needed
hospital admission due to severity of infection (56.6%) compared with other cohorts,
which may be explained by the higher prevalence of comorbidity, particularly hypertension,
the higher use of glucocorticoids or a potential selection bias towards more severe
cases.5 6
Interestingly, methotrexate was a risk factor for hospital admission, but not for
mortality, while other cDMARDs did not show differences. Notably, only one of our
patients on tocilizumab was infected while all of our infected patients on rituximab
needed hospital admission and one died. Additionally, patients on glucocorticoids
had worse survival (78.5% vs 34.2%, p<0.01; see online supplementary material). However,
mortality rate in hospitalised patients (17.4%) was lower compared with general population
in our hospital (20.7%).7
Our preliminary results suggest that COVID-19 does not have a major impact on mortality
in patients with rheumatic disease. However, glucocorticoids seem to increase the
risk of mortality, while methotrexate and rituximab may have an increased risk of
hospital admission. These findings suggest differences in drug mechanism, which may
influence COVID-19 course and emphasise the importance of further investigating the
impact of immunosuppressive treatment.