Prior treatment with immunosuppressants among coronavirus disease 2019 (COVID‐19) inpatients at one hospital in Spain

Dear editor,

Vulnerability to coronavirus disease 2019 (COVID‐19) in patients with cardiovascular risk factors is well known. However, the prognostic influence of immunosuppressive drugs or their ability to counteract the cytokine storm involving critically‐ill patients is uncertain. The scarce‐related literature mainly involves transplantation. ¹ , ² , ³

Dermatologists routinely deal with patients receiving immunosuppressants and evidence‐based‐protocols on how to proceed under the pandemic are lacking.

We evaluated patients hospitalized with COVID‐19 in the University Hospital of Guadalajara on 18 March 2020 and 28 March 2020 (4 and 14 days after the State of Emergency declaration in Spain with 13.716 and 72.248 confirmed cases according to the authorities ⁴ , ⁵ ). Duplicated cases (patients remaining as inpatients for both days) were included in the research once. Only cases with positive polymerase chain reaction (PCR) assay (nose‐throat swab samples) or rapid serology test were included. Patients receiving systemic immunosuppressants within a 3‐month period prior to hospitalization were selected. Data regarding demographic characteristics, co‐morbidities, drug type, time of treatment prior to hospitalization, drug indication as well as mortality outcome were collected from their clinical histories.

We evaluated 435 inpatients (427 with PCR confirmation and eight with positive IgM and/or IgG). Of them, 407 were not immunosuppressed (93.6%) and 28 (6.4%; 95% CI: 4.47–9.10%) had been treated with immunosuppressants within the 3‐month period prior to hospitalization. The median treatment period was 4 months (IQR: 2–18 months).

Among immunosuppressed inpatients, 27/28 (96.4%) received oral corticosteroids alone or combined with other immunosuppressants: prednisone (17); deflazacort (five); deflazacort plus methotrexate (three); prednisone plus azathioprine (one); and prednisone plus everolimus plus tacrolimus (one). Additionally, one patient received methotrexate alone. We did not observe any patients taking biological therapies (95% CI: 0–0.871%; Wilson score). Indications for corticosteroids were: rheumatological conditions (11) (rheumatoid arthritis, polymyalgia rheumatica, microcrystalline arthritis, lupus arthropathy and chondrocalcinosis); asthma or chronic obstructive pulmonary disease (eight); skin diseases (three) (eczema and acute generalized exanthematous pustulosis); organ transplant (two); ulcerative colitis (one); dental bone graft (one) and non‐specified (one). Methotrexate was used alone (one) or combined with deflazacort (three) for rheumatoid arthritis and/or polymyalgia rheumatica; azathioprine plus prednisone for autoimmune hepatitis (one) and tacrolimus plus everolimus plus prednisone for lung transplant (one).

All immunosuppressed patients had co‐morbidities such as: hypertension (17; 60.7%); hyperlipidemia (12, 42.8%); diabetes mellitus (nine, 32%); cancer (five, 17.8%); or hypothyroidism (five, 17.8%). Fatalities during hospitalization involved 69 non‐immunosuppressed (17%) and seven immunosuppressed (25%) patients.

Treatment with immunosuppressants prior to hospitalization (OR: 1.67; 95% CI: 0.67–4.0; P = 0.278) or being male (OR: 1.28; 95% CI: 0.75–2.16; P = 0.367) did not increase the mortality risk of COVID‐19. On the other hand, the older the patient was, the higher the mortality risk. On average, the patients who died were older (mean age: 76.6 years) than the patients who survived (mean age: 65.7 years; mean difference 10.97; 95% CI: 7.86–14.08; P < 0.001). Multivariate logistic regression analysis was applied to determine the effect of immunosuppression on mortality adjusted by age and sex and no increase in the mortality within immunosuppressed patients was observed either (OR: 1.14; 95% CI: 0.45–2.90; P = 0.784).

To conclude, we unanticipatedly found a low proportion of patients with prior immunosuppressive therapy, did not observe any patients taking biologics and could not find significant differences in mortality rates with regards to prior treatment with immunosuppressants among COVID‐19 inpatients. Whether immunosuppressed patients are taking extra precautions or interrupting the treatments and how this may impact our results is unknown. On the other hand, this research further suggests the impact of advanced age in the outcome of COVID‐19 inpatients since individuals who are at an advanced age have a lower survival rate. Our research represents a preliminary approach and hopefully may boost further larger studies. The need for evidence is urgent in order to create protocols guiding our practice under the current emergency circumstances.

Conflicts of interest

Authors do not have any financial, non‐financial or personal relationships between themselves or others that might be perceived by others as biasing their work. On behalf of all co‐authors, the corresponding author uploaded the electronically completed ICMJE COI Disclosure Statements forms for each author and herself.

Funding sources

This research did not receive any specific grant(s) from funding agencies in the public, commercial or not‐for‐profit sectors.