Shorter telomere length is associated with COVID-19 hospitalization and with persistence of radiographic lung abnormalities.

BACKGROUND: Age and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL. RESULTS: We analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n = 169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1 year later and compared with baseline TL. Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease. CONCLUSION: Shorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.

SARS-CoV-2-specific T-cell responses after COVID-19 recovery in patients with rheumatic diseases on immunosuppressive therapy.

BACKGROUND: In patients with immune-mediated rheumatic diseases (RMD), the development of T-cell responses against SARS-CoV-2 may be impaired by either the immune disturbances associated with the disease, or by the effects of immunosuppressive therapies. We aimed at determining the magnitude of SARS-CoV-2-specific interferon (IFN)-γ-producing T-cell response after COVID-19 recovery in a cohort of patients with RMD on different immunosuppressive therapies. PATIENTS AND METHODS: 53 adult patients with inflammatory or autoimmune RMD and 61 sex and age-matched non-RMD patients with confirmed COVID-19 were included. Peripheral blood mononuclear cells were obtained and T-cell-IFN-γ antigen-specific responses against the S1 domain of the spike glycoprotein, the nucleoprotein (N) and the membrane (M) protein from SARS-CoV-2 were assessed by FluoroSpot assay. RESULTS: Patients with RMD and COVID-19 showed positive T-cells-IFN-γ responses to SARS-COV-2 antigens, in a similar proportion and magnitude as non-RMD patients at a median of 298 [151-316] and 165 [162-167] days after COVID-19 respectively. Among RMD patients 83%, 87% and 90%, and among non-RMD patients, 95%, 87% and 93% responded to S1, N and M protein respectively. Similar responses were observed in the different diagnostic and therapeutic groups, including conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNF-α inhibitors, IL-17 inhibitors, rituximab, JAK inhibitors or other immunosuppressants. CONCLUSION: T-cell responses to the main SARS-CoV-2 antigens are present after COVID-19 recovery in most patients with RMD and are not impaired by immunosuppressive therapies.

Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study.

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases.

BACKGROUND: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. METHODS: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. RESULTS: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. CONCLUSION: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.