Background In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. Objectives The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. Methods A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections. Results Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present. Conclusions Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.

Background: In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed. Objectives: The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19. Methods: A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase, and Web of Science from 1st of December 2019 until 1 st of October 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, other oxygen therapy, length of hospital stay and secondary infections. Results: Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57-0.87). Furthermore, viral clearance time ranged from 10-29 days in the corticosteroid group and from 8-24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend towards more infections and antibiotic use was present. Conclusions: Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction of need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.

Background In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In a recent RCT (RECOVERY trial), a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation evaluating the effect of dexamethasone was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroid use in COVID-19. However, the supposed effect of corticosteroids on mortality and viral clearance remains unclear and a clear evidence-based therapeutic strategy is still lacking.Objectives The aim of this systematic review and meta-analysis was to evaluate the effect of corticosteroids on mortality, viral clearance and secondary outcomes in COVID-19 patients.Data source, study eligibility, participants, interventionsA systematic literature search was performed across Medline/PubMed, Embase, and Web of Science from 1st of December 2019 until 10th of July 2020, according to the PRISMA guidelines. RCTs and cohort studies reporting in English, on ≥15 adult COVID-19 patients, treated with any type of corticosteroid therapy were included. Studies on pregnant women, reviews and with a NOS (Newcastle Ottawa Scale for validity assessment of observational studies) score of ≤4 were excluded.Results Twenty-two articles were included, covering 9,760 patients. In eight studies, the effect of corticosteroid use was quantified. The pooled estimate of the observational studies supported the positive effect on mortality of corticosteroid therapy in COVID-19 as reported in the RECOVERY trial, in respiratory compromised COVID-19 patients, i.e. oxygen or mechanical ventilation dependent or with ARDS. The overall pooled estimate (observational studies and the RCT) showed reduced mortality in the corticosteroid group (relative risk 0.55 [95% CI 0.27-0.83]). Furthermore, mechanical ventilation rate seemed lower in corticosteroid treated COVID-19 patients, though no definite conclusions could be drawn because of a low number of studies. With regard to potential side effects of corticosteroids, the effect on viral clearance duration was ambiguous, i.e. prolonged in 4 of 9 and without effect in 5 of 9 studies.Conclusions It appears safe with respect to viral clearance to administer corticosteroids in respiratory compromised COVID-19 patients with possible improvement in mortality and conflicting effects on viral clearance.

Objectives Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of Raynaud’s phenomenon (RP) in systemic sclerosis (SSc) patients. We aim to evaluate the clinical efficiency of this intervention. Methods A multicentre double-blind randomized trial was performed, accounting for interindividual differences and external factors using a cross-over design. Patients were randomized in two groups: group 1 wore 8%-silver fibre gloves in period 1 and normal gloves in period 2, and group 2 vice versa. Each period lasted six weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference : 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. Results Eighty-five SSc-patients were included, with 76 completing the study. Mean RCS during two weeks before the study (i.e.: without gloves) was 6.4 (SD : 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (SD : 2.3) with similar course over time. There was no difference in mean RCS over time between the type of gloves (β:0.067, 95% CI:-0.006–0.19). Of secondary outcomes, total SHAQ (β:0.036, 95% CI : 0.026–0.046) was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves, vs one patient with silver fibre gloves (OR : 3.2, 95% CI : 0.32–31.1). Conclusion Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8%-silver fibre gloves is associated with less disease burden as measured in this study by RCS compared with normal gloves. Clinical trial registration number Netherlands Trial register; https://www.trialregister.nl/; NL7904

Background To investigate the presence of different isotypes of anti-carbamylated protein (CarP) antibodies in systemic sclerosis (SSc) patients and its association with skin involvement. Methods Sera of 194 SSc patients from the Leiden CCISS cohort, fulfilling ACR/EULAR 2013 criteria and a clinical diagnosis of SSc, 83 patients with other connective tissue diseases/Raynaud’s Phenomenon, 24 rheumatoid arthritis patients and 98 age and sex-matched healthy controls were tested for the presence of anti-CarP IgG, IgA and IgM, determined by ELISA. Clinical characteristics, that were evaluated in SSc patients, included age, anti-topoisomerase antibodies (ATA), anti-centromere antibodies (ACA) and modified Rodnan Skin Score (mRSS). Results The SSc patients were 55 (SD:13) years and 155 (80%) were female. Forty-four (23%) patients tested positive for ATA, and 80 (42%) ACA. The median mRSS was 2 (range: 0; 47). Prevalence of anti-CarP IgG was higher in SSc patients than in healthy controls (8% vs 3%, p = 0.007. Prevalence of anti-CarP IgA and IgM and levels of anti-CarP isotypes were comparable between SSc patients and healthy controls. Fifteen (8%) SSc patients tested positive for anti-CarP IgG, 16 (8%) for anti-CarP IgA, and 36 (19%) for anti-CarP IgM. There were no significant correlations between age and levels of anti-CarP isotypes. No correlation between anti-CarP IgG levels and mRSS was found (r = 0.141, p = 0.049), nor for anti-CarP IgM and IgA levels. Anti-CarP IgA levels were higher in ATA compared to ACA positive SSc patients (ATA: 616 aU/ml [359; 1103]; ACA: 424 aU/ml [300; 673], p = 0.015). Conclusion SSc patients can test positive for Anti-CarP IgG, IgA and IgM. We do not observe a relevant clinical association between anti-CarP antibody response and skin involvement in SSc.