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Highlights • Cytokine release syndrome seems to play a pivotal role in COVID-19 pathogenesis. • Tocilizumab is one of the most promising drugs for COVID-19. • Tocilizumab halved the mortality in critical patients compared to standard of care. • A transient respiratory function worsening is observed soon after administration. • Severe infective complications are more common than in rheumatologic setting., Background As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19. Methods This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used. Results Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262–0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088–2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events. Discussion TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events. Financial support Some of the tocilizumab doses used in the subjects included in this analysis were provided by the “Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia” (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.

Objective: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. Methods: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription–polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. Results: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. Conclusion: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.

The most common arrhythmia associated with COronaVIrus-related Disease (COVID) infection is sinus tachycardia. It is not known if high Heart Rate (HR) in COVID is simply a marker of higher systemic response to sepsis or if its persistence could be related to a long-term autonomic dysfunction. The aim of our work is to assess the prevalence of elevated HR at discharge in patients hospitalized for COVID-19 and to evaluate the variables associated with it. We enrolled 697 cases of SARS-CoV2 infection admitted in our hospital after February 21 and discharged within 23 July 2020. We collected data on clinical history, vital signs, laboratory tests and pharmacological treatment. Severe disease was defined as the need for Intensive Care Unit (ICU) admission and/or mechanical ventilation. Median age was 59 years (first-third quartile 49, 74), and male was the prevalent gender (60.1%). 84.6% of the subjects showed a SARS-CoV-2 related pneumonia, and 13.2% resulted in a severe disease. Mean HR at admission was 90 ± 18 bpm with a mean decrease of 10 bpm to discharge. Only 5.5% of subjects presented HR > 100 bpm at discharge. Significant predictors of discharge HR at multiple linear model were admission HR (mean increase = β = 0.17 per bpm, 95% CI 0.11; 0.22, p < 0.001), haemoglobin (β = −0.64 per g/dL, 95% CI −1.19; −0.09, p = 0.023) and severe disease (β = 8.42, 95% CI 5.39; 11.45, p < 0.001). High HR at discharge in COVID-19 patients is not such a frequent consequence, but when it occurs it seems strongly related to a severe course of the disease.

Fibromyalgia or fibromyalgia syndrome (FMS) is defined as a central sensitization syndrome characterized by the dysfunction of neurocircuits detecting, transmitting and processing nociceptive stimuli; the prevalent manifestation is musculoskeletal pain. In addition to pain, there are multiple accompanying symptoms, in common with other algo-dysfunctional syndromes, which are reflected in a broad spectrum of somatic, neurocognitive and neuro-vegetative manifestations. An evidence-based approach is essential in FMS management, in order to improve patient health and to reduce its social burden. Since in the last ten years new international guidelines for clinical practice (Clinical Practice Guidelines or CPGs) concerning FMS diagnosis and pharmacological/ non-pharmacological management have been published, the Italian Society of Rheumatology (SIR) has decided to adapt them to the Italian national setting. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the most recent CPGs on FMS to the needs of the Italian healthcare context. A working group of rheumatologists from SIR epidemiology unit and FMS experts identified relevant clinical questions to guide the systematic review of the literature. The target audience of these CPGs included physicians and healthcare professionals who manage FMS. The adapted recommendations were finally assessed by an external multidisciplinary panel. From the systematic search in databases (Pubmed/Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. The combination of the scientific evidence underlying the original CPGs with expert opinion lead to the development of 17 recommendations. The quality of evidence for each recommendation was reported and their potential impact on clinical practice was assessed. These SIR recommendations are expected to be a valuable aid in the diagnosis and treatment of FMS, as they will contribute to disseminate the best practice on the basis of the current scientific evidence.

Among the different CardioVascular (CV) manifestation of the COronaVIrus-related Disease (COVID) particular attention has been paid to arrhythmia and particularly to Atrial fibrillation (AF). The aim of our study was to assess the incidence of AF episodes in patients ospitalisat for COVID and to evaluate its predictors and its relationship with in-hospital all-cause mortality.

SARS-CoV-2 infection determines a disease that predominantly affects lungs. However the cytokines storms, determined by the huge immune response to the infection, could affect also other organs and apparatus such as heart and vessels. Beyond the acute inflammation itself also hypercoagulative status has been linked to SARSCoV-2 infection and this surely relates to the increase seen in prevalence of pulmonary embolism and myocardial infarction. A number of cardiac abnormalities and pathologies have been observed, with special attention to cardiac arrhythmias and myocardial involvement. Furthermore, indirect damages determined by the reduction in acute and chronic cardiovascular care, results in a strong mortality and morbidity outcomes in cardiological patients. In this review we will summarise current knowledge on both direct and indirect cardiovascular damages determined by the SARS-CoV-2 pandemia.

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Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973–0.988, < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773–0.944, = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Over the last few years, the landscape of treatments for axial spondyloarthritis (SpA) has been rapidly evolving, urging international scientific societies to draft or update existing clinical practice guidelines (CPGs) on the management of axial SpA. The Italian Society for Rheumatology (SIR) committed to provide revised and adapted evidence- and expert-based recommendations for the management of patients with axial SpA in Italy. A systematic approach to the adaptation of existing CPGs - the ADAPTE methodology - was adopted to obtain updated recommendations suitable for the Italian context. A systematic literature search was performed in Medline and Embase databases to find international CPGs and consensus statements with recommendations for the management of axial SpA published in the previous five years. A working group composed of rheumatologists with proven experience in the management of axial SpA and methodologists identified the key research questions which guided study selection and data extraction. Guideline quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The Italian recommendations were developed by endorsing or adapting and rewording some existing recommendations. The draft of the recommendations was sent to a multidisciplinary group of external reviewers for comment and rating. Six original CPGs were selected and used to create this SIR CPG, which includes a final set of 14 recommendations covering the management of patients with axial SpA across the following domains: assessment, pharmacological and non-pharmacological treatment, and follow-up. The dissemination and implementation of these SIR recommendations are expected to support an evidencebased clinical approach to the management of patients with axial SpA in Italy.

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterised by chronic joint inflammation, leading to functional disability and increased risk of premature death. Clinical practice guidelines (CPGs) are expected to play a key role in improving management of RA, across the different phases of the disease course. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2011 recommendations on management of RA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing RA CPGs to the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Research Unit and a committee with experience in RA identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage RA in practice, and the target population includes adult patients diagnosed as having RA. An external multi-disciplinary committee rated the final version of the CPGs. From the systematic search in databases (Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 8 (Management) +6 (Safety) recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the management of RA and to disseminate the best evidence-based clinical practices for this disease.

Objective Through a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020. Methods All subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR. Results The cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60–63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455–3.264] and 3.127[1.18–8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%). Conclusion SARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60–63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57–84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72–345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P

Gout is a chronic disease with an increased risk of premature death related to comorbidities. Treatment of gout has proved suboptimal and clinical practice guidelines (CPGs) are expected to have a key role in achieving improvement. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2013 recommendations on the diagnosis and management of gout. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing gout CPGs to the needs of the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Unit and a committee with experience on gout identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage gout in practice, and the target population includes adult patients suspected or diagnosed as having gout. These recommendations were finally rated by an external multi-disciplinary commission. From a systematic search in databases (Medline, Embase) and grey literature, 8 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 14 recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the diagnosis and the treatment of gout and to disseminate the best evidence-based healthcare for this disease.