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<0.001). Thanks to a ddPCR-based assay, we achieved a rapid and accurate SARS-CoV-2 diagnosis in rtPCR-negative respiratory samples of individuals with COVID-19 suspect, allowing the rapid taking care and correct management of these patients.
•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.
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.
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.
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.
TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.
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.
From February to April 2020, Lombardy (Italy) reported the highest numbers of SARS-CoV-2 cases worldwide. By analyzing 346 whole SARS-CoV-2 genomes, we demonstrate the presence of seven viral ...lineages in Lombardy, frequently sustained by local transmission chains and at least two likely to have originated in Italy. Six single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. The seven lineages, and the presence of local transmission clusters within three of them, revealed that sustained community transmission was underway before the first COVID-19 case had been detected in Lombardy.
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.
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.
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: 2.1791.455-3.264 and 3.1271.18-8.29, respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%).
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.
The use of a televisit service complying with efficiency and safety regulatory parameters was effective in significantly improving HbA1c levels of people with T1D after a one-year follow-up period. ...No acute diabetes-related complications occurred. Patients were highly satisfied with the service. Televisit is a valid option for diabetes management.
The aim of the study was to investigate the role of chronic kidney disease (CKD) on in-hospital mortality and on incident atrial fibrillation (AF) in patients infected with SARS-CoV-2. The incidence ...of acute kidney injury (AKI) was also investigated. Multivariable regression models were used to assess the association between renal function groups (estimated Glomerular Filtration Rate, eGFR, >60 mL/min, 30–59 mL/min, <30 mL/min) and in-hospital all-cause mortality and incident AF and AKI. A cohort of 2816 patients admitted in one year for COVID-19 disease in two large hospitals was analyzed. The independent predictors of mortality were severe CKD HR 1.732 (95%CI 1.264–2.373), older age HR 1.054 (95%CI 1.044–1.065), cerebrovascular disease HR 1.335 (95%CI (1.016–1.754), lower platelet count HR 0.997 (95%CI 0.996–0.999), higher C-reactive protein HR 1.047 (95%CI 1.035–1.058), and higher plasma potassium value 1.374 (95%CI 1.139–1.658). When incident AKI was added to the final survival model, it was associated with higher mortality HR 2.202 (1.728–2.807). Incident AF was more frequent in patients with CKD, but in the multivariable model only older age was significantly related with a higher incidence of AF OR 1.036 (95%CI 1.022–1.050). Incident AF was strongly associated with the onset of AKI HR 2.619 (95%CI 1.711–4.009). In this large population of COVID-19 patients, the presence of severe CKD was an independent predictor of in-hospital mortality. In addition, patients who underwent AKI during hospitalization had a doubled risk of death. Incident AF became more frequent as eGFR decreased and it was significantly associated with the onset of AKI.
(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special ...attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.
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.
Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping ...diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge.
In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted.
For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions.
Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.
Objective
To compare clinical effectiveness between tocilizumab and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA) and inadequate response to conventional ...synthetic disease‐modifying antirheumatic drugs initiating biologic therapy.
Methods
Patients prescribed tocilizumab (intravenous) or TNFi were prospectively observed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The primary observation was the change from baseline in Disease Activity Score based on 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) at week 24 using analysis of covariance for between‐groups comparison. Secondary end points included Clinical Disease Activity Index (CDAI) and patient‐reported outcomes at weeks 24 and 52.
Results
Of 1,216 patients, 35% initiated tocilizumab and 65% initiated TNFi. RA duration was shorter, and disease activity and corticosteroid use were higher in tocilizumab patients. Tocilizumab‐treated patients had greater improvement in DAS28‐ESR at weeks 24 and 52 (week 24 difference 95% confidence interval in adjusted means: −0.831 −1.086, −0.576; P < 0.001). Change from baseline in CDAI was also greater with tocilizumab (adjusted means difference: week 24, −3.48; week 52, −4.60; both P < 0.001). Tocilizumab‐treated patients had more improvement in the Health Assessment Questionnaire disability index than TNFi‐treated patients (P < 0.05). The cumulative probability of drug discontinuation at week 52 was lower with tocilizumab (15%) than TNFi (27%; P < 0.001, unadjusted analysis). Unadjusted frequencies (events per 100 patient‐years) for tocilizumab and TNFi were 6.44 and 11.99 for serious adverse events, 1.98 and 5.03 for serious infections, and 0.74 and 0.77 for deaths, respectively.
Conclusion
Patients initiating tocilizumab experienced greater effectiveness and drug survival than those initiating TNFi in an observational setting.
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