ABSTRACT
Background: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterized by heterogeneous clinical manifestations mainly involving skin, kidney and peripheral nervous system. Despite reassuring safety data from EULAR Coronavirus Vaccine (COVAX) physician-reported registry, a signifcant proportion of patients with autoimmune diseases reported unwillingness to get vaccinated against SARS-CoV-2 infection in the preliminary results of the COVAD study, due to concerns about the lack of longterm safety data, and fear of associated side effects and disease fare. Objectives: Aims of this multicentre Italian study were to investigate the prevalence of vaccination against SARS-CoV-2 in Italian population of MCV patients, to explore the reason for the missed vaccination, and to investigate short and long-term side effects of the vaccine, including vasculitis fare. Methods: All MCV patients referring to 12 Italian centres were investigated about vaccination and possible both short-(within 48 hours) and long-term (within 30 days) adverse events (AE), classifed according to FDA Toxicity Grading Scale for preventive vaccine clinical trials, and possible disease fares. Patients with MCV related to lymphoproliferative disorders or connective tissue diseases were excluded from the study. The baseline variables were expressed as percentages or mean±standard deviation. The differences between continuous variables were analysed using the Mann-Whitney nonparametric test. The chi-squared test, or Fischer's exact when appropriate, were used for categorical variables (absolute numbers and percentages) regarding baseline characteristics. Results: A total of 416 patients, 69.2% females and 30.8% males, with a mean age of 70.4±11.7 years, were included in the study. Only 7.7% of patients were not vaccinated, mainly for fear of adverse events (50%) or for medical decision (18.8%). Corminaty was the vaccine most frequently used (80.5%). Interestingly, 6 patients (1.44%) were with a heterologous vaccination (usually AstraZeneca-Corminaty). Considering ongoing treatment, not vaccinated subjects were more frequently treated with chronic glucocorticoid therapy and/or Rituximab (p=0.049 and p=0.043 respectively). AE were recorded in 31.7% of cases, mainly mild and self-limiting (grade 1). More severe adverse events, such as fare of vasculitis, were observed in 5.3% of cases. AE were not associated with the kind of vaccine used and with the clinical manifestations of vasculitis. Patients with active MCV showed a lower frequency of short-term (within 48 hours) adverse events, but patients affected by peripheral neuropathies or skin vasculitis frequently showed a fare of their symptoms, recorded in 40% and 25% of cases, respectively. Finally, patients under glucocorticoid treatment were more prone to develop a vasculitis fare within a month after vaccination. Conclusion: Vaccination in MCV patients has been performed in a high percentage of patients showing a good safety. Other than patients' fear, treatments with rituximab and glucocorticoids are the main reasons for delaying vaccination, and it should be considered by the physician before starting therapy. Vasculitis fares were observed in about 5% of cases, in line with that observed in other autoimmune diseases. Specific attention should be reserved to people with purpura or peripheral neuropathy, for the increased risk of exacerbation of their symptoms.
ABSTRACT
Background and aims: Although various reports indicated the presence of myalgia in 44–70% and “skeletal muscle injury” (increased CK and myalgia) in 23% of hospitalized patients with SARS-CoV-2 infection, the characterization of neuromuscular involvement is still unsatisfactory, and electrophysiologic studies have rarely been performed. Methods: We describe a case of acute myopathy at onset of SARS-CoV-2 infection. Results: A 73-year-old woman, with post-infarct ischemic heart disease in her medical history, presented with progressive weakness in the lower limbs and pain, without fever. On admission, neurological examination showed proximal tetraparesis, prevalent in the lower limbs, and reflexes were diminished. CK in the serum was to >6000 U/L (normal value 10–145 U/L), hepatic enzymes were elevated (GOT 814 U/L, n.v.1–31), urin Hb > 1 (n.v. absent).Polymerase chain reaction (PCR) testing for SARS-COV-2 was positive. Chest X-ray showed right lower patchy opacities, but oxygen saturation was 94% on room air. Motor nerve conduction studies (NCS) showed mild sensory polyneuropathy;the needle electromyography (EMG) demonstrated myopathic abnormalities with fibrillation potentials in the lower limbs, rapid recruitment on interference pattern and reduced compound muscle action potential amplitude. The therapy with high dose of steroids induced significative clinical improvement. In two weeks, CK levels almost normalized and the patient recovered the ability to walk with assistance. Conclusions: The severe immune activation known to occur in COVID-19 patients probably plays an important pathophysiological role for onset of rhabdomyolysis, but further studies are needed to elucidate the mechanisms, appropriate treatment, and long-term clinical outcomes of muscular manifestations associated with COVID-19 disease. [Formula presented]
ABSTRACT
People with cryoglobulinaemic vasculitis (CV) have an increased risk of infections, attributed to different causes: impairment of the immune system due to the disease itself, comorbidities, and immunosuppressive therapy. Therefore, these patients may be at high risk for a more severe course of COVID-19, including hospitalisation and death. Concerns about efficacy, immunogenicity and safety of vaccines, as well as doubts, not yet fully clarified in patients with systemic autoimmune diseases, represent other important factors for a low vaccination rate in people with (CV). Indeed, providing an expert position on the issues related to SARS-CoV-2 vaccination in patients suffering from CV is of critical relevance in order to help both patients and clinicians who are treating them in making the best choice in each case. A multidisciplinary task force of the Italian Group for the Study of Cryoglobulinaemia (GISC) was convened, and through a Delphi technique produced provisional recommendations regarding SARS-CoV-2 vaccination in cryoglobulinaemic patients.
ABSTRACT
Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg;95% CI, 1.87-16.22;P = 0.013) and the PaO2/FiO(2) ratio (median difference, 23.17;95% CI, 3.46-42.88;P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32;95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO2/FiO(2) ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only.
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Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 103 per mm3 ;IQR, 0.58-1.00 x 103 per mm3), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mug/m;IQR, 5.0-23.8 mug/m) were present. Median tidal volume was 6.7 mL/kg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH2O (IQR, 10-14 cmH2O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median follow-up of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P = 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors. Trial registration: ClinicalTrials.gov identifier: NCT04318366.
ABSTRACT
People with cryoglobulinaemic vasculitis (CV) have an increased risk of infections, attributed to different causes: impairment of the immune system due to the disease itself, comorbidities, and immunosuppressive therapy. Therefore, these patients may be at high risk for a more severe course of COVID-19, including hospitalisation and death. Concerns about efficacy, immunogenicity and safety of vaccines, as well as doubts, not yet fully clarified in patients with systemic autoimmune diseases, represent other important factors for a low vaccination rate in people with (CV). Indeed, providing an expert position on the issues related to SARS-CoV-2 vaccination in patients suffering from CV is of critical relevance in order to help both patients and clinicians who are treating them in making the best choice in each case. A multidisciplinary task force of the Italian Group for the Study of Cryoglobulinaemia (GISC) was convened, and through a Delphi technique produced provisional recommendations regarding SARS-CoV-2 vaccination in cryoglobulinaemic patients.
ABSTRACT
At the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak spread from China all around the world, causing thousands of deaths. In Italy, the hardest hit region was Lombardy, with the first reported case on 20 February 2020. San Raffaele Scientific Institute - a large tertiary hospital and research centre in Milan, Italy - was immediately involved in the management of the public health emergency. Since the beginning of the outbreak, the elective surgical activity of the hospital was rapidly reduced and large areas of the hospital were simultaneously reorganised to admit and assist patients with coronavirus disease 2019 (COVID-19). In addition, the hospital became the regional referral hub for cardiovascular emergencies in order to keep ensuring a high level of health care to non-COVID-19 patients in northern Italy. In a few days, a COVID-19 emergency department was created, improving the general ward capacity to a total number of 279 beds dedicated to patients with COVID-19. Moreover, the number of intensive care unit (ICU) beds was increased from 28 to 72 (54 of them dedicated to patients with COVID-19, and 18 to cardiology and cardiac surgery hub emergencies), both converting pre-existing areas and creating new high technology spaces. All the involved health care personnel were rapidly trained to use personal protection equipment and to manage this particular category of patients both in general wards and ICUs. Furthermore, besides clinical activities, continuously important research projects were carried out in order to find new strategies and more effective therapies to better face an unprecedented health emergency in Italy.
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Objective: Describe characteristics, daily care and outcomes of patients with coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design: Case series of 73 patients. Setting: Large tertiary hospital in Milan. Participants: Mechanically ventilated patients with confirmed COVID-19 admitted to the intensive care unit (ICU) between 20 February and 2 April 2020. Main outcome measures: Demographic and daily clinical data were collected to identify predictors of early mortality. Results: Of the 73 patients included in the study, most were male (83.6%), the median age was 61 years (interquartile range [IQR], 54-69 years), and hypertension affected 52.9% of patients. Lymphocytopenia (median, 0.77 x 10(3) per mm(3);IQR, 0.58-1.00 x 10(3) per mm(3)), hyperinflammation with C-reactive protein (median, 184.5 mg/dL;IQR, 108.2-269.1 mg/dL) and pro-coagulant status with D-dimer (median, 10.1 mu g/m;IQR, 5.0-23.8 mu g/m) were present. Median tidal volume was 6.7 mUkg (IQR, 6.0-7.5 mL/kg), and median positive end-expiratory pressure was 12 cmH(2)O (IQR, 10-14 cmH(2)O). In the first 3 days, prone positioning (12-16 h) was used in 63.8% of patients and extracorporeal membrane oxygenation in five patients (6.8%). After a median followup of 19.0 days (IQR, 15.0-27.0 days), 17 patients (23.3%) had died, 23 (31.5%) had been discharged from the ICU, and 33 (45.2%) were receiving invasive mechanical ventilation in the ICU. Older age (odds ratio [OR], 1.12;95% CI, 1.04-1.22;P= 0.004) and hypertension (OR, 6.15;95% CI, 1.75-29.11;P = 0.009) were associated with mortality, while early improvement in arterial partial pressure of oxygen (Pao(2) ) to fraction of inspired oxygen (Fio(2)) ratio was associated with being discharged alive from the ICU (P = 0.002 for interaction). Conclusions: Despite multiple advanced critical care interventions, COVID-19 ARDS was associated with prolonged ventilation and high short term mortality. Older age and pre-admission hypertension were key mortality risk factors.