A Cura di
Francesca Gallini, Camilla Gizzi, Francesca Fulceri, Maria Luisa Scattoni, Monica Fumagalli
Con la Collaborazione
Gruppo di Studio SIN di Neurologia e Follow up | Monica Fumagalli
Gruppo di Studio SIN di Auxologia Perinatale | Luigi Gagliardi
Gruppo di Studio SIN di Nutrizione e Gastroenterologia neonatale | Francesco Cresi
Gruppo di Studio SIN di Pneumologia neonatale | Camilla Gizzi
Istituto Superiore di Sanità | Maria Luisa Scattoni, Francesca Fulceri, Martina Micai, Angela Caruso
Società Italiana di Neuropsichiatria dell’Infanzia e dell’Adolescenza | Antonella Costantino
A cura di: Fabio Mosca, Beatrice Letizia Crippa, Marta Colombo, Camilla Menis
Con il contributo di:
Monica Fumagalli, Maria Lorella Giannì, Gabriella Araimo, Nicola Pesenti
Con la partecipazione dell’Osservatorio SIRP:
Generoso Andria, Raffaele Badolato, Giulia Baresi, Manuela Cortesi, Laura Dotta,
Luisa Giannone, Giuliana Giardino, Alessia Morreale, Giusy Ranucci, Stefano Rossi,
Giulio Tessarin, Lara Valeri, Fiammetta Zunica
con la collaborazione della Commissione Ricerca della SIN: Virgilio Carnielli
A cura di: Fabio Mosca, Beatrice Letizia Crippa, Marta Colombo, Camilla Menis
Con il contributo di: Monica Fumagalli, Maria Lorella Giannì, Gabriella Araimo, Nicola Pesenti
Con la partecipazione dell’Osservatorio SIRP: Generoso Andria, Raffaele Badolato, Giulia Baresi, Marta Colombo, Manuela Cortesi, Beatrice Letizia Crippa, Laura Dotta, Luisa Giannone, Giuliana Giardino, Camilla Menis, Giusy Ranucci, Stefano Rossi, Giulio Tessarin,Lara Valeri, Fiammetta Zunica
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Position Paper ad interim SIGO-AOGOI-AGUI-AGITE – 2 gennaio 2021
Condiviso da SIN – SIP – SIMP – SIERR – FNOPO
COLLABORAZIONE SIN- SIP-SIMP-SIGO-AGOI-SIMIT
Objective: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients.
Method: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients and analysed their potential impacts on COVID-19 outcomes.
Results: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe diseases, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+ and CD4+ T cells at admission.
Conclusion: Our study shows that the total, CD8+ and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.
Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.
Various comorbidities represent risk factors for severe coronavirus disease 2019 (COVID-19). The impact of smoking on COVID-19 severity has been previously reported in several meta-analyses limited by small sample sizes and poor methodology. We aimed to rigorously and definitively quantify the effects of smoking on COVID-19 severity. MEDLINE, Embase, CENTRAL, and Web of Science were searched between 1 December 2019 and 2 June 2020. Studies reporting smoking status of hospitalized patients with different severities of disease and/or at least one clinical endpoint of interest (disease progression, intensive care unit admission, need for mechanical ventilation, and mortality) were included. Data were pooled using a random-effects model. This study was registered on PROSPERO: CRD42020180920. We analyzed 47 eligible studies reporting on 32 849 hospitalized COVID-19 patients, with 8417 (25.6%) reporting a smoking history, comprising 1501 current smokers, 5676 former smokers, and 1240 unspecified smokers. Current smokers had an increased risk of severe COVID-19 (risk ratios [RR]: 1.80; 95% confidence interval [CI]: 1.14-2.85; P = .012), and severe or critical COVID-19 (RR: 1.98; CI: 1.16-3.38; P = .012). Patients with a smoking history had a significantly increased risk of severe COVID-19 (RR: 1.31; CI: 1.12-1.54; P = .001), severe or critical COVID-19 (RR: 1.35; CI: 1.19-1.53; P < .0001), in-hospital mortality (RR: 1.26; CI: 1.20-1.32; P < .0001), disease progression (RR: 2.18; CI: 1.06-4.49; P = .035), and need for mechanical ventilation (RR: 1.20; CI: 1.01-1.42; P = .043). Patients with any smoking history are vulnerable to severe COVID-19 and worse in-hospital outcomes. In the absence of current targeted therapies, preventative, and supportive strategies to reduce morbidity and mortality in current and former smokers are crucial.
Pediatric patients are excluded from most COVID-19 therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials with enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.
Background: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
Methods: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.
Results: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.
Conclusions: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.
Italy was one of the most affected nations by coronavirus disease 2019 outside China. The infections, initially limited to Northern Italy, spread to all other Italian regions. This study aims to provide a snapshot of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemiology based on a single-center laboratory experience in Rome. The study retrospectively included 6565 subjects tested for SARS-CoV-2 at the Laboratory of Virology of Sapienza University Hospital in Rome from 6 March to 4 May. A total of 9995 clinical specimens were analyzed, including nasopharyngeal swabs, bronchoalveolar lavage fluids, gargle lavages, stools, pleural fluids, and cerebrospinal fluids. Positivity to SARS-CoV-2 was detected in 8% (527/6565) of individuals, increased with age, and was higher in male patients (P < .001). The number of new confirmed cases reached a peak on 18 March and then decreased. The virus was detected in respiratory samples, in stool and in pleural fluids, while none of gargle lavage or cerebrospinal fluid samples gave a positive result. This analysis allowed to gather comprehensive information on SARS-CoV-2 epidemiology in our area, highlighting positivity variations over time and in different sex and age group and the need for a continuous surveillance of the infection, mostly because the pandemic evolution remains unknown.
Italy was one of the most affected nations by coronavirus disease 2019 outside China. The infections, initially limited to Northern Italy, spread to all other Italian regions. This study aims to provide a snapshot of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemiology based on a single-center laboratory experience in Rome. The study retrospectively included 6565 subjects tested for SARS-CoV-2 at the Laboratory of Virology of Sapienza University Hospital in Rome from 6 March to 4 May. A total of 9995 clinical specimens were analyzed, including nasopharyngeal swabs, bronchoalveolar lavage fluids, gargle lavages, stools, pleural fluids, and cerebrospinal fluids. Positivity to SARS-CoV-2 was detected in 8% (527/6565) of individuals, increased with age, and was higher in male patients (P < .001). The number of new confirmed cases reached a peak on 18 March and then decreased. The virus was detected in respiratory samples, in stool and in pleural fluids, while none of gargle lavage or cerebrospinal fluid samples gave a positive result. This analysis allowed to gather comprehensive information on SARS-CoV-2 epidemiology in our area, highlighting positivity variations over time and in different sex and age group and the need for a continuous surveillance of the infection, mostly because the pandemic evolution remains unknown.
Objective: This observational study aimed to determine optimal timing of interleukin-6 receptor inhibitors (IL6ri) administration for Coronavirus disease 2019 (Covid-19).
Methods: Patients with Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into 2 groups: those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation.
Results: 255 Covid-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.24; 95% confidence interval [CI] 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 1.43; 95% CI 1.06 – 1.93) and were less likely to be intubated (HR: 0.43; 95% CI: 0.24-0.79).
Conclusions: IL6ri administration prior to greater than 45% FiO2 requirement was associated with improved Covid-19 outcomes. This can guide clinical management pending results from randomized control trials.
Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Design: Living systematic review and network meta-analysis.
Data sources: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.
Study selection: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
Methods: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
Results: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events
Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 “mortality rate”, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.