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Background: Severe adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease., Methods: A retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children's Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated., Results: 699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963-0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power., Conclusion: In this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value., (© 2024. The Author(s).)

Background: Infective endocarditis (IE) is a rare cardiovascular complication in patients with coronavirus disease 2019 (COVID-19). IE after COVID-19 can also be complicated by acute respiratory distress syndrome (ARDS); however, the guidelines for the treatment of such cases are not clear. Here, we report a case of perioperative management of post-COVID-19 IE with ARDS using veno-venous extracorporeal membrane oxygenation (V-V ECMO)., Case Presentation: The patient was a 40-year-old woman who was admitted on day 18 of COVID-19 onset and was administered oxygen therapy, remdesivir, and dexamethasone. The patient's condition improved; however, on day 24 of hospitalization, the patient developed hypoxemia and was admitted to the intensive care unit (ICU) due to respiratory failure. Blood culture revealed Corynebacterium striatum, and transesophageal echocardiography revealed vegetation on the aortic and mitral valves. Valve destruction was mild, and the cause of respiratory failure was thought to be ARDS. Despite continued antimicrobial therapy, ARDS did not improve the patient's condition, and valve destruction progressed; therefore, surgical treatment was scheduled on day 13 of ICU admission. After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient returned to the ICU with transition to V-V ECMO, and her circulation remained stable. The patient was weaned off V-V ECMO on postoperative day 33 and discharged from the ICU on postoperative day 47., Conclusions: ARDS may occur in patients with IE after COVID-19. Owing to concerns about further exacerbation of pulmonary damage, the timing of surgery should be comprehensively considered. Preoperatively, clinicians should discuss perioperative ECMO introduction and configuration., (© 2024. The Author(s).)

One of the most relevant challenges for healthcare providers during the COVID- 19 pandemic has been assuring the continuity of care to patients with complex health needs such as people living with rare diseases (RDs). The COVID-19 pandemic accelerated the healthcare sector's digital transformation agenda. The delivery of telemedicine services instead of many face-to-face procedures has been expanded and, many healthcare services not directly related to COVID-19 treatments shifted online remotely. Many hospitals, specialist centres, patients and families started to use telemedicine because they were forced to. This trend could directly represent a good practice on how care services could be organized and continuity of care could be ensured for patients. If done properly, it could boast improved patient outcomes and become a post COVID-19 major shift in the care paradigm. There is a fragmented stakeholders spectrum, as many questions arise on: how is e-health interacting with 'traditional' healthcare providers; about the role of the European Reference Networks (ERNs); if remote care can retain a human touch and stay patient centric. The manuscript is one of the results of the European Brain Council (EBC) Value of Treatment research project on rare brain disorders focusing on progressive ataxias, dystonia and phenylketonuria with the support of Academic Partners and in collaboration with European Reference Networks (ERNs) experts, applying empirical evidence from different European countries. The main purpose of this work is to investigate the impact of the COVID-19 pandemic on the continuity of care for ataxias, dystonia and phenylketonuria (PKU) in Europe. The analysis carried out makes it possible to highlight the critical points encountered and to learn from the best experiences. Here, we propose a scoping review that investigates this topic, focusing on continuity of care and novel methods (e.g., digital approaches) used to reduce the care disruption. This scoping review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) standards. This work showed that the implementation of telemedicine services was the main measure that healthcare providers (HCPs) put in place and adopted for mitigating the effects of disruption or discontinuity of the healthcare services of people with rare neurological diseases and with neurometabolic disorders in Europe., (© 2024. The Author(s).)

Background: Post-infectious bronchiolitis obliterans (PIBO) is the most common sequelae in children with adenovirus pneumonia (ADVP). However, there are few studies on the risk factors for PIBO occurrence. This study aims to investigate the risk factors for PIBO in pediatric patients with severe ADVP, especially after invasive mechanical ventilation (IMV), as well as to build a nomogram prediction model., Methods: The clinical data, laboratory and imaging features, and treatment of 863 children with ADVP under 3 years old who were admitted to our hospital from January to December 2019 were retrospectively analyzed. Among them, 66 children with severe ADVP received IMV treatment. The situation and the influencing factors of PIBO in children with severe ADVP were explored, and a nomogram prediction model was constructed., Results: Among the 863 cases of ADVP, 46 cases (5.33%) developed PIBO. Duration of fever, IMV, complications, and neutrophil percentage were independent risk factors for PIBO in children with ADVP. Among the 66 patients with ADVP who underwent IMV, 33 patients (50.0%) developed PIBO. Gender, duration of fever, adenovirus (ADV) load, and mixed fungal coinfections were independent risk factors for PIBO. In the nomogram prediction model analysis, the area under the curve (AUC) was 0.857; in addition, Hosmer‒Lemeshow (H-L) detection reflected good alignment (χ2 = 68.75, P < 0.01)., Conclusions: A nomogram prediction model, which can be utilized to predict PIBO occurrence in pediatric patients with ADVP after IMV at an early time period, was successfully built., (© 2023. The Author(s).)

Background: Severe adenovirus (Adv.) pneumonia can cause significant mortality in young children. There has been no worldwide consensus on the impact of extracorporeal membrane oxygenation (ECMO) in immunocompetent children with severe Adv. pneumonia. This study aimed to assess the impact of ECMO in immunocompetent children with severe Adv. pneumonia., Methods: This study evaluated the medical records of 168 hospitalized children with severe Adv. pneumonia at the Guangzhou Women and Children's Medical Center between 2019 and 2020.Nineteen patients in the ECMO group and 149 patients in the non-ECMO group were enrolled., Results: Between these two groups, there were no differences in host factors such as sex, age (all P > 0.05). Significant differences were observed in shortness of breath/increased work of breathing; cyanosis; seizures; tachycardia; the partial pressure of oxygen in arterial blood (PO 2 ); the ratio of PaO 2 to the fraction concentration of oxygen in inspired air (FiO 2 ; P/F); white blood cell, lymphocyte, monocytes, lactate dehydrogenase (LDH), serum albumin, and procalcitonin levels; and, pulmonary consolidation (all P < 0.05). There were significant differences in the parameters of mechanical ventilation (MV) therapy and complications such as respiratory failure, acute respiratory distress syndrome, septic shock, length of hospitalization, and death (all P < 0.05). The maximum axillary temperatures, respiratory rates, heart rates and LDH levels after receiving ECMO were significantly lower than those before ECMO (all P < 0.05). Additionally, SPO 2 , PO 2 , and P/F were significantly higher than those before ECMO (all P < 0.05). In MV therapy, FiO 2 , PIP, and PEEP were significantly lower than those before ECMO (all P < 0.05)., Conclusions: In our study, the clinical conditions of the patients in the ECMO group were much more severe than those in the non-ECMO group. Our study showed that ECMO might be beneficial for the patients with severe Adv. pneumonia., (© 2023. The Author(s).)

Background: A radiological finding of a cavitary pulmonary lesion in a patient acutely infected with severe acute respiratory syndrome coronavirus-2 early during the coronavirus disease 2019 pandemic created a diagnostic and treatment dilemma, as invasive procedures with bronchoscopy and percutaneous needle lung biopsy posed an infection hazard to healthcare workers due to the associated risk of viral aerosolization. Available guidelines recommended delay of non-emergent procedures, but timely proceeding with those deemed urgent provided appropriate personal protective equipment and negative pressure isolation were available and exposure risk was not excessive. Thoughtful consideration by clinicians was required to avoid delay in diagnosis of a potential new malignancy and prevent unnecessary healthcare worker exposure to the virus. Additionally, acute severe acute respiratory syndrome coronavirus-2 infection in patients with malignancy complicated timing of oncologic treatment., Case Presentation: A 26-year-old otherwise healthy Caucasian male initially presented with an enlarging right upper lobe cavitary pulmonary lesion despite antimicrobial therapy. During his hospitalization and evaluation, the patient was found to be acutely infected with severe acute respiratory syndrome coronavirus-2 without hypoxia or viral pneumonia. Bronchoscopy was deemed too high risk for viral aerosolization and healthcare worker infection. He underwent computed-tomography-guided percutaneous needle biopsy of the lesion by interventional radiology while on mechanical ventilation after elective intubation by anesthesiology. Biopsy revealed classic Hodgkin lymphoma consistent with primary pulmonary Hodgkin lymphoma. After collaboration with oncology, his treatment with combined chemotherapy and immunotherapy was delayed for 3 weeks following diagnosis to allow for viral clearance., Conclusion: A careful multidisciplinary strategy is required to expeditiously diagnose and treat aggressive cancers of the respiratory tract in patients acutely infected with severe acute respiratory syndrome coronavirus-2 while observing practices to prevent healthcare worker infection during the ongoing coronavirus disease 2019 pandemic., (© 2023. The Author(s).)

Background: Severe fatal human adenoviral (HAdV) pneumonia is associated with significant mortality and no effective drug is available for clinical therapy. We evaluated the association and safety of high titer neutralizing antibodies (NAbs) plasma in pediatric patients with severe fatal HAdV pneumonia., Methods: A retrospective cohort study was performed between January 2016 to June 2021 in pediatric intensive care unit. Pediatric patients with severe fatal HAdV pneumonia were included and divided into plasma group (conventional treatment plus high titer NAbs plasma treatment) and control group (conventional treatment alone). The primary outcome was mortality in hospital. Secondary outcomes were the duration of fever after adenovirus genotype determined, duration of invasive mechanical ventilation, length of hospital stay. T-test, Mann-Whitney U-test, chi-square test, univariable and multivariable logistic regression analysis, Kaplan-Meier method and log-rank test were adopted to compare differences between two groups., Results: A total of 59 pediatric patients with severe fatal HAdV pneumonia were enrolled. They were divided into plasma group (n = 33) and control group (n = 26). The mortality in hospital was 28.8% (17/ 59). Significantly fewer patients progressed to death in plasma group than control group (18.2% vs 42.3%, p = 0.042). Sequential organ failure assessment (SOFA) score, oxygen index (OI) and high titer NAbs plasma treatment were included in multivariable logistic regression analysis for mortality risk factors. Consequentially, SOFA score (Hazard Ratio [HR] 7.686, 95% Confidence Interval [CI] 1.735-34.054, p = 0.007) and without high titer NAbs plasma treatment (HR 4.298, 95%CI 1.030-17.934, p = 0.045) were significantly associated with mortality. In addition, high titer NAbs plasma treatment were associated with faster temperature recovering in survivors (p = 0.031). No serious adverse effects occurred., Conclusions: Administration of high titer NAbs plasma were associated with a lower hazard for mortality in pediatric patients with severe fatal HAdV pneumonia. For survivors, high titer NAbs plasma treatment shorten the duration of fever., (© 2022. The Author(s).)

Background: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients., Methods: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate., Results: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO 2 /FiO 2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO 2 /FiO 2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes., Conclusions: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia., (© 2022. The Author(s).)

Background: The need for invasive mechanical ventilation (IMV) is linked to significant morbidity and mortality in patients with influenza-related pneumonia (Flu-p). We aimed to develop an assessment tool to predict IMV among Flu-p patients within 14 days of admission., Methods: In total, 1107 Flu-p patients from five teaching hospitals were retrospectively enrolled from January 2012 to December 2019, including 895 patients in the derivation cohort and 212 patients in the validation cohort. The predictive model was established based on independent risk factors for IMV in the Flu-p patients from the derivation cohort., Results: Overall, 10.6% (117/1107) of patients underwent IMV within 14 days of admission. Multivariate regression analyses revealed that the following factors were associated with IMV: early neuraminidase inhibitor use (- 3 points), lymphocytes < 0.8 × 10 9 /L (1 point), multi-lobar infiltrates (1 point), systemic corticosteroid use (1 point), age ≥ 65 years old (1 points), PaO 2 /FiO 2  < 300 mmHg (2 points), respiratory rate ≥ 30 breaths/min (3 points), and arterial PH < 7.35 (4 points). A total score of five points was used to identify patients at risk of IMV. This model had a sensitivity of 85.5%, a specificity of 88.8%, and exhibited better predictive performance than the ROX index (AUROC = 0.909 vs. 0.594, p = 0.004), modified ROX index (AUROC = 0.909 vs. 0.633, p = 0.012), and HACOR scale (AUROC = 0.909 vs. 0.622, p < 0.001) using the validation cohort., Conclusions: Flu-IV score is a valuable prediction rule for 14-day IMV rates in Flu-p patients. However, it should be validated in a prospective study before implementation., (© 2022. The Author(s).)

Background: Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia., Methods: This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups., Results: Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05)., Conclusion: For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications., (© 2021. The Author(s).)

Background: The aim of the study is to estimate the prevalence of atelectasis assessed with computer tomography (CT) in SARS-CoV-2 pneumonia and the relationship between the amount of atelectasis with oxygenation impairment, Intensive Care Unit admission rate and the length of in-hospital stay., Patients and Methods: Two-hundred thirty-seven patients admitted to the hospital with SARS-CoV-2 pneumonia diagnosed by clinical, radiology and molecular tests in the nasopharyngeal swab who underwent a chest computed tomography because of a respiratory worsening from Apr 1 to Apr 30, 2020 were included in the study. Patients were divided into three groups depending on the presence and amount of atelectasis at the computed tomography: no atelectasis, small atelectasis (< 5% of the estimated lung volume) or large atelectasis (> 5% of the estimated lung volume). In all patients, clinical severity, oxygen-therapy need, Intensive Care Unit admission rate, the length of in-hospital stay and in-hospital mortality data were collected., Results: Thirty patients (19%) showed small atelectasis while eight patients (5%) showed large atelectasis. One hundred and seventeen patients (76%) did not show atelectasis. Patients with large atelectasis compared to patients with small atelectasis had lower SatO 2 /FiO 2 (182 vs 411 respectively, p = 0.01), needed more days of oxygen therapy (20 vs 5 days respectively, p = 0,02), more frequently Intensive Care Unit admission (75% vs 7% respectively, p < 0.01) and a longer period of hospitalization (40 vs 14 days respectively p < 0.01)., Conclusion: In patients with SARS-CoV-2 pneumonia, atelectasis might appear in up to 24% of patients and the presence of larger amount of atelectasis is associated with worse oxygenation and clinical outcome., (© 2021. The Author(s).)

Background: SARS-CoV-2 infection in children is often non severe and in the majority of cases does not require long term hospitalization, nevertheless it is burdened with social issues and managing difficulties. To our knowledge there is no literature on telephonic follow up in pediatric patients with positive PCR for SARS-CoV-2 on rhino-pharyngeal swab after discharge. The aim of the study is to describe our experience in a telephonic follow up which can allow early and safe discharge from hospital while keeping the patients under close clinical monitoring., Materials and Methods: Sixty-five children were admitted for SARS-CoV-2 infection at Bambino Gesù Pediatric Hospital COVID Center from 16th March to 3rd July. We monitored through a telephonic follow-up, using a specific survey, the patients discharged still presenting a positive PCR for SARS-CoV-2. We checked if any symptoms occurred at home until recovery, defined as two consecutive negative PCR for SARS-CoV-2 on rhino-pharyngeal swabs., Results: During the follow up 7 patients had mild and self-limited symptoms related to SARS-CoV-2 infection, while 2 patients were re-hospitalized. One patient had Multisystem Inflammatory Syndrome in Children (MIS-C), the other patient had an increase in troponin and D-dimers. We also monitored the average time of viral shedding, resulting in a median duration of 28 days., Conclusion: Our experience describes the daily telephonic follow up as safe in pediatric patients discharged with positive PCR. As a matter of fact it could avoid long term hospitalization and allow to promptly re-hospitalize children with major complications such as MIS-C.

Background: Coronavirus disease highly contagious, is prevalent in all age and sex groups infecting the respiratory system. The present study seeks to investigate the epidemiology and effective factors in mortality of patients with COVID-19 in Ardabil province, northwestern Iran., Methods: In a retrospective study, the hospitalized patients with laboratory-diagnosed COVID-19 between February to August 2020 were enrolled. The data registration portal was designated according to Iranian Ministry of Health and Medical Education guidelines. In this portal, demographic information, clinical presentation, laboratory and imaging data were registered for patients in all hospitals in the same format. The Hosmer-Lemeshow strategy was used for variable selection in a multiple model., Results: Of the patients involved 2812(50.3%) were male and 150 (2.7%) had contact with a confirmed case of COVID-19 in the last 14 days. Pre-existing comorbidity was reported in 1310 (23.4%) patients. Of all patients, 477(8.5%) died due to COVID-19. the result of the multiple logistic regression model indicated that after adjusting for other factors, higher age (OR = 3.11), fever or chills (OR = 1.61), shortness of breath (OR = 1.82), fatigue (OR = 0.71), headache (OR = 0.64), runny nose (OR = 1.54), Skeletal muscle pain (OR = 1.53), hospitalization (OR = 5.66), and hospitalization in ICU (OR = 5.12) were associated with death., Conclusions: Hospitalization had the strongest effect on mortality followed by hospitalization in ICU, and higher age. This study showed that having some extra-pulmonary symptoms in contrast with pulmonary symptoms can predict as good prognostic factors.

Background: Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation., Methods: Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020-31/07/2020 were included. Epidemiological, clinical, and analytical data was collected., Results: A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8-37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473-11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578-0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340-22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840-31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery., Conclusions: Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.

Background: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm., Method: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26., Results: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation., Conclusion: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis., Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared., Results: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation., Conclusion: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

The COVID-19 pandemic is spreading worldwide. Italy emerged early on as the country with the largest outbreak outside Asia. The outbreak in Northern Italy demonstrates that it is fundamental to contain the virus' spread at a very early stage of diffusion. At later stages, no containment measure, even if strict, can prevent the saturation of the hospitals and of the intensive care units in any country. Here we show that it is possible to predict when the intensive care units will saturate, within a few days from the beginning of the exponential growth of COVID-19 intensive care patients. Using early counts of intensive care patients, we predict the saturation for Lombardy, Italy. We also assess short-term and long-term lockdown effects on intensive care units and number of deaths. Governments should use the Italian outbreak as a precedent and implement appropriate containment measures to prevent the saturation of their intensive care units and protect their population, also, and above all, in anticipation of a possible second exponential spread of infections.

Background: The recurrence of positive SARS-CoV-2 nucleic acid test results in patients with COVID-19 is becoming more important and warrants more attention., Case Presentation: This study reports 2 cases, a child with mild COVID-19 and an adult female with moderate COVID-19, who were discharged after three consecutive negative nucleic acid tests and were later readmitted to the hospital for recurrence of SARS-CoV-2 nucleic acid positivity. By tracking the patients' symptoms, serum antibodies, and imaging manifestations after readmission, we found that they showed a trend of gradual improvement and recovery throughout treatment. They were cured without additional treatment, with the appearance of antibodies and the recovery of immune functions., Conclusions: It is deemed extremely necessary to improve the discharge standard of care. At the same time, nucleic acid detection is recommended to increase the dynamic monitoring of serum antibodies and imaging, strengthen the management of discharged patients, and appropriately extend the home or centralized isolation time.

Background: The speed and reach of the COVID-19 pandemic has created special scenarios to be considered, such as those in where patients who meet criteria for hospitalization due to moderate/severe disease cannot be hospitalized due to economic constraints and saturation of national health systems. The aim of this report is to present an unusual case of a severe COVID-19 patient managed at home in a developing country, and to discuss some of the available guidelines and potential therapeutic options for this type of cases., Case Presentation: A 60-year-old female seeking medical attention through teleconsultation presents with profound dyspnea, oppressive chest pain, fatigue, episodic hallucinations, and difficulty sleeping, for what she originally sought medical attention at an ER but could not be admitted due to saturation of the health system. A positive PCR test for COVID-19, and a CT scan of the chest showing bilateral consolidations with ground-glass opacities confirmed the diagnosis. The patient was managed at home, with corticosteroids, nitazoxanide and a single dose of 40 mg of subcutaneous enoxaparin. Colchicine was added at the third day of treatment. Standard oxygen therapy through nasal cannula was also recommended. Daily follow-ups were established to monitor for signs of clinical improvement. Two weeks later from the initial consultation the patient presents marked improvement in her symptoms, as well as in her CT scan, which prompted in discontinuation of the medications and the oxygen therapy., Conclusions: There are several limitations in this report regarding the clinical data and the management, but such limitations do also reflect the state of emergency and the chaos that resides in the health care systems of developing nations. For the ambulatory care of COVID-19 patients, several aspects of disease management may differ from current guidelines and basic requirements may represent a huge challenge to cover. Further research is needed to assist physicians in the daily clinical decision making, to optimize patient outcomes, and to reduce the probability of adverse scenarios of patients with COVID-19 managed in the ambulatory setting.

Background: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted., Methods: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information., Result: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2-9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5-19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time., Conclusion: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay., Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100., Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays., Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19., Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels., Results: ICU patients showed a marked increase in neutrophils (1.24 × 10 5  ml - 1 , 0.85-2.07), lower lymphocyte (0.97 × 10 5  ml - 1 , 0.024-0.34) and macrophages fractions (0.43 × 10 5  ml - 1 , 0.34-1.62) compared to IMW patients (0.095 × 10 5  ml - 1 , 0.05-0.73; 0.47 × 10 5  ml - 1 , 0.28-1.01 and 2.14 × 10 5  ml - 1 , 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05)., Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.

Background: Coronavirus disease 2019 (COVID-19) is an emerging viral disease. Here, we report the clinical features, management, and short-term outcomes of COVID-19 patients in Wenzhou, China, an area outside Wuhan., Methods: Patients admitted to the Infectious Diseases Department of Ruian People's Hospital in Wenzhou, from January 21 to February 7, 2020, were recruited. Medical data on epidemiological history, demographics, clinical characteristics, laboratory tests, chest computerized tomography (CT) examination, treatment, and short-term outcomes were retrospectively reviewed. Blood biochemistry and routine tests were examined using standard methods and automatic machines. CT examination was performed several times during hospitalization as necessary., Results: A total of 67 confirmed COVID-19 cases were diagnosed; 64 (95.4%) were common cases and three (4.5%) were severe cases. The most common symptoms at admission were fever (86.6%), cough (77.6%), productive cough (52.2%), chest distress (17.9%), and sore throat (11.9%), followed by diarrhea (7.4%), headache (7.4%), shortness of breath (6.0%), dizziness (4.5%), muscular soreness (4.5%), and running nose (4.5%). Thirty patients (47.8%) had increased C-reactive protein levels. The CT radiographs at admission showed abnormal findings in 54 (80.6%) patients. The patients were treated mainly by oxygen therapy and antiviral drugs. By March 3, 2020, all 67 patients completely recovered and had negative nucleic acid tests. The patients were discharged from the hospital and transferred to a medical observation isolation center for further observation., Conclusion: Cases of COVID-19 in Wenzhou are milder and have a better prognosis, compared to those in Wuhan. Timely and appropriate screening, diagnosis, and treatment are the key to achieve good outcomes.

Background: Although symptoms and signs of COVID-19 (Coronavirus disease 2019) in children are milder than adults, there are reports of more severe cases which were defined as pediatric inflammatory multisystem syndrome (PIMS). The purpose of this report was to describe the possible association between COVID-19 and PIMS in children., Methods: From 28 March to 24 June 2020, 10 febrile children were admitted with COVID-19 infection showing characteristics of PIMS in Buali tertiary hospital of Sari, in Mazandaran province, northern Iran. Demographic and clinical characteristics, laboratory and imaging findings, and therapeutic modalities were recorded and analyzed., Results: The mean age of the patients was 5.37 ± 3.9 years (13 months to 12 years). Six of them were boys. Kawasaki disease, myocarditis, toxic shock syndrome, appendicitis, sepsis, urosepsis, prolonged febrile seizure, acute hemorrhagic edema of infancy, and COVID-19-related pneumonia were their first presentation. All of them had increased C-reactive protein levels, and most of them had elevated erythrocyte sedimentation rate, lymphopenia, anemia, and hypoalbuminemia. Three of them had thrombocytopenia(PLT < 10 6 ). Six of them were serologically or polymerase chain reaction positive for COVID-19, and 4 of them were diagnosed as COVID-19 just by chest computed tomography scan. Most of the patients improved without a residual sequel, except one who died with multiorgan failure and another case was discharged with a giant coronary aneurysm., Conclusions: Children with COVID-19 may present symptoms similar to Kawasaki disease and inflammatory syndromes. PIMS should be considered in children with fever, rash, seizure, cough, tachypnea, and gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain.

Genomic studies of patients with COVID-19, or exposed to it, are underway to delineate host factors associated with variability in susceptibility, infectivity, and disease severity. Here, we highlight the ethical implications-both potential benefits and harms-of genomics for clinical practice and public health in the era of COVID-19.

Background: Covid-19 is causing a pandemic and forces physicians to restructure their work. We want to share our experience in the outpatient management of potentially-infected patients with special consideration of altered national test strategies during the crisis., Methods: We analysed patients with respiratory symptoms reporting to our three rural general practitioner (GP) offices in North Rhine-Westphalia, Germany, from 27.01-20.04.2020 (n = 489 from a total of 6090 patients). A history of symptoms was taken at the doorstep following a specific questionnaire. Patients with respiratory symptoms were examined in a separated isolation area, while the others were allowed to enter the office. We applied the first recommended algorithm of the German Robert Koch Institute (RKI) to test suspected patients and compared our results with an adapted, more liberal version of the RKI, which is currently applied in Germany., Results: Eighty patients (16.36%, mean age: 47.03 years+ - 18.08) were sent to a nasopharyngeal smear. Five patients (6.25%) proved to be positive, four of whom had established risk factors for COVID-19. Overall, the most common symptoms were cough (83.75%), sore throat (71.25%), as well as myalgia and fatigue (66.25%). The most common diagnoses were rhinopharyngitis (37.22%) and acute bronchitis (30.27%). A sore throat was more common in positively-tested patients (80% vs. 12%). Applying the first RKI test strategy yielded 6.25% of positive tests (n = 80), while the more liberal later RKI recommendation would have achieved 1.36% positive tests from 369 patients. No positive test was missed by applying the conservative strategy. None of our employees called in sick during this period, which emphasises the efficacy and safety of our screening methods., Conclusion: A clinical distinction between ordinary respiratory infections and COVID-19 is not possible in a low-prevalence population. Our model to prevent unprotected physical contact, screen patients in front of the office with protective equipment, and examine respiratory infections in separated areas works in the GP setting without overt health risks for employees. Thus, this approach should be used as a GP standard to uphold patient care without major health risks for the personnel. Large multi-centre studies are necessary to work out the most suitable test strategy.

Background: In this study, we aimed to evaluate the impact of the COVID-19 epidemic on the workload and mental health of Iranian medical staff using the General Health Questionnaire (GHQ-12) and NASA -Task Load Index (NASA-TLX) Questionnaire between March and April 2020, respectively., Methods: The present cross-sectional study was conducted from March 5th to April 5th, 2020. To evaluate the workload and mental health of participants NASA-TLX and GHQ-12 online questionnaires were distributed. Data were entered into software SPSS (Version 23) and T-test, ANOVA, Regression methods were used for data analysis., Results: Health workers who encountered COVID- 19 patients, were subjected to more task load compared to those who had no contact with COVID- 19 patients at the workplace (p <  0.001). In terms of the subscale score of NASA-TLX, nurses had more scores in mental pressure, physical pressure, time pressure (temporal), and frustration compared to the other jobs (p <  0.05). Moreover, nurses had significantly more workload compared to the other jobs., Conclusions: Type of job, the shift of work, educational level, and facing COVID-19 affected the score of NASA-TLX. NASA-TLX scores were higher in nursing compared to the scores of other health staff groups. The results of this study indicate that the scores of NASA-TLX and GHQ-12 among staff who had contact with COVID-19 patients were significantly higher than those who did not face COVID-19 patients. We suggested that a comprehensive assistance should be provided to support the well-being of healthcare workers especially nurses and healthcare workers who treated COVID-19 patients.

Objectives: COVID-19 presents challenges to the emergency care system that could lead to emergency department (ED) crowding. The Huddinge site at the Karolinska university hospital (KH) responded through a rapid transformation of inpatient care capacity together with changing working methods in the ED. The aim is to describe the KH response to the COVID-19 crisis, and how ED crowding, and important input, throughput and output factors for ED crowding developed at KH during a 30-day baseline period followed by the first 60 days of the COVID-19 outbreak in Stockholm Region., Methods: Different phases in the development of the crisis were described and identified retrospectively based on major events that changed the conditions for the ED. Results were presented for each phase separately. The outcome ED length of stay (ED LOS) was calculated with mean and 95% confidence intervals. Input, throughput, output and demographic factors were described using distributions, proportions and means. Pearson correlation between ED LOS and emergency ward occupancy by phase was estimated with 95% confidence interval., Results: As new working methods were introduced between phase 2 and 3, ED LOS declined from mean (95% CI) 386 (373-399) minutes to 307 (297-317). Imaging proportion was reduced from 29 to 18% and admission rate increased from 34 to 43%. Correlation (95% CI) between emergency ward occupancy and ED LOS by phase was 0.94 (0.55-0.99)., Conclusions: It is possible to avoid ED crowding, even during extreme and quickly changing conditions by leveraging previously known input, throughput and output factors. One key factor was the change in working methods in the ED with higher competence, less diagnostics and increased focus on rapid clinical admission decisions. Another important factor was the reduction in bed occupancy in emergency wards that enabled a timely admission to inpatient care. A key limitation was the retrospective study design.

There has been mounting evidence of the disproportionate involvement of black, Asian and minority ethnic (BAME) communities by the Covid-19 pandemic. In the UK, this racial disparity was brought to the fore by the fact that the first 11 doctors to die in the UK from Covid-19 were of BAME background. The mortality rate from Covid-19 among people of black African descent in English hospitals has been shown to be 3.5 times higher when compared to rates among white British people. A Public Health England report revealed that Covid-19 was more likely to be diagnosed among black ethnic groups compared to white ethnic groups with the highest mortality occurring among BAME persons and persons living in the more deprived areas. People of BAME background account for 4.5% of the English population and make up 21% of the National Health Service (NHS) workforce. The UK poverty rate among BAME populations is twice as high as for white groups. Also, people of BAME backgrounds are more likely to be engaged in frontline roles. The disproportionate involvement of BAME communities by Covid-19 in the UK illuminates perennial inequalities within the society and reaffirms the strong association between ethnicity, race, socio-economic status and health outcomes. Potential reasons for the observed differences include the overrepresentation of BAME persons in frontline roles, unequal distribution of socio-economic resources, disproportionate risks to BAME staff within the NHS workspace and high ethnic predisposition to certain diseases which have been linked to poorer outcomes with Covid-19. The ethnoracialised differences in health outcomes from Covid-19 in the UK require urgent remedial measures. We provide intersectional approaches to tackle the complex racial disparities which though not entirely new in itself, have been often systematically ignored.

Background: Novel coronavirus disease 2019 (COVID-19) is a global public health emergency. Here, we developed and validated a practical model based on the data from a multi-center cohort in China for early identification and prediction of which patients will be admitted to the intensive care unit (ICU)., Methods: Data of 1087 patients with laboratory-confirmed COVID-19 were collected from 49 sites between January 2 and February 28, 2020, in Sichuan and Wuhan. Patients were randomly categorized into the training and validation cohorts (7:3). The least absolute shrinkage and selection operator and logistic regression analyzes were used to develop the nomogram. The performance of the nomogram was evaluated for the C-index, calibration, discrimination, and clinical usefulness. Further, the nomogram was externally validated in a different cohort., Results: The individualized prediction nomogram included 6 predictors: age, respiratory rate, systolic blood pressure, smoking status, fever, and chronic kidney disease. The model demonstrated a high discriminative ability in the training cohort (C-index = 0.829), which was confirmed in the external validation cohort (C-index = 0.776). In addition, the calibration plots confirmed good concordance for predicting the risk of ICU admission. Decision curve analysis revealed that the prediction nomogram was clinically useful., Conclusion: We established an early prediction model incorporating clinical characteristics that could be quickly obtained on hospital admission, even in community health centers. This model can be conveniently used to predict the individual risk for ICU admission of patients with COVID-19 and optimize the use of limited resources.

Background: The coronavirus pandemic has exerted significant impacts on primary care, causing rapid digital transformation, exacerbating social isolation, and disrupting medical student and General Practice [GP] trainee education. Here we report on a medical student telephone initiative set-up by a final year GP trainee (the equivalent of a family medicine resident), which aimed to support patients at high risk and vulnerable to the Coronavirus Disease of 2019 [Covid-19]. In addition, it was hoped the project would mitigate a digital divide, enable proactive anticipatory planning, and provide an active learning environment to compensate for the pandemic's impact on medical education., Methods: Thirty-three medical students conducted daily telephone conversations with high risk and vulnerable patients as specified by the initial NHSE published lists. They confirmed public health messages, offered details for voluntary support groups, established need for medication delivery, explored levels of digital connectivity, and prompted discussions around end-of-life choices. Students had access to online reflective resources and daily remote debriefing sessions with the GP trainee. A convergent mixed-methods evaluation was subsequently undertaken, using quantitative process and descriptive data and individual qualitative interviews were conducted according to a maximal variation sampling strategy with students, General Practitioners [GPs], and the GP trainee. Inductive thematic analysis was then applied with cross-validation, respondent validation, and rich evidential illustration aiding integrity., Results: Ninety-seven 'high risk' and 781 'vulnerable' calls were made. Individuals were generally aware of public heath information, but some struggled to interpret and apply it within their own lives. Therefore respondents felt students provided additional practical and psychological benefits, particularly with regard to strengthening the links with the community voluntary groups. The project was widely liked by students who reported high levels of skill development and widened awareness, particularly valuing the active learning environment and reflective feedback sessions., Conclusion: This study demonstrates utilization of medical students as wider assets within the primary health care team, with an initiative that enables support for vulnerable patients whilst promoting active medical education. Ongoing integration of students within 'normal' primary health care roles, such as chronic disease or mental health reviews, could provide similar opportunities for supported active and reflective learning.

Objective: We aim to evaluate the immediate impacts of COVID-19 stay-at-home orders on the mental well-being of Bangladeshi adults. We recruited 1404 healthy adults following the Bangladesh government's lockdown announcement. A questionnaire comprising the Warwick Edinburgh Mental Well-being Scale was used to define mental health., Results: The overall mean score for well-being was 42.4, indicating that 51.9% of adults suffered from poor mental health. And within that 48% of males and 57% of females were depressed. The mean scores for government workers, unemployed workers, and business employees were 45.1, 39.6, and 39.5, respectively. Confounding adjustments in multivariable linear regression models revealed that married women, unemployed and business communities, and individuals returning to villages were heavily depressed. Stay-at-home orders had significant repercussions on mental health and created a gender disparity in depression among adults. Suggestions include promoting mental health for women, unemployed, and business individuals. Married women need to be taken into special consideration as their mental well-being is worse. Older people (50 years of age and over) reported a high day-to-day variation in their mental health. These results should be factored in when discussing the mental health of adults and communities to cope with quarantine.

Background: The Hadassah Medical Organization operates two hospitals in Jerusalem. During the COVID-19 pandemic it made an administrative decision to operate one hospital as a COVID-19 treatment hospital (CTH) and to have the second function as a non-COVID-19 treating hospital (NCTH) offering general medical services. The purpose of this study was to assess how this decision affected hospital worker anxiety., Methods: From April 27 to May 1, during the COVID-19 pandemic in Israel, while the country was under lock-down, an electronic questionnaire survey was carried out among hospital workers of the CTH and NCTH. The questionnaire includes personal demographics and attitudes about COVID-19 and assesses present anxiety state using the State-Trait Anxiety Inventory for Adults (STAI-S) validated questionnaire. A STAI-S score of ≥45 was considered to represent clinical anxiety., Results: Completed questionnaires were received from 1570 hospital employees (24%). 33.5% of responders had STAI-S scores ≥45. Multivariable regression analysis showed that being a resident doctor (odds ration [OR] 2.13; 95% CL, 1.41-3.23; P = 0.0003), age ≤ 50 (OR, 2.08; 95% Cl, 1.62-2.67; P < .0001), being a nurse (OR, 1.29; 95% CL, 1.01-1.64; P = 0.039), female gender (OR, 1.63; 95% CL, 1.25-2.13; P = 0.0003) and having risk factors for COVID-19 (OR, 1.51; 95% CL, 1.19-1.91; P = 0.0007), but not hospital workplace (p = 0.08), were associated with the presence of clinical anxiety. 69% of the responders had been tested for COVID-19, but only nine were positive. CTH workers estimated that the likelihood of their already being infected with COVID-19 to be 21.5 ± 24.7% as compared to the 15.3 ± 19.5% estimate of NCTH workers (p = 0.0001). 50% (545/1099) of the CTH workers and 51% (168/330) of the NCTH workers responded that the most important cause of their stress was a fear of infecting their families (p = 0.7)., Conclusions: By multivariable analysis the creation of a NCTH during the COVID-19 pandemic was not found to be associated with a decrease in the number of hospital workers with clinical anxiety. Hospital worker support resources can be focused on the at-risk groups identified in this study.

Background: The acknowledgment of the mental health toll of the COVID-19 epidemic in healthcare workers has increased considerably as the disease evolved into a pandemic status. Indeed, high prevalence rates of depression, sleep disorders, and post-traumatic stress disorder (PTSD) have been reported in Chinese healthcare workers during the epidemic peak. Symptoms of psychological distress are expected to be long-lasting and have a systemic impact on healthcare systems, warranting the need for evidence-based psychological treatments aiming at relieving immediate stress and preventing the onset of psychological disorders in this population. In the current COVID-19 context, internet-based interventions have the potential to circumvent the pitfalls of face-to-face formats and provide the flexibility required to facilitate accessibility to healthcare workers. Online cognitive behavioral therapy (CBT) in particular has proved to be effective in treating and preventing a number of stress-related disorders in populations other than healthcare workers. The aim of our randomized controlled trial study protocol is to evaluate the efficacy of the 'My Health too' CBT program-a program we have developed for healthcare workers facing the pandemic-on immediate perceived stress and on the emergence of psychiatric disorders at 3- and 6-month follow-up compared to an active control group (i.e., bibliotherapy)., Methods: Powered for superiority testing, this six-site open trial involves the random assignment of 120 healthcare workers with stress levels > 16 on the Perceived Stress Scale (PSS-10) to either the 7-session online CBT program or bibliotherapy. The primary outcome is the decrease of PSS-10 scores at 8 weeks. Secondary outcomes include depression, insomnia, and PTSD symptoms; self-reported resilience and rumination; and credibility and satisfaction. Assessments are scheduled at pretreatment, mid-treatment (at 4 weeks), end of active treatment (at 8 weeks), and at 3-month and 6-month follow-up., Discussion: This is the first study assessing the efficacy and the acceptability of a brief online CBT program specifically developed for healthcare workers. Given the potential short- and long-term consequences of the COVID-19 pandemic on healthcare workers' mental health, but also on healthcare systems, our findings can significantly impact clinical practice and management of the ongoing, and probably long-lasting, health crisis., Trial Registration: ClinicalTrials.gov NCT04362358 , registered on April 24, 2020.

Background: To calculate hospital surge capacity, achieved via hospital provision interventions implemented for the emergency treatment of coronavirus disease 2019 (COVID-19) and other patients through March to May 2020; to evaluate the conditions for admitting patients for elective surgery under varying admission levels of COVID-19 patients., Methods: We analysed National Health Service (NHS) datasets and literature reviews to estimate hospital care capacity before the pandemic (pre-pandemic baseline) and to quantify the impact of interventions (cancellation of elective surgery, field hospitals, use of private hospitals, deployment of former medical staff and deployment of newly qualified medical staff) for treatment of adult COVID-19 patients, focusing on general and acute (G&A) and critical care (CC) beds, staff and ventilators., Results: NHS England would not have had sufficient capacity to treat all COVID-19 and other patients in March and April 2020 without the hospital provision interventions, which alleviated significant shortfalls in CC nurses, CC and G&A beds and CC junior doctors. All elective surgery can be conducted at normal pre-pandemic levels provided the other interventions are sustained, but only if the daily number of COVID-19 patients occupying CC beds is not greater than 1550 in the whole of England. If the other interventions are not maintained, then elective surgery can only be conducted if the number of COVID-19 patients occupying CC beds is not greater than 320. However, there is greater national capacity to treat G&A patients: without interventions, it takes almost 10,000 G&A COVID-19 patients before any G&A elective patients would be unable to be accommodated., Conclusions: Unless COVID-19 hospitalisations drop to low levels, there is a continued need to enhance critical care capacity in England with field hospitals, use of private hospitals or deployment of former and newly qualified medical staff to allow some or all elective surgery to take place.

Background: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available., Methods: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex., Results: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90)., Conclusions: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

Background: The understanding of coronavirus disease 2019 (COVID-19) is rapidly evolving. Although it is primarily a respiratory illness, other manifestations, such as Guillain-Barré syndrome, immune thrombocytopenia, and immune-mediated thrombotic thrombocytopenic purpura, have been described. We present a case of a patient with hemophagocytic lymphohistiocytosis secondary to COVID-19 treated with tocilizumab with a marked biochemical improvement., Case Presentation: In this case report we present a Caucasian patient with COVID-19 who developed a marked elevation of inflammatory parameters with ferritin 36,023 μg/L, but also elevated C-reactive protein 334 mg/L and lactate dehydrogenase 1074 U/L, 1 week after admission to the intensive care unit. He met five of eight criteria for hemophagocytic lymphohistiocytosis, but he lacked the high fever and cytopenia seen in the majority of cases. He was treated with tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, and over the next days, a rapid decrease in ferritin and C-reactive protein levels was observed. However, his respiratory failure only improved gradually, and he was weaned off the respirator 11 days later., Conclusion: COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient's case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19. Specific treatment in such patients must also be contemplated, preferably in randomized controlled trials.

The COVID-19 pandemic has negatively impacted the global public health and the international economy; therefore, there is an urgent need for an effective therapy to treat COVID-19 patients. Mesenchymal stem cells (MSCs) have been proposed as an emerging therapeutic option for the SARS-CoV-2 infection. Recently, numerous clinical trials have been registered to examine the safety and efficacy of different types of MSCs and their exosomes for treating COVID-19 patients, with less published data on the mechanism of action. Although there is no approved effective therapy for COVID-19 as of yet, MSC therapies showed an improvement in the treatment of some COVID-19 patients. MSC's therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear. The use of poorly characterized MSC products remains one of the most significant drawbacks of MSC-based therapy, which could theoretically promote the risk for thromboembolism. Optimizing the clinical-grade production of MSCs and establishing a consensus on registered clinical trials based on cell-product characterization and mode of delivery would aid in laying the foundation for a safe and effective therapy in COVID-19. In this review, we shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. We further highlight the challenges and opportunities in the use of MSC-based therapy.

Background: Determining the infectiousness of patients with coronavirus disease 2019 is crucial for patient management. Medical staff usually refer to the results of reverse transcription polymerase chain reaction tests in conjunction with clinical symptoms and computed tomographic images., Case Presentation: We report a case of a 62-year-old Japanese man who twice had positive and negative test results by polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 over 48 days of hospitalization, including in intensive care. His respiratory symptoms and computed tomographic imaging findings consistent with coronavirus disease 2019 improved following initial intensive care, and the result of his polymerase chain reaction test became negative 3 days before discharge from the intensive care unit. However, 4 days after this first negative result, his polymerase chain reaction test result was positive again, and another 4 days later, he had a negative result once more. Eight days after the second polymerase chain reaction negative test result, the patient's test result again became positive. Finally, his polymerase chain reaction results were negative 43 days after his first hospitalization., Conclusions: This case emphasizes the importance of repeat polymerase chain reaction testing and diagnosis based on multiple criteria, including clinical symptoms and computed tomographic imaging findings. Clinical staff should consider that a negative result by polymerase chain reaction does not necessarily certify complete coronavirus disease 2019 recovery.

Background: Spontaneous pneumomediastinum unrelated to mechanical ventilation is a newly described complication of COVID-19 pneumonia. The objective of this case presentation is to highlight an important complication and to explore potential predisposing risk factors and possible underlying pathophysiology of this phenomenon., Case Presentation: We present two patients with COVID-19 pneumonia complicated by spontaneous pneumomediastinum, pneumopericardium, pneumothorax and subcutaneous emphysema without positive pressure ventilation. Both patients had multiple comorbidities, received a combination of antibiotics, steroids and supportive oxygen therapy, and underwent routine laboratory workup. Both patients then developed spontaneous pneumomediastinum and ultimately required intubation and mechanical ventilation, which proved to be challenging to manage., Conclusions: Spontaneous pneumomediastinum is a serious complication of COVID-19 pneumonia, of which clinicians should be aware. Further studies are needed to determine risk factors and laboratory data predictive of development of spontaneous pneumomediastinum in COVID-19 pneumonia.

Background: Health workers (HWs) are at increased risk for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and a possible source of nosocomial transmission clusters. Despite the increased risk, the best surveillance strategy and management of exposed HWs are not yet well known. The aim of this review was to summarize and critically analyze the existing evidence related to this topic in order to support public health strategies aimed at protecting HWs in the hospital setting., Main Text: A comprehensive computerized literature research from 1 January 2020 up to 22 May 2020 was made to identify studies analyzing the burden of infection, risk assessment, surveillance and management of HWs exposed to SARS-CoV-2. Among 1623 citation identified using MEDLINE, Embase, Google Scholar and manual search, we included 43 studies, 14 webpages and 5 ongoing trials. Health workers have a high risk of acquiring infection while caring for coronavirus disease 2019 (COVID-19) patients. In particular, some types exposures and their duration, as well as the inadequate or non-use of personal protective equipment (PPE) are associated with increased infection risk. Strict infection prevention and control procedures (IPC), adequate training programs on the appropriate use of PPE and close monitoring of HWs with symptom surveillance and testing are essential to significantly reduce the risk. At the moment there is not enough evidence to provide precise indications regarding pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP)., Conclusions: During the spread of COVID-19 outbreak, numerous published papers investigated the epidemiology, risk assessment and prevention and control of SARS-CoV-2. However, more high-quality studies are needed to provide valid recommendations for better management and for the clinical and microbiological surveillance of healthcare personnel.

Introduction: A novel coronavirus named severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019. The virus, known as COVID-19, is recognized as a potentially life-threatening disease by causing severe respiratory disease. Since this virus has not previously been detected in humans, there is a paucity of information regarding its effects on humans. In addition, only limited or no information exists about its impact during pregnancy., Case Presentation: In the present case study, we report the death of a neonate born to a 32-year-old mother with coronavirus disease 2019 in Ilam, Iran, with Kurdish ethnicity. We report the infection and death of a neonate in Iran with a chest X-ray (CXR) marked abnormality 2 hours after birth demonstrating coronavirus disease 2019 disease. The neonate was born by elective cesarean section, the fetal health was assessed using fetal heart rate and a non-stress test before the birth, and there was no evidence of fetal distress. All the above-mentioned facts and radiographic abnormalities suggested that coronavirus disease 2019 is involved., Conclusions: In this case study, we report the death of a neonate born to a mother with coronavirus disease 2019, 11 hours after birth. There is a paucity of data on the vertical transmission and the adverse maternal-fetal consequences of this disease, so vertical transmission from mother to child remains to be confirmed.