Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

/pdf/pathophysiology-transmission-diagnosis-and-treatment-of-2o6dok06xg.pdf

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

Background Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19)...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2021680?articleTools=true

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

Coronavirus disease (COVID-19) pandemic.

Importance In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation. Objectives To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders. Design, Setting, and Participants Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019. Exposures Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization. Main Outcomes and Measures Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders. Results Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 20 girls [34%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively). Conclusions and Relevance In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

/pdf/clinical-characteristics-of-58-children-with-a-pediatric-3ul14x7cqa.pdf

Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2.

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.

Neurological Manifestations of COVID-19 in Children: A Case of Facial Nerve Palsy.

Chagas disease (CD) is an uncommon disease in Europe. Its epidemiology has changed because of mass migration from Latin America to Europe. Herein we describe a congenital case of CD in a Bolivian newborn in Bergamo, the main city of residence for the Bolivian community in Italy. At delivery, serological analyses evidenced IgG antibodies against Trypanosoma cruzi both in the child and mother, as expected. Hemoscopic analyses on peripheral blood were repeatedly negative during the first months of life. Eventually, thanks to T. cruzi Real Time polymerase chain reaction (RT-PCR) positivity on peripheral blood and development of progressive anemia in the following weeks, congenital Chagas disease was diagnosed and benznidazole-based therapy started. A progressive antibodies' index decrease was observed till negativity (306 days apart). RT-PCR was negative at the end of treatment. Our case is instructive and management of congenital CD is discussed from the perspective of a non-endemic country.

Congenital Chagas disease in a Bolivian newborn in Bergamo (Italy).

Background: COVID-19, a disease caused by the new coronavirus SARS-CoV-2, spread worldwide, and Bergamo was one of the most affected areas in Europe Following the first outbreak, more than half of the population of the Bergamo province had been infected We aimed to describe the patients admitted to our unit shortly after the first outbreak Methods: we retrospectively reviewed the notes of all pediatric patients diagnosed with COVID-19 We enrolled patients with positive swabs or serology and classified them based on the pattern and the timing of presentation after the first outbreak This setting was considered a reliable reflection of the consequences of unmitigated SARS-CoV-2 circulation Results: We diagnosed 35 patients over a 3-month period and we identified six patterns presenting in two temporal phases: Early phase, Group 1 (median of 20 days from epidemic start, IQR: 15-27): neonatal sepsis (n7), pneumonia (n5), flu-like symptoms (n2) Late phase, Group 2 (59:51-66 days, p < 0001): MIS-C (n18), neurological manifestations (n3) Group 1 differed from Group 2 for younger age (1 vs 8 years, p = 002), lower C-reactive protein (09 vs 166 mg/dl, p = 0008), procalcitonin (016 vs 79 ng/ml, p = 0008) and neutrophil count (3,765 vs 6,780/μl, p = 0006), higher rate of positive swabs (14/14 vs 9/21, p < 0001), higher lymphocyte count (3,000 vs 930/μl, p = 0006) and platelet count (323,000 vs 210,000/μl, p = 0009) Conclusions: Following an outbreak of unmitigated SARS-CoV-2 diffusion, infected children may present with clinical patterns suggesting two temporal clusters, the first characterized by markers of direct viral injury, the second suggesting an immune-mediated disease

/pdf/patterns-of-presentation-of-sars-cov-2-infection-in-children-1fl85a9moy.pdf

Patterns of Presentation of SARS-CoV-2 Infection in Children. Experience at the Italian Epicentre of the Pandemic

This paper evaluates the capability of MicroSeq 500 instrument to improve the diagnosis of Mycobacterium genavense The strain was isolated from a two year old child admitted to our hospital for hepatosplenomegaly and massive abdominal lymphadenopathies. DNA was extracted from a lymph node and examined by amplifying 500 bp at the 5' end of 16S rRNA gene using MicroSeq 500 16S rDNA Bacterial Identification PCR kit. Sequencing reactions were performed with MicroSeq 500 16S rDNA Bacterial Identification Sequencing kit (Applied Biosystems, USA). Afterwards, sequences were analyzed by GenBank database and identified as Mycobacterium genavense, a slow-growing nontuberculous mycobacterium. The use of 16S rRNA gene sequencing for the identification of bacteria allows the recognition of new clinically relevant agents, eliminating the culture result waiting times.

Maurizio Ruggeri

Papers

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.

Neurological Manifestations of COVID-19 in Children: A Case of Facial Nerve Palsy.

Congenital Chagas disease in a Bolivian newborn in Bergamo (Italy).

Patterns of Presentation of SARS-CoV-2 Infection in Children. Experience at the Italian Epicentre of the Pandemic

Rapid Diagnosis of Mycobacterium genavense Disseminated Infection by the Microseq 500: A Case Report in A Two Year Old HIV-Negative Child