Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Clinical Characteristics and Genotyping of Pediatric Adenovirus Pneumonia Disease and Coinfection in Southeast China.

Introduction: Human adenovirus (HAdV) is a common pathogen that can cause acute respiratory infections (ARIs) in children. Adenovirus pneumonia is the most severe respiratory disease associated with HAdV. Objective: We aimed to investigate the clinical characteristics of children hospitalized with adenovirus pneumonia in Quanzhou, China, in 2019. We also sought to determine the viral genotype in these cases and explore cases associated with severe adenovirus pneumonia. Methods: We collected oropharyngeal swabs from 99 children who were hospitalized with pneumonia in Quanzhou Women and Children's Hospital, these samples were tested for the presence of HAdV. Genotyping of the viruses was performed by real-time polymerase chain reaction. Logistic regression analysis was employed to analyze risk factors related to severe adenovirus pneumonia. The epidemiological data were examined using the Statistical Package for Social Sciences software (SPSS). Results: Among the 99 patients in our study, the median age was 21 months. We observed a 4% mortality rate among those diagnosed with adenovirus pneumonia. Adenovirus pneumonia often presents as a coinfection. Lactate dehydrogenase and neutrophil percentages of WBC's were significantly increased in patients with severe adenovirus pneumonia compared with mild HAdV disease. The predominant viral genotypes identified were type 3 and type 7. Conclusions: In the Quanzhou area of southeast China, the incidence of adenovirus pneumonia was found to be high among children younger than two years old. Type 7 HAdV was identified as the primary pathogen. A long duration of fever, dyspnea and digestive system complications were risk factors for severe adenovirus pneumonia after HAdV infection. Clinical Trial Registration number: ChiCTR2200062358.

Factors Associated with Severe Adenovirus Pneumonia in Children: A Retrospective Study from Guangzhou, China (2017-2019).

BACKGROUND Adenovirus infections are prevalent in children, typically presenting with mild or asymptomatic symptoms. However, some children develop severe pneumonia necessitating hospitalization. This retrospective study aimed to identify risk factors associated with severe adenovirus pneumonia in children. MATERIAL AND METHODS We screened consecutive children admitted for community-acquired pneumonia at the Emergency Department of Guangzhou Women's and Children's Medical Center between 2017 and 2019. Adenovirus infection was confirmed through rapid respiratory virus assay, RT-PCR assay from respiratory secretions, or serum IgM antibodies. According to Chinese guidelines, patients with pneumonia were classified into severe and mild groups. We assessed risk factors for severe adenovirus pneumonia by comparing clinical features and laboratory indicators, then included differing factors between the 2 groups in a logistic regression analysis. Data analysis was performed using SPSS 26.0 software. RESULTS Our study included 173 children diagnosed with adenovirus pneumonia (117 severe, 56 mild). The median age was 40 months, with 64 male patients. Univariate analysis and binary logistic regression analysis revealed that pleural effusion (13.449 [1.226-147.510], p=0.033), electrolyte disturbances (15.149 [2.724-84.246], p=0.002), oxygen therapy (258.219 [20.684-3223.548], p<0.001), bronchoscopy (26.781 [6.088-117.805], p<0.001), and steroid administration (6.584 [1.497-28.953], p=0.013) were associated with the severity of adenovirus pneumonia. CONCLUSIONS This single-center retrospective study identified pleural effusion, the need for bronchoscopy, oxygen therapy, and steroid treatment, along with impaired serum electrolytes, as factors associated with severe adenovirus pneumonia in children.

[Surgical treatment of COVID-19 patients during the pandemic]. / Opyt khirurgicheskogo lecheniya patsientov s COVID-19 v period pandemii.

OBJECTIVE: To analyze the results of emergency surgery in COVID-19 patients with viral pneumonia. MATERIAL AND METHODS: A retrospective study included 75 COVID-19 patients who underwent emergency surgical interventions. Comorbidities included cardiac diseases, nonspecific lung diseases, type 2 diabetes, kidney diseases, overweight, and cancer. Various combinations of these diseases were also noted. RESULTS: We carried out emergency surgeries for abdominal, thoracic, soft tissue and venous diseases. Postoperative mortality was 42.6%. The best results were obtained after minimally invasive interventions without mechanical ventilation. Extended surgery with mechanical ventilation was followed by fast progression of pneumonia according to clinical and CT data. CONCLUSION: Surgical interventions undoubtedly worsen prognosis of treatment in patients with COVID-19. Emergency minimally invasive surgery without mechanical ventilation can reduce the risk of unfavorable outcomes in patients with viral pneumonia, especially in case of concomitant cancer and other severe comorbidities.

The Contribution of Viruses and Bacteria to Childhood Community-acquired Pneumonia: 11-Year Observational Study From Norway.

BACKGROUND: Viruses are associated with pediatric community-acquired pneumonia (CAP) but are also common in the upper airways of healthy children. We have determined the contribution of respiratory viruses and bacteria by comparing children with CAP and hospital controls. METHODS: Children less than 16 years old with radiologically confirmed CAP (n = 715) were enrolled over an 11-year period. Children admitted for elective surgery during the same period served as controls (n = 673). Nasopharyngeal aspirates were tested for 20 respiratory pathogens by semiquantitative polymerase chain reaction tests and cultivated for bacteria and viruses. We used logistic regression to calculate adjusted odds ratios [aOR; 95% confidence intervals (CIs)], and estimated population-attributable fractions (95% CI). RESULTS: At least 1 virus was detected in 85% of cases and 76% of controls, and greater than or equal to 1 bacterium was detected in 70% of cases and controls. The presence of respiratory syncytial virus (RSV) (aOR, 16.6; 95% CI: 9.81-28.2), human metapneumovirus (HMPV) (13.0; 6.17-27.5) and Mycoplasma pneumoniae (27.7; 8.37-91.6) were most strongly associated with CAP. For RSV and HMPV, there were significant trends between lower cycle-threshold values indicating higher viral genomic loads, and higher aORs for CAP. The population-attributable fraction estimates of RSV, HMPV, human parainfluenza virus, influenza virus and M. pneumoniae were 33.3% (32.2-34.5), 11.2% (10.5-11.9), 3.7% (1.0-6.3), 2.3% (1.0-3.6) and 4.2% (4.1-4.4), respectively. CONCLUSIONS: RSV, HMPV and M. pneumoniae were most strongly related to pediatric CAP and accounted for half of all cases. There were positive trends between increasing viral genomic loads of RSV and HMPV, and higher odds for CAP.

Pneumonia in Children During the 2019 Outbreak in Xiamen, China.

BACKGROUND: To understand the regional epidemiology and clinical characteristics of adenovirus pneumonia in hospitalized children during the 2019 outbreak of respiratory adenoviruses in China. METHODS: We analyzed the epidemiologic trend of adenovirus in children hospitalized for acute lower respiratory tract infections in Xiamen in 2019. Adenovirus was identified using direct fluorescent antibody detection. During the peak seasons of adenovirus epidemic, 170 adenovirus-positive specimens were obtained for molecular typing, and the clinical data were collected. RESULTS: Among the 9890 children hospitalized for acute lower respiratory tract infection, 609 (6.2%) were tested positive for adenovirus. The detection rate of adenovirus was significantly higher in boys than in grils (9.5% vs. 4.6%, P < 0.05). Adenovirus activity increased markedly between April and August with the prevalence of 7.3%-12.4%. During the outbreak season, type 7 accounted for 70.6%, followed by type 3 (28.8%) and type 4 (0.6%). Of the 155 cases of adenovirus pneumonia, the median age was 3.0 years (range: 4 month to 9 years), 153 (98.7%) had fever with a mean fever duration of 9.04 ± 5.52 days, 28 (16.5%) had wheezing, 93 (60%) showed segmental or lobar consolidation with atelectasis and 13 (8.4%) showed pleural effusion. Forty-six (29.6%) cases developed severe pneumonia, 7 (4.1%) required mechanical ventilation and 2 (1.2%) died. Younger age, longer duration of fever and higher fever spike were more frequently seen in severe cases (P < 0.05). Twenty-five (16.2%) had C-reactive protein ≥ 40 mg/L, and 91 (58.7%) had procalcitonin ≥ 0.25 mg/L. CONCLUSIONS: Adenovirus types 7 and 3 caused the outbreak of adenovirus pneumonia in community children during late spring to summer in 2019 in Xiamen. The majority of adenovirus pneumonia resembles bacterial pneumonia. The incidence of severe pneumonia was high when type 7 predominantly prevailed. Adenovirus type 7 was more common in severe cases than in nonsevere cases.

Clinical and imaging findings of patients diagnosed with adenovirus-positive pneumonia during 2015-2019 in Shanghai, China.

BACKGROUND: This study was to describe the clinical characteristics, chest CT image findings, and potential role of T cells immunity in adenovirus positive pneumonia. METHODS: In this retrospective study, medical records of 53 adult Adv+ patients who were admitted to the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2015 to August 2019 were included. The presence of adenovirus and other respiratory viruses was detected using polymerase chain reaction of throat swabs samples. Clinical features and chest computed tomography (CT) findings were compared between patients with Adv+ pneumonia and Adv+ non-pneumonia. RESULTS: The top 3 most commonly occurring symptoms in Adv+ pneumonia patients were fever (66.7%), cough (63.3%), and tachypnea (16.7%). Patients with Adv+ pneumonia showed significantly higher rates of cough and fever and longer duration of hospitalization than patients with Adv+ non-pneumonia. In the Adv+ pneumonia group, consolidation (73.3%) was the most common imaging finding on chest CT scan, and the likelihood of involvement of bilateral lobes (60%) was high. Classical conspicuous consolidation with surrounding ground-glass opacity was observed in 5 (16.6%) patients with Adv+ pneumonia. Patients with Adv+ pneumonia showed a higher inhibition of T-cell immunity than did patients with Adv+ non-pneumonia, and counts of CD3+, CD4+, and CD8+ T-cells may predict the presence of pneumonia in Adv+ patients. DISCUSSION: With regard to Adv+ pneumonia, the most frequent symptoms were cough and fever, and the most common CT pattern was consolidation; classical CT findings such as consolidation with surrounding ground-glass opacity could also be observed. Furthermore, our data indicated the incidence of abrogated cellular immunity in patients with Adv+ pneumonia.

Clinical features, treatment and outcomes of an outbreak of type 7 adenovirus pneumonia in centralized residence young adults.

BACKGROUND: Human adenovirus type B7 (HAdV-B7) has been reported to cause pneumonia. However, there are limited data about the epidemiological and clinical features of HAdV-B7 pneumonia in young adults. METHODS: This retrospective observational study included 52 patients diagnosed of human adenovirus B7 pneumonia in Nanjing, China from February 7, 2016, to February 20, 2016. We retrospectively collected and analyzed clinical, laboratory, and radiologic features, treatments and outcomes. RESULTS: The median age of the 52 patients was 19.5 years (IQR 18.0-21.0). The most common symptoms were fever (50, 96.2%), cough (49, 94.2%), and expectoration (48, 92.3%). Most of the routine hematology and blood chemistry parameters were within the normal range. The predominant abnormal patterns seen on chest CT were unilateral (33, 66%), multifocal (36, 72%), and ground-glass opacity (27, 54%), mainly involving the left lower lobes (41 [36.0%] of 114 affected segments). As the disease progressed in the second week after symptom onset, consolidation and mixed patterns became more common, while the ground glass opacity pattern decreased. The single-agent ribavirin therapy group had a significantly shorter duration of nonrespiratory symptoms, and no statistically significant difference was observed between the single-agent methylprednisolone group and the nonglucocorticoid group. CONCLUSIONS: The main symptoms in immunocompetent patients with adenovirus type 7 are fever, cough and sputum, with no significant abnormalities in laboratory tests. Chest CT scan mostly shows a ground-glass opacity at the beginning of the disease, which subsequently changes to a mixed pattern. Ribavirin and glucocorticoids did not shorten the course of disease.

Abdominal pain in covid times: time to think twice.

We report a case of abdominal pain followed by acute systolic heart failure due to multisystem inflammatory syndrome in children (MIS-C). This multisystem disease typically appears several weeks after infection with COVID-19 in children and young adults. There is a wide spectrum of presentation with MIS-C: some present with features of shock, others with a condition that has overlapping characteristics with Kawasaki disease (KD), and others with more non-specific features. Very often the symptoms include gastrointestinal symptoms. Our 17-year-old patient presented with fever, abdominal pain and inflammatory laboratory results. Rapidly after admission he developed acute heart failure with biopsy-confirmed myocarditis. The diagnostic criteria of MIS-C were met. This case emphasizes the changing diagnostic landscape. However rare, we want to raise awareness for MIS-C in children and young adults presenting with abdominal pain. Because of the risk of rapid clinical deterioration, early recognition and a multidisciplinary approach can be life-saving.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.

Epidemiological characteristics, clinical characteristics, and prognostic factors of children with atopy hospitalised with adenovirus pneumonia.

BACKGROUND: Atopy may be associated with disease severity and a poor prognosis of human adenovirus (HAdV) pneumonia in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in children with atopy and HAdV pneumonia in China. METHODS: Children hospitalised with HAdV pneumonia from June 2018 to December 2019 were analysed. All children were divided into atopic with HAdV, non-atopic with HAdV, and atopic without HAdV infection group. Each group was further divided into the mild and severe pneumonia groups according to disease severity. Standard treatment was initiated after admission, and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics and pulmonary radiological changes in children with and without atopy were evaluated. Risk factors associated with small airway lesions in patients with HAdV pneumonia were analysed. RESULTS: The eosinophil count in the atopic group was significantly higher than that in the non-atopic group (P < 0.05). Severe coughing, wheezing, and small airway lesions on chest high-resolution computed tomography (HRCT) upon admission, after discharge and 1 month after discharge were significantly higher in the atopic group (with or without HAdV infection) than in the non-atopic group (P < 0.05). There were significant differences in the number of patients with wheezing and small airway lesions during hospitalisation and after discharge among the three groups (P < 0.05). The risks of small airway lesions in children with a family or personal history of asthma, severe infection, atopy, and HAdV infection were 2.1-, 2.7-, 1.9-, 2.1-, and 1.4-times higher than those in children without these characteristics, respectively. CONCLUSIONS: Children with atopy and HAdV pneumonia may experience severe coughing in mild cases and wheezing in mild and severe cases. Children with atopy are more susceptible to the development of small airway lesions, recurrent wheezing after discharge and slower recovery of small airway lesions as observed on pulmonary imaging than non-atopic children after HAdV infection. A family or personal history of asthma, atopy, severe infection, and HAdV infection are independent risk factors associated with the development of small airway lesion as observed on chest HRCT.

[Epidemiological characteristics of adenovirus infection in hospitalized children with acute respiratory tract infection in Kunming during 2019].

Objective: To investigate the epidemiology and clinical characteristics of adenovirus (ADV)-caused acute respiratory tract infection among hospitalized children in Kunming, China. Methods: Clinical and laboratory data were collected from 467 children with adenovirus infection who were hospitalized from January 1, 2019 to December 31, 2019 in 6 grade A class Ⅲ hospitals in Kunming area. The basic characteristics, epidemiology, mixed infection and adenovirus genotypes of the patients were retrospectively analyzed. The patients diagnosed with adenovirus pneumonia (AP) were divided into two groups, severe AP (SAP) group and general AP(GAP) group according to the severity of illness. Mann-Whitney U test or χ2 test was used for comparison between groups, while multivariate regression was applied to analyze the risk factors of SAP. Results: Among 15 635 hospitalized children with respiratory tract infection, 467 cases were adenovirus positive, with a detection rate of 2.99%. Of the 467 patients with adenovirus infection, 284 were male and 183 female, the age was 2.4 (1.1,3.9) years, including 44 cases (9.4%) < 0.5 years, 59 cases (12.6%) of 0.5 to<1.0 years, 176 cases (37.7%) of 1.0 to <3.0 years, 150 cases (32.1%) of 3.0 to <7.0 years, and 38 cases (8.1%) of 7.0 to 14.0 years. Adenovirus infection was common in autumn and winter, and the high incidence months were October to December, which accounted for 51.6% (241/467) of the whole year cases. Co-infection was detected in 226 cases (48.4%) out of 467 patients, in which one pathogen co-infection was the most frequent form (172 cases, 76.1%). Of the 262 pathogen detected 108 (41.2%) were Mycoplasma pneumoniae. In 144 of ADV-positve cases (30.8%) were taken geno-typing was done by PCR amplification, the results showed that 74 cases (51.4%) were ADV 3, 7 subtypes and 65 cases (45.1%) of ADV 1, 2,6 subtypes. Of the 467 cases of ADV infection, 320 (68.5%) were diagnosed with pneumonia, 82 (17.6%) with upper respiratory tract infection and pharyngeal tonsillitis, and 65 (13.9%) with bronchitis, laryngeal bronchitis, and asthmatic bronchitis. Among the 320 patients with AP, 56 cases were severe and 264 cases were general. Two cases (3.6%) in severe group died. Compared with the GAP group, the age was young [17 (11,42) months vs. 24 (14,44) months, Z=2.222, P=0.026], the fever duration was long [8 (5,14) days vs. 6 (3,9) days, Z=3.380, P<0.01], and the proportions of preterm birth and having underlying diseases were high [respectively 19.6% (11/56) vs. 6.1% (16/264), 26.8% (15/56) vs. 10.2% (27/264), χ2=8.965,11.109, P<0.05] in SAP group. Referring to laboratory markers, white blood cell count, C-reactive protein, creatine kinase-MB and lactate dehydrogenase were significantly increased in SAP group as compared to GAP group(all P<0.05). Multivariate Logistic regression analysis showed that preterm birth (OR=3.284, 95%CI 1.079-9.993, P=0.036), underlying disease (OR=3.284, 95%CI 1.079-9.993, P=0.036), fever duration ≥10 d (OR=2.523,95%CI 1.195-5.328, P=0.015) and C-reactive protein ≥50 mg/L (OR=3.156, 95%CI 1.324-7.524, P=0.010) were positively correlated with the risk of SAP. Conclusions: The incidence of adenovirus infection among hospitalized children in Kunming was lower than the national level, and no outbreak occurred in 2019. Subtype 3 and 7 of ADV are the predominant strains for infection, which usually occurs in autumn and winter and mainly causes pneumonia. Premature birth, underlining diseases, long fever duration and markedly increased C-reactive protein are the risk factors for developing into severe pneumonia. This paper presents the prevalence and clinical characteristics of adenovirus infection in children at high altitude area.

Characteristics of immune and inflammatory responses among different age groups of pediatric patients with COVID-19 in China.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. METHODS: We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1-6, 7-10, and 11-15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. RESULTS: Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P < 0.01). CD19+ B cells were the only significantly elevated immune cells, especially among patients under 1 year old (cell proportion: n = 12, 30.0%, P < 0.001; cell count: n = 13, 32.5%, P < 0.001). While, low levels of immune related makers, such as immunoglobulin (Ig) G (P < 0.001), IgA (P < 0.001), IgM (P < 0.001) and serum complement C3c (P < 0.001), were also mostly found among patients under 1 year old, together with elevated levels of inflammation related markers, such as tumor necrosis factor γ (P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P < 0.001), and procalcitonin (P = 0.007). CONCLUSION: The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.

Comorbidities and in-hospital death of viral pneumonia adults admitted to SUS (2002-2015).

OBJECTIVE: To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS: This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS: Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS: Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

One Hundred Twenty-Day Mortality Rates for Hip Fracture Patients with COVID-19 Infection.

BACKGROUND: Increased 30-day mortality rates have been reported for patients with hip fractures and a concurrent diagnosis of coronavirus disease 19 (COVID-19) infection. Due to nosocomial spread of infection and the variable incubation period with the virus, follow-up past 30 days after injury is required to evaluate the true mortality amongst these patients. We aim to assess 120-day mortality rates in hip fracture patients with COVID-19 infection and compare this to hip fracture patients without COVID-19 infection presenting during the same time period. METHODS: This is a retrospective multicenter review of all patients aged ≥ 60 years admitted with a fractured neck of femur between March 5 and April 5, 2020, at nine U.K. trauma units. COVID-19 status, demographic data, comorbidities, and date of death (if applicable) were collected. RESULTS: Data were collected for 265 hip fracture patients. Forty-six patients (17.4%) tested positive for COVID-19 infection. There were no significant differences in age or Charlson comorbidity score between those with or without COVID-19. Those with COVID-19 infection were more likely to be male (p = 0.01). Patients with COVID-19 had a 30-day mortality of 35% versus 10% in patients without (p < 0.01). One hundred twenty-day mortality was also greater in those with COVID-19 infection at 63% compared to those without at 17% (p < 0.01). Previous history of myocardial infarction was the only independent factor that showed to increase mortality rate (p = 0.03). Subgroup analysis also revealed significantly increased mortality rates at 120 days in men (27% vs. 67%), women (14% vs. 59%), and those undergoing surgery (56% vs. 30%). CONCLUSIONS: We report a significantly increased mortality rate at 30 and 120 days after injury in an already high-risk cohort of surgical patients. With nearly half of patients being diagnosed with COVID-19 at 14 days or greater following admission, this study highlights the importance of taking appropriate measures to decrease the incidence of nosocomial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hip fracture patients.

Monoclonal Antibodies vs COVID-19: Eduardo Ojito-Magaz MS General Director, Molecular Immunology Center.

Cuba has five COVID-19 vaccines in clinical trials and is on track to receive emergency use authorization from the country's regulatory agency to begin mass vaccination with two of those candidates: Abdala and SOBERANA 02. Results from phase 1 and 2 trials of these vaccines, the first developed and produced in Latin America, have been encouraging, both in terms of safety and immunogenicity. The ongoing phase 3 trials will continue to look at safety, together with efficacy; parallel intervention studies involving over a million people in Havana will begin generating data on effectiveness. Coordination between Cuba's biotechnology sector and its public health system-particularly throughout the different levels of primary care-to control and treat COVID-19 is a cornerstone of the Cuban strategy and one that could serve as a blueprint for future pandemics. Another Cuban product, itolizumab, is showing positive results mitigating cytokine release syndrome (CRS) in COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Developed in collaboration with Biocon (India), itolizumab is administered under an expanded access program to treat vulnerable populations in Cuba. Marshaling complementary capacities of dozens of institutions belonging to BioCubaFarma-the country's biotech conglomerate-and developing therapies, vaccines and medical technologies together, is another cornerstone of Cuba's strategy to combat COVID-19 and improve population health. The Molecular Immunology Center (CIM) is a key player in this strategy. Founded in 1992, CIM is a powerhouse in monoclonal antibody research and production, with 6 registered products and 22 in the pipeline. Known for several novel therapeutic cancer treatments, CIM has over two decades' experience producing complex recombinant proteins in mammalian cells on an industrial scale. Once Cuba's Innovation Committee (convened in January 2020 as part of the National COVID-19 Prevention & Control Plan) determined Cuban researchers would pursue protein subunit vaccine candidates, they turned to CIM to produce the required receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, among other responsibilities. CIM's General Director, Dr Eduardo Ojito-Magaz, is a chemical engineer and holds a master's degree in biotechnology. He spoke with MEDICC Review just days before 1.7 million Havana residents began participating in the country's largest intervention study with the COVID-19 vaccines his center helped make possible.