Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Synthetic 1,4-pyran naphthoquinones are potent inhibitors of dengue virus replication.

Dengue virus infection is a serious public health problem in endemic areas of the world where 2.5 billion people live. Clinical manifestations of the Dengue infection range from a mild fever to fatal cases of hemorrhagic fever. Although being the most rapidly spreading mosquito-borne viral infection in the world, until now no strategies are available for effective prevention or control of Dengue infection. In this scenario, the development of compounds that specifically inhibit viral replication with minimal effects to the human hosts will have a substantial effect in minimizing the symptoms of the disease and help to prevent viral transmission in the affected population. The aim of this study was to screen compounds with potential activity against dengue virus from a library of synthetic naphthoquinones. Several 1,2- and 1,4-pyran naphthoquinones were synthesized by a three-component reaction of lawsone, aldehyde (formaldehyde or arylaldehydes) and different dienophiles adequately substituted. These compounds were tested for the ability to inhibit the ATPase activity of the viral NS3 enzyme in in vitro assays and the replication of dengue virus in cultured cells. We have identified two 1,4-pyran naphthoquinones, which inhibited dengue virus replication in mammal cells by 99.0% and three others that reduced the dengue virus ATPase activity of NS3 by two-fold in in vitro assays

Inhibition of the ATPase activity of purified NS3 by naphthoquinones.

<p>(A) NaphSDS-Page analysis of the purification full-length NS3 (NS3FL) from <i>E coli</i>. Lane 1, molecular weight marker; lane 2, 10xHis-NS3FL (10xHis-Ubiquitin site) after refolding by dialysis; lane 3 and 4, NS3FL after 10xHis-Ubiquitin site tag excision by YUH in ratio 1:5 and 1:1, respectively; and lane 5, purified NS3FL protein following His-TRAP column chromatography. The gel was stained with Comassie brilhant blue G. (B) A range of pyran naphthoquinones was tested for their activity against ATPase site. The screening was performed in buffer containing 40 mM Tris-HCl (pH 7.5), 5 mM DTT, 100 mM KCl, and 5 mM MgCl₂. The compounds were pre-incubated with 600nM NS3FL for 10 min at 30 °C followed by the addition of 1 mM ATP. The screening was carried out in duplicate and the unpaired t-test was used for the statistical analysis. Those compounds showing statistical difference from the control (p < 0.05) were labeled with an asterisk.</p

Inhibition of the ATPase activity of full-length NS3 by the compounds 9b and 9c.

<p>Increasing concentrations of naphthoquinones 9b and 9c were tested for their activity against ATPase site. The reaction was performed in buffer containing 40 mM Tris-HCl (pH 7.5), 5 mM DTT, 100 mM KCl, and 5 mM MgCl₂. The compounds were pre-incubated with 600nM NS3FL for 10 min at 30 °C followed by the addition of 1 mM ATP. Each point represents the average of three independent replicates in different concentrations of the compounds.</p

General scheme used for preparation of pyran naphthoquinones.

<p>The o-QM intermediate is generated in situ by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone (7) with formaldehyde and arylaldehydes. The subsequent hetero Diels-Alder reaction with substituted dienophiles in aqueous ethanol media yields high amounts of α- and β-lapachone derivatives.</p

Dose-response curves and citotoxicity of 1,4-pyran naphthoquinones 9b and 9c in DENV-2-infected Vero cells.

<p>Vero cells were infected with DENV-2 at an m.o.i of 0.1 in the presence of increasing concentrations of the 1,4-pyran naphthoquinones 9b and 9c. 72 hours after infection the cell-free supernatants were harvested and processed for the quantification of produced viral progeny by qPCR. (A) The percentage of inhibition was calculated using the ΔΔCT values. (B) The concentration of each compound that inhibit 50% of the viral replication (IC₅₀) was determined by a Hill’s regression curve after logarithmic interpolation of the data using the GraphPad 6 software. (C) The potential cytotoxic effect of each compound was evaluated in uninfected cells by the vital neutral red staying and represented as percentage of the untreated control. Data represent mean values ± standard deviations (SD) for three independent experiments.</p

Multisystem inflammatory syndrome associated with coronavirus disease in children a multi-centered study in Belem, Para, Brazil

Fundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil / Metropolitan University Center of the Amazon. Department of child health. Belém, PA, Brazil.Universidade Federal do Rio Grande do Sul. Department of Pediatrics. Division of Pediatric Intensive Care. Porto Alegre, RS, Brazil.Fundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil.Fundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Santa Casa de Misericórdia do Pará Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, BrazilFundação Hospital das Clínicas Gaspar Viana’s Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil.Pró-Infantil’s Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil.Pronto Socorro Municipal Mário Pinotti’s Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil.Pronto Socorro Municipal Mário Pinotti’s Hospital. Department of Pediatrics. Division of Pediatric Intensive Care. Belém, PA, Brazil.Universidade Federal do Rio Grande do Sul. Department of Pediatrics. Division of Pediatric Intensive Care. Porto Alegre, RS, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.We described the characteristics of 11 children with pediatric multisystem inflammatory syndrome-temporally associated with SARS-CoV-2. The main clinical indications for hospital admission were vasogenic toxic shock (n = 2), Kawasaki disease (n = 4), and Kawasaki disease shock syndrome (n = 5). The echocardiography findings were abnormal in 63% of cases. All patients had 2 or more organ dysfunctions, and the mortality rate was 18%