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1.
Journal of Structured Finance ; 28(2):33-41, 2022.
Article in English | Scopus | ID: covidwho-2024400

ABSTRACT

The conflict between Russia and Ukraine has resulted in additional burdens on the aviation industry, compounding the impact of the COVID pandemic. Airline manufacturers and operators are suffering extra costs due to the steep rise in commodities prices, especially those linked to energy costs, and the decline in the supply of crucial manufacturing materials like titanium, as a result of supply chain issues and sanctions. The sanctions, led by the United States and the European Union, impacted Russia multilaterally. They included prohibiting the transfer of maintenance materials and technologies;forbidding aircraft leases to Russian operators;airspace closure;and suspension of airworthiness certificates. Russia responded to the sanctions by suspending bilateral agreements and unilaterally re-registering leased aircraft in Russia. Russia’s responses have impeded aircraft lessors seeking to repossess their assets and forced an inevitable write-down of asset values, leading lessors and financiers to file insurance claims. This has dampened the global aviation finance and ABS markets. © 2022 The Journal of Structured Finance. All rights reserved.

2.
Annals of the Rheumatic Diseases ; 81:971-972, 2022.
Article in English | EMBASE | ID: covidwho-2009130

ABSTRACT

Background: Enpatoran is a selective and potent dual toll-like receptor (TLR) 7/8 inhibitor in development for the treatment of cutaneous and systemic lupus erythematosus (CLE/SLE). Enpatoran inhibits TLR7/8 activation in vitro and suppresses disease activity in lupus mouse models.1 Enpatoran was well tolerated and had linear pharmacokinetic (PK) parameters in healthy volunteers.2 As TLR7/8 mediate immune responses to single-stranded RNA viruses, including SARS-CoV-2, it was postulated that enpatoran may prevent hyperinfammation and cytokine storm in COVID-19. Objectives: In response to the COVID-19 pandemic, we conducted an exploratory Phase II trial to assess safety and determine whether enpatoran prevents clinical deterioration in patients (pts) hospitalized with COVID-19 pneumonia. PK and pharmacodynamics (PD) of enpatoran were also evaluated. Methods: ANEMONE was a randomized, double-blind, placebo (PBO)-con-trolled study conducted in Brazil, the Philippines, and the USA (NCT04448756). Pts aged 18-75 years, hospitalized with COVID-19 pneumonia (WHO 9-point scale score =4) but not mechanically ventilated, with SpO2 <94% and PaO2/FiO2 ≥150 (FiO2 maximum 0.4) were eligible. Those with a history of uncontrolled illness, active/unstable cardiovascular disease and SARS-CoV-2 vaccination were excluded. Pts received PBO or enpatoran (50 or 100 mg twice daily [BID]) for 14 days, with monitoring to Day 28 and safety follow-up to Day 60. Primary outcomes were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (time to clinical status >4, WHO 9-point scale) was a secondary outcome. Exploratory endpoints were enpatoran and biomarker concentrations (cytokines, C-reactive protein [CRP], D-dimer and interferon gene signature [IFN-GS] scores) assessed over time. Results: 149 pts received either PBO (n=49), or enpatoran 50 mg (n=54) or 100 mg (n=46) BID;88% completed treatment and 86% received concomitant steroids. Median age was 50 years (77% <60 years old), 66% were male, and 50% had ≥1 comorbidity (40% hypertension, 24% diabetes). Overall, 59% pts reported a treatment-emergent adverse event (TEAE) with three non-treatment-related deaths;11% reported a treatment-related TEAE. The proportion of pts in the enpatoran group reporting serious TEAEs was low (50 mg BID 9%;100 mg BID 2%) vs PBO (18%). Gastrointestinal disorders were most common (PBO 8%;50 mg BID 28%;100 mg BID 9%). The primary outcome of time to recovery with enpatoran vs PBO was not met;medians were 3.4-3.9 days. A positive signal in time to clinical deterioration from Day 1 through Day 28 was observed;hazard ratios [95% CI] for enpatoran vs PBO were 0.39 [0.13, 1.15] (50 mg BID) and 0.30 [0.08, 1.08] (100 mg BID). Mean enpatoran exposure was dose-proportional, and PK properties were within expectations. The median (quartile [Q]1-Q3) interleukin 6 (IL-6), CRP and D-dimer baseline concentration across the groups were 5.7 (4.0-13.5) pg/mL, 30.04 (11.40-98.02) and 0.62 (0.39-1.01) mg/L, respectively. Baseline IFN-GS scores were similar across groups. Conclusion: The ANEMONE trial was the frst to evaluate the safety and efficacy of a TLR7/8 inhibitor in an infectious disease for preventing cytokine storm. Enpa-toran up to 100 mg BID for 14 days was well tolerated by patients acutely ill with COVID-19 pneumonia. Time to recovery was not improved with enpatoran, perhaps due to the younger age of patients who had fewer comorbidities compared to those in similar COVID-19 trials. However, there was less likelihood for clinical deterioration with enpatoran than placebo. This trial provides important safety, tolerability, PK and PD data supporting continued development of enpatoran in SLE and CLE (NCT04647708, NCT05162586).

3.
Chinese Journal of Biologicals ; 34(6):699-703, 2021.
Article in Chinese | EMBASE | ID: covidwho-1894085

ABSTRACT

Objective To explore the application and safety of apheresis technology in collection of Coronavirus Disease 2019 (COVID-19) convalescent plasma (CP), and to analyze the quality characteristics of the plasma. Methods The general data of COVID-19 convalescent plasma (CP) donors, including gender, age, date of discharge or release from medical isolation, were collected based on informed consent. After physical examination, the CP was collected by apheresis technology with plasma separator, inactivated with methylene blue, and determined for severe acute respiratory symptom Coronavirus 2 (SARS-CoV-2) nucleic acid and specific antibody (RBD-IgG) against SARS-CoV-2. Results The collection process went well, and no serious adverse events related to plasma collection were reported during or after the collection. The average age of COVID-19 CP donors was 38 years (n = 933). The distributions of blood groups A, B, AB and 0 in RhD (+) COVID-19 CP were 33. 4%, 29. 2%, 10% and 27. 2% respectively. The plasma donation date was 18 d from the discharge date in average. All the test results of SARS-CoV-2 nucleic acid in CP were negative, while the proportion of plasma samples at SARS-CoV-2 antibody titer of more than 1: 160 was 92. 60%. Conclusion Apheresis technology was safe and reliable. The COVID-19 CP contained high titer antibody. Large-scale collection and preparation of inactivated plasma against SARS-CoV-2 played an important role in the treatment of COVID-19.

4.
Topics in Antiviral Medicine ; 30(1 SUPPL):179, 2022.
Article in English | EMBASE | ID: covidwho-1880576

ABSTRACT

Background: Enpatoran, a selective and potent toll-like receptor 7 and 8 (TLR7/8) inhibitor, is in development for treating autoimmune diseases. Enpatoran may prevent hyperinflammation and cytokine storm in COVID-19 by targeting pro-inflammatory pathways induced by SARS-CoV-2. Methods: The ANEMONE study, a phase II, randomized, double-blind, placebo-controlled trial conducted in the US, the Philippines, and Brazil, assessed the safety and efficacy of enpatoran in COVID-19 pneumonia (NCT04448756). Eligible hospitalized patients were aged 18-75 years, with a WHO 9-point scale score of 4, confirmed COVID-19 pneumonia, SpO2 <94%, PaO2/FiO2 ≥150 (FiO2 max 0.4) and not on mechanical ventilation. Key exclusion criteria were active/unstable cardiovascular disease, history of uncontrolled illness and SARS-CoV-2 vaccination. Randomized patients (N=149) received placebo (PBO;n=49), enpatoran 50 mg twice daily (BID;n=54) or 100 mg BID (n=46) for 14 days, with monitoring up to Day 28 and safety follow-up to Day 60. Primary outcomes were safety and time to recovery (WHO 9-point scale ≤3). Clinical deterioration (time to clinical status >4, WHO 9-point scale) was a secondary outcome. Results: 88% of patients completed treatment (66% male, median age 50 years);50% had ≥1 comorbidity (including 40% hypertension, 24% diabetes). Treatment-emergent adverse events (TEAEs) were reported by 59% of patients;11% reported treatment-related TEAEs (Table). Serious TEAEs were higher with PBO (18%) than enpatoran (6%). Three non-treatment-related deaths occurred. Gastrointestinal disorders were most common (PBO 8%;50 mg BID 28%;100 mg BID 9%). Infections and infestations were reported by 18% (PBO), 17% (50 mg BID) and 4% (100 mg BID);COVID-19 worsening (PBO 8%;50 mg BID 9%) and bacterial sepsis (PBO 4%) were most common. Headache and dizziness were only reported with enpatoran (<3% across groups). Psychiatric disorders were higher with PBO (14%) than enpatoran (50 mg BID 7%;100 mg BID 4%). There was no dose effect on TEAEs. Median [95% CI] time to recovery from Day 1 through Day 28 was 3.4 [2.7, 4.9] (PBO), 3.7 [2.6, 4.0] (50 mg BID) and 3.9 [2.0, 4.8] (100 mg BID) days. A positive signal in time to clinical deterioration from Day 1 through Day 28 was observed;hazard ratios [95% CI] for enpatoran versus PBO were 0.39 [0.13, 1.15] (50 mg BID) and 0.30 [0.08, 1.08] (100 mg BID). Conclusion: Enpatoran was considered safe and well tolerated in hospitalized patients with acute COVID-19 pneumonia.

5.
Journal of Vascular Surgery-Venous and Lymphatic Disorders ; 10(3):799-799, 2022.
Article in English | Web of Science | ID: covidwho-1857650
6.
Open Forum Infectious Diseases ; 8(SUPPL 1):S360-S361, 2021.
Article in English | EMBASE | ID: covidwho-1746479

ABSTRACT

Background. Enpatoran, formerly known as M5049, is a potential first-in-class small molecule antagonist of toll-like receptors (TLR) 7 and 8, which may prevent viral-associated hyperinflammatory response and progression to 'cytokine storm' in coronavirus disease 2019 (COVID-19) patients. The objective of this study was to leverage existing population pharmacokinetic/pharmacodynamic (popPK/PD) models for enpatoran to inform dose selection for an accelerated Phase II study in COVID-19 patients with pneumonia. Methods. The popPK/PD models were based on plasma PK and PD biomarker (ex vivo-stimulated interleukin [IL]6 and interferon α [IFNα] secretion) data from the enpatoran first-in-human Phase I study in healthy participants (Port A, et al. Lupus Sci Med 2020;7(Suppl. 1): P135). A two-compartment model describing PK used a sigmoidal Emax model with proportional decrease from baseline characterizing the PD response across the investigated single and multiple daily dose range of 1-200 mg (N=72). Concentrations that inhibited 50% and 90% (IC50/IC90) of cytokine secretion were estimated and stochastic simulations were performed to assess target coverage under different dosing regimens. Results. Simulations suggested that, to achieve maximal inhibition of IL-6 over time, enpatoran PK concentrations would be maintained above the IC90 throughout the dosing interval with doses of 100 mg and 50 mg twice daily in 90% and 30% of participants, respectively. In comparison, IFNα inhibition was predicted to be lower, with IC90 coverage in 60% and 8% of participants with twice daily doses of 100 mg and 50 mg enpatoran, respectively. Conclusion. Utilization of existing popPK/PD models allowed for the accelerated development of enpatoran in COVID-19 to address an unprecedented global pandemic. Rational model-informed dose selection was supported by data from a Phase I study in which there were no safety concerns.

7.
Engineering Construction and Architectural Management ; ahead-of-print(ahead-of-print):17, 2022.
Article in English | Web of Science | ID: covidwho-1684968

ABSTRACT

Purpose To meet the rapidly increasing demand for medical treatment during the outbreak of COVID-19, Huoshengshan and Leishenshan Hospital are rapidly built (9-12 days) in Wuhan. These two urgent emergency projects are unprecedented. In general, substantial literature suggests that the possibility of shortening a schedule by more than a quarter of its original duration is implausible. By contrast, the two projects had successfully compressed the schedules from months and years to about ten days. This study aims to investigate how this was done and provide references for future projects. Design/methodology/approach The study uses qualitative case study techniques to analyze the project practices in two urgent emergency projects. Data were gathered through semi-structured interviews and archival research. During interviews, interviewees were asked to describe the project practices adopted to overcome the challenges and freely share their experiences and knowledge. Findings The results illustrate that a high degree of schedule compression is achievable through tactful crashing, substitution and overlapping applications. The successful practices heavily rely on the high capacity of participants and necessary organization, management and technology innovations, such as three-level matrix organizational structure, reverse design method, site partition, mock-up room first strategies and prefabricated construction technology. For instance, the reverse design method is one of the most significant innovations to project simplification and accelerate and worthy of promotion for future emergency projects. Practical implications The empirical findings are significant as they evoke new thinking and direction for addressing the main challenges of sharp schedule compression and provide valuable references for future emergency projects, including selecting high-capacity contractors and replacing the conventional design methods with reverse design. Originality/value Substantial studies indicate that the maximum degree of schedule compression is highly unlikely to exceed 25%, but this study suggests that sharp compression is possible. Although with flaws in its beauty (i.e. compressing schedule at the expense of construction cost and quality), it is also a breakthrough. It provides the building block for future research in this fertile and unexplored area.

8.
Chinese General Practice ; 24(34):4349-4355, 2021.
Article in Chinese | Scopus | ID: covidwho-1600044

ABSTRACT

Background: In the context of public health emergencies, for example, the COVID-19 pandemic, community hospitals may face challenges to provide diagnosis and treatment services and to reduce the disease burden for patients with mental problems. However, general practitioners(GPs)' capabilities in diagnosing and treating mental disorders are unsatisfactory. Objective: To develop a system for identifying community-dwelling outpatients with mental disorders needing emergency management amid a public health emergency by GPs, to promote GPs' capabilities in diagnosing and treating mental disorders, and the health of such patients. Methods: From May to June 2020, based on a literature review and an investigation of work requirements for GPs, we formed a framework for identifying community-dwelling outpatients with mental disorders needing emergency management amid a public health emergency by GPs with indicators initially determined. Then we screened and revised the indicators according to the results of a two-round Delphi survey with 15 experts(in the field of general practice or mental health medicine), and finally determined the indicators(with a mean value of weighted importance>3.5, coefficient of variation <25%, and rate of getting full marks >20%) for the formal system identifying community-dwelling outpatients with mental disorders needing emergency management amid a public health emergency by GPs. Results: Information of the experts surveyed: 13 of them had a graduate degree, and 10 had a senior professional title. Positive coefficients of the experts: All the experts(100%) actively responded to the two rounds of survey. Authority coefficients of the experts: the authority coefficient of the six domains were >0.70. The degree of agreement between the experts: the Kendall's W in the second round of survey was 0.278(χ2=100.197, P<0.001), which was higher than 0.245(χ2=73.597, P<0.001)in the first round of survey. The final indicators: 24 indicators in six domains involving mental symptoms, diagnosis of mental illness, severity of mental illness, personality, physical status, family and social background. Conclusion: Our system may help GPs to high-efficiently identify community-dwelling outpatients with severe mental disorders needing emergency treatment or referrals. However, the accuracy of the system needs to be verified further. Copyright © 2021 by the Chinese General Practice.

9.
Russian Journal of Anesthesiology and Reanimatology /Anesteziologiya i Reanimatologiya ; - (4):48-53, 2021.
Article in Russian | Scopus | ID: covidwho-1566867

ABSTRACT

Objective. To study an efficacy and safety of therapeutic plasma exchange in the treatment of COVID-19. Material and methods. Efficacy and safety of plasma exchange in severe COVID-19 were retrospectively analyzed. Plasma exchange was performed within 24 hours after admission to ICU. Circulating plasma volume (70-150%) was replaced with donor fresh frozen plasma, CovRec plasma ≤300 ml and balanced crystalloid solutions ≤800 ml. Mean volume of exchange was 3000 ml (min 2000 ml, max 4000 ml). We analyzed mortality and need for mechanical ventilation in patients after plasma exchange in addition to standard therapy (main group) and in the control group (standard therapy alone). Results. Mortality in the main group was 16.67% (n=5), in the control group — 57.41% (n=31) (p=0.001). Conclusion. Plasma exchange is an effective and safe method significantly reducing mortality in patients with severe COVID-19. These data are confirmed by laboratory data. A multiple-center study of efficacy and safety of plasma exchange in the treatment of severe COVID-19 is needed. © S.S. OCHKIN, A.S. SAMOYLOV, YU.D. UDALOV, N.M. KRUGLYAKOV, G.I. BAGZHANOV.

10.
Chest ; 160(4):A532, 2021.
Article in English | EMBASE | ID: covidwho-1458312

ABSTRACT

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-COV2) is the virus responsible for the coronavirus disease 2019 (COVID-19) which has caused a pandemic generating over half a million deaths in the United States. Lymphopenia is common at presentation in COVID-19 and has been associated with disease severity. Furthermore, patients with severe infection are more likely to have multifocal, bilateral, peripheral ground glass opacities on chest computerized tomography (CT). COVID-19 is diagnosed with a polymerase chain reaction (PCR) test using a nasopharyngeal swab (NPS) for SARS-COV2. The turnaround time for this test has improved;however, as the pandemic continues there have been shortages of reagents leading to continued challenges in timely testing. The aim of our study is to evaluate whether CT chest findings combined with absolute lymphocyte count (ALC) can predict positive COVID-19 PCR swab result. METHODS: We included 3544 patients who presented to the emergency department at a large, urban academic center between March and September 2020. All patients had a NPS for the presence of SARS-CoV-2 using the Luminex NxTAG CoV Extended Panel, a low-resolution chest CT scan without contrast, and a complete blood count with differential to determine ALC. CT scans were classified into three standardized categories by a board-certified chest radiologist based on features of multifocal pneumonia. Category 1 is consistent with multifocal pneumonia, category 2 is indeterminate for multifocal penumonia, and category 3 is inconsistent with multifocal pneumonia. In our analysis we combined categories 2 and 3 into one group. Using the Youden index (J) method, a joint test was performed on CT scan and lymphocyte count. Logistic regression was used determine the parameters of our model. RESULTS: We found that patients with category 1 CT scans and ALC < 1.6 K/mm

12.
Medical Radiology and Radiation Safety ; 66(1):49-53, 2021.
Article in Russian | Scopus | ID: covidwho-1328284

ABSTRACT

Purpose: To develop a methodology for determining the muscle mass index (MMI) at the level of Th12 based on the computed tomography of the chest;to estimate the impact of MMI on the outcome of the COVID19 patients as a prognostic factor. Material and methods: The medical data and computed tomography of the chest of 247 patients with confirmed pneumonia caused by SARS-Cov2 were used. A technique has been developed for determining MMI based on the cross-sectional area of paraspinal muscles at the level of the Th12 vertebra and the length of the thoracic spine. A correlation analysis of MMI calculated based on the length of the thoracic spine MMI(L) and height MMI(H) was performed. A statistical analysis of the differences of the MMI(L) in the groups of male and female patients with fatal outcome and recovered, as well as younger and older than 65 years were performed. Results: A strong correlation was found between the MMI calculated on the basis of the length of the thoracic spine and height (r = 0.861, p <0.001). The age threshold, which was associated with an increase in the likelihood of death, in men was 60 years (Se 77.3 %, Sp 60.5 %, PPV 51.5 %, NPV 83.1 %, Youden's index 0.378, area under ROC- curve 0.728), in women 65 years old (Se 72.2 %, Sp 68.6 %, PPV 49.1 %, NPV 85.5 %, Youden's index 0.408, the area under the ROC curve 0.734). The odds ratio of death when the age thresholds are exceeded was 5.2 for men (95 % CI: 2.3 - 12.0), for women - 5.7 (95 % CI: 2.4 - 13.4). MMI(L) 3.37cm2/m2 is a threshold value, below which the probability of death in male patients under 60 years increased 26.3 times (95 % CI: 4.8 - 143.0). In female patients, there was no statistically significant threshold value of MMI(L), which would be associated with a higher risk of death. Conclusion: MMI, calculated at the level Th12 on the basis of the length of the thoracic spine, can be reliably used as a tool to estimate sarcopenia associated muscle atrophy, if there is no anthropometric data. The MMI(D) less than 3.37 cm2/m2 is a strong predictor of death in men under 60 years of age. Further work is needed to study the effect of sarcopenia on the severity and outcome of COVID19 in female patients, taking into account comorbid conditions. © 2021 State Research Center, Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. All rights reserved.

13.
Biophysics (Oxf) ; 65(4): 703-709, 2020.
Article in English | MEDLINE | ID: covidwho-894831

ABSTRACT

A hypothesis is proposed that the cytokine storm syndrome, which complicates COVID-19 in some patients, is a consequence of antibody-dependent enhancement of virus infection, which is in turn happens due to a change in dominant antigenic determinants of SARS-CoV-2 S-protein. The antibody-dependent enhancement of virus infection is a phenomenon in which virus-specific antibodies that are not neutralizing enhance the entry of infectious virus into immune cells causing their death. Antibody-dependent enhancement has been reported for different coronaviruses. This phenomenon happens due to a decrease in the binding strength of neutralizing antibodies to the virus, which converts these antibodies into suboptimal-not neutralizing ones. According to our hypothesis, such a decrease in affinity may be associated with a change in the conformation of the viral S-protein. We believe that this conformational change is the major factor in the switching of antibodies affinity, which triggers antibody-dependent enhancement. However, other factors that contribute to antigen drift and antigenic determinant changes may also play a role.

14.
Korean Journal of Veterinary Research ; 60(3):133-137, 2020.
Article in English | Scopus | ID: covidwho-891697

ABSTRACT

Diarrhea is the most common cause of death in calves, and remains a major health challenge. Although there are many studies on the related pathogens, the understanding of the clinicopathological changes is limited. This study aimed to identify the pathogens and observe the clinicopathological changes in electrolytes and acute phase proteins (APPs) associated with diarrhea. Blood samples and fecal samples were collected from 141 calves for the determination of APPs, electrolyte and acid-base status and identification of enteropathogens, respectively. Single or co-infections with enteropathogens, including virus (bovine viral diarrhea virus, coronavirus, and rotavirus), Eimeria, Cryptosporidium, and Escherichia coli K99 were detected in both non-diarrheic and diarrheic calves. Levels of APPs such as serum amyloid A, haptoglobin and fibrinogen were comparable between diarrheic and non-diarrheic calves. Hypoglycemia, high blood urea, electrolytes and acid-base imbalance (hyponatremia, hypochloremia, and decreased bicarbonate), and strong ion difference (SID) acidosis showed a significant association in diarrheic calves (p < 0.01). Particularly, significant hyponatremia, bicarbonate loss, SID acidosis, hypoglycemia, and elevated blood urea nitrogen were found in rotavirus-infected calves. Monitoring the clinicopathological parameters of APPs and electrolyte levels could be vital in the clinical management of diarrheic calves. © 2020 Korean Society of Veterinary Science. All rights reserved.

15.
Biofizika ; 65(4):824-832, 2020.
Article in English | Web of Science | ID: covidwho-859390

ABSTRACT

A hypothesis is proposed that the cytokine storm syndrome, which complicates the process of severe COVID-19 patients, is a consequence of antibody-dependent enhancement of viral infection, which in turn according to our hypothesis happens due to a variation in dominant antigenic determinants of the SARS-CoV-2 S protein. The antibody-dependent enhancement of viral infection is a phenomenon in which virus-specific antibodies which are not neutralizing enhance viral entry into immune complexes through the binding to receptors resulting in the death of the host cells. Antibody-dependent enhancement has been reported to be exploited by a variety of coronaviruses. In these cases, enhancement of viral infection can be triggered by variation in antigenic determinants of the S protein. This variation, according to our hypothesis, may lead to weaker binding of neutralizing antibodies to the virus, affecting the efficiency of these antibodies in protection against the virus - instead of neutralization viral suppression appears to be suboptimal. Variation in antigenic determinants (linear epitopes and conformational epitopes) may occur due to variation in S protein amino-acid composition. Variation in S protein amino acid composition is a consequence of the genetic diversity of quasi-species. We hypothesize that this variation may cause not only structural changes in the S protein, but also affect the dynamics of changes in its conformations. All these events can be observed in individuals infected with SARS-CoV-2 thereby explaining a severe course of the disease. Предложена гипотеза о том, что цитокиновый шторм, возникающий как осложнение у больных COVID-19, является следствием феномена антителозависимого усиления инфекции, а сам феномен в свою очередь обусловлен изменением доминантных антигенных детерминант в шиповидном S-белке вируса SARS-CoV-2. Антителозависимое усиление инфекции - это явление, при котором связывание вируса с субоптимальными антителами, которые не являются нейтрализующими, индуцирует проникновение вируса в клетки иммунной системы, что приводит к их массовой гибели. Явление антителозависимого усиления инфекции показано для ряда коронавирусов. Усиление инфекции в этих случаях может быть спровоцировано изменением антигенных детерминант S-белка. Такое изменение может приводить, согласно нашей гипотезе, к уменьшению прочности связывания нейтрализующих антител с вирусом, превращая их в субоптимальные - не нейтрализующие. Изменчивость линейных и/или конформационных антигенных детерминант S-белка может реализоваться за счет вариабельности ряда аминокислот в этом белке. Эта вариабельность является следствием генетического разнообразия квазивидов. Подобная изменчивость может вызывать не только структурные изменения в S-белке, но и влиять на динамику смены его конформаций. Все эти явления могут происходить в процессе вирусной инфекции SARS-CoV-2 и объяснять тяжелое течении болезни у некоторых зараженных.

16.
Medical Radiology and Radiation Safety ; 65(3):85-94, 2020.
Article in Russian | Scopus | ID: covidwho-830934

ABSTRACT

Purpose: The article covers issues related to providing personal protection equipment (PPE) for medical staff exposed to coronavirus (or similar infection) in the face of global pandemic and insufficient supply of infectious hospitals with disposable overalls. As many polymeric materials used to make such overalls do not feature required thermal stability and consequently they cannot be treated with heat disinfection, radiation treatment of protective overalls with electron accelerators for the purpose of their reuse was considered. Due to rich experience in addressing the issues of providing high-efficient, physiologically acceptable PPE for the personnel of radiation and chemical hazardous facilities, in particular during Chernobyl nuclear disaster elimination, the Laboratory of PPE for the Personnel of Hazardous Production Facilities, Burnasyan Federal Medical Biophysical Center, could extend methods of assessment and techniques of human protection against high-toxic substances to establishment of protection against microbiological threats. Results: The article provides results of analysis and tests of materials for overalls and respiratory PPE currently in use. Based on the material tests for radiation stability, air permeability, liquid penetration and protective properties with respect to aerosols, recommendations for improvement of efficiency and comfort of the PPE suite have been developed. Conclusion: The study showed feasibility of reusing overalls after radiation treatment. However, such treatment is appropriate only in periods of major emergencies during peacetime and wartime, when there are no production capabilities for manufacturing of new products. Location of the irradiation facility in the vicinity of consumers (e.g. medical institutions) is a prerequisite for this treatment. It should be emphasized that radiation treatment must be performed under strict supervision of accredited test facilities. Further research is required for development and enhancement of PPE and system of its application. This will allow to make longtime wear of PPE more comfortable without sacrificing its protective efficiency and develop a manual on product-specific radiation treatment. © 2020 State Research Center, Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. All rights reserved.

17.
Journal Biomed ; 16(2):39-46, 2020.
Article | Web of Science | ID: covidwho-790234

ABSTRACT

This communication presents the experience of using mobile pressure chambers in patients with the confi rmed novel coronavirus infection in hospital settings. The obtained preliminary results indicate positive antihypoxic effects of hyperbaric oxygen therapy (HBO) applied in the form of increased saturation. After a session of HBO, patients demonstrated an increase in the oxygen saturation of capillary blood hemoglobin at the average level of 3.71 points. Differences between SatO2 levels prior to and following HBO treatment were signifi cant in the CT2, CT3 and CT4 groups (p0.05). As expected, the effi cacy of HBO in terms of the oxygen saturation of capillary blood hemoglobin was the greatest in the patient groups showing pronounced clinical and radiological changes in the lungs. В сообщении представлен опыт применения мобильных барокамер пациентам с подтвержденной новой коронавирусной инфекцией в стационарных условиях. Полученные первичные обнадеживающие результаты свидетельствуют о положительных антигипоксических эффектах применения гипербарической оксигенации (ГБО) в виде повышения сатурации. Средний прирост насыщения гемоглобина капиллярной крови кислородом среди наблюдаемых пациентов после сеанса ГБО составил 3,71 пункта. Различия между уровнем SatO2 до и после процедуры ГБО были достоверными в группах КТ2, КТ3 и КТ4 (p0,05). Как и можно было ожидать, эффективность процедуры ГБО в плане воздействия на показатель насыщения гемоглобина капиллярной крови кислородом оказалась наибольшей в группах лиц с выраженными клинико-рентгенологическими изменениями в лёгких.

18.
Clean Technol Environ Policy ; 22(6): 1359-1370, 2020.
Article in English | MEDLINE | ID: covidwho-597157

ABSTRACT

Abstract: The global scientific community has intensified efforts to develop, test, and commercialize pharmaceutical products to deal with the COVID-19 pandemic. Trials for both antivirals and vaccines are in progress; candidates include existing repurposed drugs that were originally developed for other ailments. Once these are shown to be effective, their production will need to be ramped up rapidly to keep pace with the growing demand as the pandemic progresses. It is highly likely that the drugs will be in short supply in the interim, which leaves policymakers and medical personnel with the difficult task of determining how to allocate them. Under such conditions, mathematical models can provide valuable decision support. In particular, useful models can be derived from process integration techniques that deal with tight resource constraints. In this paper, a linear programming model is developed to determine the optimal allocation of COVID-19 drugs that minimizes patient fatalities, taking into account additional hospital capacity constraints. Two hypothetical case studies are solved to illustrate the computational capability of the model, which can generate an allocation plan with outcomes that are superior to simple ad hoc allocation.

19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(5): 491-493, 2020 May 06.
Article in Chinese | MEDLINE | ID: covidwho-243449

ABSTRACT

The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.


Subject(s)
Asymptomatic Infections , Coronavirus Infections/diagnosis , Family Health , Pneumonia, Viral/diagnosis , Antibodies, Viral/blood , Betacoronavirus , COVID-19 , China , Humans , Immunoglobulin M/blood , Male , Pandemics , SARS-CoV-2
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(0): E032, 2020 Apr 01.
Article in Chinese | MEDLINE | ID: covidwho-27070

ABSTRACT

Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.

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