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1.
JBMR Plus ; 5(1): e10405, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1898823

ABSTRACT

Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic T-regulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

2.
J Am Coll Emerg Physicians Open ; 1(4): 569-577, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1898677

ABSTRACT

Background: The SARS-CoV-2 (COVID-19) virus has wide community spread. The aim of this study was to describe patient characteristics and to identify factors associated with COVID-19 among emergency department (ED) patients under investigation for COVID-19 who were admitted to the hospital. Methods: This was a retrospective observational study from 8 EDs within a 9-hospital health system. Patients with COVID-19 testing around the time of hospital admission were included. The primary outcome measure was COVID-19 test result. Patient characteristics were described and a multivariable logistic regression model was used to identify factors associated with a positive COVID-19 test. Results: During the study period from March 1, 2020 to April 8, 2020, 2182 admitted patients had a test resulted for COVID-19. Of these patients, 786 (36%) had a positive test result. For COVID-19-positive patients, 63 (8.1%) died during hospitalization. COVID-19-positive patients had lower pulse oximetry (0.91 [95% confidence interval, CI], [0.88-0.94]), higher temperatures (1.36 [1.26-1.47]), and lower leukocyte counts than negative patients (0.78 [0.75-0.82]). Chronic lung disease (odds ratio [OR] 0.68, [0.52-0.90]) and histories of alcohol (0.64 [0.42-0.99]) or substance abuse (0.39 [0.25-0.62]) were less likely to be associated with a positive COVID-19 result. Conclusion: We observed a high percentage of positive results among an admitted ED cohort under investigation for COVID-19. Patient factors may be useful in early differentiation of patients with COVID-19 from similarly presenting respiratory illnesses although no single factor will serve this purpose.

3.
Turk Kardiyol Dern Ars ; 48(Suppl 1): 1-48, 2020 03.
Article in Turkish | MEDLINE | ID: covidwho-1835514

ABSTRACT

In December 2019, in the city of Wuhan, in the Hubei province of China, treatment-resistant cases of pneumonia emerged and spread rapidly for reasons unknown. A new strain of coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) was identified and caused the first pandemic of the 21st century. The virus was officially detected in our country on March 11, 2020, and the number of cases increased rapidly; the virus was isolated in 670 patients within 10 days. The rapid increase in the number of patients has required our physicians to learn to protect both the public and themselves when treating patients with this highly infectious disease. The group most affected by the outbreak and with the highest mortality rate is elderly patients with known cardiovascular disease. Therefore, it is necessary for cardiology specialists to take an active role in combating the epidemic. The aim of this article is to make a brief assessment of current information regarding the management of cardiovascular patients affected by COVID-19 and to provide practical suggestions to cardiology specialists about problems and questions they have frequently encountered.


Subject(s)
Betacoronavirus , Cardiology/standards , Cardiovascular Diseases/therapy , Cardiovascular Diseases/virology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , COVID-19 , Cardiovascular Diseases/epidemiology , Consensus , Humans , Pandemics , SARS-CoV-2 , Societies, Medical , Turkey
4.
Turk Kardiyol Dern Ars ; 48(Suppl 1): 1-87, 2020 05.
Article in Turkish | MEDLINE | ID: covidwho-1835513

ABSTRACT

In December 2019, in the city of Wuhan, in the Hubei province of China, treatment-resistant cases of pneumonia emerged and spread rapidly for reasons unknown. A new strain of coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) was identified and caused the first pandemic of the 21st century. The virus was officially detected in our country on March 11, 2020, and the number of cases increased rapidly; the virus was isolated in 670 patients within 10 days. The rapid increase in the number of patients has required our physicians to learn to protect both the public and themselves when treating patients with this highly infectious disease. The group most affected by the outbreak and with the highest mortality rate is elderly patients with known cardiovascular disease. Therefore, it is necessary for cardiology specialists to take an active role in combating the epidemic. The aim of this article is to make a brief assessment of current information regarding the management of cardiovascular patients affected by COVID-19 and to provide practical suggestions to cardiology specialists about problems and questions they have frequently encountered.


Subject(s)
Cardiovascular Diseases , Coronavirus Infections , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Cardiology/standards , Cardiovascular Diseases/complications , Cardiovascular Diseases/therapy , Consensus , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , SARS-CoV-2
5.
Knee Surg Sports Traumatol Arthrosc ; 28(6): 1712-1719, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1826408

ABSTRACT

PURPOSE: The aim of the present study was to evaluate the impact of the coronavirus (COVID-19) pandemic on joint arthroplasty service in Europe by conducting an online survey of arthroplasty surgeons. METHODS: The survey was conducted in the European Hip Society (EHS) and the European Knee Associates (EKA). The survey consisted of 20 questions (single, multiple choice, ranked). Four topics were addressed: (1) origin and surgical experience of the participant (four questions); (2) potential disruption of arthroplasty surgeries (12 questions); (3) influence of the COVID-19 pandemic on the particular arthroplasty surgeon (four questions); (4) a matrix provided 14 different arthroplasty surgeries and the participant was asked to state whether dedicated surgery was stopped, delayed or cancelled. RESULTS: Two-hundred and seventy-two surgeons (217 EHS, 55 EKA) from 40 different countries participated. Of the respondents, 25.7% stated that all surgeries were cancelled in their departments, while 68.4% responded that elective inpatient procedures were no longer being performed. With regard to the specific surgical procedures, nearly all primary TJA were cancelled (92.6%) as well as aseptic revisions (94.7%). In most hospitals, periprosthetic fractures (87.2%), hip arthroplasty for femoral neck fractures and septic revisions for acute infections (75.8%) were still being performed. CONCLUSION: During the current 2020 COVID-19 pandemic, we are experiencing a near-total shutdown of TJA. A massive cutback was observed for primary TJA and revision TJA, even in massively failed TJA with collapse, dislocation, component failure or imminent dislocation. Only life-threatening pathologies like periprosthetic fractures and acute septic TJA are currently undergoing surgical treatment. LEVEL OF EVIDENCE: V.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Delivery of Health Care/statistics & numerical data , Elective Surgical Procedures/statistics & numerical data , Orthopedic Procedures/statistics & numerical data , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Europe/epidemiology , Health Care Surveys , Humans , Internet , Male , Prospective Studies , SARS-CoV-2
6.
J Healthc Leadersh ; 12: 85-94, 2020.
Article in English | MEDLINE | ID: covidwho-1793328

ABSTRACT

PURPOSE: The aim of the study is to evaluate the prevalence and extent of burnout among physicians and investigate the factors related with burnout and the influence of the fight against coronavirus (COVID-19) on the burnout syndrome. METHODS: A cross-sectional survey design was adopted and conducted on 200 actively working physicians in Izmir/Turkey. Personal Information Form and Maslach Burnout Inventory were used in the survey. RESULTS: The findings showed that the emotional exhaustion level of the physicians was medium, the levels of depersonalization and personal accomplishment were low, and the level of total burnout was low. It was observed that the burnout levels of males and females, and married and single physicians were similar. The emotional exhaustion level of 18-23-year-old physicians was lower than the rest of the physicians. Physicians' level of satisfaction with their income is not effective on burnout. The burnout level of physicians who did not choose their profession willingly was determined to be higher than the burnout level of the physicians who chose their profession willingly. One important finding showed that the burnout level of physicians who actively involved in the fight against COVID-19 was lower than the burnout level of the physicians who did not actively involve in the fight against COVID-19. CONCLUSION: Although the impact of some demographic variables, such as gender, marital status and satisfaction of income on burnout, was similar among the groups, total burnout level was lower in physicians who actively fought with the virus. This result may suggest that those physicians who were actively involved in the fight against COVID-19 had a high sense of meaningfulness of work which will result in high satisfaction with the work itself and, thus, creating less burnout. Also, they had a stronger feeling of personal accomplishment as they faced the immediate outcomes of their care for people infected by COVID-19.

7.
Minerva Cardiol Angiol ; 70(2): 160-166, 2022 04.
Article in English | MEDLINE | ID: covidwho-1786557

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has rapidly spread globally. Due to different testing strategies, under-detection of positive subjects and COVID-19-related-deaths remains common. Aim of this analysis was to assess the real impact of COVID-19 through the analysis of 2020 Italian all-cause mortality data compared to historical series. METHODS: We performed a retrospective analysis of 2020 and 2015-2019 all-cause mortality data released by the Italian National Institute for Statistics (ISTAT) for the time period January 1st-March 21st. This preliminary sample included 1084 Italian municipalities showing at least 10 deaths during the above-mentioned timeframe and an increase in mortality of more than 20% as compared to the previous five years (2015-2019), with a resulting coverage of 21% of Italian population. The difference between 2020 observed and expected deaths (mean of weekly deaths in 2015-2019) was computed, together with mortality rate ratio (MRR) for each of the four weeks following detection of the first autochthonous COVID-19 case in Italy (February 23rd, 2020 - March 21st, 2020), as well as for this entire timeframe. Subgroup analysis by age groups was also performed. RESULTS: Overall MRR was 1.79 [1.75-1.84], with an observed excess mortality of 8750 individuals in the investigated sample, which in itself outweighs Italian Civil Protection report of only 4,825 COVID-19-related deaths across Italy, as of March 21. Subgroup analysis did not show any difference in mortality rate in '0-14 years' age group, while MRRs were significantly increased in older age groups, in particular in patients >75 years (MRR 1.84 [1.79-1.89]). In addition, week-by-week analysis showed a progressive increase in MRR during this period, peaking in the last week (March 15th, 2020 - March 21st, 2020) with an estimated value of 2.65 [2.53-2.78]. CONCLUSIONS: The analysis of all-cause mortality data in Italy indicates that reported COVID-19-related deaths are an underestimate of the actual death toll. All-cause death should be seen as the epidemiological indicator of choice to assess the real mortality impact exerted by SARS-CoV-2, given that it also best reflects the toll on frail patient subsets (e.g. the elderly or those with cardiovascular disease).


Subject(s)
COVID-19 , Cardiovascular Diseases , Aged , Cardiovascular Diseases/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
8.
J Cardiovasc Nurs ; 36(6): 595-598, 2021.
Article in English | MEDLINE | ID: covidwho-1706374

ABSTRACT

BACKGROUND: The COVID-19 pandemic has altered catheterization laboratory (cath lab) practices in diverse ways. OBJECTIVE: The aim of this study was to understand the impact of COVID-19 on Veterans Affairs (VA) procedural volume and cath lab team experience. METHODS: Procedural volume and COVID-19 patient data were obtained from the Clinical, Assessment, Reporting and Tracking Program. A mixed methods survey was emailed to VA cath lab staff asking about the COVID-19 response. Descriptive and manifest content analyses were conducted. RESULTS: Procedural volume decreased from April to September 2020. One hundred four patients with known COVID-19 were treated. Survey response rate was 19% of staff (n = 170/902) from 83% of VA cath labs (n = 67/81). Reassignment to other units, confusion regarding COVID-19 testing, personal protective equipment use, and low patient volume were reported. Anxiety, burnout, and leadership's role on team morale were described. CONCLUSIONS: Some teams adapted. Others expressed frustration over the lack of control over their practice. Leaders should routinely assess staff needs during the current and future crises.


Subject(s)
COVID-19 , Veterans , COVID-19 Testing , Catheterization , Humans , Laboratories , Pandemics , SARS-CoV-2 , United States
9.
Eur J Gastroenterol Hepatol ; 33(12): 1578-1581, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1595632

ABSTRACT

AIM: Coronavirus disease 2019 (COVID-19) is a recently encountered disease that was declared a pandemic by WHO in 2020. Obesity and other components of the metabolic syndrome may aggravate the severity of COVID-19. Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome. The aim of this study was to investigate a possible association between MAFLD and COVID-19 severity. METHODS: We performed a retrospective, case-control study, enrolling 71 consecutive COVID-19 patients who were divided into two groups according to the presence or absence of fatty liver by computed tomography scan. All medical records of eligible patients were reviewed including demographic, clinical, laboratory parameters and data regarding the presence of NAFLD and COVID-19 severity. RESULTS: NAFLD was identified in 22/71 (31%) of the study group. Out of 71, thirteen suffered from severe COVID-19. NAFLD patients had more severe COVID-19 compared with non-NAFLD subjects, 8/22 (36.3%) vs. 5/49(10.2%), (P < 0.005), respectively. Multiple logistic regression analysis showed that NAFLD subjects were more likely to have severe COVID-19 disease (odds ratio 3.57, 95% confidence interval: 1.22, 14.48, P = 0.0031). CONCLUSION: NAFLD represents a high risk for severe COVID-19 irrespective to gender, and independent of metabolic syndrome specifically in male gender. Moreover, obesity, hypertension and metabolic syndrome were also significantly associated with severe COVID-19.


Subject(s)
COVID-19 , Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Case-Control Studies , Humans , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2
10.
Front Vet Sci ; 8: 572012, 2021.
Article in English | MEDLINE | ID: covidwho-1574919

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great harm to global public health, resulting in a large number of infections among the population. However, the epidemiology of coronavirus has not been fully understood, especially the mechanism of aerosol transmission. Many respiratory viruses can spread via contact and droplet transmission, but increasing epidemiological data have shown that viral aerosol is an essential transmission route of coronavirus and influenza virus due to its ability to spread rapidly and high infectiousness. Aerosols have the characteristics of small particle size, long-time suspension and long-distance transmission, and easy access to the deep respiratory tract, leading to a high infection risk and posing a great threat to public health. In this review, the characteristics of viral aerosol generation, transmission, and infection as well as the current advances in the aerosol transmission of zoonotic coronavirus and influenza virus are summarized. The aim of the review is to strengthen the understanding of viral aerosol transmission and provide a scientific basis for the prevention and control of these diseases.

11.
J Emerg Med ; 60(3): 321-330, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1454285

ABSTRACT

BACKGROUND: The use of anticoagulant medications leads to a higher risk of developing traumatic intracranial hemorrhage (tICH) after a mild traumatic brain injury (mTBI). The management of anticoagulated patients can be difficult to determine when the initial head computed tomography is negative for tICH. There has been limited research on the risk of delayed tICH in patients taking direct oral anticoagulant (DOAC) medications. OBJECTIVE: Our aim was to determine the risk of delayed tICH for patients anticoagulated with DOACs after mTBI. METHODS: We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched several medical databases to examine the risk of delayed tICH in patients on DOACs. RESULTS: There were 1252 nonduplicate studies that were identified through an initial database search, 15 of which met our inclusion and exclusion criteria and were included in our analysis after full-text review. A total of 1375 subjects were combined among the 15 studies, with 20 instances of delayed tICH after mTBI. Nineteen of the 20 patients with a delayed tICH were discharged without any neurosurgical intervention, and 1 patient on apixaban died due to a delayed tICH. CONCLUSIONS: This systematic review confirms that delayed tICH after mTBI in patients on DOACs is uncommon. However, large, multicenter, prospective studies are needed to confirm the true incidence of clinically significant delayed tICH after DOAC use. Due to the limited data, we recommend using shared decision-making for patients who are candidates for discharge.


Subject(s)
Brain Concussion , Intracranial Hemorrhage, Traumatic , Anticoagulants/therapeutic use , Brain Concussion/complications , Humans , Intracranial Hemorrhage, Traumatic/etiology , Multicenter Studies as Topic , Prospective Studies , Retrospective Studies
12.
Interv Neuroradiol ; 26(5): 557-565, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1455862

ABSTRACT

BACKGROUND: The Low-profile Visualized Intraluminal Support device (LVIS) has been successfully used to treat cerebral aneurysm, and the push-pull technique has been used clinically to compact the stent across aneurysm orifice. Our aim was to exhibit the hemodynamic effect of the compacted LVIS stent. METHODS: Two patient-specific aneurysm models were constructed from three-dimensional angiographic images. The uniform LVIS stent, compacted LVIS and Pipeline Embolization Device (PED) with or without coil embolization were virtually deployed into aneurysm models to perform hemodynamic analysis. Intra-aneurysmal flow parameters were calculated to assess hemodynamic differences among different models. RESULTS: The compacted LVIS had the highest metal coverage across the aneurysm orifice (case 1, 46.37%; case 2, 67.01%). However, the PED achieved the highest pore density (case 1, 19.56 pores/mm2; case 2, 18.07 pores/mm2). The compacted LVIS produced a much higher intra-aneurysmal flow reduction than the uniform LVIS. The PED showed a higher intra-aneurysmal flow reduction than the compacted LVIS in case 1, but the results were comparable in case 2. After stent placement, the intra-aneurysmal flow was further reduced as subsequent coil embolization. The compacted LVIS stent with coils produced a similar reduction in intra-aneurysmal flow to that of the PED. CONCLUSIONS: The combined characteristics of stent metal coverage and pore density should be considered when assessing the flow diversion effects of stents. More intra-aneurysmal flow reductions could be introduced by compacted LVIS stent than the uniform one. Compared with PED, compacted LVIS stent may exhibit a flow-diverting effect comparable to that of the PED.


Subject(s)
Embolization, Therapeutic/methods , Intracranial Aneurysm/therapy , Stents , Subarachnoid Hemorrhage/therapy , Angiography, Digital Subtraction , Cerebral Angiography , Computer Simulation , Hemodynamics , Humans , Hydrodynamics , Imaging, Three-Dimensional , Intracranial Aneurysm/diagnostic imaging , Magnetic Resonance Angiography , Prosthesis Design , Subarachnoid Hemorrhage/diagnostic imaging
13.
Int J Mol Med ; 47(5)2021 05.
Article in English | MEDLINE | ID: covidwho-1448967

ABSTRACT

Circular RNAs (circRNAs) are a class of non­coding RNAs with a circular, covalent structure that lack both 5' ends and 3' poly(A) tails, which are stable and specific molecules that exist in eukaryotic cells and are highly conserved. The role of circRNAs in viral infections is being increasingly acknowledged, since circRNAs have been discovered to be involved in several viral infections (such as hepatitis B virus infection and human papilloma virus infection) through a range of circRNA/microRNA/mRNA regulatory axes. These findings have prompted investigations into the potential of circRNAs as targets for the diagnosis and treatment of viral infection­related diseases. The aim of the present review was to systematically examine and discuss the role of circRNAs in several common viral infections, as well as their potential as diagnostic markers and therapeutic targets.


Subject(s)
MicroRNAs/genetics , RNA, Circular/physiology , RNA, Messenger/genetics , Virus Diseases/genetics , Biomarkers/analysis , Humans , RNA, Circular/genetics , Virus Diseases/diagnosis , Virus Diseases/therapy , Virus Diseases/virology
14.
Clin Trials ; 18(3): 286-294, 2021 06.
Article in English | MEDLINE | ID: covidwho-1400653

ABSTRACT

BACKGROUND: Vaccines are potent tools to prevent outbreaks of emerging infectious diseases from becoming epidemics and need to be developed at an accelerated pace to have any impact on the course of an ongoing epidemic. The aim of this study was to describe time use in the execution of vaccine trials, to identify steps that could be accelerated to improve preparedness and planning for future emerging infectious diseases vaccine trials. METHODS: We used a mixed-methods approach to map time use and process steps that could be accelerated during vaccine trials. Trials for vaccines against infectious diseases registered in three global trial databases reported in the period 2011-2017 were eligible to join the survey. We invited sponsors to contribute data through a predefined structured questionnaire for clinical trial process metrics. Data were stratified by trial phase, disease type (i.e. emerging infectious diseases or not emerging infectious diseases), sponsor type, and continent. Qualitative interviews were conducted with purposively selected sponsors, and thematic analysis of the interview transcripts was performed. RESULTS: Based on data from 155 vaccine trials including 29,071 subjects, 52% were phase I, 23% phase II, and 25% phase III. We found that the regulatory approval, subject enrollment, study execution, and study close-out accounted for most of the cycle time of the vaccine trial process. Cycle times for the regulatory and ethical approvals, contract agreement, site initiation, and study execution were shorter in trials conducted during outbreaks. Qualitative interviews indicated that early engagement of the regulatory and independent ethical committee authorities in planning the vaccine trials was critical for saving time in trial approval. Furthermore, adapting the trial implementation to the reality of the study sites and active involvement of the local investigators during the planning of the trial and protocol writing were stated to be of paramount importance to successful completion of trials at an accelerated pace. CONCLUSION: The regulatory approval, subject recruitment, study execution, and close-out cycle times accounted for most of the vaccine trial time use and are activities that could be accelerated during a vaccine trial planning and implementation. We encourage tracking of key cycle time metrics and facilitating sharing of knowledge across industry and academia, as this may serve to reduce the time from index case detection to access of a vaccine during emerging infectious diseases epidemics.


Subject(s)
Clinical Trials as Topic , Communicable Diseases, Emerging , Epidemics , Vaccines , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Epidemics/prevention & control , Humans , Research Design , Time
15.
Mol Biol Evol ; 38(2): 702-715, 2021 01 23.
Article in English | MEDLINE | ID: covidwho-1387955

ABSTRACT

Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming to identify the unique molecular elements in the SARS-CoV-2 proteome that may explain the differing consequences. By combining protein modeling and molecular dynamics simulations, we suggest nonconservative substitutions in functional regions of the spike glycoprotein (S), nsp1, and nsp3 that are contributing to differences in virulence. Particularly, we explain why the substitutions at the receptor-binding domain of S affect the structure-dynamics behavior in complexes with putative host receptors. Conservation of functional protein regions within the two taxa is also noteworthy. We suggest that the highly conserved main protease, nsp5, of SARS-CoV and SARS-CoV-2 is part of their mechanism of circumventing the host interferon antiviral response. Overall, most substitutions occur on the protein surfaces and may be modulating their antigenic properties and interactions with other macromolecules. Our results imply that the striking difference in the pervasiveness of SARS-CoV-2 and SARS-CoV among humans seems to significantly derive from molecular features that modulate the efficiency of viral particles in entering the host cells and blocking the host immune response.


Subject(s)
Molecular Dynamics Simulation , Proteomics , SARS Virus/chemistry , SARS Virus/pathogenicity , SARS-CoV-2/chemistry , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Animals , Humans , Protein Domains , SARS Virus/metabolism , SARS-CoV-2/metabolism , Species Specificity , Viral Proteins/metabolism
16.
Clin Res Cardiol ; 109(12): 1549-1566, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1384407

ABSTRACT

BACKGROUND: Myocardial involvement induced by SARS-CoV-2 infection might be important for long-term prognosis. The aim of this observational study was to characterize the myocardial effects during SARS-CoV-2 infections by echocardiography. RESULTS AND METHODS: An extended echocardiographic image acquisition protocol was performed in 18 patients with SARS-CoV-2 infection assessing LV longitudinal, radial, and circumferential deformation including rotation, twist, and untwisting. Furthermore, LV deformation was analyzed in an age-matched control group of healthy individuals (n = 20). The most prevalent finding was a reduced longitudinal strain observed predominantly in more than one basal LV segment (n = 10/14 patients, 71%). This pattern reminded of a "reverse tako-tsubo" morphology that is not typical for other viral myocarditis. Additional findings included a biphasic pattern with maximum post-systolic or negative regional radial strain predominantly basal (n = 5/14 patients, 36%); the absence or dispersion of basal LV rotation (n = 6/14 patients, 43%); a reduced or positive regional circumferential strain in more than one segment (n = 7/14 patients, 50%); a net rotation showing late post-systolic twist or biphasic pattern (n = 8/14 patients, 57%); a net rotation showing polyphasic pattern and/or higher maximum net values during diastole (n = 8/14 patients, 57%). CONCLUSION: Myocardial involvement due to SARS-CoV-2-infection was highly prevalent in the present cohort-even in patients with mild symptoms. It appears to be characterized by specific speckle tracking deformation abnormalities in the basal LV segments. These data set the stage to prospectively test whether these parameters are helpful for risk stratification and for the long-term follow-up of these patients.


Subject(s)
COVID-19/complications , Echocardiography , Heart/diagnostic imaging , Myocarditis/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Female , Heart/physiopathology , Heart/virology , Host-Pathogen Interactions , Humans , Male , Middle Aged , Myocarditis/physiopathology , Myocarditis/virology , Predictive Value of Tests , SARS-CoV-2/pathogenicity , Severity of Illness Index , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/virology , Ventricular Function, Left
17.
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1389392

ABSTRACT

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.


Subject(s)
Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/physiology , Lung Diseases/physiopathology , Lung/physiology , Alveolar Epithelial Cells/cytology , Animals , COVID-19/physiopathology , Humans , Immunity, Innate , Ions/metabolism , Lung/anatomy & histology , Lung Diseases/etiology , Lung Diseases/pathology , Pulmonary Surfactant-Associated Proteins/metabolism , Regeneration
18.
Br J Clin Pharmacol ; 87(9): 3439-3450, 2021 09.
Article in English | MEDLINE | ID: covidwho-1373788

ABSTRACT

AIM: We hypothesized that viral kinetic modelling could be helpful to prioritize rational drug combinations for COVID-19. The aim of this research was to use a viral cell cycle model of SARS-CoV-2 to explore the potential impact drugs, or combinations of drugs, that act at different stages in the viral life cycle might have on various metrics of infection outcome relevant in the early stages of COVID-19 disease. METHODS: Using a target-cell limited model structure that has been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to inform on the combinations of therapeutics targeting specific rate constants. The endpoints and metrics included viral load area under the curve (AUC), duration of viral shedding and epithelial cells infected. Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. RESULTS: Our simulations suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of viral shedding exceeds the effect on sparing epithelial cells from infection or impact on viral load AUC. Furthermore, the impact on reduction on duration of shedding may extend further in patients who exhibit a prolonged shedder phenotype. CONCLUSIONS: Our work highlights the use of model-informed drug repurposing approaches to better rationalize effective treatments for COVID-19.


Subject(s)
COVID-19 , Drug Repositioning , SARS-CoV-2 , COVID-19/drug therapy , Drug Combinations , Humans , Kinetics , SARS-CoV-2/drug effects
19.
J Pediatr Gastroenterol Nutr ; 73(3): 299-305, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1367080

ABSTRACT

ABSTRACT: Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection, including vomiting, diarrhoea, abdominal pain, and difficulty in feeding, although these symptoms tend to be mild. The hepato-biliary system and the pancreas may also be involved, usually with a mild elevation of transaminases and, rarely, pancreatitis. In contrast, a late hyper-inflammatory phenomenon, termed multisystem inflammatory syndrome (MIS-C), is characterized by more frequent gastrointestinal manifestations with greater severity, sometimes presenting as peritonitis. Gastrointestinal and hepato-biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells, hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines. Specific conditions such as inflammatory bowel disease (IBD) and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 (COVID-19) but as adult data accumulate, paediatric data is still limited. The aim of this review is to summarize the current evidence about the effect of COVID-19 on the gastrointestinal system in children, with emphasis on the emerging MIS-C and specific considerations such as patients with IBD and liver transplant recipients.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Diarrhea , Gastrointestinal Diseases/etiology , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
20.
Exp Ther Med ; 22(1): 790, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1359309

ABSTRACT

Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione], the main component of turmeric (Curcuma longa, a flowering plant of the ginger family, Zingiberaceae), is known to possess different pharmacological activities, particularly anti-inflammatory and antioxidant properties. Since an underlying inflammatory process exists in several ocular conditions, such as anterior uveitis, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR), the aim of the present review was to summarize the pleiotropic effects exerted by this molecule, focusing in particular on its beneficial role in retinal diseases. The anti-inflammatory activity of curcumin has also been described in numerous systemic inflammatory pathologies and tumors. Specifically, the biological, pharmaceutical and nutraceutical properties of curcumin are associated with its ability to downregulate the expression of the following genes: IκBα, cyclooxygenase 2, prostaglandin E2, interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor-α. According to this finding, curcumin may be useful in the treatment of some retinal disorders. In DR, proliferative vitreoretinopathy and AMD, beneficial effects have been observed following treatment with curcumin, including slowing down of the inflammatory process. Despite the aforementioned evidence, the main disadvantage of this substance is that it possesses a low solubility, as well as poor oral bioavailability due to its reduced absorption, rapid metabolism and rapid elimination. Therefore, several curcumin analogues have been synthesized and tested over the years, in order to improve the possible obtainable therapeutic effects. The purpose of the present review was to identify new aspects that could guide future research on this important traditional medicine, which is a well-tolerated natural product, and is widely considered safe and economical.

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