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1015 covid-19 Wiley Open Research Preprints

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covid-19 ace2 allergy and immunology methods: t cells methods: cytokines GEMFIBROZIL human childhood cancer evaluation protein engineering interferons patient education thermal stability during storage respiratory tract infections clinical governance glycosylation prevention methods: igg IMMUNE MODULATING TREATMENT asthma sars-cov-2 and covid-19 prospective studies covid methods: b cells avidity + show more keywords
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Please note: These are preprints and have not been peer reviewed. Data may be preliminary. Preprints should not be relied on to guide medical practice or health-related decisions. News media reporting on preprints should stress that the research should not yet be considered conclusive.
The role of primary healthcare physicians in the COVID-19 pandemic: a cross-sectional...
Rami Saadeh
Mahmoud  Alfaqih

Rami Saadeh

and 7 more

November 03, 2020
Background: Following the remarkable spread of coronavirus disease 2019 (COVID-19), worldwide, it quickly became apparent that many public health systems worldwide were not prepared to manage such a pandemic. We aimed to assess the perceptions of primary care physicians (PCPs) in Jordan toward their role during COVID-19. Methods: A cross-sectional study using a self-administered questionnaire was performed. The study participants included PCPs from the Ministry of Health, academic institutions, and the private sector in Jordan. Results: A total of 221 PCPs participated in the study. Most participants reported not having received any training on infection control (59.7%) or COVID-19 (81%). More than half PCPs (53.4%) felt positive about the way patients received and/or complied with their instructions. More than half PCPs (55.7%) educated their patients on protective measures against COVID-19 infection and considered this as part of their role and responsibility. Over 80% of the participants would apply social distancing, hand sanitation, facial masks, and patient education, but only half (51.1%) reported planning to order COVID-19 test kits. Conclusions: PCPs had a positive attitude toward controlling COVID-19 infection and showed a willingness to educate patients on how to protect themselves. However, PCPs should be provided special training on COVID-19.
ACE2-Based Decoy Receptors for SARS Coronavirus 2
Wenyang Jing
Erik Procko

Wenyang Jing

and 1 more

November 03, 2020
SARS-CoV-2 is neutralized by proteins that block receptor-binding sites on spikes that project from the viral envelope. In particular, substantial research investment has advanced monoclonal antibody therapies to the clinic where there are signs of partial efficacy in reducing viral burden and hospitalization. An alternative is to use the host entry receptor, ACE2, as a soluble decoy that broadly blocks SARS-associated coronaviruses with limited potential for viral escape. Here, we summarize efforts to engineer higher affinity variants of soluble ACE2 that rival the potency of affinity-matured antibodies. Strategies have also been used to increase the valency of ACE2 decoys for avid spike interactions and to improve pharmacokinetics via IgG fusions. Finally, the intrinsic catalytic activity of ACE2 for the turnover of the vasoconstrictor angiotensin II may directly address COVID-19 symptoms and protect against lung and cardiovascular injury, conferring dual mechanisms of action unachievable by monoclonal antibodies. Soluble ACE2 derivatives therefore have the potential to be next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.
COVID-19: GEMFIBROZIL AS A POTENTIAL ADJUVANT IMMUNE MODULATING TREATMENT

Marciano Lee

and 5 more

November 03, 2020
Marciano Lee1, Elise Anderson1, Ali Farooq1, Mohammed Yasin1, Yazan Alkawaleet1, Frank Annie2Charleston Area Medical Center, Department of Cardiology, 3200 MacCorkle Ave. SE,Charleston, WV 25304CAMC Health Education and Research Institute, 3200 MacCorkle Ave. SE,Charleston, WV 25304Corresponding:Frank Annie MA; MPA; PhDResearch Scientist (Department of Cardiology)CAMC Health Education and Research Institute3200 MacCorkle Ave. SE,Charleston, WV 25304Cell 304 -395 – 3830Phone 304-388-9921Fax: 304-388-9921Email: Frank.H.Annie@camc.orgKeywords:COVID-19, GEMFIBROZIL, IMMUNE MODULATING TREATMENTAbstract:The current Covid-19 viral infection has been declared a pandemic causing significant global morbidity and mortality predominantly from the manifestation of severe acute respiratory syndrome (SARS). It has been designated as SARS-CoV 2. Epidemiological studies show predilection in patients with associated chronic medical conditions including those with cardiovascular disease. Exaggerated host immune response known as cytokine storm syndrome (CSS) leading to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is the proposed mechanism for the development of SARS in Covid-19 infection. Gemfibrozil has proven benefits in patients with cardiovascular disease. More importantly, it has established anti-inflammatory, anti-oxidative, and anti-migratory properties. Gemfibrozil has shown survival benefits as immune modulation of ALI/ARDS from viral pathogens. This article reviews the potential of gemfibrozil as adjuntive immue modulating therapy for SARS associated with Covid-19 infected patients who have associated cardiovascular disease.Introduction:The severe acute respiratory syndrome (SARS) seen in Covid-19 infection share similarities with previous coronavirus epidemics, particularly SARS-CoV 1 and the Middle East Respiratory Syndrome (MERS-CoV). (1) It has been designated SARS-CoV 2. Acute lung injury (ALI) with subsequent development of acute respiratory distress syndrome (ARDS) from robust host hyper-immune response is the proposed pathophysiological mechanism. This so called ”cytokine storm” may be independent of viral load and replication. (2) Thus, the rationale for adding immune modulating strategies on top of antiviral/antimicrobial therapies is warranted to prevent this complication and hopefully improve survival. The development of ALI/ARDS amplifies mortality in Covid-19 infection, more so in patients with associated chronic medical conditions including cardiovascular disease. (3)Gemfibrozil, a drug discovered over 40 years ago, have beneficial effects and safety profile in both primary and secondary prevention of cardiovascular disease. (4) In addition to its lipid lowering ability, it has important immune modulating properties that inhibit pro-inflammatory factors involved in cytokine storms.(5) It is a peroxisome proliferators-activated receptor (PPAR) agonist known to reduce the release of inflammatory cytokines including interleukin-6 (IL-6), tumor necrosing factors (TNF) and interferon-gamma (IFN-g).IL-6 elevation have been reported as an important marker of severity with Covid-19 infection. (3) Together with other markers for inflammation such as CRP, the degree of IL-6 elevation correlates with increased morbidity and mortality.Gemfibrozil has shown survival benefits by attenuating ALI/ARDS development from viral etiologies. (6) Since gemfibrozil is currently indicated for patients with cardiovascular disease, its adjunctive use does not have to be repurposed for SARS associated with Covid-19 infection. Therefore, Gemfibrozil’s potential as an immune modulating strategy to prevent ALI/ARDS cannot be ignored.Immune Modulating Targets for Gemfibrozil in Covid-19 SARS pathogenesis:Gemfibrozil has been shown to attenuate pro-inflammatory effects of disease states through its immune-modulating, anti-inflammatory and anti-migratory properties. (5). It belongs to the fibrate family of drugs used to lower plasma lipds and cholesterol. They are one of several known synthetic lignads acting as agonists to the PPARs. (7) Their action in turn decrease serum levels of TNF, IFN-g and IL-6. (8,9)As an an anti-inflammatory, gemfibrozil reduces superoxide production and expression of nuclear factor kB (NF-kB). (10) Moreover, it inhibits astrocyte production of TNF, IL-1b, IL-6 and nitric oxide (NO) production. (11) Gemfibrozil also promotes the production of anti-inflammatory cytokine IL-4. (12) It reduces the production of C-reactive protein (CRP), TNF-a and IL-6 in peripheral blood mononuclear cells. It inhibits the production of cyclooxygenase-2 (COX-2) and prostaglandins. (13)As an immune-modulating agent, gemfibrozil attenuates pro-inflammatory transcription factor activation. This includes IFN-g regulatory factor 1 (IRF-1)bidning to gamma activation site (GAS), nuclear factor-kB (NF-kB), activator protein 1 (AP-1), and CCAT/enhancer binding protein beta (C/EBPb). (5) It also promotes switching of T helper (Th) cells from the pro-inflammatory Th1 to anti-inflammatory Th2. Production of Th2-specific cytokines is amplified including IL-4, IL-5 and IL-10. (14)As an anti-oxidant, gemfibrozil not only prevents low density lipoprotein (LDL) peroxidation but also acts on other signals of inflammation. Reactive oxygen species (ROS) have emerged as important signaling molecules during inflammatory conditions. Excessive ROS generation results in damage to most cellular components of the living organism. Gemfibrozil is known to inhibit ROS-mediated inflammation. (15) It has free radical scavenging ability as well. Its para-hydroxyl metabolite has been shown to reduce the burden of ROS. (16)As an anti-migratory agent, gemfibrozil affects the expression of cell-surface adhesion molecules icluding intracellular adhesion molecule 1 (ICAM-1), VCAM-1 and selectins inhibiting trans endothelial migration of mononuclear cells and macrophages. (17) It also down-regulates the expression of chemokines including monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 (MIP-1), monokines induced by IFN-g (MIG) and IL-8. The expression of IL-8 induces inflammation, monocyte/macrophage recruitment, angiogenesis and vascular smooth muscle migration. Thus, gemfibrozil can function as an anti-migratory factor by down-regulating the expression of different soluble chemokines and inhibit the expression of different cell surface proteins and selectins.Discussion:Over the years, viral pathogens including Influenzas and Coronaviruses cause ALI/ARDS from excessive release of pro-inflammatory cytokines and chemokines described in cytokine storm syndromes. They induce much higher transcription and up regulation of TNF genes including TNF related aptoptosis-inducing lignad and TNF-mRNA in human monocyte-derived macrophages. (18) This macrophage activation syndrome (MAS) seen with the current SARS-CoV 2 may be a dysregulated host response to Covid-19 viral induced immunosuppression and lymphopenia leading to unintended ALI/ARDS consequences at the site of infection. (19) The development of ALI/ARDS and the need for ventilator support portends to increased mortality rates. Markers of inflammation including CRP and IL-6 have been used as surrogates for MAS, and their degree of elevation have correlated well with disease severity. (3)Experiments with SARS-CoV indicate that MAS induced cytokine storms result more from amplification of gene related inflammatory signals regardless of viral load. In one model, immune modulation of receptor sites or alteration of recruitment signals resulted in dramatic improvement in host survival with viral load remaining constant. (20) This suggests that immune modulating therapy may have as important a role in addition to antiviral therapy in altering the course of Covid-19 infection. Reports of clinical improvement have been reported with the adjuvant use of IL-6 antagonists including tocilizumab. However, cost and repurposing use of these medications may be limiting factors.Gemfibrozil has been in clinical use for patients with cardiovascular disease and has achieved generic status. In addition, it has vital immune modulating properties against cytokine storms that mitigate the development of ALI/ARDS from both viral and nonviral pathogens. (21). It not only reduces the levels of IL-6, TNF and IFN-g. But it has also been shown to attneuate gene recruiting signals of inflammation utlizing human equivalent dosing. In one animal study, the adjuvant use of gemfibrozil resulted in enhanced host survival that developed ALI/ARDS from viral pathogens. (6) Enhanced survival is seen even after exposure to the virus. This implies that gemfibrozil has the potential to be a treatment rather than a preventive therapy in human disease.Therefore, the potential of gemfibrozil as adjunct immune modulating therapy in conjunction with antiviral treatment for SARS associated with Covid-19 infection in patients with associated cardiovascular disease is emphasized.References:1. Petrosillo N, Vicenconte G, et al. Covid-19, SARS and MERS: are they closely related? JCMI. 20202. Smits S, Lang A, et al. Exacerbated inane host response to SARS-CoV in aged non-human primates. PLos Patholog. 20103. Zhou F, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with Covid-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020. 3954. Rubins HB, Robins SJ, et al. Gemfibrozil for the secondary prevention of coronary aretery disease inmen with low levels of high-density lipoprotein cholesterol. Veterans Affairs high-density lipoprotein cholesterol intervention trial group. N Engl J Med. 1999. 341: 410-4185. Roy A, Pahan K, et al. Gemfibrozil, stretching the arms beyond lipid lowering. Immunopharmacol Immunotoxicol. 2009. 31: 339-3516. Budd A, Alleva L, et al. Increased survival after gemfibrozil treatment of severe mouse influenza. Antimicrobial Agents and Chemotherapy. 2007. 2965-29687. Berger J, Moler DE. The mechanisms of action of PPARs. Annu Rev Med. 53: 409-4358. Madej A, Okopien B, et al. Effects of fenofibrate on plasma cytokine concentrations in patients with atherosclerosis and hyperlipoproteinemia IIb. Int J Clin Pharmacol. 36: 345-3499. Staels B, Koenig W, et al. Activation of human oartic smooth muscle cells is inhibited by PPARa. Nature. 303: 790-79310. Calkin AC, Cooper KA, et al. Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation. Diabetologia. 49: 766-77411. Xu J, Chavis JA, et al. Gemfibrozil reduces release of tumor necrosis factor-alpha in peripheral blood mononuclear cells from healthy subjects and patients with coronary heart disease. Clin Chem Acta. 332: 61-6712. Lovette-Racke AE, Hussain RZ, et al. Peroxisome proliferator-activated receptor-alpha agonists as therapy for autoimmune diesease. J Immunol. 172: 5790-579813. neve BP, Frutchart JC, et al. Role of PPAR in atherosclerosis. Biochem Pharmacol. 2000. 60: 1245-125014. Heyworth PG, Bohl BP, et al. Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its ineteraction with flavocytochrome b558. J Biol Chem. 1994. 269: 30749-3075215. Aviram M, Rosenblat M, et al. Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. Ahterosclerosis. 1998. 138: 271-28016. Dasgupta S, Roy A, et al. Gemfibrozil ameliorates relapsing-remitting experimental autoimmune encephalomyelitis of peroxisome proliferator-acivated receptor-alpha. Molecular Pharmacol. 2007. 72: 934-94617. Zhou JF, Law HK, et al. Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian flu influenza virus-infected macrophages. J Infect Dis. 193: 945-95318. Xu J, Shi I, et al. Pathological findings of Covid-19 associated with acute respiratory distress syndrome. Lancet. 2020. Epub ahead of print19. McGonagle D, Sharif K, et al. The role of cytokines including interleukin-6 in Covid-19 induced pneumonia and macrophage activation syndrome-like disease. J AutRev. 2020. 10253720. Channappanavar AR, Fehr R, et al. Dysregulated type 1 interferon and inflammatory monocytes-macrophage responses cause lethal pneumonia in SARS-CoV infected mice. Cell Host Microbe. 2016.19: 181-19321. Kim YS, Kim JK, et al. The peroxisome proliferator-activated receptor-alpha agonist gemfibrozil promotes defense against mycobacterium abcessus infections. Cells. 2020. 9: 648
The effect of COVID-19 stay-at-home order and campus closure on the prevalence of acu...
Oluwasanmi Adenaiye
Paul Jacob Bueno de Mesquita

Oluwasanmi Adenaiye

and 6 more

November 02, 2020
Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.
The Prognostic Impact of Thyroid Hormonal Disorders and Thyroid Nodule According to t...
Mehmet Güven
Hamza Gültekin

Mehmet Güven

and 1 more

October 31, 2020
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause thyroid hormonal disorders. In addition, tracheal compression by thyroid nodules can aggravate hypoxia in critically-ill patients. No studies have investigated the effect of thyroid nodules on the prognosis of patients with COVID-19. In this study, we investigated the effect of thyroid hormonal disorders and thyroid nodules on the prognosis of patients with COVID-19. Material and Methods: This prospective study was conducted at the Şırnak State Hospital (Pandemic hospital in Turkey) between 15 March and 15 August 2020. We evaluated thyroid hormonal disorder and thyroid nodules in 125 patients who were admitted to the non-intensive care unit (non-ICU) due to mild COVID-19 pneumonia (group 1) and 125 critically-ill patients who were admitted to the ICU (group 2). Results: Thyroid stimulating hormone levels (TSH) were not significantly different between groups 1 and 2 ; however, group 2 patients had significantly lower levels of free thyroxine (FT4) and free triiodothyronine (FT3) as compared to group 1 (p = 0.005, p < 0.0001, respectively). FT3 level showed a negative correlation with length of hospital stay and C-reactive protein level (rho: −0.216, p: 0.001; rho: - 0.383, p < 0.0001). Overt thyroid disorder was observed in 13 patients [2 patients in group 1 (both with overt thyrotoxicosis) and 11 patients in group 2 (3 overt hypothyroidism, 8 overt thyrotoxicosis) (p = 0.01)]. Thyroid nodules sized ≥1 cm were found in 9 patients (7 %) in group 1 and 32 patients (26%) in group 2 (p < 0.0001). Conclusion: Overt thyroid hormonal disorders were more common in critically-ill COVID-19 patients. FT3 level at hospital admission is a potential prognostic marker of COVID-19 patients. Thyroid nodules may be associated with severe COVID-19 disease.
Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi...
Nikolaos Papadopoulos
Alexander Mathioudakis

Nikolaos Papadopoulos

and 41 more

October 30, 2020
Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 on childhood asthma outcomes. Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.
COVID-19, When fourteen days are not enough -- A case series of affected healthcare w...
Catherine Murphy
Noirin Noonan

Catherine Murphy

and 7 more

October 30, 2020
This case series identified a sub cohort of healthcare workers with COVID-19 who experienced a prolonged symptomatic course and remained unable to return to work for many weeks. It notes their demographic and clinical characteristics and suggest ways to support them returning to work in a graded and supported manner.
Could LUTS be Early Symptoms of COVID-19
Yeliz Kaya
Coskun Kaya

Yeliz Kaya

and 4 more

October 29, 2020
Aim: To show if lower urinary tract symptoms (LUTS) could be symptoms of COVID-19 with validated questionnaires. Methods: The 96 COVID-19 patients who were hospitalized at a tertiary center were collected retrospectively. After the exclusion criteria, 46 patients were consisted as the study population. The male and female patients then fill formed the International Prostate Symptom Score and Urinary Symptom Profile respectively. All patients responded to these questions for the three period. Results: 27 female (58.6 %) and 19 male (41.4 %) COVID-19 patients answered the questions In the male patients, while there were no statistically significant differences in the total IPSS, the voiding IPSS score, and quality of life between the three periods (p=0.148; p=0.933, p=0.079, respectively), the storage IPSS scores had a significant difference between the three periods (p=0.05). In the female patients, low stream scores, were similar between the three periods (p=0.368). The scores of stress incontinence and an overactive bladder had a significant difference between the three periods (p=0.05 and p=0.05). Conclusion: LUTS, especially storage symptoms, might be one of the initial symptoms of COVID-19 and the clinicians should evaluate LUTS with other known symptoms of the virus when a patient is suspected of having COVID-19.
EXAMINATION OF THE EFFECT OF COVID-19 ON SEXUAL DYSFUNCTION IN WOMEN
Yeliz Kaya
Coskun Kaya

Yeliz Kaya

and 4 more

October 29, 2020
ABSTRACT Aim: To investigate the effect of COVID-19 on sexual dysfunction in women. Materials and Methods: The women diagnosed with COVID-19 and hospitalized at a tertiary hospital were included. They completed the Introductory Data Form, the Female Sexual Function Index-(FSFI), and the Short Form-36 Quality of Life Scale (SF-36). Results: 15 women between the ages of 19-49 who completed the treatment protocol, discharged at least 14 days before, and who had not been diagnosed as sexual dysfunction sexually active earlier were included to the study. It was detected that weekly sexual intercourse before and after COVID-19 significantly differed (p=0.047). The frequency of relationships decreased statistically after COVID-19. The mean value of the FSFI satisfaction score differs from COVID-19 before and after diagnosis (p=0.012). The mean satisfaction score before COVID-19 was 3.47, and after COVID-19 was 2.93. The score of the subgroups of FSFI did not differ from COVID-19 before and after diagnosis (p>0.050). The median value of SF-36 pain differs from COVID-19 before and after diagnosis (p=0.008). Conclusion: it was concluded that the frequency of sexual intercourse, sexual satisfaction in women decreased after COVID-19 disease, and the quality of life scores did not change in a statistically significant way.
COVID-19 in Pediatric Survivors of Childhood Cancer and Hematopoietic Cell Transplant...
Lauren Kurlander
Zoltan Antal

Lauren Kurlander

and 8 more

October 29, 2020
Childhood cancer survivors are at increased risk for treatment-related late effects; data are lacking on how COVID-19 infection impacts this cohort. We assessed COVID-19-related symptoms; SARS-CoV-2 IgG seroprevalence; and rate of COVID-19-related hospitalization among 321 asymptomatic survivors of childhood cancer or transplantation seen for routine long-term follow-up between May-September 2020 in a New York City tertiary cancer center. While 11% (n=35) reported possible COVID-19-related symptoms, 7.8% (n=20) of those tested had positive SARS-CoV-2 IgG, and only 1 patient (0.3%) required COVID-19 related hospitalization. This report suggests that childhood cancer survivors are at low risk for COVID-19 complications.
COVID-19: The Rising Cost of Cardiac Surgery and Disease
Fatima Osman
Noah Caplin

Fatima Osman

and 2 more

October 24, 2020
The coronavirus disease 19 (COVID-19) pandemic has resulted in widespread economic, health and social disruptions. The delivery of cardiovascular care has been stifled during the pandemic in order to adhere to infection control measures as a way of protecting patients and the workforce at large. This cautious approach has been protective since individuals with COVID-19 and cardiovascular disease are anticipated to have poorer outcomes and an increased risk of death. The combination of postponing elective cardiovascular surgeries, reduced acute care and long-term cardiac damage directly resulting from COVID-19 will likely have increased the demand for cardiac care, particularly from patients presenting with more severe symptoms. The combination of increased demand and inhibited supply will likely result in huge backlog of unmet patients’ needs. The novelty, virulence and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused substantial morbidity and mortality which have necessitated modifications to the UK government’s healthcare strategy. Without improving cost efficiency, the UK’s ageing population will likely need an increasing spend on cardiac surgery simply to maintain the same level of service. However, the government’s short-term increase in spending is unsustainable especially in the face of ongoing economic uncertainty. This means that the long-term impact of COVID-19 will only increase the need to find innovative ways of delivering equivalent or superior cardiac care at a reduced unit cost.
Reply to “Saved by cabbage, killed by cabbage, and COVID-19”
Jean Bousquet
Josep Anto

Jean Bousquet

and 1 more

October 23, 2020
To the Editor,We appreciate the interest and comments of Soriano and Ancochea1 regarding our papers 2. Further to the suggestion that “it would be of interest to repeat their statistics conducted during the first wave of COVID-19, again with the current estimates during the ongoing second wave, or later ones”, we would like to emphasize that our geographical observation was a type of anecdotal evidence that contributed to formulating a hypothesis. In a previous paper, we found that after adjusting for potentially relevant country-level confounders, there was a negative ecological association between COVID-19 mortality and the consumption of cabbage and cucumber in European countries 3. In this study, we acknowledged that “As in any ecological study, any inference from the observed association should be made at the country level, as the possibility of ecological fallacy precludes inferences at the individual level; and that further testing in properly designed individual studies would be of interest”. Indeed, what would be useful is testing the hypothesis in robust observational studies and/or clinical trials.Regarding our observation that COVID-19 could be considered as a disease of the Anthropocene 4 , other authors have recently provided a more complete description of the links between the disruption of the natural ecosystems that characterize the Anthropocene and the occurrence of zoonosis 5 6.1. Soriano J and Ancochea J. Saved by cabbage, killed by cabbage, and COVID-19. Allergy 2020; in press.2. Bousquet J, Anto JM, Czarlewski W, et al. Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19. Allergy 2020. DOI: 10.1111/all.14549.3. Fonseca S, Rivas I, Romaguera D, et al. Association between consumption of vegetables and COVID-19 mortality at a country level in Europe. MedRix 2020; 10.1101/2020.07.17.201558464. O’Callaghan C and Anto J. COVID-19: The Disease of the Anthropocene.Env Res 2020; 187: 109683.doi: 109610.101016/j.envres.102020.109683. Epub 102020 May 109615.5. Morens DM and Fauci AS. Emerging Pandemic Diseases: How We Got to COVID-19. Cell 2020; 182: 1077-1092. 2020/08/28. DOI: 10.1016/j.cell.2020.08.021.6. Roche B, Garchitorena A, Guegan JF, et al. Was the COVID-19 pandemic avoidable? A call for a ”solution-oriented” approach in pathogen evolutionary ecology to prevent future outbreaks. Ecol Lett 2020 2020/09/02. DOI: 10.1111/ele.13586.JM AntoISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. IMIM (Hospital del Mar Research Institute), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.J BousquetCharité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany. MACVIA-France, Montpellier, France.
ABO Blood Groups in Covid-19 Patients; Cross-sectional study
Ihsan Solmaz
Songül Araç

Ihsan Solmaz

and 1 more

October 23, 2020
Aim: The aim of this study was to investigate the ABO and Rh blood group distribution and clinical characteristics in patients with Covid-19. Materials and Methods: The clinical characteristics and blood groups of 1667 patients who were hospitalized due to Covid-19 (with a positive PCR test) between 16 March and 10 July were reviewed cross-sectionally.. Results: When blood groups of patients diagnosed with Covid-19 and control group were compared, it was observed that there was increase in the number of Covid-19 patients with blood groups A and AB, decrease in the number of Covid-19 patients with blood group O, a statistically significant increase in the number of individuals with blood group A in Covid-19 patients compared to healthy individuals, and almost significant increase in the number of Covid-19 patients with blood group AB and a very significant decrease in the number of Covid-19 patients with blood group O. Conclusion: Our study has found that having blood group O may be protective, that blood group A may have greater susceptibility to the disease, but this does not affect the course of the disease and is not associated with mortality.
COVID-19 Visiting Restrictions -- Improving Communication with Relatives
William Jones
Kathy Woolson

William Jones

and 2 more

October 23, 2020
A document by William Jones. Click on the document to view its contents.
The coping strategies of community  pharmacists and pharmaceutical services provided...
Kok Pim Kua
Shaun Lee

Kok Pim Kua

and 1 more

October 28, 2021
Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists’ readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges.Objective This study aims to examine community pharmacists’ views on their work environment, policies, and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic.Setting An online survey of pharmacists practicing in community pharmacy setting in Malaysia.Method A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilizing a snowball sampling method. Main outcome measure Community pharmacists’ perceptions on safety, resilience, organizational support, and pharmaceutical services offered during COVID-19 pandemic.Results A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitizers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services.  Conclusion The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.
Cryptococcemia in a Patient with COVID-19: A Case Report
Mohamad  Khatib
Amna  Ahmed

Mohamad Khatib

and 4 more

October 22, 2020
Cryptococcus neoformans infection is a known cause of meningoencephalitis in immunocompromised patients. However, it is less frequent in immunocompetent individuals. Here we report a case of a 60 years old COVID-19 patient with a history of several co-morbidities who received tocilizumab and corticosteroids, which lead to Cryptococcemia.
Paediatric Attendances and Acuity in the Emergency Department during the COVID-19 Pan...
Katy Rose
Kerry Van Zyl

Katy Rose

and 4 more

October 22, 2020
Aim: To investigate the difference in both numbers and acuity of presentations to the Paediatric Emergency Department (PED) during the peak time period of the current global SARS-CoV-2 pandemic. Design: This single centre retrospective observational study used routinely collected electronic health data to compare patient presentation characteristics between 21st March and 26th April 2020 compared to the equivalent time period in 2019. Results: There was a 90% decrease in attendances to PED, with a 10.23% reduction re-attendance rate. Children presenting were younger during the pandemic, with a median age difference of 2 years. They were more likely to present in an ambulance (9.63%), be admitted to hospital (5.75%) and be assigned the highest two Manchester triage categories (6.26%). There was a non-significant trend towards longer lengths of stay. The top 10 presenting complaints remained constant (although the order changed) between time periods. There was no difference in mortality or admission to PICU. Implications: Our data demonstrates that there has been a significant decrease in numbers of children seeking emergency department care. It suggests that presenting patients were proportionally sicker during the pandemic; however, we would argue that this is more in keeping with appropriate acuity for PED presentations, as there were no differences in PICU admission rate or mortality. We explore some of the possible reasons behind the decrease in presentations and the implications for service planning ahead of the winter months.
Coronavirus-19 Outbreak in Children: Different clinical status of a disease in childr...
Yaşar Hüseyin  Onganlar
Havva Hande Keser Şahin

Yaşar Hüseyin Onganlar

and 2 more

October 21, 2020
COVID-19 disease, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first appeared in Wuhan, China, and spread throughout the world in a short period of time (1). On 30 January 2020, WHO declared the outbreak a Public Health Emergency of International Concern (PHEIC) and than on 11 March 2020, WHO declared the Coronavirus as a pandemic. The pandemic was called as COVID-19.
Knowledge of Syrian refugee mothers and their attitude towards Covid-19 disease in ch...
Shereen Hamadneh
Jehan Hamadneh

Shereen Hamadneh

and 4 more

October 21, 2020
Objectives: To explore Knowledge and perceptions about COVID-19, among Syrian refugee mothers in Irbid governorate, the first outbreak of coronavirus in Jordan. Methods: This is an exploratory cross-section study was conducted among Syrian refugee mothers, who were currently pregnant or have a newborn child. The data collected through an online survey in April 2020 in North Jordan. Results: A total of 389 Syrian refugee mothers have participated in the study. The study showed that 66% of mothers often access information regarding COVID-19. The main used resources for information, were Facebook pages’ posters (87%), WhatsApp groups’ messages (69%), Television News (53%). While 21% indicated that they access a professional database or governmental websites. In general, Syrian refugee mothers appear well knowledgeable about COVID-19 the transition ways and prevention measures, and aspects that should be considered when diagnosing Coronavirus cases. However, they appeared to have a lack of knowledge about the aspects that should be considered for the transition of COVID-19 between the mother and the child and the concepts about the smoking risks associated with COVID-19. Conclusions: There is less focusing on media on aspects or still understudying of concepts about the smoking risks associated with COVID-19 and concepts around the transition of COVID-19 between the mother and the child. Providing health education regarding COVID-19 to mothers in Irbid would be helpful.
Production of high-quality SARS-CoV-2 antigens: impact of bioprocess and storage on g...
Rute Castro
Lígia Nobre

Rute Castro

and 24 more

October 19, 2020
SARS-CoV-2 is an RNA coronavirus that causes severe acute pneumonia, also known as COVID 19 disease. The World Health Organization declared the COVID-19 outbreak in January 2020 and a pandemic 2 months later. Serological assays are valuable tools to study virus spread among the population and, importantly, to identify individuals that were already infected and would be potentially immune to a virus re-infection. SARS-CoV-2 Spike protein and its Receptor Binding Domain (RBD) are the antigens with higher potential to develop SARS-CoV-2 serological assays. Moreover, structural studies of these antigens are key to understand the molecular basis for Spike interaction with angiotensin converting enzyme 2 receptor, hopefully enabling the discovery and development of COVID-19 therapeutics. Thus, it is urgent that significant amounts of this protein became available at the highest quality. In this work we evaluated the impact of different and scalable bioprocessing approaches on Spike and RBD production yields and, more importantly, in these antigens’ quality attributes. Using negative and positive sera collected from human donors, we show an excellent performance of the produced antigens, assessed in serologic ELISA tests, as denoted by the high specificity and sensitivity of the test. We have shown that, despite of the human cell host and the cell culture strategy used, for production scales ranging from 1 L to up to 30 L, final yields of approx. 2 mg and 90 mg per liter of purified bulk for Spike and RBD, respectively, could be obtained. To the best of our knowledge these are the highest yields for RBD production reported to date. An in-depth characterization of SARS CoV-2 Spike and RBD proteins was also performed, namely the antigens oligomeric state, glycosylation profiles and thermal stability during storage. The correlation of these quality attributes with ELISA performance show equivalent reactivity to SARS CoV 2 positive serum, for all Spike and RBD produced, and for all the storage conditions tested. Overall, we provide herein straightforward protocols to produce high-quality SARS CoV-2 Spike and RBD antigens, that can be easily adapted to both academic and industrial settings; and integrate, for the first time, studies on the impact of bioprocess with an in-deep characterization of these proteins, correlating antigens glycosylation and biophysical attributes to performance of COVID-19 serologic tests. We strongly believe that our work will contribute to advance the current and recent knowledge on SARS-CoV-2 proteins and support the scientific society that is persistently searching for solutions for COVID-19 pandemics.
Association between asthma and clinical mortality/morbidity in COVID-19 patients usin...
Hyo Geun Choi
Jee Hye Wee

Hyo Geun Choi

and 9 more

October 15, 2020
Association between asthma and clinical mortality/morbidity in COVID-19 patients using clinical epidemiologic data from Korean Disease Control & PreventionHyo-Geun Choi1, Jee Hye Wee2, So Young Kim2, Joo-Hee Kim3, Hwan Il Kim3, Ji-Young Park3, Sunghoon Park3, Yong Il Hwang3, Seung Hun Jang3, and Ki-Suck Jung31 Departments of Otorhinolaryngology-Head & Neck Surgery, Hallym UniversitySacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea2 Department of Otorhinolaryngology-Head & Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea3 Division of Pulmonary, Allergy, and Critical Care Medicine, Department ofMedicine, Hallym University Sacred Heart Hospital, Hallym University Collegeof Medicine, Anyang, Korea
Immunological Reason for Mild Effection of Children to COVID-19, A Key Factor for Nov...
Esmaeil Farshi
John Smith

Esmaeil Farshi

and 1 more

October 09, 2020
Coronaviruses are important human and animal pathogens. We will show that probably antibodies don’t have essential role in immunity against COVID-19 in long term, but a type of white globules named T cells may have critical role in immunity against COVID-19. T cells have long time memory to remain in blood. The most important point for investigation of such issue is mild effection of children to COVID-19. While the milder COVID-19 disease in children is remained secretly till this paper, but its understanding will provide important information about the disease. It may also suggest important protective mechanisms and targets for future therapies. Then a main factor in producing a vaccine for COVID-19 maybe consideration of mild infection report of children by COVID-19 comparing adults’ infection that causes conclusion of higher resistance of immune system of children comparing adults. We identified this could be because immunity of children is based on innate immunity (phagocytes) while adults are based on antibodies. Our results show innate immune system including phagocytes contribute severely to the elimination of COVID-19 in both mouse model and human. Our results also show the elimination of COVID-19 required the activation of B cells by CD4+ T cells. CD4+ T cells play an important role in elimination of COVID-19 in primary effection. We measured IgM and IgG in human patients including adults and kids and found that IgM and IgG in kids’ patients are much higher than other adults patients.
SARS-CoV-2 infection in pregnancy during the first wave of COVID-19 in the Netherland...
Evelien Overtoom
Ageeth Rosman

Evelien Overtoom

and 6 more

October 09, 2020
Objective: Description of characteristics, risk factors, management strategies and maternal, obstetric and neonatal outcomes of SARS-CoV-2 infected pregnant women in the Netherlands. Design: Multi-centre prospective nationwide population-based cohort study. Setting: Nationwide. Population: All pregnant women in the Netherlands with confirmed SARS-CoV-2 infection in home-isolation or admitted to hospital between March 1st, 2020 and August 31st, 2020. Methods: Pregnant women with positive PCR or antibody tests were registered using the Netherlands Obstetrics Surveillance System. Testing occurred according to national guidelines (selective testing). Data from the national birth registry (Perined) and Dutch National Institute for Public Health and the Environment (RIVM) were used as reference. Main Outcome Measures: Incidence of pregnant women with SARS-CoV-2 infection. Maternal, obstetric and neonatal outcomes including hospital and critical care admission, clinical management and mode of birth. Results: Of 312 registered women, 65 (20%) were admitted to hospital, of whom 5 (2%) to intensive care and 9 (14%) to obstetric high care units. Risk factors for admission were non-Caucasian background (n=28; OR 6.67, 95%CI 4.08-10.90) and being overweight or obese (n=38; OR 2.64, 95%CI1.51 to 4.61). Hospital and intensive care admission were higher compared to age-matched infected women (respectively, OR 14.57, 95%CI 10.99-19.03 and OR 5.02, 95%CI 2.04-12.34). One maternal death occurred. Caesarean section after labour onset was increased (OR 2.50; 95%CI 1.57-3.97). Conclusions: Pregnant women with SARS-CoV-2 infection are at increased risk of hospital admission, ICU admission and caesarean section. Funding: No funding was received. Keywords: Pregnancy, COVID-19, SARS-CoV-2, Pregnancy complications, Pregnancy outcome, Obstetric surveillance system.
Risk factors for severe and critically ill COVID-19 patients: a review
Ya-dong Gao
Mei Ding

Ya-dong Gao

and 19 more

October 08, 2020
The coronavirus disease 2019 pandemic (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global social and economic impact, and numerous deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung disease, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type-I interferon secretion capacity, and pregnancy. Possible complications include acute respiratory distress syndrome, shock, disseminated coagulopathy, acute kidney injury, pulmonary embolism, and secondary bacterial pneumonia. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1, Krebs von den Lungen-6 (KL-6) and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of COVID-19.
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