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Please note: These are preprints and have not been peer reviewed.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.
Impact of COVID-19 on Coronary Artery Surgery: Hard lessons learned
Luis Alberto Dallan
Luiz Augusto Ferreira Lisboa

Luis Alberto Dallan

and 3 more

June 12, 2021
Impact of COVID-19 on Coronary Artery Surgery: Hard lessons learnedAuthor: Luis Alberto O. Dallan1; Luiz Augusto F. Lisboa1; Luis Roberto P. Dallan1; Fabio B. Jatene1.1 Department of Cardiovascular Surgery, Heart Institute from University of São Paulo Medical School (InCor), São Paulo, São Paulo, Brazil.Corresponding author:  Luis Alberto O. Dallan, Dr. Enéas de Carvalho Aguiar, 44, Postal Code:05403-900. Pinheiros, São Paulo, SP – Brazil. Phone: +55 (11) 2661-5014. E-mail: dcidallan@incor.usp.br.Since March 11th, 2020 when coronavirus disease 2019 (COVID-19) was declared a pandemia, hospitals had to be adapted quickly to increase the assistance capacity for a large part of the population that needed hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1,2). Major disruptions on routine hospital services have occurred, with health professionals needed to assume functions beyond their usual routines and beds were adapted for intensive care due to the increased demand in the treatment of severe acute respiratory failure. Cardiovascular surgery was particularly affected by the coronavirus outbreak, since most of the elective surgeries were canceled and ICU beds, normally dedicated to the postoperative period of cardiac surgery, were transferred to patients with COVID-19 (3-5).In this context, Kalil and Col.(6) examine the impact of the Covid-19 pandemic in the number of procedures and death rate of CABG performed in 2020 in Brazil. They analyzed patients undergoing CABG in the public health system between 2008 and 2020. The data were collected from DATASUS, the data processing system of the Brazilian Ministry of Health, which collects information from every patient who needs in-hospital care and was admitted to a public hospital. Patients operated on the private system were not captured in the database and were excluded from the analysis. The results showed that in 2020, during the pandemic period, there was an average reduction of 25% in the number of CABG performed in Brazil, with the majority of procedures (75%) being performed in the south and southeast regions of the country. Regarding postoperative mortality, they observed an opposite effect with an increase in mortality from 5.6% to 6.3% during this pandemic period (6).This study has some limitations due to results extracted from an administrative database, good for epidemiological analysis such as gender, age, number and type of surgeries performed. Considering the reduction in surgical volume during the pandemic period, surgical status was analyzed altogether (whether elective, or urgent or emergency CABG), expressing a general view of the situation.Brazil was the epicenter of the coronavirus outbreak in Latin America and other publications from Brazil showed different and more detailed results in relation to the pandemic period (7,8). One by Omar et al. (7) who used data from the São Paulo Registry of Cardiovascular Surgery (REPLICCAR), a multicenter registry, showed a 60% reduction in surgical CABG volume during COVID-19 pandemic. Regarding mortality, CABG surgeries had a 2.8-fold increased mortality risk (CI95%,1-7.6, P=0.041), patients who evolved with COVID-19 had a 11-fold increased mortality risk (CI95%, 2.2-54.9, P<0.003), rates of morbidities and readmission to the intensive care unit. (7), compared to 2019.In our own series at the Heart Institute University of Sao Paulo Medical School - Brazil, we observed a 65.8% reduction in cardiac surgery volume in 2020, during the pandemic period, and 2/3 of these were urgent or emergency procedures. Regarding the CABG in-hospital mortality, there was increased from 1.2% (2019) to 3.0% (2020) among elective procedures and from 4.5% (2019) para 18.2% (2020) among urgent or emergency procedures. Patients who had postoperative COVID-19, the in-hospital mortality rate was significantly higher (38.5%).Other publications reported a reduction in surgical volume of more than 70% during the peak disruption due to COVID-19 (9,10). Salenger et al. (11) reported that the volume of cardiac surgery fell to 54% of baseline after the restrictions were implemented and they also estimated a necessity of 2.5 times increase in numbers of procedures in post-COVID-19 era to restore balance to elective surgeries waiting lists. In the COVIDSurg collaborative, in a multi centric cohort of surgeries performed in 24 countries (235 hospitals), found that 75% of the procedures from 1 January and 31 March 2020, were non-elective and the mortality was 24%. Their cohort included 50 patients who underwent cardiac surgery and 30-day mortality was 34%, among the patients who had perioperative SARS-CoV-2 infection (12). Clinical studies have shown that in addition to severe acute respiratory distress syndrome, the coronavirus-2 infection also affects micro-circulation, has prothrombotic state and can cause myocardial injury, even in patients without coronary artery disease (13-14). This may be one of the reasons for the high mortality among patients who undergo surgery and present COVID-19 in the perioperative period, particularly in CABG surgery, where there is also a higher incidence of elderly, hypertensive and diabetic patients.While the COVID-19 pandemic continues to increase globally, measures to control SARS-CoV-2 infection and patient safety need to be established to maintain cardiovascular surgery, even if in small numbers. The consequences of delayed recognition of a patient with COVID-19 are significant. Protocols for triage, early diagnosis, isolation in specific areas and treatment of patients with COVID-19 with cardiovascular complications should be developed to minimize the risk of in-hospital transmission and greater safety for hospitalized patients without COVID-19 and healthcare professionals (15,16).A large number of operations were canceled or postponed due to interruptions caused by COVID-19. Coincidentally, our institution have reported an increased number of mechanical complications, that maybe related to decreased number of patients seeking for medical assistance (17).Studies conducted in the first months of the pandemic showed that if countries increased their normal surgical volume by 20%, it would take an average of 45 weeks to balance the backlog of operations resulting from the interruption of COVID-19 (18). Patients awaiting elective cardiac surgery need to be proactively managed, reprioritizing those with high-risk anatomy or whose clinical status is deteriorating. In this regard, governments must mitigate this heavy burden on patients by developing recovery plans and implementing strategies to safely restore surgical activity as soon as possible.
Determinants of COVID-19 Case and Death Rates: An Ecological Study
Christopher El Mouhayyar
Luke T. Jaber

Christopher El Mouhayyar

and 3 more

June 09, 2021
Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has had a variable worldwide impact, likely related to country-level characteristics. In this ecological study, we explored the association of COVID-19 case rates (per 100,000 people) and death rates (per 100,000 people) with country-level population health characteristics, economic and human development indicators, and habitat-related variables. Methods: To calculate country-level COVID-19 case and death rates, the number of cases and deaths were extracted from the Johns Hopkins Coronavirus Resource Center for 2020. Country-level population health characteristics, economic and human development indicators, and habitat-related variables were extracted from several publicly available online sources of international organizations. Results were tabulated according to world zones and country economies. Univariate and multivariable linear regression analyses were performed to examine determinants of COVID-19 case rates and death rates. Results: A total of 187 countries and territories were analyzed, with an aggregate COVID-19 case rate of 779 per 100,000 people, a death rate of 19 per 100,000 people, and a case-fatality rate of 2.4%. For country-level population health characteristics, a higher percentage rate of adults with obesity and a higher percentage rate of adults with high blood pressure was independently associated with a higher COVID-19 case rate, and a higher percentage rate of adults with obesity was associated with a higher COVID-19 death rate. For country-level economic and human development indicators, only a higher gross domestic product percentage rate spent on total health expenditure and a higher human development index was independently associated with a higher COVID-19 case rate and death rate. A higher percentage of urban population was independently associated with a higher COVID-19 death rate, whereas a higher income per capita was independently associated with a lower COVID-19 death rate. For country-level habitat-related variables, a higher average household size and a higher percentage rate of population with primary reliance on polluting fuels and technologies was independently associated with a lower COVID-19 case rate and death rate whereas a higher percentage rate of households with at least one-member age 65 years or over was associated with a higher case rate and death rates. Conclusion: This ecological study informs the need to develop country-specific public health interventions to better target populations at high risk for COVID-19, and test environmental interventions to prevent indoor transmission of SARS-CoV-2, taking into consideration population health characteristics, economic and human development indicators, and habitat-related variables that are unique to each country.
Influenza and Respiratory Syncytial Virus during the COVID-19 pandemic: time for a ne...
Emma Binns
marianne  koenraads

Emma Binns

and 12 more

June 09, 2021
Seasonal epidemics of influenza and the respiratory syncytial virus are the cause of substantial morbidity and mortality among children. During the global COVID-19 pandemic, the epidemiology of these viruses seems to have changed dramatically. In Australia and New Zealand, a significant decrease in both influenza and bronchiolities have been noticed during usual peak seasons. Data from early months of winter seasons in Europe are showing similar trends. This current scenario imposes a reconsideration of the paradigm that toddlers and young schoolchildren are the main drivers of seasonal RSV outbreaks and respiratory epidemics in general. In this paper, we summarize current literature, address current knowledge or role of adults in the respiratory syncitial virus epidemiology, describe the lessons learned from pertussis epidemics and call the international community to better understand the community transmission dynamics of respiratory infections in all age-groups. This can allow the establishment of better and more affordable preventive measures in the whole population level, which can ultimately save millions of child lives.
Analysis of continuous glucose tracking data in people with Type 1 Diabetes (T1DM) af...
Adrian Heald
Rustam Rea

Adrian Heald

and 8 more

June 08, 2021
Introduction The COVID-19 vaccination programme is under way. Anecdotal evidence is increasing that some people with Type 1 Diabetes Mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before and after vaccination. Methods We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle® Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage(%) BG readings in the designated target range 3.9-10mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). Results There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ±se 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ±se 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1-13.9%/ ≥14%. There was no significant change in BG variability in the 7days post COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). Conclusion In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.
Cytokine Filter Application in COVID-19 Patients; Island of Hope for Crash and Burn P...
Ali Ghodsizad

Ali Ghodsizad

June 07, 2021
Cytokine Filter Application in COVID-19 Patients; Island of Hope for Crash and Burn Patients or Future Solution for All Septic Acute Respiratory Distress Syndrome (ARDS) PatientsAli Ghodsizad MD, PhD, FACC, FETCS, FACSThe COVID-19 pandemic crisis certainly has challenged the scientific community as well as entire world. While incidence numbers have decreased following expedited vaccination and precautions, still some patients present with COVID 19 related pneumonia and ARDS requiring Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) support to survive.In COVID-19 patients a cytokine release syndrome concomitant with ARDS can lead to overwhelming clinical scenario. Geraci and colleagues report on their single center feasibility study looking at application of the CytosorbTM hemadsorption device which was used as a parallel circuit within the VV ECMO circuit.The authors give evidence for safety and feasibility of the CytosorbTM hemadsorption device use in 10 patients with COVID-19 related ARDS in combination with VV ECMO. They show a reduction of inflammatory markers and cytokines following hemadsorption treatment. The cytokine storm can cause a critical clinical picture of septic shock. Only under high vasopressor and inotropic support end organ perfusion can be maintained. The required invasive pressure ventilation with high PEEP and peak pressure can decrease the intrathoracic venous return further and contributes more to the shock physiology (1). We have to look at inspiring results from current single center experience carefully understanding the evolving nature of COVID-19 related ARDS. Other groups have used plasmapheresis and CVVH modifications in COVID-19 cases. Dominik et al have shown a significant benefit only using hemadsorption comparing to other used protocols (2).We have shown successful application of somatic stem cells in COVID-19 patients on VV ECMO at our center. We could observe a reduction of inflammatory markers following somatic stem cell application (3). COVID 19 ARDS patients who required VV ECMO support, underwent a Pulmonary Artery (PA)-catheter placement and allogenic human stem cell injection into the PA using the PA-catheter as part of our expanded access protocol (3,4).Brouwer and colleagues, another group working with hemadsorption, have actually shown reduced survival in patients undergoing hemadsorption therapy (5). Geraci and colleagues describe their overall VV ECMO survival for COVID 19 related respiratory failure to be > 90%. Others including our center have experienced a much lower survival in that patient population. So patient selection clearly is a key point. The results presented by Geraci and colleagues have to be taken as a pioneering step, which can help in ARDS and septic clinical scenarios with different pathology in future.
HYPERTENSION AS A MANIFESTATION OF COVID-19 PNEUMONIA
Makhabbat Bekbossynova
Ainur Tauekelova

Makhabbat Bekbossynova

and 1 more

June 07, 2021
This clinical case represents an unusual manifestation of COVID-19 pneumonia which started as arterial hypertension as well as the development of post-viral inflammatory complications and long-covid syndrome. Several factors such as hypertension, bile duct disease, and age can affect the duration of COVID which can lead to long COVID
RAPID AND COST-EFFECTIVE PROCESS BASED ON INSECT LARVAE FOR SCALE-UP PRODUCTION OF SA...
Ignacio Smith
Gregorio Mc Callum

Ignacio Smith

and 18 more

June 06, 2021
Serology testing for COVID-19 is important in evaluating active immune response against SARS-CoV-2, studying the antibody kinetics, and monitoring reinfections with genetic variants and new virus strains, in particular, the duration of antibodies in virus-exposed individuals and vaccine-mediated immunity. In this work, recombinant S protein of SARS-CoV-2 was expressed in Rachiplusia nu, an important agronomic plague. One gram of insect larvae produces an amount of S protein sufficient for 150 determinations in the ELISA method herein developed. We established a rapid production process for SARS-CoV-2 S protein that showed immunoreactivity for anti-SARS-CoV-2 antibodies and was used as a single antigen for developing the ELISA method with high sensitivity (96.2%) and specificity (98.8%). Our findings provide an efficient and cost-effective platform for large-scale S protein production, and the scale-up is linear, thus avoiding the use of complex equipment like bioreactors.
SARS-CoV-2 superinfection and reinfection with three different strains
Darío García de Viedma
laura Pérez-Lago

Darío García de Viedma

and 12 more

June 03, 2021
We report a COVID-19 case with unprecedented viral complexity. In the first severe episode, two different SARS-CoV-2 strains (superinfection) were identified within a week. Three months after discharge, patient was readmitted and was infected in a nosocomial outbreak with a different strain, suffering a second milder COVID-19 episode.
Serum periostin levels in COVID-19: is it useful as a new biomarker?
mehmet çabalak
Serdar Doğan

Mehmet Çabalak

and 3 more

June 03, 2021
Objectives: Severe disease characterized by interstitial pneumonia may develop in some cases of coronavirus disease (COVID-19). Periostin has been associated with many respiratory diseases. In this study, we aimed to investigate whether periostin could be a useful new biomarker in the follow-up and severity assessment of the disease in patients with COVID-19 pneumonia. Methods: In the study, 32 patients followed up during May–July 2020 due to COVID-19 and 24 healthy controls were included. The patients were divided into two groups, namely, mild/moderate and severe, according to the severity of the disease. Serum periostin and transforming growth factor beta (TGF-β) levels were tested using an enzyme-linked immunosorbent assay (ELISA) method using commercially available ELISA kits. Results: It was observed that the periostin level was significantly higher in both mild/moderate cases and severe cases compared to the control group at first presentation. However, TGF-β levels at first presentation were similar between the groups. Conclusions: Our study is the first study to investigate periostin levels in patients with COVID-19, and we believe that periostin can be used as a new biomarker. Keywords: COVID-19, Periostin, TGF-β, Pneumonia, New Biomarker Coronaviruses are among the main pathogens that mainly target the human respiratory system. Severe disease characterized by interstitial pneumonia develops in 10-20% of patients. Periostin has recently been shown to be an indicator of disease progression in idiopathic pulmonary fibrosis and asthma. In this study, we aimed to investigate whether periostin could be a useful new biomarker in the follow-up and severity assessment of the disease in patients with COVID-19 pneumonia. This article demonstrated that periostin is a useful new biomarker for disease follow-up and severity in patients with COVID-19 pneumonia. It is also the first study on periostin levels in patients with COVID-19
Transition from Transesophageal Echocardiography to Cardiac Computed Tomography for t...
Tauseef Akhtar
Ryan Wallace

Tauseef Akhtar

and 8 more

June 02, 2021
Background Transesophageal echocardiography (TEE) is variably performed before atrial fibrillation (AF) ablation to evaluate left atrial appendage (LAA) thrombus. We describe our experience with transitioning to the pre-ablation cardiac computed tomography (CT) approach for the assessment of LAA thrombus during the COVID-19 pandemic. Methods We studied consecutive patients undergoing AF ablation at our center. The study cohort was divided into pre- vs. post-COVID groups. The pre-COVID cohort included ablations performed during 1 year before the COVID-19 pandemic; pre-ablation TEE was used routinely to evaluate LAA thrombus in high-risk patients. Post-COVID cohort included ablations performed during the 1 year after the COVID-19 pandemic; pre-ablation CT was performed in all patients, with TEE performed only in patients with LAA thrombus by CT imaging. The demographics, clinical history, imaging, and ablation characteristics, and peri-procedural cerebrovascular events (CVE) were recorded. Results A total of 637 patients (pre-COVID n=424, post-COVID n=213) were studied. The mean age was 65.6  10.1 years in the total cohort, and the majority were men. There was a significant increase in pre-ablation CT imaging from pre to post-COVID cohort (74.8 vs. 93.9%, p=<0.01), with a significant reduction in TEEs (34.6 vs. 3.7%, p=<0.01). One patient in the post-COVID cohort developed CVE following negative pre-ablation CT. However, the incidence of peri-procedural CVE between both cohorts remained statistically unchanged (0 vs. 0.4%, p=0.33). Conclusion Implementation of pre ablation CT-only imaging strategy with selective use of TEE for LAA thrombus evaluation is not associated with increased CVE risk during the COVID- 19 pandemic.
Heart Transplantations Amidst the COVID-19 Pandemic: ‘In The Midst of Chaos, There is...
Andrea Amabile
Arnar Geirsson

Andrea Amabile

and 1 more

June 02, 2021
A document by Andrea Amabile, written on Authorea.
Promoting Factfulness in the Covid-19 pandemic-related policymaking: a map to underst...
Raffaella Nenna
Hana Zeric

Raffaella Nenna

and 4 more

June 01, 2021
Introduction: In the era of data-driven decision-making, an unacceptable haziness and inconsistency surrounds the yearlong scientific and public debate on the school closure policy in the COVID-19 pandemic mitigation efforts. Aim: The present literature review stems out of the need for a clear scaffold collecting in one place all current evidence, as well as helping organizing incoming future evidence, concerning both the role of schools in driving the Sars-CoV-2 community spread and the cost-effectiveness of school closure in containing such spread. Methods: References for this review were initially identified through searches of PubMed, Scopus and Cochrane Library for articles published from March, 2020, to March, 2021 by use of the terms “Schools” “COVID-19” “pandemic” “clusters” “outbreak” “seroprevalence”. Further search was undertaken through Google Scholar and ResearchGate, and finally through Google. Results: School closure at times of high background prevalence of COVID-19 should not be considered a measure implemented to protect the health of children. Children had lower secondary attack rates than adults and that they infrequently represented the index case. One year of pandemic has been sufficient for the emergence of one indication of concern: a potentially increased burden of paediatric mental health disorders. Conclusions: A fact-based understanding of what is currently known on such a consequential policy is required to provide a basis of evidence for an advocacy of either school closure or school opening at times of high intensity community transmission of Sars-CoV-2.
Subclinical left ventricular dysfunction in COVID-19 recovered patients using speckle...
Sudhanshu Mahajan
Shekhar Kunal

Sudhanshu Mahajan

and 12 more

June 01, 2021
Objectives: Myocardial injury during active coronavirus disease-2019 (COVID-19) infection is well described however, its persistence during recovery is unclear. We assessed left ventricle (LV) global longitudinal strain (GLS) using speckle tracking echocardiography (STE) in COVID-19 recovered patients and studied its correlation with various parameters.Methods: A total of 134 subjects within 30-45 days post recovery from COVID-19 infection and normal LV ejection fraction were enrolled. Routine blood investigations, inflammatory markers (on admission) and comprehensive echocardiography including STE were done for all. Results: Of the 134 subjects, 121 (90.3%) were symptomatic during COVID-19 illness and were categorized as mild: 61 (45.5%), moderate: 50 (37.3%) and severe: 10 (7.5%) COVID-19 illness. Asymptomatic COVID-19 infection was reported in 13 (9.7%) patients. Subclinical LV and right ventricle (RV) dysfunction were seen in 40 (29.9%) and 14 (10.5%) patients respectively. Impaired LVGLS was reported in 1 (7.7%), 8 (13.1%), 22 (44%) and 9 (90%) subjects with asymptomatic, mild, moderate and severe disease respectively. LVGLS was significantly lower in patients recovered from severe illness (mild: -21 ± 3.4%; moderate: -18.1 ± 6.9%; severe: -15.5 ± 3.1%; P < 0.0001). Subjects with reduced LVGLS had significantly higher interleukin-6 (P < 0.0001), C-reactive protein (P = 0.001), lactate dehydrogenase (P = 0.009) and serum ferritin (P = 0.03) levels during index admission. Conclusions: Subclinical LV dysfunction was seen in nearly a third of recovered COVID-19 patients while 10.5% had RV dysfunction. Our study suggests a need for closer follow-up among COVID-19 recovered subjects to elucidate long-term cardiovascular outcomes.
Outcomes of Extracorporeal Membrane Oxygenation in Influenza vs. COVID-19 During the...
Cameron Blazoski
Michael Baram

Cameron Blazoski

and 2 more

May 29, 2021
Purpose: Extracorporeal membrane oxygenation (ECMO) is a refractory treatment for acute respiratory distress syndrome (ARDS) due to influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also referred to as COVID-19). We conducted this study to compare the outcomes of influenza patients treated with veno-venous-ECMO (VV-ECMO) to COVID-19 patients treated with VV-ECMO, during the first wave of COVID-19. Materials and Methods: Patients in our institution with ARDS due to COVID-19 or influenza who were placed on ECMO between August 1, 2010 and September 15, 2020 were included in this comparative, retrospective study. To improve homogeneity, only VV -ECMO patients were analyzed. The clinical characteristics and outcomes were extracted and analyzed. Results: 28 COVID-19 patients and 17 influenza patients were identified and included. ECMO survival rates were 68% (19/28) in COVID-19 patients and 94% (16/17) in influenza patients (p=0.04). 30-day survival rates after ECMO decannulation were 54% (15/28) in COVID-19 patients and 76% (13/17) in influenza patients (p=0.13). COVID-19 patients spent a longer time on ECMO compared to flu patients (21 days vs. 12 days, p=0.025), and more COVID-19 patients (26/28 vs. 2/17) were on immunomodulatory therapy prior to ECMO initiation (p<0.001). COVID-19 patients had higher rates of new infections during ECMO (50% vs. 18%, p=0.03) and bacterial pneumonia (36% vs 6%, p=0.024). Conclusions: COVID-19 patients who were treated in our institution with VV-ECMO had statistically lower ECMO survival rates than influenza patients. It is possible that COVID-19 immunomodulation therapies may increase the risk of other superimposed infections.
What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on...
Enrico Maggi
Bruno  Azzarone

Enrico Maggi

and 3 more

May 26, 2021
The coronavirus disease 2019 (COVID-19) pandemic started over one year ago and produced almost 3.5 million deaths worldwide. We have been recently overwhelmed by a wide literature on how the immune system recognizes Severe Acute Respiratory Syndrome Coronavirus 2 and contributes to COVID-19 pathogenesis. Although originally considered a respiratory viral disease, COVID-19 is recognized as a far more complex, multi-organ-, immuno-mediated-, and mostly heterogeneous disorder. Though efficient innate and adaptive immunity may control infection, when the patient fails to mount an adequate immune response, a high innate-induced inflammation can lead to different clinical outcomes through heterogeneous compensatory mechanisms. The variability of viral load and persistence, the genetic alterations of virus-driven receptors/signaling pathways and the plasticity of innate and adaptive responses may all account for the extreme heterogeneity of pathogenesis and clinical patterns. As recently done for some inflammatory disorders as asthma, rhinosinusitis with polyposis and atopic dermatitis, herein we suggest to define different endo-types and the related phenotypes along COVID-19. Patients should be stratified for evolving symptoms and tightly monitored for surrogate biomarkers of innate and adaptive immunity. This would allow to preventively identify each endo-type (and its related phenotype) and to treat patients precisely with agents targeting pathogenic mechanisms.
Has the Spring 2020 lockdown modified the relationship between air pollution and COVI...
Isabella Annesi
Cara Maesano

Isabella Annesi-Maesano

and 5 more

May 26, 2021
A document by Isabella Annesi, written on Authorea.
From COVID-19 or because COVID-19?
Guglielmo Actis Dato

Guglielmo Actis Dato

May 22, 2021
Infections and pandemics will condition us in an increasingly predominant way regarding diagnostic, medical and surgical activities in all specialist areas; and this particularly in cardiovascular one. Nevertheless in the future the need to cohabit with pandemic events and to be able to continue an elective and not only emergency cardiac surgery program represents an imperative.
Advances and highlights in biomarkers of allergic diseases
Ismail Ogulur
Yağız Pat

Ismail Ogulur

and 27 more

May 20, 2021
Allergic diseases include asthma, atopic-dermatitis, allergic-rhinitis, drug hypersensitivity and food-allergy. During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical-burden. A large fraction of allergic diseases is characterized by a type-2 immune response involving Th2 cells, type-2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and non-invasive methods. In recent years, a plethora of research has been directed towards finding novel biomarkers of allergic diseases. Promising biomarkers of type-2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric-oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body-fluids and exhaled-air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic-urticaria, atopic-dermatitis, allergic-rhinitis, chronic-rhinosinusitis, food-allergies, anaphylaxis, drug hypersensitivity and allergen-immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.
COVID-Q: validation of the first COVID-19 questionnaire based on patient-rated sympto...
Giacomo Spinato
Cristoforo Fabbris

Giacomo Spinato

and 9 more

May 19, 2021
Objectives The aim of the present study is to develop and validate the COVID-Q, a novel symptom questionnaire specific for COVID-19 patients, to provide a comprehensive and standard clinical evaluation. A secondary goal of the present study was to evaluate the performance of the COVID-Q in identifying subjects at higher risk of being tested positive for COVID-19. Material and methods 460 subjects (230 COVID-19 cases and 230 healthy controls), answered the COVID-Q. Parallel Analysis and Principal Component Analysis were used to identify clusters of items measuring the same dimension. The IRT-based analyses evaluated the functioning of item categories, the presence of clusters of local dependence among items, item fit within the model and model fit to the data. Results Parallel analysis suggested the extraction of six components, which corresponded to as many clinical presentation patterns: asthenia, influenza-like symptoms, ear and nose symptoms, breathing issues, throat symptoms, and anosmia/ageusia. The final IRT models retained 27 items as significant for symptom assessment. The total score on the questionnaire was significantly associated with positivity to the molecular SARS-CoV-2 test. Subjects with multiple symptoms were significantly more likely to be affected by COVID-19 (p < .001). Older age and male gender also represented risk factors. None of the examined comorbidities had a significant association with COVID-19 diagnosis. Conclusion The application of the novel COVID-Q to everyday clinical practice may help identifying subjects who are likely to be affected by COVID-19 and address them to a nasopharyngeal swab in order to achieve an early diagnosis.
Possible influence of anti-vector immunity and SARS-CoV-2 variants on efficacy of ChA...
Loris Zamal
Marco Rocchi

Loris Zamal

and 1 more

May 19, 2021
The present work analyses in detail the published data on ChAdOx1 nCoV-19 vaccine and provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as the regimen of homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with efficacy of the vaccine when the interval between prime and boost doses is less than three months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides sub-optimal efficacy against UK variant of SARS-CoV-2, which appears to have an increased transmissibility over the ancestral SARS-CoV-2 among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility; however, if the vaccinated individuals do not maintain everyday preventive actions, they could turn into potential spreaders, thus accelerating the process of generation of new viral variants due to the selective pressure of immune response. Prediction and possible consequences of the SARS-CoV-2 evolution and repeated anti-SARS-CoV-2 vaccinations are discussed. Since the impact of emerging SARS-CoV-2 variants suggests that vaccines are unlikely to be effective in quickly solving the pandemic crisis, it is highlighted the need to keep searching for new and more efficacious pharmacotherapy for COVID-19, such as those targeting ACE2 and ADAM17 zinc-metalloprotease activities.
SARS-CoV-2 re-positivity within the first 3 months of COVID-19 recovery; probable re-...
sara sadr
Melika Arab Bafrani

sara sadr

and 12 more

May 16, 2021
Objectives Possibility of reinfection with SARS-CoV-2 changes our view on herd immunity and vaccination, and can impact worldwide quarantine policies. We performed RT-PCR follow-up studies on recovered patients to assess possible development of reinfections and re-positivity. Method During a 6-month period, 202 PCR-confirmed recovering COVID-19 patients entered this study. Follow-up RT-PCR tests and symptoms assessment were performed one month after the initial Positive results. patients who tested negative were tested again one and three months later. The Serum IgG and IgM levels were measured in the last follow-up session. Results In the first two follow-up sessions, 82 patients continued their participation, of which four patients tasted positive. In the second follow-up 44 patients participated, three of whom tested positive. None of the patients who tested positive in the first and second follow-up session were symptomatic. In the last session, 32 patients were tested and four patients were positive, three of them were mildly symptomatic and all of them were positive for IgG. Conclusion A positive RT-PCR in a recovering patient may represent reinfection. While we did not have the resources to prove reinfection by genetic sequencing of the infective viruses, we believe presence of mild symptoms in the three patients who tested positive over 100 days after becoming asymptomatic, can be diagnosed as reinfection. The IgG may have abated the symptoms of the reinfection, without providing complete protection.
SARS-CoV-2 Re-Infection versus Prolonged Shedding: A Case Series
Erin Nicholson
Vasanthi Avadhanula

Erin Nicholson

and 8 more

May 16, 2021
Since the start of the SARS-CoV-2 pandemic, it has been difficult to differentiate between SARS-CoV-2 re-infection and prolonged RNA shedding. In this report, we identified patients with positive rtPCR results for SARS-CoV-2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS-CoV-2 re-infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re-infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS-CoV-2 re-infection from prolonged RNA shedding.
Successful treatment of COVID-19-related acute respiratory distress syndrome with rar...
Hiroyuki Yamada
Shigeru Ohtsuru

Hiroyuki Yamada

and 13 more

May 15, 2021
A 62-year-old man with rare blood type exhibited severe respiratory failure due to novel coronavirus. Extracorporeal membrane oxygenation was inapplicable, which requires numerous blood products with the same blood type. We thoroughly restricted fluid volumes by sacrificing renal function. He was discharged with complete recovery of respiratory and renal functions.
SARS-CoV-2 RNA stability in saliva and dry swabs for storage and transport at ambient...
Alonzo Alfaro-Núñez
Stephanie Crone

Alonzo Alfaro-Núñez

and 9 more

May 13, 2021
During the current COVID-19 pandemic, different methods have been used to evaluate patients suspected with infection of SARS-CoV-2. In this study, we evaluate the longevity of saliva and dry swab samples to retain SARS-CoV-2 for storage and transport at different environmental settings. Our results show that at ambient temperature of 20°C, SARS-CoV-2 RNA remains stable for up to 9 days giving a long span of time for transport and storage without compromising clinical results. Additionally, this study demonstrates that sali­­­va and dry swabs specimens can also be stored at -20°C and +4°C for up to 26 days without affecting RT-qPCR results. Our data is relevant for low-and middle-income countries, which have limited access to rapid refrigerated transport and storage of samples representing an economical alternative. Finally, our study demonstrates that dry swabs provide clear advantages over using transport medium.
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