ABSTRACT Background: COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11st, 2020. Responses to this crisis integrated resource allocation for the increased amount of infected patients, while maintaining an adequate response to other severe and life-threatening diseases. Though cardiothoracic patients are at high risk for Covid-19 severe illness, postponing surgeries would translate in increased mortality and morbidity. We reviewed our practice during the initial time of pandemic, with emphasis on safety protocols. Methods: From March 11st to May 15th 2020, 148 patients underwent surgery at the Department of Cardiothoracic Surgery of CHUSJ. The clinical characteristics of the patients were retrospectively registered, along with novel containment and infection prevention measures targeting the new Corona Virus. Results: The majority of adult cardiac patients were operated on an urgent basis. Hospital mortality was 1.9% (n = 2 patients). Most of adult thoracic patients were admitted from home, with a diagnosis of neoplasic disease in 60% patients. Hospital mortality was 3.3% (1). Fifteen children underwent cardiothoracic surgery. There was no mortality. The infection prevention procedures applied, totally excluded the transmission of Covid-19 in the Department. Conclusion: While guaranteeing a prompt response to emergent, urgent and high priority cases, novel safety measures in individual protection, patients circuits and pre-operative diagnose of symptomatic and asymptomatic infection were adopted. The surgical results corroborate that it was safe to undergo cardiothoracic surgery during the initial time of Covid-19 pandemic. The new policies will be maintained while the virus stays in the community.

Epidemic diseases contiguously propagate between propitious substances, along with sub-rosa characteristics specifically contiguousness and replication speed may expound ferocity of epidemic diseases such as COVID-19. Most likely, due to high contiguous velocity; in very short time COVID-19 may have become global pandemic disease and key menace to manhood. Deterrence of propagation may help in devastate virus transmogrify using instantaneous traceability of individualized health activities and trackability of public footprints using smart devices, radiography, and social networks.

As college courses transition to online instruction in response to COVID-19 incorporating inquiry-based learning is all the more essential for student engagement. However, implementation can prove challenging for instructors. I describe a strategy for inquiry-based learning that is straightforward to apply in a variety of course modalities, including asynchronous and synchronous online courses. I describe an assignment where students explore the developmental basis of morphological evolution. Flowers offer an excellent example to address this concept and are easy for students to access and describe. Students were asked to conduct research on local flowering plants by collecting and dissecting flower specimens to determine their whorl patterns and then generate hypotheses to explain the developmental genetic basis of the patterns identified. This task allowed students to apply their scientific thinking skills, explore nature, and connect their understanding of the developmental basis of evolutionary change to everyday life. I designed this assignment to be completed asynchronously, and it can be easily modified for synchronous online and traditional face-to-face meetings. Incorporating inquiry using readily available, tangible, tractable real-world examples is a pragmatic and effective approach during and beyond COVID-19.

The biological father of an 11-year-old girl infects his daughter, who returns to her biological mother's family before the father's diagnosis. The daughter endures a 1-day, mild illness. However, despite close physical contact prior to and during the girl's illness, her mother, stepfather and 1-year-old half-brother were not infected.

Updated, peer reviewed and published at Canadian Journal of Medicinehttps://cjm.cikd.ca/article_60573.htmlUntil recently, ibuprofen has been avoided in all COVID-19 protocols world-wide. The author has been trying since March, 2020 to publish a paper that disputes this unfortunate incident and he finally managed since May 2020 to publish two manuscripts that not only prove non-steroidal anti-inflammatory drugs not harmful for COVID-19, rather they were shown to possess a potential to cure the disease based on a unique new theory suggested to explain COVID-19 pathogenesis and he suggested NSAIDs to be added to unique protocol he suggested using nitazoxanide/azithromycin to manage early cases of COVID-19. In this manuscript, considered the fourth related to the subject, the author represents the first clinical results of using NSAIDs/Nitazoxanide/Azithromycin protocol, used partly or fully, that includes relatively cheap FDA approved drugs used in seventeen Egyptian patients, whether confirmed or suspected, including children, adults and two pregnant ladies whom have been mostly symptoms-free in five days. The manuscripts also presents a road-map to illustrate how to deal efficiently with early cases of COVID-19 according to the author’s clinical experience.

We describe two cases of favorable and unexpected recovery in positive patients with COVID-19, suffering from multiorgan comorbidity and already assisted with the left ventricular assist device. We have observed that, although in the presence of more comorbidities, when the maintenance of a valid support of the cardiovascular function is guaranteed, the possibility of successfully overcoming the SARS-CoV-2 infection is still alive.

The current coronavirus (COVID-19) pandemic is associated with severe pulmonary and cardiovascular complications. This report describes a young patient with COVID-19 without any comorbidity presenting with severe cardiovascular complications, manifesting with pulmonary embolism, embolic stroke, and right heart failure. Management with short-term mechanical circulatory support, including different cannulation strategies, resulted in a successful outcome despite his critical cardiovascular status.

Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS-CoV) caused SARS pandemic in 2003 and SARS-CoV-2 caused the ongoing COVID-19 pandemic. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Especially, SARS-CoV-2 tended not to use murine or non-mammal ACE2s. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

Aims In light of the recent safety concerns relating to NSAID use in COVID-19, we sought to evaluate cardiovascular and respiratory complications in patients taking NSAIDs during acute lower respiratory tract infections. Methods We carried out a systematic review and meta-analysis of randomised controlled trials and observational studies. Studies of adult patients with short-term NSAID use during acute lower respiratory tract infections, including bacterial and viral infections, were included. Primary outcome was all-cause mortality. Secondary outcomes were cardiovascular, renal and respiratory complications. Results In total, eight studies including two randomised controlled trials, three retrospective and three prospective observational studies enrolling 44140 patients were included. Five of the studies were in patients with pneumonia, two in patients with Influenza, and one in patients with acute bronchitis. There was uncertainty as to the effects on mortality (RR 0.87 [0.63, 1.18]), but pleuro-pulmonary complications were more common with NSAID use (RR 2.62 [1.96, 3.50]). However, all studies exhibited high risks of bias, primarily due to lack of adjustment for confounding variables. Cardiovascular outcomes were not reported by any of the included studies. Conclusion Short-term NSAID use during acute lower respiratory tract infections was associated with more pleuro-pulmonary complications although this may be due to confounding by indication. There remains significant uncertainty on the effects on mortality. Such results should be interpreted cautiously given the very low quality of evidence. Mechanistic and clinical studies addressing the captioned subject are urgently needed, especially in relation to COVID-19.

The “coronavirus disease 2019 (COVID-19)” outbreak was first reported in December 2019 (China). Since then, this disease has rapidly spread across the globe and in March 2020 the World Health Organization (WHO) declared the COVID-19 pandemic.1 Since the outbreak was first announced, our journal has extensively focused on the clinical features, outcomes, diagnosis, immunology, and pathogenesis of COVID-19 and its infectious agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We published our first COVID-19 article on 19 February, focusing for the first time on the clinical characteristics of 140 cases of human-to-human coronavirus transmission without any links to the Huanan Wet Market.2 Hypertension and diabetes were mentioned as risk factors and there was no increased prevalence in allergic patients. This early study reported that the main symptoms at hospital admission were fever (91.7%), cough (75.0%), fatigue (75.0%), gastrointestinal symptoms (39.6%), and dyspnea (36.7%). Lymphopenia and eosinopenia were also reported as important signs and biomarkers for monitoring and severity of the patients.2 The prevalent eosinopenia in COVID-19 patients and the possible anti-viral role of eosinophils were further discussed in several following publications inAllergy .3,4 Our second COVID-19 paper brought attention to the wide range of clinical manifestations of this disease, from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia as well as with only diarrhea.5Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with pre-existing chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were severe. Another article, timely appearing in our journal, alerted the scientific community that even in experienced hands there was a 14.1% false negative polymerase chain reaction (PCR) diagnosis in COVID-19 cases and were later diagnosed positive after repeated tests.6 A pediatric article was also published extensively analyzing 182 cases and it was reported that children with COVID-19 showed a mild clinical course.7 Patients with pneumonia had a higher proportion of fever and cough and increased inflammatory biomarkers compared to those without pneumonia. There were 43 allergic patients in this series and there was no significant difference between allergic and non-allergic COVID-19 children in disease incidence, clinical features, laboratory, and immunological findings. Allergy was not a risk factor for disease and severity of SARS-CoV-2 infection and did not significantly influence the disease course of COVID-19 in children.7The immunology of COVID-19 was extensively reviewed in two articles from leading experts with a comprehensive discussion of the tip of the iceberg in COVID-19 epidemiology, anti-viral response, antibody response to SARS-CoV-2, acute phase reactants, cytokine storm, and pathogenesis of tissue injury and severity. 8,9Two studies timely reported the role of possible trained immunity in countries with a Bacillus Calmette-Guérin (BCG) vaccination programme and a relatively low COVID-19 prevalence and mortality rate.10,11 In an extensive RNA sequencing analyses of SARS-CoV-2 receptor and their molecular partners revealed that ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells.12Allergists, respiratory physicians, pediatricians, and other health care providers treating patients with allergic diseases are frequently in contact with patients potentially infected with SARS-CoV-2. Practical considerations and recommendations given by experts in the field of allergic diseases can provide useful recommendations for clinical daily work. Since the beginning of this current pandemic, our journal has disseminated clinical reports, 2,3,5,6,13 statements on the urgent need for accuracy in designing and reporting clinical trials in COVID-19,14 preventive measures,10,11,15 and Position Statements elaborated by experts in the field in close collaboration with the European Academy of Allergy and Clinical Immunology (EAACI) and its task force “Allergy and Its Impact on Asthma (ARIA) ”.16-28 (keynote information in table 1). A compendium answering 150 frequently encountered questions regarding COVID-19 and allergic diseases has been recently published by experts in their respective area.29 In addition, readers can put further questions regarding this “living ” compendium electronically to the authors and their answers will be available through a new category in the journal’s webpage.30Besides, EAACI in collaboration with ARIA, has provided recommendations on operational plans and practical procedures for ensuring optimal standards in the daily clinical care of patients with allergic diseases, whilst ensuring the safety of patients and healthcare workers.23Table 1: Examples of recently published recommendations, statements and Position Papers of the EAACI

Distance learning has been a means to provide an education to those who are unable to participate in on-campus, face-to face classes. Teams of instructional design specialists that focus on online education put significant effort into course development. This planned process is very different from emergency remote education in response to a crisis. In early 2020, it was discovered that an extremely contagious respiratory illness termed COVID-19 had spread to every corner of the earth. As of mid-March 2020, the need to transition from face-to-face classroom instruction to exclusively online education landed on the doorstep of America’s universities. COVID-19 has catalyzed a transition in the ecology of American education for all students, but especially the underserved and minoritized. Ecology, by definition, is concerned with the interactions of an organism and its environment. The circumstances of the pandemic have caused vast and rapid change in both the internal and external environments of the organisms (e.g., students) and the systems in which they reside (e.g., U. S. educational systems). The purpose of this paper is to provide some considerations for instructors who find themselves “thrown into teaching remotely,” and help them think about how best to create sustainable systems, broaden participation and build capacity in a more equitable and inclusive manner.

Background: The liberal administration of hydroxychloroquine-sulphate (HCQ) to COVID-19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID-19 patients treated with HCQ and of the existence of concomitant alternative causes. Methods: All COVID-19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical center were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite endpoint comprised of either an increase ≥ 60 milliseconds (ms) in the QTc interval compared with pretreatment QTc, and/or a maximal QTc interval >500 ms. Results: Ninety patients were included. Median age was 65 years (IQR 55-75) and 57 (63%) were male. Thirty-nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n=23 each, 26%). QTc prolongation evolved in fourteen patients (16%). Age > 65 years, congestive heart failure, severity of disease, C-reactive protein level, hypokalemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalemia [OR 5, (95% CI, 1.3-20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01-13.7)]. Conclusion: In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalemia and furosemide treatment.

Objective: We aimed to investigate the demographic shifts in emergency service admissions, possible measures and room for improvement in emergency services during the Covid-19 pandemic. Methodology: Our study retrospectively analyzed the demographic features and clinical admission types of patients admitted to Batman District State Hospital Emergency Service at two different time periods, one prior to the Covid-19 pandemic and the other during the Covid-19 pandemic. The results were compared between the two periods designated as the pandemic period and the pre-pandemic period. Results: The number of patients admitted to emergency service was 47.681 in the pre-pandemic period and 9455 in the pandemic period (p<0.01). The number of patients admitted for trauma was 1247(2.61%) in the pre-pandemic period and 59(0.62%) in the pandemic period (p<0.01). The number of patients hospitalized to cardiology department or coronary care unit for acute coronary syndrome was 602(1.26%) in the pre-pandemic period and 29(0.3%) in the pandemic period (p<0.01). The number of patients hospitalized to neurological intensive care unit for acute cerebrovascular disease was 542(1.13%) in the pre-pandemic period and 22(0.2%) in the pandemic period (p<0.01). The number of patients hospitalized to pulmonary diseases department or intensive care unit for dyspnea was 622(1.21%) in the pre-pandemic period and 515 (5.4%) in the pandemic period (p <0.01). Conclusion: Measures taken to prevent the spread of Covid-19 infection have caused a significant drop in emergency service admissions. We are of the opinion that this will lead to an increase in deaths occurring at home, and we will soon encounter patients with worse prognosis and overcrowded emergency services. In order to prevent this problem, we believe that the public awareness about emergency conditions requiring emergency service admission should be heightened alongside of the ‘stay home’ calls.

Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a “better fit” to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).

Aim: Pharmacovigilance data are primarily used to identify adverse drug reactions. However, scanning for associations of drugs and adverse events that occur less frequently than expected provides hypotheses for drug repurposing, i.e. a known drug could be therapeutically beneficial for a new indication like the coronavirus disease (COVID-19). Methods: Drugs associated with viral respiratory tract infections and/or influenza were extracted from the U.S. FAERS pharmacovigilance data using OpenVigil2.1-MedDRA17, filtered for significant inverse associations (punadj<0.05), checked for plausibility, and categorised by their WHO Anatomical Therapeutic Chemical (ATC) classification code. Results: ATC clustering of 82 candidate drugs revealed anti-diabetics, neuropharmacologic sigma-receptor agonists, peptidase inhibitors, kinase inhibitors and anti-androgens. Chloroquine appears as a statistically significant risk factor for viral diseases supporting actual knowledge. Conclusion: OpenVigil 2 delivers new hypotheses for drug repurposing, theoretically for all indications. There is affirmative data for some of our results; the remaining proposed candidate drugs without already known antiviral mechanism of action should stimulate further exploration.

Dear Editor,We read with interest the published article by Ikeda et al. [1], they performed thoracic endovascular aortic repair (TEVAR) in a patient with Marfan syndrome (MFS) for acute complicated type B aortic dissection (TBAD) during COVID-19 pandemic.The evidence around TEVAR for MFS is scarce and open repair remains the gold treatment[2]. During the COVID-19 pandemic, many patients are either being denied treatment or given inferior options on the basis of age, comorbidities and risk of COVID pneumonia; however, the guidelines for aortic intervention in the United Kingdom have remained largely unchanged from pre-COVID-19 era [3]. Our questions to the authors relate to whether their solution was an unnecessary compromise. There is no clear indication defined in their case as a cold leg doesn’t necessary means an ischaemic limb. The TEVAR procedure performed aiming to minimise hospital stay, yet this approach may have put the patient at higher risk of developing paraplegia and visceral organ malperfusion, while compromising her long-term care.There is need to clarify if she had risk factors that prone her to a higher risk acquiring severe COVID-19 which necessitated deviating from the traditional open surgery recommended for MFS patients with TBAD [2]. The authors did not report on renal function, evidence of bowel malperfusion or whether there was resistant hypertension that needed immediate intervention. If the need to expediate intervention was the fear of limb ischaemia, is it conceivable a femoro-femoral bypass could have saved the limb and definitive open surgery on her aorta could have been performed at a later stage, especially since she was haemodynamically stable.Moreover, as Marfan-diseased aortas are prone to further dilatation, we believe their justification for opting for endovascular repair should also have been more balanced, exploring the know high rate of long-term TEVAR-associated complications in MFS patients including endoleaks, retrograde dissection, stent-graft-induced new entry tears, surgical conversions and reintervention. There is also need for imaging follow-up to assess the success of TEVAR and early detection of aforementioned complications.

The COVID-19 pandemic has transformed lives across the world. In the UK there has been a public health driven policy of population ‘lockdown’ that had enormous personal and economic impact. We compare UK response/outcomes including excess deaths with European countries with similar levels of income/healthcare resources. We calibrate estimates of the economic costs as different %loss in GDP against possible benefits of avoiding life years lost, for different scenarios where local COVID-19 mortality/comorbidity rates were used to calculate the loss in life expectancy. We apply quality-adjusted life years (QALY) value of £30,000 (maximum under NICE guidelines). The implications for future lockdown easing policy in the UK are also evaluated. The spread of cases across European countries was extremely rapid. There was significant variation both in severity and timing of both implementation and subsequent reductions in social restrictions. There was less variation in the trajectory of mortality rates and excess deaths, which have fallen across all countries during May/June 2020. The average age at death and life expectancy loss for non-COVID-19 was 79.1 and 11.4years respectively while COVID-19 were 80.4 and 10.1years; including for life-shortening comorbidities and quality of life reduced this to 5QALY for each COVID-19 death. The lowest estimate for lockdown costs incurred was 50% higher than highest benefits from avoiding the worst mortality case scenario at full life expectancy tariff and in more realistic estimation they were over 50 times higher. Application to potential future scenarios showed in the best case a QALY value of £220k (7xNICE guideline) and in the worst-case £3.7m (125xNICE guideline) was needed to justify the continuation of the lockdown. The evidence suggests that the costs of continuing severe restrictions in the UK are so great relative to likely benefits in numbers of lives saved so that a substantial easing in restrictions is now warranted.

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Multisystem inflammatory syndrome in children (MIS-C) during the COVID-19 pandemic raised a global alert from the Centers for Disease Control and Prevention’s Health Alert Network. The main manifestations of MIS-C in the setting of a severe inflammatory state include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes, and in some cases it progressed to multi-organ failure. The low percentage of children with asymptomatic cases compared with mild illness and moderate illness could be correlated with the rare cases of MIS-C. One potential explanation for the progression to severe MIS-C disease despite the presence of readily detectable anti-SARS-CoV-2 antibodies could be due to potential role of antibody-dependent enhancement (ADE). We reason that the incidence of the ADE phenomenon whereby the pathogen-specific antibodies can promote pathology should be considered in vaccine development against SARS-COV-2.

The difference in morbidity and mortality between adult and pediatric COVID-19 infections is dramatic. Understanding pediatric-specific acute and delayed immune responses to SARS-CoV-2 is critical for the development of vaccination strategies, immune-targeted therapies, and treatment and prevention of MIS-C. The goal of this review is to highlight research developments in understanding of the immune responses to SARS-CoV-2 infections, with a specific focus on age-related immune responses.

To the editor,Following the online podcast recorded the 31 March 2020 by the International Committee of the American Thoracic Society Pediatrics Assembly and recently published in Pediatric Pulmonology1, we have interesting discussion with my international colleagues about the likelihood of acute bronchiolitis caused by SARS-CoV-2 infection in absence of RSV co-infection. Here, we report 2 cases of COVID-19 in infants < 3 months old admitted to our paediatric unit. The infants presented fever and neurological symptoms and after a short period, acute bronchiolitis.Case 1 : A term-born boy with unremarkable history was admitted to the emergency department with poorly tolerated high fever (38.8°C) and rhinitis. The parents, who had no history of asthma or allergy, showed clinical signs suggesting SARS-CoV-2 infection. RT-PCR for SARS-CoV-2 on a nasopharyngeal swab was positive for the father and the grandfather, who was hospitalized in the intensive care unit. Neurologic examination of the infant revealed lethargy and hypotonia with a bulging anterior fontanelle. The respiratory condition and clinical examination findings including hemodynamics were normal.The first blood test showed isolated lymphopenia (lymphocyte count 1.56 x109/L; normally 4-6x109/L) without modification of biological inflammatory parameters, as assessed by normal levels of C-reactive protein (CRP) and procalcitonin (PCT). Spinal fluid analysis, cytobacteriological urine analysis and blood culture were negative. RT-PCR of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for respiratory syncytial virus (RSV) and influenza virus (IV). The patient received fluid volume expansion(20 ml/Kg of 0.9% sodium chloride solution) together with antibiotic treatment (cefotaxime, amoxicillin and gentamicin at meningeal doses) for 24 hr, that was stopped with a positive RT-PCR test for SARS-CoV-2 and negative blood culture. Favourable clinical outcome was obtained shortly thereafter, allowing the infant to return home 2 days later.Ten days later, the child returned with acute bronchiolitis. Respiratory symptoms included polypnea, shortness of breath, wheezing and hypoxia (SpO2< 92 %). Lung ultrasonography revealed signs of interstitial syndrome with thickened and irregular pleural line associated with confluent B lines and small multifocal subpleural consolidations. RT-PCR for RSV and IV remained negative. Treatment associated supplemental oxygen and enteral nutrition for 6 days. A second episode of acute bronchiolitis occurred 1 month later, but a RT-PCR test for SARS-CoV-2 was negative. The chest X-ray was normal. The child remained hospitalized for 5 days with enteral nutrition support but did not require oxygen supplementation. Long-term treatment with inhaled daily corticosteroids (fluticasone) was introduced.Case 2 : A term-born eutrophic male with otherwise unremarkable neonatal history was referred for poorly tolerated high fever at age 2 months. Both parents had clinical signs of COVID-19 but were not tested (a member of the family had a positive test). The neurologic examination revealed lethargia and hypotonia in the child; the respiratory condition and clinical examination findings including hemodynamics were normal. The first blood test showed lymphopenia (lymphocyte count: 1.86 x109/L; normally 4-6x109/L)without modification of biological inflammatory parameters. Cytobacteriological examination of urine and blood culture were negative and spinal fluid analysis was not performed. RT-PCR testing of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for RSV and IV. The patient did not receive any antibiotics. On day 3 after admission, the respiratory condition progressively worsened, with retraction, wheezing, increased respiratory rate at 80/min and hypoxia (SpO2 < 92%) requiring supplemental oxygen together with enteral nutrition for 3 days. The chest X-ray was normal, and no lung ultrasonography was performed. The infant was returned to the emergency department 2 weeks later with a non-severe wheezing episode and was discharged at home.These 2 cases of COVID-19 in infants hospitalized for poorly tolerated high fever and neurological symptoms in whom acute bronchiolitis developed at a delay of 2 to 8 days suggest that SARS-CoV-2 infection may cause acute bronchiolitis in absence of viral co-infection such as RSV. Pneumonia is the most common diagnosis among symptomatic children with COVID-191. High-resolution CT scan usually shows ground-glass opacities or bilateral lung consolidations, especially in the periphery, and lung ultrasonography, as in our case 1, reveals signs of lung involvement. In contrast, to the best of our knowledge, acute bronchiolitis due to SARS-CoV-2 infection has never been reported. The wheezing episodes described in our patients were likely due to SARS-CoV-2 infection for the following reasons: first, RT-PCR tests for RSV and IV were always negative in both children, and second, the epidemic season for both viruses was over and the lockdown in France was still active at the time of the cases. Finally, previous study of virus repartition in positive respiratory samples from infants with acute bronchiolitis detected close to a 5% frequency of coronaviruses OC43 and 229E2. Moreover, a recent experimental model of COVID-19 in ferrets showed lung lesions compatible with bronchiolitis3. Our patients showed bronchiolitis symptoms several days after those of COVID-19, which may explain the lack of wheezing episodes reported in the literature. Case 2 was diagnosed with recurrent wheezing presumably due to SARS-CoV-2 infection. RSV as well as rhinovirus bronchiolitis is a risk factor for recurrent wheezing and asthma4,5,but little is known about the long-term impact of SARS-CoV-2 infection in lung function trajectory, which emphasizes the need to follow these children. Whether the infection in symptomatic or asymptomatic infants may predispose to recurrent wheezing or asthma remains to be determined.

Objective: To investigate temporal bone findings in COVID-19 Design: Retrospective study Settings: Using the database of our tertiary pandemic hospital, patients with COVID-19 infection with a positive PCR test and temporal bone tomography imaging were evaluated. Participants: 42 PCR positive COVID-19 patients with temporal bone imaging. Main outcome measures: A grading system was created to evaluate effusion in the middle ear and mastoid air cells. Also any specific sign in temporal bone imaging. Results: Patients were divided into two groups according to their chest CT findings. Group 1 had specific chest CT findings and included 26 patients, group 2 had no findings in chest CT and included 16 patients. No obvious temporal bone involvement was observed in any of the patients. Temporal bone imaging findings were compared according to a grading system and there was no difference between the groups (p=0,50). Conclusion: The SARS-CoV-2 does not affect the temporal bone. There was no sign of effusion in mastoid air cells or the middle ear or any specific sign in the temporal bone in our study group.

Intense effort is underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely-researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.

At present, Corona virus disease 2019(COVID-19) has become a major concern all over the world and leads to huge medical pressure. Antibody-dependent enhancement (ADE) of viral infection has been researched extensively in many viruses. It is not yet clear whether SARS-CoV-2 infection causes ADE effects. However, there is evidence that ADE may be found in COVID-19. We have discussed the possibilities of ADE effect induced by COVID-19 and proposed a series of measures to deal with it.