Background: In severe cases, the COVID-19 viral pathogen produces hypoxic respiratory failure unable to be adequately supported by mechanical ventilation. The role of extracorporeal membrane oxygenation (ECMO) remains unknown, with the few publications to date lacking detailed patient information or management algorithms all while reporting excessive mortality. Methods: Case report from a prospectively maintained institutional ECMO database for COVID-19. Results: We describe veno-venous (VV) ECMO in a COVID-19 positive woman with hypoxic respiratory dysfunction failing mechanical ventilation support while prone and receiving inhaled pulmonary vasodilator therapy. After nine days of complex management secondary to her hyperdynamic circulation, ECMO support was successfully weaned to supine mechanical ventilation and the patient was ultimately discharged from the hospital. Conclusions: With proper patient selection and careful attention to hemodynamic management, ECMO remains a reasonable treatment option for COVID-19 patients.

SARS-COV-2 infection can be asymptomatic or mildly symptomatic. The effect of chemotherapy on an asymptomatic infected patient is unknown. Three hundred-thirty-four and 56 NFS were performed as screening for SARS-CoV-2 infection in 247 and 34 pediatric patients undergoing chemotherapy and stem cell transplantation, respectively. NFS was positive in 10 patients. All positive patients withdrew from chemotherapy. Nine patients became negative. One patient is still positive after 38 days.The identification of asymptomatic SARS-COV-2 infection is important to reduce the hospital spread of infection. Further studies are needed to define the least risky management of chemotherapy in asymptomatic SARS-CoV-2 patients.

SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.

COVID-19 in a child with severe aplastic anemiaYunus Murat Akçabelen1, Ayça Koca Yozgat1, Aslı Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editörRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID-19). It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.

A novel bat coronavirus (2019-nCoV) caused an outbreak of infectious pneumonia termed COVID-19 in the world. This reminds us of another notorious bat coronavirus, SARS-CoV, which mysteriously broke out in China 17 years ago and killed nearly 800 people worldwide. A key to its efficient human attack is adopting angiotensin-converting enzyme 2 (ACE2) as the receptor. The relationship between 2019-nCoV and SARS-CoV has aroused much public concern. To our surprise, we found that the two CoV lineages may frequently exchange their genetic materials through homologous recombination. Particularly 2019-nCoV might thereby acquire the receptor-binding domain from the SARS-CoV clade, enabling it to make use of ACE2 as well and thus spread rapidly in humans. Our findings suggest the accomplice role of a virus of SARS-CoV clade in COVID-19 and warn of the possible emergence of more mosaic CoVs capable of launching severe epidemic.

Abstract The objective of this study was to describe early respiratory outcomes of asymptomatic COVID-19 patients after cardiac surgery. In this retrospective clinical study (case series) we reviewed and analyzed patient clinical data of 25 covid-19 asymptomatic patients that underwent urgent or emergent cardiac surgery between February 29 and April 10, 2020 in Tehran Heart Center Hospital. Median of age was 63 years (IQR, 52-67), Euro SCORE 7.50 (IQR, 6.5-8.5) and body mass index 26.3 (IQR, 22.5-28.6). 68% of patients had one or more comorbidities. Hypertension (56%) was the most common followed by Diabetes type 2 (40%). Off-pump cardiac surgery was done in 4 patients and on-pump on 21 patients with median CPB time of 85 minutes (IQR, 50-147.50). Median anesthesia time was 4.5 hours (IQR, 4-5). Median oxygen index and Fio2 on ventilator were 10 cmH20 (IQR, 9.5-10.5) and 0.64(IQR, 0.60-0.64) respectively. Median pao2/Fio2 was 231(IQR, 184-261). There was one case of extubation failure. The Median intubation time and length of ICU stay were 13 hours (IQR, 9.5-18) and 3 days (IQR, 2-4) respectively. Overall mortality was 16%. Readmission rate to ICU was 16% with. In this group respiratory outcome was worse with median Pao2/Fio2 84.5 (75-122), oxygen index of 4.38(IQR, 3.77-5.1) and morality rate of 75%. Conclusion: Based on the results of this study, very early post-cardiac surgery respiratory outcomes in asymptomatic COVID-19 patients are apparently smooth; nonetheless, readmission to the ICU is high. Overall respiratory outcomes are poor especially for those who readmitted to ICU.

Abstract: Background: COVID-19 burst in Wuhan China in December 2019 and soon became a worldwide emergency. To help further understand COVID-19. Here we report the epidemiological, clinical features, potential biomarkers, and CT changes of cases in Wenzhou. Methods:All 64 cases were diagnosed by positive of PCR test. Clinical laboratory tests, CT and treatment were performed in the level 3 of protection. Data and clinical characteristics feature were collected by 4th March. The correlation was analyzed. Results:Most cases were light. The average of latency was 3.4 days, ranged from 1-14. The median age was 44, ranged from 2.2-67; 36 male and 28 female; 59 had fever, 38 with high temperate (>38℃); 45 had respiratory symptoms; 28 had gastrointestinal symptoms; 39 weakness; one asymptomatic case was found. Most with low LC, K+, Na+, OI and high LDH, CRP, D-dimer. Pneumonia, both lungs involvement, ground-glass opacity and consolidation were shown by CTs. Minor had electrocardiography change. Conclusions:The clinical features, abnormality lab indexes and CT characteristics of COVID-19 were like SARS, majored in fever, weakness along with dry cough, diarrhea. LC, LDH could be good biomarkers monitoring progress. The elders, hypertension patients and smokers were more vulnerable. COVID-19 was milder, but more transmissible than SARS. Latency could be up to 14 days without symptoms. CT and PCR shall be both considered in clinical high suspicion. There are still further efforts to be made as to preventing and control the epidemic and the cost in world wild.

References 1. Wang H, Li T, Barbarino P, Gauthier S, Brodaty H, Molinuevo JL, Xie H, Sun Y, Yu E, Tang Y, Weidner W. Dementia care during COVID-19. Lancet. 2020;395(10231):1190.2. Caraci F, Sultana J, Drago F, Spina E. Clinically relevant drug interactions with anti-Alzheimer’s drugs. CNS & Neurological Disorders-Drug Targets. 2017;16(4):501-13.3. University of Liverpool. COVID-19 Drug Interactions. 2020. https://www.covid19-druginteractions.org. Accessed 21 April, 2020.4. Pytliak M, Vargová V, Mechírová V. Drugs and hypoglycemia. Hypoglycemia–causes and occurrences. Shanghai: InTechOpen. 2011:131-48.5. Pasqualetti G, Tognini S, Calsolaro V, Polini A, Monzani F. Potential drug–drug interactions in Alzheimer patients with behavioral symptoms. Clinical Interventions in Aging. 2015;10:1457.

AIMS To report the major characteristics and clinical outcomes of COVID-19 patients treated with ACE inhibitors and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients. METHODS This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension. RESULTS Among 198 patients, 58 (29.3%) and 16 (8.1%) were on were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and ARDS when compared with patients treated with ACEI alone or not receiving RAAS blocker (P＜0.05). The Kaplan-Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend towards a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27; 95% CI, 0.07-1.02; P=0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox-regression analysis to compared ACEI vs. ARB groups showed a significantly lower mortality rate in the ARB group (adjusted hazard ratio, 0.03; 95% CI, 0.00-0.58; P=0.02). CONCLUSIONS Our data may provide some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.

Currently as of May 2020, there are more than 8 potential candidate vaccines against COVID19 in clinical evaluation and another 100 in preclinical evaluation. Considering the governing rules and regulations with respect to non-clinical and clinical evaluations, it may take around 5-6 months at the earliest to have an efficacious COVID 19 vaccine. The question lies ‘DO WE HAVE THAT MUCH TIME?’ The challenges faced today not only have implications to the public health but also the masked social and economic implications as well. Hence, it is imperative to have a Blitz Krieg solution against COVID19.

Our experience: Surgical tracheostomy in 20 patients with COVID- 19 pneumonitis Key pointsThe potential for transmission of the SARS -CoV-2 virus to healthcare workers performing the tracheostomy necessitates changes to standard tracheostomy proceduresSurgical tracheostomy performed in a theatre environment enables surgical and anaesthetic teams to support critical care staff by taking ownership of this aspect of patient careAll ENT and Maxillofacial teams used PPE including FFP3 facemasks, visors, and disposable hoodsMedian (interquartile range) day to tracheostomy after intubation was 19 days (16-26.3). Median follow up was 17.5 days (range 3-24).None of the healthcare workers involved were clinically or PCR positive for COVID -19 in the post-operative periodKeywords SARS-CoV-2, Novel Coronavirus, COVID-19, Tracheostomy, Mechanical Ventilation

Key Points: 1. Clinical areas where Fibreoptic nasoendoscopy (FNE) and larygoscopy (FOL) are performed are high risk areas in the COVID-19 era as they are potential aerosol generating procedures (AGP). 2. Barrier protection remains the key to prevent transmission. This device is one that patients can wear to reduce potential aerosol contamination of the surroundings. 3. Seal can be verified and tested by the patient placing a thumb over the filter. 4. This device is simple, reproduceable, easy to use, economical and well tolerated. Full personal protection equipment (PPE) is still advisable to be worn by the operator. 5. This device may reduce potential aerosolisation and thus reduce the need to allow air changes in clinic rooms, freeing up clinical resources.

The world is in front of a risky epidemic due to novel coronavirus (2019-CoV or COVID-19). This virus is not only affected human health but it affected the economy and caused completely paralysis in many countries of the world. Various therapeutic, medicinal, scientific, and technological communities are demanding to find out specifically and to approve successful strategies for discovering the effective vaccine which can lead to stop the virus expansion, recognize medication, reduce humanity health hazards, serious infections, death rates. The importance of natural effective nutritious food and diet having peculiar immunity is highlighted which pointed out the unconfirmed dietary option risks which would lead to decline effective precautionary procedures. This report is aimed to focus on the most effective food and nutrients which trigger the body immunity system and prevent the coronavirus type infections.

The 2019 novel coronavirus disease (COVID-19) has affected all aspects of life globally and care of children with malignancies is no exception. We are part of a large tertiary care 2000 bedded university hospital in North India. Approximately 450 new malignancies are diagnosed annually, translating to 10 patients per week. About 200 children attend the clinics every week. Additionally, 15-20 walk-in patients are evaluated daily in the daycare. Patients travel from distances as far as 500 km to reach our center.  Merely 20% live within 50 km of the hospital, and approximately 35% reside at a distance exceeding 200 km. Two-third of the patients hail from urban areas and one third belong to rural areas. The majority of families stay in a patient hostel in the hospital premises, and a few rent a flat in the city for the 4-9 months duration of intensive phase of therapy. The Government of India mandated a lockdown on the 24th March 2020 in response to the coronavirus pandemic and the outpatient services of the hospital were closed. The borders with the neighboring states were sealed & vehicular movement curtailed with barring of public transport & suspension of all interstate and intercity travel. The citizens were advised to maintain social distancing. The unit was faced with the formidable challenge of ensuring the well-being of children under our care from a wide geographical spread with minimal access to Pediatric Oncology services in their   hometowns. How did we manage our patients?

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

Rationale: Whether asthma constitutes a risk factor for COVID-19 is unclear. Here we aimed to assess whether asthma, the most common chronic disease in children, is a risk factor for COVID-19 in pediatric populations. Methods: We performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS-CoC-2 and COVID-19 in pediatric populations, and reviewed their primary articles; second, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; third, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. Results: In the first search, eight systematic reviews were found, of which five were done in pediatric population; after reviewing 67 primary studies we found no data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 34 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 23 pre-prints in MedRxiv were identified with data on asthma, but again none with pediatric data. We found only one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had “chronic lung diseases including asthma”. Conclusion: There is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.

The aim of this paper is to apply the Differential Transformation Method (DTM) to analyze and obtain the solution for the mathematical model described by the system of non-linear ordinary differential equations which describe the epidemiology of the most threatening virus called \textbf{Corona-virus} later labeled as COVID-19. Finally, the present study may help you to examine the wild class of real-world models and also aid to predict their behavior with respect to parameters considered in the model. The purpose of this study is to estimate the effectiveness of preventive measures, predicting future outbreaks, and potential control strategies using the mathematical model.

CDC recommends the use of N-95 respirator or surgical mask (if N-95 masks are not available) when taking care of the COVID-19 suspected or positive patients. N-95 respiratory mask should be used instead of a face-mask when present or carrying out aerosol-generating procedures such as intubation, bronchoscopy1. WHO has also recommended to wear a mask in simple encounters with COVID-19 patients and reserve the N-95 respirators for aerosol producing procedures2. CDC reports that the spread of the virus is mainly from person to person in the form of respiratory droplets when the infected COVID 19 patient sneezes or coughs3. WHO reported the transmission of the virus between people through droplets and contact and not through airborne precautions4. However, there are recent experimental studies that suggest the plausibility of aerosol transmission of COVID-19. We describe a case of an emergency health care worker acquiring COVID-19 in a short encounter with an index COVID-19 positive patient (patient X) in the hospital despite the use of a surgical mask and gloves.

There is currently scant data on COVID-19 related death cases among physicians with different medical specialties. Mortality data among physicians in Italy show that General Practitioners (GPs) are the most affected group. They currently represent the 43% of the total COVID-19 related death cases among physicians, whereas the estimated proportion of GPs compared to other doctors is of 15%. This high number among GPs is attributable to a work-related contagion happened massively during the first weeks of the epidemic, but constantly continuing also in the weeks following the national lock-down. There are various reasons for these higher contagion rates: GPs use to daily perform a lot of medical examinations in close contacts with patients, and in addition it should be considered that SARS-CoV-2 can resist on the clinics’ surfaces for several hours and it can be transmitted also at distances longer than two meters, persisting in the air after an aerosolization process. Furthermore, especially at the beginning of the epidemic GPs might have scant information on specific safety procedures for the prevention of COVID-19 transmission (e.g. there was scant knowledge on the possibility of contagions from asyntomatic patients) and, morever, the availability of personal protective equipment was insufficient. Following these observations, and considering the high tribute in term of lives from the GPs, Covid-19 pandemic will probably revolutionize the approach to patients in the general practice. Clear and effective guidelines are absolutely and urgently needed, for the refinement of adequate measures to prevent SARS-CoV-2 infections among GPs.

Identifying candidate drugs effective in the new coronavirus disease 2019 (Covid-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that Cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons: 1) High-CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARΥ agonist, it can display a direct antiviral activity 4) PPARΥ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID-19 pandemic.

Background The Corona virus disease 2019 (COVID-19), evolving into a pandemic, resulted in medical resources being shifted to crisis management. Anecdotal evidence suggests that treatment of retinoblastoma, the most common intraocular cancer, is compromised by policy changes during the pandemic, risking children’s lives. Procedure The Global Retinoblastoma Study Group that comprises most retinoblastoma treatment centers across the world conducted a survey focusing on the impact of COVID-19 on retinoblastoma management from March 29 to April 4 2020. Data on COVID-19, including number of positive cases and reported deaths, in the same period were retrieved from the World Health Organization. Results Overall, 194 retinoblastoma centers from 94 countries and 6 continents representing nearly half of the estimated global annual incidence of retinoblastoma participated. As of April 4 2020, the number of COVID-19 positive patients and reported deaths in the participating countries were 1,165,380 and 63,720, respectively, representing over 95% of the global burden. Forty-two percent of the centers reported that families were restricted from travelling to them, and 38% reported disruption to retinoblastoma management from shortage or reallocation of personnel or equipment. Enucleation was still available in 90% and intravenous chemotherapy in 97% of the centers, but 54% of them reported that changes and restrictions outside or within the center were potentially affecting the lives of retinoblastoma patients. Conclusions Shift in health care resources and pandemic policies at a national level may be hazardous for children with retinoblastoma.

COVID outbreak has incapacitated the healthcare system around the world. Existing resources and manpower are being redirected to take care of the COVID-19 disease patients. People with head and neck cancers with the need of post ablative reconstruction are in difficult situation owing to multiple factors like poor general condition, disease progression and potential chance of getting an infection of COVID -19 in a health care facility as well as doubt regarding treatment completion i.e. adjuvant treatment. Appropriate reconstruction following ablative surgery, especially in advanced disease, facilitates functional recovery and thus adding to the quality of life of the patients.The reconstructive procedures are resource-intensive, requiring long hours of surgery, trained manpower, and multiple team members. However, if adequate surgical excision demands the reconstructive procedure, then it should not be a hindrance for the standard treatment.  We need to review our approach in the face of the devastating COVID-19 pandemic. We are presently working in resource constraints like limited availability of staff and limited availability of personal protective equipment especially in plastic surgery procedures which requires the use of loupes and microscope. Thus, the challenge is to ensure proper reconstruction with limited available resources and maintaining safety standards for the staff in the operation theatre. This work is based on our experience and evidence from the literature.

Key points:Covid-19 patients are often intubated for a long time, with indication to tracheotomy, at high risk for transmitting the disease.Open surgical sub-isthmic tracheotomy above the ETT cuff should always be performed on fully paralyzed patients, to minimize the airflow and aerosolisation from alveolar space.Other technical refinements described in the paper are finalized to reduce the “no seal” time from ETT cuff deflation and cannula cuff inflation, which can become shorter than 2 seconds.Risks connected to tracheotomy in Covid-19, a conceptually extremely hazardous procedure, can be significantly reduced by rational measures and teamwork.Dear Editor,Tracheotomy, more than any other procedure, increases the risk of transmission from Covid-19 patients to operators because of aerosolisation1: a cough with an opened trachea and no seal from a cuff is the worst exposure situation.We describe our experience with tracheotomy in Covid-19, analyzing steps at risk and describing technical refinements to minimize such risk.