COVID-19 has now become a global epidemic, prevailing over 213 countries of the world including Pakistan. To date, there have been more than 12000 cases and above 220 deaths reported in Pakistan. The outbreak is caused by a β-coronavirus called SARS-CoV-2, similar in characteristics to the SARS and MERS-CoV. It shows symptoms like pneumonia and may lead to death. Despite lockdown and possible isolation system, it is spreading rapidly. Lack of precautionary measures, specific vaccine and delayed diagnosis may be the major reasons for its spread. Several researches on COVID-19 have described its various features to extend its knowledge in order to help the scientific world in preparation of vaccine. Current review aimed to cover all essential data such as clinical characteristics, pathology, detailed morphology and structure, antigenicity of COVID-19 virus, role of structural proteins in anti-viral drug development and possible treatments being used. This manuscript would be helpful to select the best possible treatment depending on the availability and condition of the patient. Moreover, further research is needed for assistance in designing a virus-specific drug or vaccine.

The current pandemic of the novel coronavirus SARS-CoV-2 infection has affected over 6 million humans around the planet. The clinical manifestations of Coronavirus disease 2019 (COVID-19) are diverse, ranging from asymptomatic or mild flu-like symptoms to atypical pneumonia, severe respiratory distress syndrome, systemic inflammation, immune dysregulation and dyscoagulation.Inborn errors of immunity (IEI) are a heterogenous group of more than 430 rare congenital disorders with increased susceptibility to infection, autoimmunity, atopy, hyperinflammation and cancer. Autosomal recessive ARPC1B deficiency is an actinopathy, as are DOCK8 deficiency and the Wiskott-Aldrich Syndrome. Defective actin polymerization affects hematopoietic cells, impairing their migration and immunological synapse1, which results in a combined immune deficiency characterized by leukocytosis, eosinophilia, platelet abnormalities and hypergammaglobulinemia; and clinically, by eczema and food allergy, infections caused by bacteria, fungi and viruses, vasculitis, and bleeding diathesis2.Here, we describe a male infant patient with known ARPC1B deficiency who was hospitalized for COVID-19 pneumonia and improved without requiring intensive care or mechanical ventilation.An 8-month-old infant was brought to the emergency department with high-grade fever. His family history is remarkable for one brother who died as a newborn from intracranial bleeding, and an 11-year-old sister with the same genetic defect who underwent hematopoietic stem-cell transplantation twice without success, and is currently on antimycobacterial treatment, antimicrobial prophylaxis and regular subcutaneous immunoglobulin. The patient was first seen at age 1-month old for eczema and rectal bleeding attributed to cow milk protein allergy. At age 4 months, he developed bronchiolitis caused by respiratory syncytial virus (RSV) and oral candidiasis. Laboratory workup revealed leukocytosis (17,500-33,600/mm3), eosinophilia (5,600-20,100/mm3) and a marginally high (467,000) platelet count; as well as high serum IgG (737 mg/dL) and IgA (165 mg/dL) with normal IgM (37.7 mg/dL). CD8+ T lymphocytes were low at 3% (257 cells) and B cells were elevated at 48% (4,116 cells). Whole exome sequencing identified a homozygous 46 base-pair deletion in exon 8 of ARPC1B(chr7:99,392,784 hg38; p.Glu300fs).Upon his arrival to the emergency department he was febrile with tachycardia and signs of septic shock requiring rapid fluid resuscitation. He showed no respiratory or gastrointestinal signs. He also had a post-traumatic ulcerated lesion under the tongue with dark discoloration, which raised a concern for fungal infection. Intravenous antibiotics (ciprofloxacin) with antifungal coverage were started within the first hour, and a dose of intravenous immunoglobulin (IVIG) at 1g/kg. Blood counts revealed leukocytosis, neutrophilia, and mild eosinophilia without lymphopenia, while platelets were initially found within normal limits. A day later, blood culture had grownPseudomonas aeruginosa .During his second day of hospitalization, the patient persisted febrile, tachycardic and tachypneic, with oxygen desaturation into the low 80s. Chest X-ray showed nonspecific bilateral interstitial opacities in the perihilar regions (Figure 1 ). Real-time Polymerase chain reaction (RT-PCR) for SARS-Cov2 came back positive, and he was then transferred to a COVID-19 isolation area. The potassium hydroxide (KOH) test for oral thrush was negative for yeast cells, after which amphotericin was switched to fluconazole. Supplemental oxygen was discontinued on day 6 of hospitalization, when mild thrombocytopenia and a prolonged thromboplastin time (aPTT) (but normal fibrinogen and ferritin serum levels) were reported. After completing 14 days of antimicrobial treatment, the patient was discharged without ever requiring intensive care unit admission or mechanical ventilation.The behavior of COVID-19 in patients with IEI might help dissect the immune response to SARS-Cov2. A few cases of adults with COVID-19 and predominantly antibody deficiencies have been reported3,4; some of them developed acute respiratory distress syndrome (ARDS), while some had a milder course of illness. Based on what we know, innate immune defects in genes involved in type 1 interferon response (such as IRF7, IRF9, TLR3) are the most likely candidates to result in severe disease and death in patients with flu-like virus infection5. In a few cases of fatal influenza A (H1N1), variants in genes associated with familial hemophagocytic lymphohistiocytosis (FHL) and a decreased cytolytic function of NK cells, were also reported6.Our patient was on monthly supplemental IVIG treatment, and he received an additional dose during his hospital stay. This, and his young age, might have ameliorated the clinical course7. He had a favorable evolution, despite the known susceptibility to viral infection and immune dysregulation in ARPC1B deficient patients1. There were no signs of severe infection, ARDS, hyperinflammation or of “cytokine storm” unleashed by SARS-CoV-2. Despite his having a combined immune deficiency, our patient fully recovered without the need of additional supportive measures other than IVIG, supplemental oxygen and antibiotic treatment directed against the documented bacteremia.Although pediatric cases of COVID-19 are fewer compared to adults, some severe presentations and deaths among children have been reported. The presence of a restricted repertoire of IgG (since infants have no previous exposure to coronaviruses) might play a role in the better outcome seen in pediatric patients. Antibody-dependent enhancement has been implicated in the development of severe COVID-19 in the elderly8. Additionally, lung cells from children and women show a lower expression of membrane-bound ACE-2, which may also be protective against severe pneumonia.Conceivably, some immune defects could protect patients with certain IEIs from mounting a full uncontrolled inflammatory response against SARS-Cov2. The cytoskeleton is a regulator of gene transcription, coupling cell mechanics with the activity of NF-κB. Coronaviruses are thought to alter the cytoskeleton architecture to facilitate viral replication and output9. Thus, ARPC1B deficiency and other actinopathies might limit SARS-CoV-2 replication. Furthermore, Th2 cytokines modulate ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 expression in airway epithelial cells10, and children with allergies (asthma and/or allergic rhinitis) have a lower expression of ACE211. Patients with ARPC1B deficiency often have allergic diseases; their Th2-biased response could help explain the milder presentation seen in our patient. Insights from protective mechanisms in children, with and without certain immune defects, could facilitate the identification of therapeutic targets.Lina Maria Castano-Jaramillo1, MDMarco Antonio Yamazaki-Nakashimada1, MDSelma Cecilia Scheffler Mendoza1, MD, MSJuan Carlos Bustamante-Ogando2, MD, MSSara Elva Espinosa-Padilla2, MD, PhDSaul O. Lugo Reyes2, MD, MS.From the (1) Clinical Immunology Service, and the (2) Immunodeficiencies Research Unit, at the National Institute of Pediatrics, Mexico City, Mexico.Conflict of interests: NoneEthical statement: The patient and his family gave written informed consent for the diagnostic procedures and for publication of the case report.KEY WORDS: Primary immune deficiency, inborn errors of immunity, combined immune deficiency, ARPC1B deficiency, actinopathy, children, COVID-19, SARS-Cov-2, allergy, pneumonia, sepsis.

The outbreak of the Covid-19 pandemic obliged us all to handle many dilemmas, some of which we took upon ourselves as philosophers, ethicists, doctors and nurses to discuss around four key ethical notions : responsibility, dignity, fairness and honouring death. The following collection of the symposium acts held online in May 2020 with the Paris Global Center of Columbia University and Columbia Global Centers, attempts to testify to the ongoing pandemic emergency and difficult challenges while evaluating whether the ethical principles in the official recommendations were able to meet the lived reality. Looking at accountability and consistency in regard to the context of exercise, it seemed equally important to examine, through an international exchange, whether the contextuality of Coronavirus across countries and cultures affected the ethical decision making processes. We hope that our discussion can serve as a resource for advanced care planning, helping medical providers and other specialists to consider the shared important aspects of medical ethics in times of great uncertainty.

In this issue of BJOG, Mendoza and colleagues report in an observational study the occurrence of a preeclampsia-like syndrome in six out of eight pregnant patients with novel coronavirus disease (COVID-19) who were admitted to the Intensive Care Unit (ICU) with severe pneumonia (Mendoza M, et al. BJOG 2020). There were no symptoms of preeclampsia amongst the 34 pregnant women who had mild forms of COVID-19. Importantly, the authors recorded not only routine laboratory test results, but also measured biophysical and biochemical markers that are typically altered in women with preeclampsia (uterine artery pulsatility index on Doppler ultrasound, serum soluble fms-like tyrosine kinase-1 [sFLT-1] and placental growth factor [PlGF]). Such markers were normal in five of the six cases, in whom the symptoms of preeclampsia resolved after improvement of the maternal clinical situation.The intriguingly high cumulative incidence of preeclampsia symptoms in women with severe coronavirus disease needs to be interpreted with caution due to the observational nature of the study, the small number of pregnant women with severe infection and the possible role of confounding factors. The normal biomarker results in most cases, nevertheless, suggest that severe coronavirus disease can lead to symptoms that mimic those of preeclampsia in the absence of defective placentation, which is further corroborated by the resolution of the symptoms without the delivery of the placenta when overall clinical improvement occurs. It is plausible that such manifestations are the result of widespread inflammation and endothelial damage, in a process that has been denominated “cytokine storm”, responsible for many of the symptoms of the coronavirus-related organ injury (Mehta P, et al. Lancet 2020;395:1033-34) This mechanism includes activation of inflammation pathways that convert arachidonic acid to prostaglandins, thromboxane and eicosanoids, ultimately provoking significant cytokine release. The cascade of events, however, does not appear to influence the levels of specific preeclampsia angiogenic and anti-angiogenic markers such as sFLT-1 and PlGF.A normal sFLT-1: PlGF ratio in women with clinically suspected preeclampsia can be reliably used predict the short-term absence of disease (Zeisler H, et al. N Engl J Med 2016;374:13-22). Although the definition of preeclampsia has changed over the last 20 years to incorporate less specific clinical features of end-organ damage, biomarkers will likely become part of the disease definition in the years to come or, at least, a valuable tool to select subgroups of women at higher risk of preeclampsia-related morbidity and mortality who require closer monitoring or immediate delivery.While larger cohorts derived from national datasets or international registries of coronavirus disease in pregnancy will be essential to confirm or refute this association, the preliminary data published in this study indicate that delivery during severe coronavirus disease should not be based on preeclampsia symptoms alone, particularly at early gestational ages, and that the use of ultrasound and serum biomarkers such as the sFLT-1: PlGF ratio might help to guide clinical management by distinguishing hypertension and endothelial dysfunction caused by COVID-19-related inflammation from true preeclampsia.No disclosures: A completed disclosure of interest form is available to view online as supporting information.

Under the unprecedented pressures of the global coronavirus disease 2019 (COVID-19) pandemic, there is an urgent requisite for successful strategies to safely deliver cardiac surgery. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first described in early December 2019, and the rapid spread and emergence of this virus has caused significant disruptions in the delivery of healthcare services worldwide.1,2 In particular, provision of cardiac surgery has been disproportionally affected due to reallocation of intensive care resources, such as ventilators.2Additionally, patients with pre-existing cardiovascular disease are likely to have comorbidities which are associated with poorer clinical outcomes in confirmed SARS-CoV-2 cases.3,4 Despite this, Yandrapalli and colleagues have reported the first case of a successful coronary artery bypass graft (CABG) operation in a patient with asymptomatic SARS-CoV-2 infection, which offers insights into how cardiac surgery could be adapted to solve the challenges of this pandemic.5In response to the burden of COVID-19 on healthcare systems in the United Kingdom (UK), elective cardiac surgeries have been delayed owing to the redistribution of intensive care resources and the unquantifiable risk of acquiring COVID-19.2 Likewise, cardiac surgery services have undergone structural remodelling into a centralised system in an attempt to continue provisions of emergency surgery alongside hospital management of COVID-19 patients.2Unsurprisingly, most cardiac surgery units across the globe have seen a sharp decline in surgeries as a result, and one unit reported an 83% reduction in cardiac index cases between 23rd March to 4th May 2020.2 Similar models have been used in Europe to manage healthcare services and increase intensive care capacity. For example in the Lombardy region of Italy, 16 out of 20 cardiac surgical units discontinued services and all urgent cases have been consequently diverted to the remaining four units for centralised services.6 Whilst these measures have been beneficial for supporting the focused management of COVID-19 patients, it is important to reflect upon the future consequences of delayed elective cardiac surgery. Indeed, such patients are likely to have progressive conditions and further work is needed to investigate the long-term impact of COVID-19 on mortality and morbidity in this cohort.The case report by Yandrapalli and colleagues highlight the importance of routine SARS-CoV-2 testing for all patients requiring cardiac surgery, especially for detecting asymptomatic or subclinical infections.5 Active SARS-CoV-2 infection may precipitate an overproduction of early response proinflammatory cytokines in post-operative period, leading to unfavourable surgical outcomes.7,8 Moreover, preliminary studies have shown that patients with established cardiovascular diseases may have a greater risk of increased SARS-CoV-2 infection severity and prognosis.9 Taken together, assessment for active infection is crucial for risk stratification. In addition, clinicians should consider the threshold for surgery when selecting patients for cardiac surgery. An international, multi-centre cohort study by COVIDSurg Collaborative which included 1128 confirmed SARS-CoV-2 patients undergoing a broad range of surgeries revealed that 30-day mortality risk was significantly associated with the patient demographics of male sex, an age of 70 years or older, and poor preoperative physical health status.10 Collectively, the risks and benefits of cardiac surgery should be carefully considered in such patients due to higher mortality risk.10Alternative therapeutic procedures with rapid discharge, such as percutaneous intervention or medical therapy, may be more appropriate to reduce SARS-CoV-2 related mortality and nosocomial infection risk.11Current evidence is limited for postoperative outcomes in cardiac surgery cases. In the aforementioned cohort study by COVIDSurg Collaborative, the 30-day mortality rate was 23.8%.10In addition, the study reported that 51.2% of patients had postoperative pulmonary complications, which was associated with a higher mortality rate of 38.0%.10 In another case report describing an emergency CABG operation, the asymptomatic patient succumbed to pulmonary complications arising from a SARS-CoV-2 infection confirmed postoperatively.12 The authors acknowledge that the undiagnosed infection may have triggered a refractory pathological response after cardiac surgery. Indeed, recent literature has suggested that patients with SARS-CoV-2 are at higher risk of developing thromboembolisms, possibly mediated by the interaction with angiotensin-converting enzyme 2 (ACE2) receptors.13Similarly, there is a consensus that SARS-CoV-2 has direct adverse effects on the myocardium due to high expression of ACE2.14 As such, SARS-CoV-2 can potentially trigger multisystem complications which require vigilant monitoring, especially in patients requiring cardiopulmonary bypass and at high risk of developing thromboembolisms. Cardiac surgery patients represent a vulnerable patient population, and this cohort may experience worse outcomes with SARS-CoV-2 infection based on the current available evidence. In the latest recommendation, UK currently advises all patients who are listed for elective cardiac surgery to self-isolate for 14 days prior to surgery date, in a measure to limit and contain the exposure of such cohort to the smallest possibilities of acquiring COVID-19.Currently, the future of cardiac surgery after the pandemic is unclear as the evidence is still emerging. However, the lessons learnt from these unprecedented times can be taken forward to inform future service planning. Moving forwards, routine screening of patients for SARS-CoV-2 infection will undoubtedly play a key role in identifying asymptomatic or subclinical infections. The preoperative UK National Health Service testing recommendations should be broadened so that all patients undergoing cardiac surgery are screened, given the higher risk of postoperative complications in this population. Similarly, repeat testing is important for monitoring patients for concomitant infections. Alongside changes to hospital protocol, service delivery will inevitably shift. The successful application of telemedicine during the pandemic has already been reported in the delivery of oncology services.15 Moreover, the benefits of telecardiology outside of the COVID-19 era have been previously reported, and cardiology services will likely embrace the utilisation of telemedicine for managing outpatient consultations.16 Units will also have to address the vast backlog of surgeries caused by cancellation of elective cardiac operations in a sustainable manner, with adequate hospital space and personal protective equipment availability.17 In order to resume success services, planning for this eventuality should begin now and patients at significant mortality risk due to delayed surgery need to be prioritised.Ultimately, clear guidelines should be implemented to ensure safe resumption of surgical services, whilst also reassuring patients concerned about safety.3 Whilst the future trajectory of this pandemic is uncertain, the insights from the impact of COVID-19 on cardiac surgery will undoubtedly shape the future delivery of cardiac surgery.

The outbreak of the Covid-19 pandemic obliged us all to handle many dilemmas, some of which we took upon ourselves as philosophers, ethicists, doctors and nurses to discuss around four key ethical notions : responsibility, dignity, fairness and honouring death. The following collection of the symposium acts held online in May 2020 with the Paris Global Center of Columbia University and Columbia Global Centers, attempts to testify to the ongoing pandemic emergency and difficult challenges while evaluating whether the ethical principles in the official recommendations were able to meet the lived reality. Looking at accountability and consistency in regard to the context of exercise, it seemed equally important to examine, through an international exchange, whether the contextuality of Coronavirus across countries and cultures affected the ethical decision making processes. We hope that our discussion can serve as a resource for advanced care planning, helping medical providers and other specialists to consider the shared important aspects of medical ethics in times of great uncertainty.

Background Currently, the coronavirus disease 2019 (COVID-19) has become pandemic globally. 10-20% of the cases are severe and more than 397,000 deaths have occurred. The risk factors for the mortality of critically ill COVID-19 patients remain to be elucidated. Conclusions Survived severe and non-survived COVID-19 patients had distinct clinical and laboratory characteristics, which were separated by principle component analysis. Logistic regression revealed several risk factors such as elder age, greater affected lobe numbers and higher level of serum CRP for the mortality of severe COVID-19 patients. Longitudinal changes of laboratory findings indicate the advancement of the disease and may be helpful in predicting the progression of severe patients.

Asthma control, self-management and healthcare access during the COVID-19 Epidemic in BeijingChun Chang a* M.D., Linlin Zhanga*B.S., Fawu Dong a* B.S., Ying Liang a M.D., Yahong Chen a M.D., Ying Shang a B.S., Mairipaiti Abulikemua B.S., Yongchang Suna# M.D.aDepartment of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.#, Corresponding to Yongchang Sun:Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.North Garden Rd. 49.Haidian District, Beijing, 100191, ChinaTel: +86 010 139 1097 9132Fax +86 108 226 6989E-mail: suny@bjmu.edu.cn* Chun Chang, Linlin Zhang and Fawu Dong contributed equally to this work;To the Editor:The pandemic of COVID-19, caused by the pathogen SARS-CoV-2, has now spread around the globe. Social distancing and restriction measures during COVID-19 pandemic may have impacts on asthma control and management in terms of medication availability and healthcare access. International societies responded quickly by releasing guidance on the management of asthma during the COVID-19 pandemic1-4. However, these temporary guidelines were based largely on previous asthma guidelines and expert consensus, because evidence from related studies was lacking. Therefore, we investigated the status of asthma control, self-management, medications and healthcare utilization of asthma patients during the COVID-19 epidemic in Beijing, aiming to provide data for guideline recommendations on asthma managements during the emergency.Patients with asthma, selected randomly from our hospital database, were interviewed by phone call. Detailed description of items in the questionnaire is available in this article’s online supplementary material.We contacted 286 patients, of whom 178 (62.2%) responded with valid results. Sociodemographic data and clinical characteristics of the patients before the COVID-19 pandemic are provided as online supplements. During the COVID-19 epidemic in Beijing (January 25, 2020 to April 25, 2020), the majority (74.2%, 132/178) of the patients felt that their symptoms had not changed as compared with usual times, while 18.0% (32/178) felt better, and 7.9% (14/178) felt worse. The mean ACT score of the 178 patients was 22.76 ± 3.06 (ranging from 8 to 25) in the last 4 weeks before the survey. According to the criteria of ACT scoring from GINA, asthma was classified as well-controlled in 89.3%, not well-controlled in 6.2%, and very poorly controlled in 4.5% of the patients. During this period, only 24.7% (44/178) of the patients had ever visited a hospital or clinic for asthma, of whom 11 patients had 2 visits, and 6 had ≥3 visits, totaling 74 visits. 14.9% (11/74) of all medical visits were due to exacerbation of asthma, while the remaining visits (63/74, 85.1%) were for regular prescription of asthma medications. Only 6 patients (3.4%) sought consultation online. (Table 1)Notably, 25.6% (45/176) of the patients experienced aggravation of asthma symptoms during the COVID-19 epidemic, but 75.6% (34/45) of them did not see a doctor, because 67.6% (23/34) of the patients thought that they did not need to go to the hospital and took more medications by themselves, and the remaining 32.4% (11/34) worried about cross-infection of COVID-19 in the hospital. No patient said that they did not see a doctor because they could not arrange an appointment. Eleven patients went to the hospital due to aggravation, 81.8% (9/11) to the outpatient, while only 18.2% (2/11) to the Emergency Department (ED).Table 1 Asthma control and management during the COVID-19 epidemic in Beijing

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces the coronavirus infectious disease 19 (COVID-19). Its pandemic form in human population and its probable animal origin, along with recent case reports in pets, make drivers of emergence crucial in carnivore domestic pets, especially cats, dogs and ferrets. Few data are available in these species; we first listed forty-six possible drivers of emergence of COVID-19 in pets, regrouped in eight domains (i.e. pathogen/disease characteristics, spatial-temporal distance of outbreaks, ability to monitor, disease treatment and control, characteristics of pets, changes in climate conditions, wildlife interface, human activity, and economic and trade activities). Secondly, we developed a scoring system per driver, then elicited experts (N = 33) to: (i) allocate a score to each driver, (ii) weight the drivers scores within each domain and (iii) weight the different domains between them. Thirdly, an overall weighted score per driver was calculated; drivers were ranked in decreasing order. Fourthly, a regression tree analysis was used to group drivers with comparable likelihood to play a role in the emergence of COVID-19 in pets. Finally, the robustness of the expert elicitation was verified. Five drivers were ranked with the highest probability to play a key role in the emergence of COVID-19 in pets: availability and quality of diagnostic tools, human density close to pets, ability of preventive/control measures to avoid the disease introduction or spread in a country (except treatment, vaccination and reservoir(s) control), current species specificity of the disease causing agent and current knowledge on the pathogen. As scientific knowledge on the topic is scarce and still uncertain, expert elicitation of knowledge, in addition with clustering and sensitivity analyses, is of prime importance to prioritize future studies, starting from the top five drivers. The present methodology is applicable to other emerging pet diseases.

We present a late presentation of saddle pulmonary embolism and thrombus-in-transit straddle the patent foramen on patient who successfully recovered from severe acute respiratory syndrome coronavirus-2 (COVID-19) pneumonia. Seven days post-discharge (i.e. 28 days after initial COVID-19 symptom onset), she was readmitted to hospital for severe dyspnea. Computer tomography angiogram and echocardiography confirmed the diagnosis. Severe pro-inflammatory and pro-thrombotic states with endothelial involvement have been reported associated with severe COVID-19 infection. However the duration of hypercoagulable state has not yet known. This case highlights the risk of thromboembolic phenomena for prolonged periods of times after recovering from COVID-19 pneumonia.

Point-of-care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID-19 by providing timely information to guide decision-making, but data on real-world performance are in short supply. Besides SARS-CoV2-specific tests, there is growing interest in the role of surrogate (non-specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza-like illnesses. This short communication assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS-CoV2-specific POCTs. While FebriDx shows some potential in supporting triage for early-stage infection in acute care settings, this is dependent on SARS-CoV2 being the most likely cause for influenza-like illnesses, with reduction in discriminatory power when COVID-19 case numbers are low, and when co-circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts and further evaluation is needed. Reliable SARS CoV2-specific POCTs – when they become available – are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.

Coronavirus disease 2019 (COVID-19) may present with different symptoms and complications. Acrocyanosis and digital necrosis may be associated with COVID-19. We describe two patients with COVID-19 who died with acrocyanosis and digital necrosis at the terminal stage of their illness.

An increasing number of COVID-19 cases worldwide has overwhelmed the healthcare system. Physicians are struggling to allocate resources and to focus their attention on high-risk patients, partly because early identification of high-risk individuals is difficult. This can be attributed to the fact that COVID-19 is a novel disease and its pathogenesis is still partially understood. However, machine learning algorithms have the capability to correlate a large number of parameters within a short period of time to identify the predictors of disease outcome. Implementing such an algorithm to predict high-risk individuals during the early stages of infection, would be helpful in decision making for clinicians. Here, we propose recommendations to integrate machine learning model with electronic health records so that a real-time risk score can be developed for COVID-19.

Most common clinical manifestations of COVID-19 are fever, dry cough, dyspnea, fatigue, myalgia, sore throat, expectoration, hemoptysis, nausea, diarrhoea, abdominal pain and headache. But pleuritic chest pain as lone presenting symptom with COVID-19 is not reported till date.

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).

The covid-19 pandemic has forced citizens worldwide to rely on social distancing measures as the main tools to prevent the rapid spreading of the virus (1). In pediatric oncology, there were important initial concerns for immunocompromised patients who were considered to be at higher risk of developing severe form of the disease (2,3). Consequently, potential challenges (2) have been identified and advice given by the principal child cancer organizations (3). Although more experience from countries that have been facing the pandemic are being published, results are inconsistent so far ranging from reassuring in Milano (4), Madrid (5) or New York (6) to worrying in France where 4 out of 33 Covid-19 positive patients required intensive care and 1 death at last follow up (7).Over the last weeks, despite the pandemic we were able to maintain “normal“ care for pediatric cancer patients in our institution, including high-dose chemotherapy followed by peripheral stem cells transplantations, or recruitment in early phase clinical trials. Only follow-up visits have been re-scheduled or switched to remote consultations. After almost 2 months of lock-down and still ongoing social distancing measures, an unexpected challenge has emerged. Inddeed, during that period, as usual we had to break bad news: for diagnosis, for relapse or palliative care. Initially, when breaking bad news, I had the feeling something was going wrong, or at least was not going as usual. Was I doing something wrong? Was stress induced by a high level of anxiety due to the lack of specific information on the real risk for adolescents/children with cancer both among the medical team and or parents affecting the “breaking bad news” process?Why didn’t I take that teenagers in my arms after disclosing her a metastatic relapse and she looked in such a distress?Social distancing!Masks to start with. They are of course a barrier to saliva droplets potentially containing covid-19, but most importantly they are also a barrier to adequately transmit and discriminate emotions just relying on eyes expression, looks…beyond tears. Silent communication with long looks without words can sometimes be enough and better that long talks but do parents and children feel the same when half of the face is covered. I asked about it to one of my patients and he answered“I think can read your eyes” . By increasing the physical space between people to avoid virus spreading, but here again, for physicians and some parents/patients, holding hands, holding shoulders, hugging are important non-verbal elements of communications and help showing compassion.We might break social distancing to break bad news, but if not pre-agreed by the patient or its parents, is it acceptable? Couldn’t it be perceived as an additional threat, contribute to alter intuitive communication which is characterized by broad, shared goals and mutual respect?Breaking bad news while trying to maintain social distancing is an unexpected new challenge associated with Covid-19. We will very likely learn to better communicate, read & share our respective emotions even with masks and physical distancing and sometimes allow ourselves exceptions to social distancing. Meanwhile, this impact shall be further evaluated among all stakeholders: patients, their parents, and physicians and adapted strategies to better cope with it developed.

The pandemic of the novel coronavirus disease, COVID-19 is having a serious impact on pediatric patients with cancer. Social distancing, self-quarantining and nationwide lockdown have resulted in restricted movements of patients and families across the country. This has made the optimum management of children with cancer difficult. In this clinical perspective, we discuss the issues related to COVID-19 and pediatric cancer and how we have attempted to optimize the treatment for our patients using telemedicine, reorganizing the day care services, triaging our patients and modifying their treatment plans, partnered with the NGOs and local medical centres to provide care to our patients.

With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of SARS-CoV-2 in culture supernatants was tested by routine adventitious virus testing of fermenter harvest.

Flying fox (Pteropus hypomelanus) belongs to the frugivorous bats, which play a crucial role in maintaining proper functioning of an ecosystem and conservation of environment. Bats are well known carriers of pathogenic viruses such as BatCov RaTG13 from the coronavirus family that share 90.55% with SARS-CoV-2, the pathogen causing recent global pandemic coronavirus disease 19 (COVID-19). However, bats’ possible role as a carrier of pathogenic bacteria is less explored. Here, using metagenomic analysis through high-throughput sequencing, we explored the gut microbiome composition of different island populations on the east and west coasts of Peninsula Malaysia. The 16S rRNA gene in samples from Redang Island, Langkawi Island, Pangkor Island and Tinggi Island was amplified. Bacterial community composition and structure were analyzed with α and β diversity metrics. In contrast to recent studies of host-microbe associations in other mammals, we found no correlation between host phylogeny and bacterial community dissimilarity across four island populations. Our analyses suggest that the significant linear relationship between Redang Island and Langkawi Island implies high bacteria diversity which supporting latitudinal correlation. We found geographic locality is a strong predictor of microbial community composition and observed a positive correlation between ecological features and bacterial richness.

Tracing and isolation of close contacts is used to control outbreaks of coronavirus disease 2019 (COVID-19) in China. However, risk factors associated with occurrence of COVID-19 among close contacts have not been well described. 106 household contacts were included in this study, of whom 19 were developed into COVID-19 cases and the secondary attack rate was 17.9%. Multivariable analysis showed increasing risk of occurrence of COVID-19 among household contacts associated with female of index patients (Adjusted Hazard Ratio [aHR] = 5.61, 95%CI = 1.51-20.83), critical disease of index patients ([aHR] = 7.58, 95%CI = 1.66-34.66), effective contact duration with index patients >2 days ([aHR] = 4.21, 95%CI = 1.29-13.73), and effective contact duration >11 days ([aHR] = 17.88, 95%CI = 3.26-98.01).The sex and disease severity of index COVID-19 patients, and longer effective contact duration with COVID-19 confirmed cases could help epidemiologists to identify potential COVID-19 case among household contacts at an early stage.

The SARS-CoV-2 strain of the coronavirus is responsible for the current COVID-19 pandemic, with an ongoing toll of over 5 million infections and 333 thousand deaths worldwide within the first 5 months. Insight into the phylodynamics and mutation variants of this strain is vital to understanding the nature of its spread in different climate conditions. The incidence rate of COVID-19 is increasing at an alarming pace within subtropical Southeast Asian nations with high temperatures and humidity. To understand this spread, we analyzed 60 genome sequences of SARS-CoV-2 available in GISAID platform from 6 Southeast Asian countries. Multiple sequence alignments and maximum likelihood phylogenetic analyses were performed to analyze and characterize the non-synonymous mutant variants circulating in this region. Global mutation distribution analysis showed that the majority of the mutations found in this region are also prevalent in Europe and North America, and the concurrent presence of these mutations at a high frequency in Australia and Saudi Arabia indicate possible transmission routes. Unique spike protein and non-structural protein mutations were observed circulating within a localized area. We divided the circulating viral strains into 4 major groups and 2 sub-groups on the basis of the most frequent non-synonymous mutations. Strains with a unique set of 4 co-evolving mutations were found to be circulating at a high frequency within India, specifically, group 2 strains characterized by two co-evolving NS mutants which alter in RdRp (P323L) and spike protein (D614G) common in Europe and North America. These European and North American variants (Nextstrain clade A2) have rapidly emerged as dominant strains within Southeast Asia, increasing from a 0% presence in January to an 85% presence by May 2020. These variants may have an evolutionary advantage over their ancestral types and could present the largest threat to Southeast Asia for the coming winter.

Title: Age-related risk of household transmission of COVID-19 in SingaporeRachael Pung1, Minah Park2,3, Alex R Cook2,3, Vernon J Lee1,21 Ministry of Health, Singapore2 Saw Swee Hock School of Public Health, National University of Singapore3 National University Health System

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is overwhelming healthcare resources and infrastructure worldwide. Cardiac surgical operating capacity during the COVID-19 pandemic is dramatically lower due to postponement or cancellation of elective or semi-urgent procedures. Earlier reports have demonstrated complicated post-operative courses and high fatality rates in patients undergoing emergent cardiothoracic surgery who were diagnosed post-operatively with COVID-19. These reports raise the possibility that active COVID-19 might precipitate a catastrophic pathophysiogical response to infection in the post-operative period and lead to unfavorable surgical outcomes. Hence, it is imperative to screen patients with SARS-CoV-2 infection prior to surgery and to carefully monitor them in the post-operative period to identify any early signs of active COVID-19. In this report, we present the successful outcome of coronary artery bypass grafting (CABG) operation in a patient with asymptomatic SARS-CoV-2 infection presenting with an acute coronary syndrome and requiring urgent surgical intervention. We employed a meticulous strategy to identify subclinical COVID-19 disease, and after confirming the absence of active disease, proceeded with the CABG operation. The patient outcome was successful with the absence of any overt COVID-19 manifestations in the post-operative period.

The authors share their experience of managing the cardiac surgery services across London during the challenging Covid-19 pandemic. The Pan London Emergency Cardiac Surgery Service model could serve as a blueprint to design policies applicable to other surgical specialities and parts of the UK and worldwide.