COVID-19 and its implications for the future global influence of the European Union

From the editors: The COVID-19 crisis and its implications for pediatric surgeons

Perspective: COVID-19, implications of nasal diseases and consequences for their management

Cross-talk between SARS-CoV-2 infection and the insulin/IGF signaling pathway: Implications for metabolic diseases in COVID-19 and for post-acute sequelae of SARS-CoV-2 infection

Spatial technologies to strengthen traditional testing for SARS-CoV-2.

Pathogenesis of SARS-CoV-2 induced cardiac injury from the perspective of the virus

COVID-19 in children: the link in the transmission chain

The response of Milan's Emergency Medical System to the COVID-19 outbreak in Italy

SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.

Chloroquine or Hydroxychloroquine for COVID-19: Is Cardiotoxicity a Concern?

IntroductionA rare but serious condition often requiring intensive care, multisystem inflammatory syndrome in children (MIS-C) is characterized by hyperinflammatory shock related to the SARS-CoV-2 pandemic. This resource teaches residents, pediatric emergency medicine fellows, and advanced practice providers who care for children to recognize and manage MIS-C and associated sequelae while applying the basic principles of pediatric resuscitation.MethodsThe simulation case was based on a real patient who presented to the emergency department with fever, rash, and cardiogenic shock. We designed the scenario to be used with a high-fidelity school-age mannequin in an emergency center resuscitation room or simulation lab. The case took 25 minutes to run, followed by a 15- to 20-minute debrief session. Personnel required for the case included a simulation technician, case instructor, emergency department nurse, parent, and consultant. Learners had to recognize the syndrome and treat the resultant shock and arrhythmia with a combination of vasopressors, antiarrhythmics, and defibrillation. Afterward, learners participated in a formal debriefing session and completed a written evaluation.ResultsTwenty-five learners (six pediatric emergency medicine fellows, 12 residents, and seven advanced practice providers) participated in the scenario over a 3-month period. The written evaluation was completed by 20 of the 25 participants; all 20 felt their confidence, comfort, and knowledge regarding the topic had increased, with an average score of 5 (strongly agree) on a 5-point Likert scale.DiscussionThis simulation case offers an effective experience for learners to become comfortable and confident in recognizing and managing MIS-C.

To the Editors, Severe acute respiratory syndrome coronavirus 2 is the formidable viral pathogen of β-coronavirus family that causes coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. It has thus far infected over seven million individuals, and over 0.4 million patients have already succumbed to complications as per the World Health Organization (WHO) situation report – 142 (June 10, 2020).[1] Competent immune system is crucial in determining the prognosis of COVID-19 infection; however, this might not be true for kidney transplant recipients receiving immuno-suppressive regimen. A substantial number of COVID-19 patients demonstrate lymphopenia, and reduced lymphocyte count has been shown to be associated with COVID-19 severity.[2] Pro-inflammatory cytokines such as interleukin-6 (IL-6)and tumor necrosis factor-alpha, part of cytokine storm, are reportedly elevated in critically ill COVID-19 patients, reemphasizing the notion that heightened immune activity might affect morbidity and mortality in COVID-19 and underlining the importance of fine balance between defensive and aggressive host immune activity.[3] Immunosuppressive drugs possess intrinsic ability to impede the physiological function of lymphocytes and/or precipitate lymphopenia. Owing to lack of definite treatment for COVID-19 infection, most of the kidney transplant societies endorse moderation in immunosuppression considering the patient safety. However, this might not be a pragmatic approach for patients with imminent transplant rejection. In the present commentary, we aim to summarize the potential management approaches used in transplant centers for kidney transplant patients diagnosed with COVID-19. Kidney transplant recipients necessitate longterm maintenance immunosuppressive therapy. To prevent kidney allograft rejection at slightly higher risk of transplant infection, the standard clinical practice is to perform therapeutic drug monitoring to ensure safety and efficacy. Given the scarcity of data on management of kidney transplant recipients with confirmed COVID-19, it is plausible to minimize maintenance immunosuppressive therapy. Nonetheless, how much reduction in maintenance immuno-suppressive therapy is needed to contain COVID-19 and simultaneously avoid allograft rejection is yet to be established. Immuno-suppressive drugs, especially calcineurininhi-bitors (CNIs), significantly condense the T-lymphocyte immune response and thereby enhance the risk of unrestrained viral shedding and invasion. Lately, it has been reported in an in vitro study that nonimmunosuppressive derivatives of cyclosporinA can reduce the N protein expression, required for viral reproductive cycle, of human coronavirus 229E.[4] This underscores the possible implication of cyclos-porin A as the ideal CNI for kidney transplant recipients with COVID-19 infection. In vitro data regarding tacrolimus for the aforementioned activity is unavailable. Research reports on kidney transplant recipients with COVID-19 infection are now accumulating.[56789101112] In accordance with the recent literature, elderly kidney transplant patients are at an increased predisposition to develop severe COVID-19 and progress toward death.[13] The initiation and management of patients with immunosup-pressive, immunomodulatory, and antiviral therapy drastically fluctuate between published research reports Table 1. The data related to the use of anticytokine therapy, for instance, anti-IL-6 or complement inhibitors, are also uncertain. Of late, a mega SOLIDARITY trial (ISRCTN83971151) by the WHO is underway that will examine remdesivir, lopinavir-ritonavir, lopinavir-ritonavir + interferon-β1a, and chloroquine or hydroxychloroquine treatment options for COVID-19 patients. Kidney transplant patients are also part of the SOLIDARITY trial, and we are optimistic that something groundbreaking will show up soon. It is noteworthy to mention here that a number of antiviral medicines interact with CNIs, and meticulous drug monitoring for cyclosporin A or tacrolimus would be required. Finally, transplant physicians need to be wary of patient characteristics while making decisions regarding treatment of COVID-19 in kidney transplant recipients.Table 1: Case reports of immunosuppressive and COVID-19 treatment regimen used in kidney transplant recipients with COVID-19 infection.In summary, evidence on optimal treatment regimen for kidney transplant recipients to treat COVID-19 and avoid transplant rejection is not well-established. The present commentary was based on recent case reports evidence and warranted further substantiation in future work. Conflict of interest None declared.

Safety and efficacy of early high-dose IV anakinra in severe COVID-19 lung disease

* Abbreviations: COVID-19 — : coronavirus disease 2019 MIS-C — : multisystem inflammatory syndrome in children SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 SNP — : single-nucleotide polymorphism Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in December 2019. It rapidly spread across the world, and on March 11, 2020, the World Health Organization declared COVID-19 a global pandemic.1 In adults, SARS-CoV-2 can manifest as severe interstitial pneumonia and hyperinflammation, with∼3% to 5% of infections requiring admission to critical care.2,3 In contrast, severe illness and death due to SARS-CoV-2 infection in children is rare.4 However, recently, a small number of cases of shock and multisystem inflammation have been reported in children who have either tested positive for SARS-CoV-2 (by polymerase chain reaction or serology) or have had epidemiological links to it. This new syndrome, which has overlapping features of Kawasaki disease, is called multisystem inflammatory syndrome in children (MIS-C).5 The exact pathogenesis of MIS-C is as yet unknown. However, it has been suggested that part of the SARS-CoV-2 viral spike protein may resemble a superantigen that could drive the development of MIS-C and trigger … Address correspondence to Judith Breuer, MD, Research Department of Infection, Division of Infection and Immunity, University College London, Cruciform Building, Gower St, London WC1E 6BT, United Kingdom. E-mail: j.breuer{at}ucl.ac.uk

Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

Phase-3 Randomized Controlled Trials on Exclusion of Participants With Kidney Disease in COVID-19