We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

OBJECTIVE: To collect and review data from consecutive patients admitted to Queen’s Hospital, Burton on Trent for treatment of Covid-19 infection, with the aim of developing a predictive algorithm that can help identify those patients likely to survive. DESIGN: Consecutive patient data was collected from all admissions to hospital for treatment of Covid-19. Data was manually extracted from the electronic patient record for statistical analysis. RESULTS: Data, including outcome data (discharged alive / died) was extracted for 487 consecutive patients, admitted for treatment. Overall, patients who died were older, had very significantly lower Oxygen saturation (SpO2) on admission, and higher CRP as evidenced by a Bonferroni-corrected P<0.0056). Evaluated individually, platelets and lymphocyte count were not statistically significant but when used in a logistic regression to develop a predictive score, platelet count did add predictive value. The prediction algorithm we developed was: P(survival) = ___________________1______________________ 1+e-1(-16.7104-3.3810LN(age)+6.5592LN(SpO2)-0.4584LN(CRP)+0.7183LN(Plt)) CONCLUSION: Age, SpO2 on Admmission, CRP and platelets were an effective marker combination that helped identify patients who would be likely to survive. The AUC under the ROC Plot was 0.737 (95% Conf. Interval 0.689-0.784; P< 0.001). Further research adding extra markers, is underway.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is a new strain of coronavirus that has not been previously identified in humans. SARS-CoV-2 is recognized as a highly contagious respiratory virus with severe morbidity and mortality, especially in vulnerable populations. Being a novel disease, everyone is susceptible, there are no vaccine and no treatment. To contain the spread of the disease, health authorities throughout the world have restricted the social interactions of individuals in various degrees. Allergists like other physicians are faced with the challenge of providing care for their patients, while protecting themselves and patients from getting infected, with strategies that are in continuous evolution as States work through the different stages of social distance. Allergist provides care for patients with the most common noncommunicable disease in the world: asthma, allergic rhinitis, food allergy, venom allergy, drug allergy atopic dermatitis, and urticarial. Some of these diseases are not only considered risk factors for severe reactions but also have symptoms like cough and sneezing that are in differential diagnosis with COVID-19, and as we move forward may prevent allergy patient from working, go to school or access medical services that increasingly are allowing only asymptomatic patients. In this review, we will outline how to take care safety of different allergic patients during the pandemic.

Coronavirus disease 2019 (COVID-19)diagnosis is based on molecular detection of SARS-CoV-2 in respiratory samples such as nasal swab (NS). However, the evidence that NS in patients with pneumonia were sometimes negative raise the attention to collect other clinical specimens. SARS-CoV-2 was shown in 10.3%rectal swabs (RS), 7.7% plasma,1% urine, 0% feces from 143NS positive patients. Potential infection by fluids different from respiratory secretion is possible but unlikely.

The raw case fatality rate (CFR, reported number of COVID-19 deaths divided by the number of cases) is a useful indicator to quantify the severity or treatment efficacy in a locality. In many countries, the pandemic showed a two-wave pattern now, namely the daily reported cases once reached a low level and now went up. To our knowledge, no study has compared the CFR for the two waves. In this work, we report that in 53 countries or regions with the highest deaths, the CFR is reduced in 43 countries or regions in the on-going second wave. We discussed the possible reasons. Also, we compare the two-wave pattern of COVID-19 with the weekly influenza positive tests. The influenza activity in pre-pandemic era provided an indicator for climate in a country, since it is well-known that influenza is driven by weather. The sharp drop in 2020 influenza activity is an indicator of the effects of social distancing.

Abstract Background: Transthoracic echocardiography (TTE) in prone position is challenging. Innovative use of transesophageal echocardiography (TEE) probe to perform TTE for such patients was described; but reproducibility and correlation of the TTE measurements by this technique with those obtained by the standard supine TTE study are still unknown. Methods: We enrolled 30 non-COVID-19 individuals, with a mean (SD) age 35 (10.9) years and 11 females, to study the agreement between the transthoracic measurements of the left ventricular (LV), left atrial (LA) and aortic dimensions obtained in prone position using an external TEE probe versus the standard supine position using the conventional TTE probe. Results: There were no significant differences between LV end-diastolic and end-systolic diameters, septal wall thickness, posterior wall thickness and aortic root dimensions in the prone versus the supine positions. While the mean ejection fraction (EF) (60.3% vs. 63.1%, P = 0.014) and mean LA dimensions (1.8 vs. 1.9 cm/m2, P < 0.001) were significantly lower in the prone position. The mean time of scans was significantly longer in the prone as compared to the supine (12.5 vs 4.5 minutes, P < 0.001). All supine studies had good quality while in the prone position 4 studies were of poor quality, and one was non-diagnostic. Conclusions: Assessment of cardiac dimensions and systolic function in the prone position using transthoracic TEE probe was feasible. LV and aortic dimensions agreed well with the standard TTE in supine position, however, LA dimensions and EF were lower in the prone position.

Aim: To investigate the mean thrombocyte volume (MPV) in asymptomatic children infected with COVID-19. Methods: The study included 55 children infected with COVID-19 and 60 healthy children for the comparison of leukocyte and thrombocyte count, MPV, and serum C-reactive protein (CRP) levels. Demographic data and clinical findings of all the cases were recorded, including age, gender, weight, temperature, cough, shortness of breath and contact history. Results: The MPV values were determined to be statistically significantly high (p<0.001) and the lymphocyte values were significantly low (p:0.002) in the asymptomatic children infected with COVID-19 compared to the healthy control children. No difference was determined between the groups in respect of CRP level, leukocyte and thrombocyte counts (p>0.05). The optimal cutoff point for MPV was determined as 8.74 fl (Area under the curve-AUC:0.932) with 81.82% sensitivity and 95% specificity for the determination of children infected with COVID-19. A cutoff value of <2.12/mm3 for lymphocytes (AUC:0.670) was determined with 49.09% sensitivity and 86.67% specificity for the prediction of COVID-19. Based on the ROC analysis, the sensitivity and specificity of MPV was determined to be higher than that of lymphocyte levels. Conclusion: The results of this study that MPV levels are significantly high in asymptomatic children infected with COVID-19 demonstrate that this is an important predictive value and has better predictive capacity than lymphocyte values. The evaluation of MPV and lymphocyte levels together could increase diagnostic success in asymptomatic COVID-19 cases.

Fever clinics are designed to provide prompt assessment, management, laboratory examination and decision-making for the potential infected cases, which serves as the crucial first-line of defense to control nosocomial infection. Guided by the primary principle of ‘early assessment, early detection, and early isolation’, fever clinics played a significant role in triaging suspected cases and minimize the risk of nosocomial infection during the Coronavirus Disease 2019 (COVID-19) combat in China. However, fever clinics failed to function normally as expected, with an astonishing number of healthcare workers infected. In this comment, we systematically evaluated the current limitations of fever clinics and recommended several countermeasures, aiming to enhance and maximize the capability and capacity of fever clinics for acute infectious diseases.

Trained immunity refers to the fact that the innate immune system also demonstrates memory, resulting in a faster and more profound second innate reaction, days to weeks after a first reaction to another pathogen or vaccine. Thus, trained immunity is heterologous, non-specific. We applied this principle with MMR vaccination during the COVID-19 pandemic.In a prospective, observational, single-center study 255 subjects, most at high risk for infection with COVID-19, received preventive MMR vaccination; 36 got infected with COVID-19; all had a mild course, even though 40% had risk factors. This might in part be due to trained immunity, conveying innate immune memory secondary to MMR vaccination, enhancing the innate immune response once the subject gets infected with SARS-CoV-2.As a result the well-known immune suppression brought about by coronavirus might not work so well, as the innate immune system is primed, allowing the body to finally eliminate the virus more efficiently.

The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to international health care systems. Management of the current pandemic puts a huge strain on health care sectors and leads to new strategies conducting by health care systems in countries across the world. In the present article, we review the epidemiologic data, Iranian health care system response, as well as the effects of COVID-19 pandemic on cardiac surgery practice in Iran

The current COVID-19 pandemic offers a unique opportunity to examine the utility of Internet search data in disease modelling across multiple countries. Google Trends data (GTD) indicating the volume of Internet searching on ‘Coronavirus’ were obtained for a range of European countries along with corresponding incident case numbers. Significant positive correlations between GTD with incident case numbers occurred across European countries, with the strongest correlations being obtained using contemporaneous data for most countries. GTD was then integrated into a lag distributed model; this improved model quality for both the increasing and decreasing epidemic phases.

To the Editor: The spread of the coronavirus disease-2019 (COVID-19) remains a worsening global health crisis. Although many studies have reported risk factors for severe COVID-19, asthma characterization in COVID-19 is still controversial, with different early reports from China and recent reports from the Europe and United States.1 Prolonged viral shedding is not only a risk factor for poor outcome of COVID-19, but also clues to host immune response against the virus. However, there is limited data on this except for results from relative small group studies.2 In this study, 2 200 adult patients hospitalized for COVID-19 in Daegu were evaluated for prevalence of asthma and clinical outcomes with COVID-19 according to asthma. In addition, the risk factors for delayed viral clearance were evaluated.The prevalence of asthma in patients with COVID-19 was 3.2% which was not different from its prevalence in the Korea National Health and Nutrition Examination Survey (KNHANES) (Figure 1A and Table S1). By age group, the prevalence of asthma showed a similar U-shaped pattern as the general prevalence pattern in Korea. However, the prevalence of asthma in the 19–29-year age group (2.1%) was lower than that of KNHANES (Figure 1B).Table S2 compares the characteristics between the asthma group and the non-asthma group. Older age, overweight, and comorbidity of chronic obstructive pulmonary disease, and initial symptoms of dyspnea and nausea/vomiting were more common in the asthma group. Compared with the non-asthma group, the asthma group had a greater risk of death (13.6%vs. 6.4%, P = 0.02) and a greater need for high-flow oxygen therapy (18.2% vs . 10.5%, P = 0.048) (Figure 1C and Table S3). The higher mortality rate in asthma patients compared with non-asthmatic patients was particularly noticeable in female and overweight patients. Older patients (> 65 years) with asthma tended to have a higher mortality rate than those without asthma (Figure 1D). After adjusting for potential confounders, asthma had no significant association with clinical outcomes of COVID-19 (Figure 1E and Table S4). Meanwhile, older age, male gender, and comorbid diseases including overweight, diabetes, chronic kidney disease, cancer, autoimmune disease, dementia, and other psychological disorder were significant risk factors for mortality (Tables S5 and S6).Asthma is considered to have a lower risk of death than other well-known risk factors.3, 4 However, asthma is a heterogeneous disease and is often associated with atopic and eosinophilic asthma in younger patients. Meanwhile, obese asthma and elderly asthma are known to have common neutrophilic phenotypes.5, 6 The recent results of higher expression of COVID-19 receptors in respiratory specimens with neutrophilic asthma phenotype compared with the eosinophilic asthma phenotype.7 Considering prevalence and clinical outcome results, it is possible that neutrophilic asthma is a risk factor for infection and poor prognosis of COVID-19 rather than eosinophilic asthma.When delayed viral clearance was divided into two groups based on 30 days, 906 patients were included in the non-delayed viral clearance group and 415 patients in the delayed viral clearance group. After adjusting for potential confounders, delayed viral clearance was not significantly associated with asthma (Figure 1E and Table S4). However, older age >65 years (Odds ratio (OR) 2.002, 95% Confidence interval (CI) 1.292–3.101; P = 0.002), comorbid diseases including dementia (OR 3.123, 95% CI 1.833–5.321; P<0.001), and other psychological disorder (OR 2.084, 95% CI 1.178–3.687; P = 0.012), initial symptom of skin rash (OR 15.943, 95% CI 1.613–157.535; P = 0.018), and initial laboratory abnormalities including hemoglobin <10 g/dL (OR 2.156, 95% CI 1.161–4.003; P = 0.015) and C-reactive protein (CRP) ≥1.0 mg/dL (OR 1.588, 95% CI 1.061–2.377; P = 0.025) were significant risk factors for delayed viral clearance. On the other hand, male sex (OR 0.752, 95% CI 0.567–0.997; P = 0.047), hypertension (OR 0.704, 95% CI 0.519–0.953; P = 0.023), and initial symptom of headache (OR 0.673, 95% CI 0.485–0.932; P = 0.017) were significant protective factors for delayed viral clearance (Figure 2A and Table S7). In particular, when limited to the mild COVID-19 group classified as no activity limitations in the outcome parameters, older age, dementia, initial symptoms of skin rash and headache, and initial hemoglobin <10 g/dL showed significant differences (Figure 2B, Table S8).Several factors related to the nervous system were identified as important risk factors for delayed viral clearance. Previous studies have shown that the coronavirus can initially invade the peripheral nerves and enter the central nervous system through a synapse path.8 It is hypothesized that the ability of the immune system to find and remove viruses that have penetrated the nervous system is important for virus clearance. Male sex, hypertension and elevated CRP did not show a significant difference when analyzed only mild patients, and these may be indicators associated with severity rather than a direct effect on viral clearance.Anti-inflammatory drugs such as hydroxychloroquine and systemic steroid were shown to be risk factors for mortality and delayed viral clearance (Table S6 and S8). These medications were used more often when the hospitalization period was extended or when showing poor prognosis factors. Notwithstanding these, our results suggest that anti-inflammatory drugs need to be used with proper consideration of appropriate indications.On May 9, 2020, there were 6,859 patients with PCR-confirmed COVID-19 in Daegu. This data excluded asymptomatic or minimal symptomatic patients who did not require hospitalization. However, our study covered almost all hospitalized patients diagnosed with COVID-19 in Daegu from February to May ,therefore, selection bias is minimized.9 In Korea, most hospitals decided to terminate the quarantine by repeating PCR every week. In addition, the Korea Centers for Disease Control & Prevention (KCDC) thoroughly managed the criteria for quarantine termination and PCR results. Through this, in our study, we were able to perform a large-scale study to confirm the risk factors for delayed viral clearance.In summary, despite the positivity of differences depending on phenotypes, the prevalence of asthma was not significantly different in patients with COVID-19, and asthma did not affect the outcomes of COVID-19. Age, dementia, and initial presentations of headache, skin rash, and anemia were independently associated with viral clearance.

To our knowledge, this is the first description of a cytomegalovirus end-organ infection complicating severe COVID-19 disease in an immunocompetent host. Suspicion threshold for opportunistic coinfections should be lowered in severe COVID-19. Serum CMV polymerase chain reaction and colonoscopy should be discussed in presence of persistent digestive disturbances.

We describe scalable and cost-efficient production of full length, His-tagged SARS-CoV-2 spike glycoprotein trimer by CHO cells that can be used to detect SARS-CoV-2 antibodies in patient sera at high specificity and sensitivity. Transient production of spike in both HEK and CHO cells mediated by PEI was increased significantly (up to 10.9-fold) by a reduction in culture temperature to 32ºC to permit extended duration cultures. Based on these data GS-CHO pools stably producing spike trimer under the control of a strong synthetic promoter were cultured in hypothermic conditions with combinations of bioactive small molecules to increase yield of purified spike product 4.9-fold to 53 mg/L. Purification of recombinant spike by Ni-chelate affinity chromatography initially yielded a variety of co-eluting protein impurities identified as host cell derived by mass spectrometry, which were separated from spike trimer using a modified imidazole gradient elution. Purified CHO spike trimer antigen was used in ELISA format to detect IgG antibodies against SARS-CoV-2 in sera from patient cohorts previously tested for viral infection by PCR, including those who had displayed COVID-19 symptoms. The antibody assay, validated to ISO 15189 Medical Laboratories standards, exhibited a specificity of 100% and sensitivity of 92.3%. Our data show that CHO cells are a suitable host for the production of larger quantities of recombinant SARS-CoV-2 trimer which can be used as antigen for mass serological testing.

Italy has been hard hit by SarV CO2 infection with more than 240,000 cases and 35,000 deaths. During the acute phase of the pandemic the italian government decided on the lockdown which lasted about 2 months. During this period all surgical activities were limited to non-deferable procedures only. The sudden closure posed problems with the management of the heart surgery waiting which at that time included 135 patients. Among these were selected cases with the worst clinical characteristics that were progressively operated on. Compared with a similar period in 2019, the cardiac surgery activity of the “Lancisi Cardiovascular Center” in Ancona has been reduced by 65%. With pandemic mitigation, heart surgery activity has gradually resumed but many open questions remain. Above all, there is the problem of living with a low but persistent level of presence of the virus with the need to organize the activity in order to ensure patients and staff safety and an optimal level of performance.

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses SARS CoV-2 has evolved strategies to circumvent innate immune detection including low CpG levels in the genome, glycosylation to shield essential elements including the receptor binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion SARS-CoV-2 infection does activate innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines, and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin-angiotensin system due to downregulation of angiotensin converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.

The global pandemic of COVID-19 caused by coronavirus has had a profound impact on the delivery of health care in the United States and globally. Boston was among the earliest hit cities in the United States, and within Boston, the Massachusetts General Hospital provided care for more patients with COVID -19 than any other hospital in the region. This necessitated a massive re-allocation of resources and priorities, with near doubling of intensive care bed capacity and a halt in all deferrable surgical cases. During this crisis, the Division of Cardiac Surgery responded in a unified manner, dealing honestly with the necessity to reduce Intensive Care Unit resource utilization, for the benefit of both the institution and our community, by deferring non-emergent cases while also continuing to efficiently care for those patients in urgent or emergent need of surgery. Many of the interventions that we instituted have continued to support teamwork as we adapt to the remarkably fluid changes in resource availability during the recovery phase. We believe that the culture of our division and the structure of our practice facilitated our ability to contribute to the mission of our hospital to support the community in this crisis, and now to its recovery. We describe here the challenge we faced in Boston and some of the details of the structure and function of our division.

This program director survey attempts to determine how coronavirus 2019 (COVID-19) pandemic is impacting current training in cardiothoracic surgery. A transition to virtual didactic sessions may prove beneficial with increasing attendance. On the other hand, decreasing live simulation and case volumes may jeopardize achieving competency in surgical skills.

Aim: To assess effect of high-dose vitamin C on cardiac injury in coronavirus disease 2019 (COVID-19). Methods: The study was designed based on the severe and critically ill COVID-19 with cardiac injury. Demographics and baseline clinical characteristics were collected and analyzed in addition to laboratory examinations including inflammatory markers on admission and at 14 days after treatment from the electronic medical records. Participants were followed-up for 14 days after treatment with high-dose vitamin C in addition to conventional therapy. Result: The patients (n = 113) were categorized into the improved cardiac injury (ICI) group (n = 70) and the non-improved cardiac injury (NICI) group (n = 43). Overall, 51 (45.1%) patients were administrated with high-dose vitamin C, the percentages of patients treated with high-dose vitamin C were higher in the ICI group than that in the NICI group (52.8% vs 32.5%, P = 0.035). Further analysis showed that concentrations of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6 and IL-8 significantly decreased at 14 days after treatment in patients treated with high-dose vitamin C compared with those in patients administrated without high-dose vitamin C. Meanwhile, similar results were also observed regarding changes in inflammatory markers from baseline to 14 days after treatment in patients receiving high-dose vitamin C. Conclusion: High-dose vitamin C can improve cardiac injury through preventing hyper-inflammatory response in severe and critically ill COVID-19.

Having lived through the havoc of COVID-19 in a hospital situated in one of the hardest hit zip codes in the United States, the thought that another wave could loom in the fall is bracing. Obstetricians at our institution have cared for well over 200 COVID-19-infected pregnant women, and are acutely aware of the herculean effort it took to reorganize the service to accommodate the needs of women infected with this new pathogen.1 Many institutions, including ours, modified the frequency of prenatal visits, among other measures, to minimize in-person contacts, in an effort to reduce the likelihood of viral spread. However, it is those changes, along with our prior experience of treating women unimmunized against influenza that leads to our concern that a singular focus on COVID-19 could leave pregnant women at risk from a more familiar threat.While COVID-19 is a threat to the health of individuals and society, its effect on pregnancy is less clear. Thus far, few COVID-19-infected pregnant women have required ICU care, and to date three maternal deaths has been reported in the United States.2-4 The toll of influenza in pregnancy is more clearly documented and is more severe.5Now that the first wave is ebbing in New York, we are seeing fewer and fewer cases but still diagnose about 15 infections per week in our hospital. That pattern is the converse of what is being seen in large swaths of the country. Despite the higher prevalence seen earlier in the epidemic in New York, and the fact that many of those women needed respiratory support, only two women in our hospital required admission to the intensive care unit (ICU), and only one needed ventilator support. Mercifully, none died. During the preceding influenza season, whose end overlapped with the start of the COVID-19 pandemic, we treated six women with influenza who required admission to the ICU, only one of whom had been vaccinated against influenza. As opposed to our COVID-19 cases (putting aside the more rigorous application of social distancing), there were clearly missed opportunities to have prevented some of the morbid events caused by influenza.Admittedly, the higher admission rate to the ICU may be misleading. It is certainly possible that criteria for admission to ICUs, like almost all other aspects of care, evolved during the COVID-19 crisis. There was such a rapid and dramatic increase in the need for ICU beds in our hospital (from a baseline of 40 mid-March, 2020 to a peak of 140 mid-April; 2020, internal data) that more stringent criteria for admission may have been applied and some of our COVID-19 patients that were cared for on the wards, may have been cared for in an ICU in less harrowing times. But even given that possibility, the fact that a similar number of women were extremely ill with influenza raises grave concerns going forward.In the first instance, co-infection with COVID-19 and influenza, as well as other viruses, has been reported.6 Co-infection events will make diagnosis of either entity more difficult, and could potentially increase morbidity. Thus, both because of the risks of co-infection, and the known risks of influenza in pregnancy, providers can’t afford to take their “eye off the ball,” and become less vigilant about vaccinating patients, even if some of the new protocols for fewer visits or telehealth visits remain in place. With fewer visits comes the risk of missing both the vaccination “window” and the opportunity to incorporate vaccination as an essential component of health maintenance. In addition, obstetricians’ performance as vaccinators has been less than ideal as only approximately half of pregnant women get influenza vaccines.7In addition to vaccination, obstetricians must remain vigilant in order to prevent progression of disease among those who get infected. Oseltamivir provides the opportunity for secondary prevention.8 It has been shown to reduce maternal ICU admission and mortality.9 Yet, as with vaccination, even before the COVID-19 epidemic, it was underutilized.10Beyond committing to better use of medical interventions for influenza, obstetricians have to assure that just because they have lived through COVID-19, and the world’s attention remains fixed on COVID-19, they don’t become so COVID-19-focused, that they fail to include influenza in the differential diagnosis of women reporting respiratory symptoms in the fall. Every fever and ache will not be COVID-19. If we delay consideration of the diagnosis of influenza, we will lose the opportunity to use Oseltamivir before the window of eligibility closes. In the post-pandemic world, it will be hard to avoid cognitive biases, such as the availability heuristic (a strategy for making judgments about likelihood of occurrence based on the salience of the information) and confirmation bias (the tendency to gather evidence that confirms preexisting expectations, typically by emphasizing or pursuing supporting evidence while dismissing or failing to seek contradictory evidence). These can result in physicians being hammers and every respiratory symptom, a COVID-19 nail; especially when rapid COVID-19 tests are not uniformly available and don’t yet have uniformly high quality. This is the reverse of one of the most cited examples of the availability heuristic, “In influenza season, it is tempting to consider all patients with fever and myalgias as having influenza.”11 An enhanced situational awareness, i.e., recognizing the influence of recent diagnoses on your diagnostic proclivities, will become an ever more crucial antidote to the hard earned reflex response to fevers and aches that developed during the first wave of COVID-19.We know from history that influenza recurs both in epidemic and pandemic forms, and that an initial wave can be a “herald wave” for the following one.12 Hence, it is our responsibility not to let the current COVID pandemic prevent us from properly dealing with the possibility of overlapping epidemics (seasonal influenza and COVID) in the fall. Vaccination, rapid recourse to antivirals (e.g., Oseltamivir), and community mitigation measures will be more important than ever. COVID-19 can kill, but so can influenza, and if we do our jobs, we can reduce that toll.

A novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide appeared in 2019. Currently, we do not have a medicament that treats the disease. One of the rea-sons for the absence of treatment is related to the scarcity of detailed scientific knowledge of the members of the Coro-naviridae family, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Structural studies of the MERS-CoV proteins in the current literature are extremely limited. We present here detailed characterization of the struc-tural properties of MERS-CoV macro domain in aqueous solution at the atomic level with dynamics. For this study, we conducted extensive replica exchange molecular dynamics simulations linked to a generative neural networks and we use the resulting trajectories for structural analysis. We perform structural clustering based on the radius of gyration and end-to-end distance of MERS-CoV macro domain in aqueous solution with dynamics at the atomic level. We also report and analyze the residue-level intrinsic disorder features, flexibility and secondary structure. Furthermore, we study the pro-pensities of this macro domain for protein-protein interactions and for the RNA and DNA binding. Results are in agree-ment with available nuclear magnetic resonance spectroscopy findings and present more detailed insights into the struc-tural properties of MERS CoV macro domain. Overall, this work further shows that neural networks can be used as an exploratory tool for the studies of CoV family molecular conformational space at the nano level.

During the first phase of COVID-19 pandemic in Italy, several strategies have been taken to deal with the pandemic outbreak. The Regional Authority of Lombardy remodeled the hospitalization system in order to allocate appropriate resources to treat COVID-19 patients and to identify “Hub/Spoke” hospitals for highly specialized medical activities. The Hubs hospitals were required to guarantee full time evaluation of all patients presenting with cardiovavascular diseases with an independent pathway for patients with suspect or confirmed COVID-19 infection. San Raffaele Hospital was identified as Hub for cardiovascular emergencies and the Vascular Surgery Department was remodeled to face this epidemic situation. Surgical treatment was reserved only to symptomatic, urgent or emergent cases. Large areas of the hospital were simultaneously reorganized to assist COVID-19 patients. During this period, 135 patients were referred to San Raffaele Vascular Surgery Department. COVID-19 was diagnosed in 24 patients and, among them, acute limb ischemia was the most common cause of admission. At this time, the COVID-19 trend is in decline in Italy and the local authorities reorganized the health care system in order to return to normal activities avoiding new escalations of COVID-19 cases. Several strategies have been taken to ensure the safety of the San Raffaele hospital, and maintaining potentially suspected patients with COVID-19 separated from other patients. The aim of this paper is to report the remodeling of the Vascular Surgery Department of San Raffaele Hospital as regards the strategies of preparation, escalation, de-escalation and return to normal activities during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic introduced an abrupt change in human behavior globally. Here, we discuss unique insights into the eco-evolutionary role of pathogens in ecosystems and present data that indicates the pandemic can fundamentally change our learning choices. This pathogen has indirectly affected many organisms and processes by globally changing the behavior of humans to avoid being infected. The pandemic also changed our learning behavior by affecting the relative importance of information and forcing teaching and learning into a framework that accommodates human behavioral measures to avoid disease transmission. Not only are these indirect effects on the environment occurring through a unique mechanistic pathway in ecology, the pandemic along with its effects on us provides a profound example of the role risk can play in the transmission of information between the at-risk. Ultimately, these changes in our learning behavior led to this special issue “Taking learning online in Ecology and Evolution.” The special issue was a call to the community to take learning in new directions, including online and distributed experiences. The topics examined include a significant component of DIY ecology and evolution that is experiential and but done individually, opportunities to use online tools and apps to be more inclusive, student-focused strategies for teaching online, how to reinvent conferences, strategies to retain experiential learning safely, emerging forms of teaching such as citizen science, apps and podcasting, and ideas on how to accommodate ever changing constraints in the college classroom, to name a few. The collective consensus in our fields is that these times are challenging but we can continue to improve and innovate on existing developments, and more broadly and importantly, this situation may provide an opportunity to reset some of the existing practices that fail to promote an effective and inclusive learning environment.

Aim. Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and pediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provides a baseline risk assessment and identifies gaps for targeted investigation. Methods. Clinical trials have been searched and reviewed; twenty-three repurposed drugs and drug combinations and 9 candidate vaccines have been assessed regarding the availability of relevant data in pediatrics and pregnant women and to evaluate expected or unanticipated risk. Results. Thirteen of the repurposed drugs or drug combinations are indicated for use in pediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have pediatric subgroups been planned for enrollment. Data from individual case studies and RWD may suggest that subpopulations of both pediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. Conclusion. In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in pediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.