The current SARS-CoV-2 outbreak, which causes COVID-19, is particularly devastating for individuals with chronic medical conditions, in particular those with Down Syndrome (DS) who often exhibit a higher prevalence of respiratory tract infections, immune dysregulation and potential complications. The incidence of Alzheimer's disease (AD) is much higher in DS than in the general population, possibly increasing further the risk of COVID-19 infection and its complications. Here we provide a biological overview with regard to specific susceptibility of individuals with DS to SARS-CoV-2 infection as well as data from a recent survey on the prevalence of COVID-19 among them. We see an urgent need to protect people with DS, especially those with AD, from COVID-19 and future pandemics and focus on developing protective measures, which also include interventions by health systems worldwide for reducing the negative social effects of long-term isolation and increased periods of hospitalization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children, and older or immunocompromised adults. Although aerosolized ribavirin was licensed for RSV treatment on the basis of data demonstrating a reduced need for supplemental oxygen, ribavirin use is limited because of issues with efficacy, safety, and cost. Currently, the treatment of RSV is primarily supportive. New antiviral treatments for RSV are in the early stages of development, but it will be years until any of these may be licensed by the US Food and Drug Administration (FDA). Palivizumab, an RSV monoclonal antibody [immunoprophylaxis (IP)], has demonstrated effectiveness in disease prevention and is the only licensed IP for RSV disease in specific high-risk pediatric populations. Although its efficacy is well established, some challenges that may interfere with its clinical use include cost, need for monthly injections, and changing policy for use by the American Academy of Pediatrics (AAP). Preventing RSV disease would be possible through RSV vaccine development (e.g., live-attenuated, vector-based subunit, or particle-based). Alternatively, new long-acting monoclonal antibodies have demonstrated promising results in early clinical trials. Despite scientific advances, until new agents become available, palivizumab should continue to be used to reduce RSV disease burden in high-risk patients for whom it is indicated.

Respiratory syncytial virus (RSV) disease is a significant cause of morbidity and socioeconomic burden worldwide among young children. The majority of RSV-associated lower respiratory tract infections (LRTI) and mortality occurs in developing countries and is associated with various sociodemographic risk factors. Independent risk factors for severe RSV disease include age and premature birth. While RSV mortality in developed countries is lower relative to developing countries, high-risk infants with comorbidities experience higher rates of mortality. RSV LRTI is often severe and is associated with hospitalization, increased need for intensive care unit admission and mechanical ventilation, long-term complications, and caregiver stress and loss of work productivity. Overall, these factors translate to higher health care resource utilization and costs and should be factored into the consideration for RSV prophylaxis. Multiple vaccine candidates and long-acting monoclonal antibodies are in various stages of clinical development. Currently, palivizumab is the only approved RSV immunoprophylaxis available for use in specific high-risk pediatric populations. This review will discuss the socioeconomic impact and health care resource utilization of RSV-related hospitalization (RSVH) as well as various sociodemographic risk factors that can be used to identify children at high risk of developing severe RSV disease.

Despite being a leading cause of hospitalization due to lower respiratory tract infections, the treatment of respiratory syncytial virus (RSV) infection is primarily supportive. Palivizumab is the only licensed immunoprophylaxis (IP) available for preventing severe RSV infection in high-risk populations including ≤ 35 weeks' gestational age (wGA) infants and children with chronic lung disease of prematurity or congenital heart disease. The American Academy of Pediatrics (AAP) has published its IP recommendations since the approval of palivizumab. In 2014, the AAP stopped recommending RSV IP in 29-34 wGA infants without comorbidities and stated that RSV hospitalization (RSVH) risk in otherwise healthy ≥ 29 wGA infants and term infants was similar. Since then, experts in the field have debated the appropriateness of the 2014 policy change, and several real-world evidence studies at the national and regional levels in the US have examined the impact of the AAP policy on 29-34 wGA infants. Overall, these studies showed a significant decline in RSV IP use and a concurrent increase in RSVH risk among 29-34 wGA infants relative to term infants in the seasons after the 2014 policy change. A similar decrease in IP use and increase in RSVH risk was also observed among < 29 wGA infants relative to term infants after the 2014 policy change. This decrease could be an unintended consequence as < 29 wGA infants are an in-policy population recommended to receive RSV IP. According to the National Perinatal Association, strong evidence exists to support the use of RSV IP in all ≤ 32 wGA and 32-35 wGA infants with risk factors such as attending day care, having ≥ 1 school-aged siblings, twin or greater multiple gestation, younger age, and exposure to parental smoking. Until new preventive and treatment options become available, palivizumab can help prevent and mitigate RSV disease burden among high-risk preterm infants.

Klebsiella oxytoca is rising as a significant opportunistic pathogen causing nosocomial infections in neonates as well as adults. This pathogen's prevalence varies from 2 to 24%, but outbreaks of infections due to multidrug-resistant strains can be fatal in immunocompromised individuals with comorbidities. Klebsiella oxytoca is responsible for a wide range of ailments from colitis to infective endocarditis, other than the common urinary and respiratory tract infections. The microbe's pathogenicity has been attributed to cytotoxins' production- Tilivalline and Tilimycin, in some intestinal disorders. Klebsiella oxytoca is reported to be resistant to a wide range of antibiotics. Here, we have tried to showcase a brief overview of the emergence of Klebsiella oxytoca in healthcare facilities and the nature of resistance in this species of Klebsiella.

Elizabethkingia species are environmental bacteria associated with opportunistic infections in vulnerable populations. Traditionally, Elizabethkingia meningoseptica was considered the predominant pathogenic species. However, commercial identification systems have routinely misidentified Elizabethkingia anophelis as E. meningoseptica, leading to a mischaracterization of clinical strains and an underestimation of the role of E. anophelis in human disease. Elizabethkingia spp. harbor multidrug resistance (MDR) genes that pose challenges for treatment. Differentiation between Elizabethkingia spp. is particularly important due to differences in antimicrobial resistance (AMR) and epidemiological investigation. In this study, we describe a case of MDR E. anophelis isolated from the blood and lower respiratory tract of a patient who was successfully treated with minocycline. These isolates were initially misidentified by matrix assisted laser desorption ionization-time of flight as E. meningoseptica, whereas whole genome sequencing (WGS) confirmed the isolates as E. anophelis with the closest related strain being E. anophelis NUHP1, which was implicated in a 2012 outbreak in Singapore. Several AMR genes (blaBlaB, blaBlaGOB, blaCME, Sul2, erm(F), and catB) were identified by WGS, confirming the mechanisms for MDR. This case emphasizes the utility of WGS for correct speciation, elucidation of resistance genes, and relatedness to other outbreak strains. As E. anophelis is associated with a high mortality and has been found in hospital system sinks, WGS is critically important for determining strain relatedness and tracking outbreaks in the hospital setting.

SARS-CoV-2 affects the cardiovascular system triggering a proinflammatory response which results in direct and indirect myocardial injury. The objective of this article is to describe the underlying mechanisms and clinical implications.

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

2020 will go down in history as a year marked in every respect by the emergence and astonishingly rapid spread of the first major global viral pandemic in a century. It seems like nearly every event or story of the year was influenced in some way by COVID-19, and in that respect, the year ended on a high note with the authorization for emergency use of the first vaccines to prevent SARS-CoV-2 infection and drugs to treat COVID-19. Despite the pandemic's dominance of the 2020 headlines, productivity was at a record high level across all therapeutic areas, as seen by the number of products in this year's review: approximately 50% more than the previous year. Notable achievements include the launch of the first treatment for hepatitis D; regulatory decisions on a suite of biologics for the prevention and treatment of Ebola virus disease, fruit of the 2016-2018 outbreak in the Democratic Republic of Congo; the approval of the first-ever drug to treat Hutchinson-Gilford progeria syndrome, a rare genetic disorder that leads to premature aging; the first treatment developed specifically for thyroid eye disease, also known as Graves' ophthalmopathy; the first nonhormonal, on-demand, vaginal pH-regulating contraceptive; and the first oral allergen immunotherapy for peanut allergy.

Globally there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate to severe COVID-19 disease, we demonstrate the high efficacy of PiN-21 to prevent and treat SARS-CoV-2 infection. Intranasal delivery of PiN-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduces viral burdens in both lower and upper airways compared to control. Aerosol delivery of PiN-21 facilitates deposition throughout the respiratory tract and dose minimization to 0.2 mg/kg. Inhalation treatment quickly reverses animals' weight loss post-infection and decreases lung viral titers by 6 logs leading to drastically mitigated lung pathology and prevents viral pneumonia. Combined with the marked stability and low production cost, this novel therapy may provide a convenient and cost-effective option to mitigate the ongoing pandemic.

Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs.

CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

CME/Answers: Hypertension and the COVID-19 Pandemic: What to Consider in Medical Practice Abstract. The COVID-19 pandemic represents a major public health problem. A fraction of the population is at increased risk of developing complications of this disease, in particular older subjects as well as diabetic, obese and hypertensive patients. With regard to patients with high blood pressure, the existence of an increased risk remains to be confirmed in large controlled trials. So far the findings regarding this question are reassuring, whether these patients are treated or not. There seems to be no reason to worry when using blockers of the renin-angiotensin system. The observations available to date suggest that COVID-19 vaccine can be administered safely to hypertensive patients. In conclusion, there is no reason to implement changes in the care of hypertensive patients due to the pandemic.

Evidence supporting the notion that diabetes predisposes to an increased risk of infection continues to be inconclusive. In fact, in patients with diabetes, the percentage of outpatient visits to a physician because of an infection ranges from 1.6% to 5.1%, whereas individuals without diabetes average 2.6%–3.6% outpatient visits to physicians as a result of an infection. Additionally, compared to the general population, the percentage of deaths due to infection in those diagnosed with diabetes ranges from 2.7% to 3.4% compared to a range of 4.1% to 4.6% in individuals without diabetes. In individuals with diabetes, the mechanisms have not been clearly elucidated but are partly attributed to the effect of hyperglycemia on the immune system, increased risk of local tissue ischemia, and neuropathy. The available evidence suggests that individuals with diabetes are more likely to develop certain infections, including asymptomatic bacteriuria (especially women), urinary tract infection, pyelonephritis, renal and perinephric abscess, lower extremity infections, deep subcutaneous tissue infections, postoperative sternal wound infections, and tuberculosis compared to individuals without diabetes. In 2010, 2.8% of hospital discharges for persons diagnosed with diabetes were due to foot ulcers, a stark contrast when compared to only 0.6% of discharges due to foot ulcers in individuals without diabetes. There is inadequate evidence linking diabetes to an increased risk of pneumonia or influenza. The case fatality rate among individuals with diabetes who are diagnosed with a respiratory tract infection, such as influenza, sinusitis, and bronchitis, ranges from 1% to 1.4% compared to a range of 1.9% to 2.4% in individuals without diabetes. Most clinical guidelines recommend persons with diabetes receive the pneumonia and influenza vaccines. Similar to the evidence linking diabetes to respiratory tract infections, the evidence linking diabetes to an increased risk of fungal infections, superficial bacterial skin and soft tissue infections, sinusitis, or bronchitis, is weak. However, there are infections that occur almost exclusively among individuals with diabetes, including: emphysematous pyelonephritis and emphysematous cholecystitis, malignant otitis externa, and rhinocerebral mucormycosis. Additionally, diabetes has been identified as a risk factor for invasive group B streptococcal infections in nonpregnant adults. Immunological defects, microangiopathy, and autonomic and sensory neuropathy have all been implicated as risk factors for the aforementioned infections in individuals with diabetes. This chapter summarizes the body of evidence on the relationship between diabetes and infectious disease risks and outcomes.

Over the last couple of months physicians world wide are struggling to prevent the novel coronavirus (COVID-19) spread all over the world. It has become obvious that our health care systems should under go modifications in order to successfully confront similar pandemics, since this is considered the ''century of pandemics'', due to the high incidence of new virus attacks with expressly high virulence (Hong Kong flu in 1968, AIDS, SARS in 2002, H1N1 pandemic in 2009, MERS in 2012 and COVID-19 in 2020) (1).

SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein Receptor Binding Domain, neutralizes SARS-CoV-2 and exhibits in vivo prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6mg/kg, corresponding to 0.03mg/kg of lung deposited dose, reduced viral burden below the detection limit, and mitigated lung pathology. The therapeutic efficacy of an exceedingly low-dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits as compared to the conventional parenteral route of administration. These results suggest clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered.

This study aimed to identify the spatial patterns of lower respiratory tract infections (LRIs) and their association with fine particulate matter (PM2.5). The disability-adjusted life year (DALY) database was used to represent the burden each country experiences as a result of LRIs. PM2.5 data obtained from the Atmosphere Composition Analysis Group was assessed as the source for main exposure. Global Moran's I and Getis-Ord Gi* were applied to identify the spatial patterns and for hotspots analysis of LRIs. A generalized linear mixed model was coupled with a sensitivity test after controlling for covariates to estimate the association between LRIs and PM2.5. Subgroup analyses were performed to determine whether LRIs and PM2.5 are correlated for various ages and geographic regions. A significant spatial auto-correlated pattern was identified for global LRIs with Moran's Index 0.79, and the hotspots of LRIs were clustered in 35 African and 4 Eastern Mediterranean countries. A consistent significant positive association between LRIs and PM2.5 with a coefficient of 0.21 (95% CI 0.06-0.36) was identified. Furthermore, subgroup analysis revealed a significant effect of PM2.5 on LRI for children (0-14 years) and the elderly (≥ 70 years), and this effect was confirmed to be significant in all regions except for those comprised of Eastern Mediterranean countries.

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.