Prevention of Laboratory Animal Allergy and Impact of COVID-19 on Prevention Programs in the United States: A National Survey 10-Year Update.

OBJECTIVE: Laboratory animal allergy (LAA) is common and preventable. This study provides a 10-year update on LAA prevention programs in the United States and the effect of COVID-19 on prevention practices. METHODS: An electronic survey was e-mailed to designated institutional officials at laboratory animal facilities identified by the National Institutes of Health Office of Laboratory Animal Welfare. Results were compared with the prior survey. RESULTS: A total of 141 institutions employing 58,224 laboratory animal workers responded. Results were similar to the prior survey with wide variation in practices. Medical surveillance increased (58%-71%), but N95 respirator use decreased (17%-13%). As before, only 25% of institutions knew their LAA incidence and prevalence rates. COVID-19 had a small time-limited effect on personal protective equipment use. CONCLUSIONS: Universal use of evidence-based practices and improved medical surveillance would provide greater worker protection from LAA.

Development of highly stable and de-immunized versions of recombinant alpha interferon: Promising candidates for the treatment of chronic and emerging viral diseases.

Human interferon alpha (hIFN-α) administration constitutes the current FDA approved therapy for chronic Hepatitis B and C virus infections. Additionally, hIFN-α treatment efficacy was recently demonstrated in patients with COVID-19. Thus, hIFN-α constitutes a therapeutic alternative for those countries where vaccination is inaccessible and for people who did not respond effectively to vaccination. However, hIFN-α2b exhibits a short plasma half-life resulting in the occurrence of severe side effects. To optimize the cytokine's pharmacokinetic profile, we developed a hyperglycosylated IFN, referred to as GMOP-IFN. Given the significant number of reports showing neutralizing antibodies (NAb) formation after hIFN-α administration, here we applied the DeFT (De-immunization of Functional Therapeutics) approach to develop functional, de-immunized versions of GMOP-IFN. Two GMOP-IFN variants exhibited significantly reduced ex vivo immunogenicity and null antiproliferative activity, while preserving antiviral function. The results obtained in this work indicate that the new de-immunized GMOP-IFN variants constitute promising candidates for antiviral therapy.

Telemedicine-based sleep services for a complex child: optimizing care during a pandemic and beyond.

A 12-year-old male with nonverbal autism and morbid obesity was referred to a pediatric sleep center during the SARS-CoV-2 pandemic for complaints of snoring with tonsillar hypertrophy and difficulty falling asleep. Due to social challenges, the family had not sought in-person care in the past. Through telemedicine consultation and home sleep apnea testing, the patient was diagnosed with obstructive sleep apnea as well as an irregular sleep-wake disorder. This unique utilization of the health care system in the care of a complex patient with multiple sleep disorders demonstrates the utility of remote care and testing. There is a great benefit to continuing to provide pediatric sleep care in this way beyond the pandemic.

A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein.

The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 (COVID-19) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is a lack of proven effective treatments or cures for COVID-19. In this study, we have presented a synergistic computational platform, including molecular dynamics simulations and immunoinformatics techniques, to rationally design a multi-epitope vaccine candidate for COVID-19. This platform combines epitopes across Linear B Lymphocytes (LBL), Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocytes (HTL) derived from both mutant and wild-type spike glycoproteins from SARS-CoV-2 with diverse protein conformations. In addition, this vaccine construct also takes the considerable glycan shield of the spike glycoprotein into account, which protects it from immune response. We have identified a vaccine candidate (a 35.9 kDa protein), named COVCCF, which is composed of 5 LBL, 6 HTL, and 6 CTL epitopes from the spike glycoprotein of SARS-CoV-2. Using multi-dose immune simulations, COVCCF induces elevated levels of immunoglobulin activity (IgM, IgG1, IgG2), and induces strong responses from B lymphocytes, CD4 T-helper lymphocytes, and CD8 T-cytotoxic lymphocytes. COVCCF induces cytokines important to innate immunity, including IFN-γ, IL4, and IL10. Additionally, COVCCF has ideal pharmacokinetic properties and low immune-related toxicities. In summary, this study provides a powerful, computational vaccine design platform for rapid development of vaccine candidates (including COVCCF) for effective prevention of COVID-19.Communicated by Ramaswamy H. Sarma.

The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update.

NONE: The COVID-19 pandemic led to widespread use of telemedicine and highlighted its importance in improving access to sleep care and advocating for sleep health. This update incorporates the lessons learned from such widespread utilization of telehealth to build on the American Academy of Sleep Medicine's 2015 position paper on the use of telemedicine for diagnosing and treating sleep disorders. Important key factors in this update include an emphasis on quality and value, privacy and safety, health advocacy through sleep telemedicine, and future directions.

Repurposing of FDA-Approved Toremifene to Treat COVID-19 by Blocking the Spike Glycoprotein and NSP14 of SARS-CoV-2.

The global pandemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the death of more than 675,000 worldwide and over 150,000 in the United States alone. However, there are currently no approved effective pharmacotherapies for COVID-19. Here, we combine homology modeling, molecular docking, molecular dynamics simulation, and binding affinity calculations to determine potential targets for toremifene, a selective estrogen receptor modulator which we have previously identified as a SARS-CoV-2 inhibitor. Our results indicate the possibility of inhibition of the spike glycoprotein by toremifene, responsible for aiding in fusion of the viral membrane with the cell membrane, via a perturbation to the fusion core. An interaction between the dimethylamine end of toremifene and residues Q954 and N955 in heptad repeat 1 (HR1) perturbs the structure, causing a shift from what is normally a long, helical region to short helices connected by unstructured regions. Additionally, we found a strong interaction between toremifene and the methyltransferase nonstructural protein (NSP) 14, which could be inhibitory to viral replication via its active site. These results suggest potential structural mechanisms for toremifene by blocking the spike protein and NSP14 of SARS-CoV-2, offering a drug candidate for COVID-19.

Infectious Disease: Protecting Workers and Organizations-The Role of Compensation & Benefits.

Infectious diseases at work can be endemic such as seasonal influenza and emerging such as the novel coronavirus 2019. Infectious diseases have an impact on employees and other types of workers. Compensation and benefits professionals are often at the forefront of preventing workplace infections, addressing workplace infections, and ensuring the continuity of talent when workplace outbreaks and business shutdowns occur. This article provides an overview of pertinent laws, key compensation decisions, and ways to refocus existing benefit programs to meet the challenge of not only just safety, health, and wellness but also infection prevention and control.

New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis.

BACKGROUND: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown. MAIN BODY: In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19. CONCLUSION: This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.

Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2.

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV-host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the "Complementary Exposure" pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.