Studies have shown that severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) is a highly infectious disease, with global deaths rising to about 360,438 as of 28 May 2020. Different countries have used various approaches such as lockdown, social distancing, maintenance of personal hygiene, and increased establishment of testing and isolation centers to manage the pandemic. Poor biomedical waste (BMW) management, treatment, and disposal techniques, especially SARS-CoV-2 infected BMW, may threaten the environmental and public health in most developing countries and, by extension, impact the economic status of individuals and the nation at large. This may increase the potential for the transmission of air/blood body fluid-borne pathogens, increase the growth of microorganisms, risk of mutagenesis, and upsurge of more virulent strain. In contrast, uncontrolled substandard burning could increase the potential spread of nosocomial infection and environmental exposure to toxic organic compounds, heavy metals, radioactive, and genotoxic bio-aerosols which might be present in the gaseous, liquid, and solid by-products. The paucity of understanding of pathophysiology and management of the SARS-CoV-2 pandemic has also necessitated the need to put in place appropriate disposal techniques to cater for the sudden increase in the global demand for personal protective equipment (PPE) and pharmaceutical drugs to manage the pandemic and to reduce the risk of preventable infection by the waste. Therefore, there is a need for adequate sensitization, awareness, and environmental monitoring of the impacts of improper handling of SARS-CoV-2 infected BMWs. Hence, this review aimed to address the issues relating to the improper management of increased SARS-CoV-2 infected BMW in low middle-income countries (LMICs).

The coronavirus disease 2019 (COVID-19) pandemic has imposed a considerable burden on hospitals and healthcare workers (HCWs) worldwide, increasing the risk of outbreaks and nosocomial transmission to "non-COVID-19" patients, who represent the highest-risk population in terms of mortality, and HCWs. Since HCWs are at the interface between hospitals on the one hand and the community on the other, they are potential reservoirs, carriers, or victims of severe acute respiratory syndrome coronavirus 2 cross-transmission. In addition, there has been a paradigm shift in the management of viral respiratory outbreaks, such as the widespread testing of patients and HCWs, including asymptomatic individuals. In hospitals, there is a risk of aerosol transmission in poorly ventilated spaces, and when performing aerosol-producing procedures, it is imperative to take measures against aerosol transmission. In particular, spatial separation of the inpatient ward for non-COVID-19 patients from that designated for patients with suspected or confirmed COVID-19 as well as negative-pressure isolation on the floor of the ward, using an airborne infection isolation device could help prevent nosocomial infection.

Autoimmune phenomena and clinically apparent autoimmune diseases, including autoimmune hepatitis, are increasingly been reported not only after natural infection with the SARS-CoV-2 virus, but also after vaccination against it. We report the case of a 63-year old man without a history of autoimmunity or SARS-CoV-2 natural infection who experienced acute severe autoimmune-like hepatitis seven days after the first dose of the mRNA-1273 SARS-CoV-2 vaccine. Liver histology showed inflammatory portal infiltrate with interface hepatitis, lobular and centrilobular inflammation with centrilobular necrosis, in absence of fibrosis and steatosis. Serum immunoglobulin G was slightly elevated. Autoimmune liver serology showed an indirect immunofluorescence pattern on triple rodent tissue compatible with anti-mitochondrial antibody (AMA), but, unexpectedly, this pattern was not mirrored by positivity for primary biliary cholangitis (PBC)-specific molecular tests, indicating that this antibody is different from classical AMA. Anti-nuclear antibody (ANA) was also positive with a rim-like indirect immunofluorescence pattern on liver and HEp2 cell substrates, similar to PBC-specific ANA; however, anti-gp210 and a large panel of molecular-based assays for nuclear antigens were negative, suggesting a unique ANA in our patient. He carries the HLA DRB1*11:01 allele, which is protective against PBC. Response to prednisone treatment was satisfactory. The clinical significance of these novel specificities needs to be further evaluated in this emerging condition.

Bereaved people suffer from loneliness and loneliness is associated with poor mental health. In this study, this topic is reviewed. An agenda is suggested for future research. Research that is theory-driven, addresses measurement consistency, correlates of loneliness in bereaved and non-bereaved, and treatment is necessary for prevention and intervention.

Great expectations are placed in vaccines against COVID-19 to control the pandemic. We reviewed the antibody titres in a cohort of healthcare workers (HCWs) vaccinated with BNT162b2 to assess the influence of a previous infection on them. We stratified the results according to the individual history of nasopharyngeal swab (NPS) and symptoms. Among 3475 HCWs the highest titres were recorded among those infected more than 6 months before vaccination, independently of symptoms, followed by those infected less than 6 months before vaccination, especially in those with symptoms, and by uninfected HCWs. Vaccination with BNT162b2 can boost immunity acquired through infection, particularly in those infected more than 6 months before vaccination.

The Covid-19 pandemic required rapid scale of telemedicine as well as other digital workflows to maintain access to care while reducing infection risk. Both patients and clinicians who hadn't used telemedicine before were suddenly faced with a multi-step setup process to log into a virtual meeting. Unlike in-person examination rooms, locking a virtual meeting room was more error-prone and posed a risk of multiple patients joining the same online session. There was administrative burden on the practice staff who were generating and manually sending links to patients, and educating patients on device set up was time-consuming and unsustainable. A solution had to be deployed rapidly system-wide, without the usual roll out across months. Our answer was to design and implement a novel EHR-integrated web application called the Switchboard, in just two weeks. The Switchboard leverages a commercial, cloud-based video meeting platform and facilitates an end-to-end virtual care encounter workflow, from pre-visit reminders to post-visit SMS text message-based measurement of patient experience, with tools to extend contact-less workflows to in-person appointments. Over the first 11 months of the pandemic, the in-house platform has been adopted across 6 hospitals and >200 practices, scaled to 8,800 clinicians who at their peak conducted an average of 30,000 telemedicine appointments/week, and enabled over 10,000-20,000 text messages/day to be exchanged through the platform. Furthermore, it enabled our organization to convert from an average of 75% of telehealth visits being conducted via telephone to 75% conducted via video within weeks.

The ongoing COVID-19 pandemic has generated a global health crisis that needs well management of not only patients but also environments to reduce SARS-CoV-2 transmission. The gold standard RT-qPCR method is sensitive and rapid to detect SARS-CoV-2 nucleic acid, but does not answer if PCR-positive samples contain infectious virions. To circumvent this problem, we report an SDS-propidium monoazide (PMA) assisted RT-qPCR method that enables rapid discrimination of live and dead SARS-CoV-2 within 3 h. PMA, a photo-reactive dye, can react with viral RNA released or inside inactivated SARS-CoV-2 virions under assistance of 0.005% SDS, but not viral RNA inside live virions. Formation of PMA-RNA conjugates prevents PCR amplification, leaving only infectious virions to be detected. Under optimum conditions, RT-qPCR detection of heat-inactivated SARS-CoV-2 resulted in larger than 9 Ct value differences between PMA-treated and PMA-free groups, while less than 0.5 Ct differences were observed in the detection of infectious SARS-CoV-2 ranging from 20 to 5148 viral particles. Using a cutoff Ct difference of 8.6, this method could differentiate as low as 8 PFU live viruses in the mixtures of live and heat-inactivated virions. Further experiments showed that this method could successfully monitor the natural inactivation process of SARS-CoV-2 on plastic surfaces during storage with comparable results to the gold standard plaque assay. We believe that the culture-free method established here could be used for rapid and convenient determination of infectious SARS-CoV-2 virions in PCR-positive samples, which will facilitate better control of SARS-CoV-2 transmission.

T cells of aged people, and of patients with either cancer or severe infections (including COVID-19), are often exhausted, senescent and dysfunctional, leading to increased susceptibilities, complications and mortality. Neurotransmitters and Neuropeptides bind their receptors in T cells, and induce multiple beneficial T cell functions. Yet, T cells of different people vary in the expression levels of Neurotransmitter and Neuropeptide receptors, and in the magnitude of the corresponding effects. Therefore, we performed an individual-based study on T cells of 3 healthy subjects, and 3 Hepatocellular Carcinoma (HCC) patients. HCC usually develops due to chronic inflammation. The inflamed liver induces reduction and inhibition of CD4+ T cells and Natural Killer (NK) cells. Immune-based therapies for HCC are urgently needed. We tested if selected Neurotransmitters and Neuropeptides decrease the key checkpoint protein PD-1 in human T cells, and increase proliferation and killing of HCC cells. First, we confirmed human T cells express all dopamine receptors (DRs), and glutamate receptors (GluRs): AMPA-GluR3, NMDA-R and mGluR. Second, we discovered that either Dopamine, Glutamate, GnRH-II, Neuropeptide Y and/or CGRP (10nM), as well as DR and GluR agonists, induced the following effects: 1. Decreased significantly both %PD-1+ T cells and PD-1 expression level per cell (up to 60% decrease, within 1 h only); 2. Increased significantly the number of T cells that proliferated in the presence of HCC cells (up to 7 fold increase), 3. Increased significantly T cell killing of HCC cells (up to 2 fold increase). 4. Few non-conventional combinations of Neurotransmitters and Neuropeptides had surprising synergistic beneficial effects. We conclude that Dopamine, Glutamate, GnRH-II, Neuropeptide Y and CGRP, alone or in combinations, can decrease % PD-1+ T cells and PD-1 expression per cell, in T cells of both healthy subjects and HCC patients, and increase their proliferation in response to HCC cells and killing of HCC cells. Yet, testing T cells of many more cancer patients is absolutely needed. Based on these findings and previous ones, we designed a novel "Personalized Adoptive Neuro-Immunotherapy", calling for validation of safety and efficacy in clinical trials.

This paper focuses on the study of multilevel COVID-19 X-ray image segmentation based on swarm intelligence optimization to improve the diagnostic level of COVID-19. We present a new ant colony optimization with the Cauchy mutation and the greedy Levy mutation, termed CLACO, for continuous domains. Specifically, the Cauchy mutation is applied to the end phase of ant foraging in CLACO to enhance its searchability and to boost its convergence rate. The greedy Levy mutation is applied to the optimal ant individuals to confer an improved ability to jump out of the local optimum. Furthermore, this paper develops a novel CLACO-based multilevel image segmentation method, termed CLACO-MIS. Using 2D Kapur's entropy as the CLACO fitness function based on 2D histograms consisting of non-local mean filtered images and grayscale images, CLACO-MIS was successfully applied to the segmentation of COVID-19 X-ray images. A comparison of CLACO with some relevant variants and other excellent peers on 30 benchmark functions from IEEE CEC2014 demonstrates the superior performance of CLACO in terms of search capability, and convergence speed as well as ability to jump out of the local optimum. Moreover, CLACO-MIS was shown to have a better segmentation effect and a stronger adaptability at different threshold levels than other methods in performing segmentation experiments of COVID-19 X-ray images. Therefore, CLACO-MIS has great potential to be used for improving the diagnostic level of COVID-19. This research will host a webservice for any question at https://aliasgharheidari.com.

Immunocompromised individuals were not included in formal trials of SARS-CoV-2 mRNA vaccines. Subsequent studies in patients with haematological malignancies and solid organ transplant recipients suggest inferior responses to vaccination. We determined antibody responses to a single dose of vaccines in one of the most vulnerable patient groups, allogeneic haematopoietic cell transplant (allo-HCT) recipients. Pfizer-BioNTech or AstraZeneca SARS-CoV-2 vaccines were administered at least 3 months post-transplant to 55 adult allo-HCT recipients. We found that older age and concurrent use of immunosuppressive medications were significantly associated with lack of antibody response to vaccination. Only 21% of those on systemic immunosuppression mounted a response, compared to 58% of patients who were not taking immunosuppression (p=0.006). We also show that responses to the AstraZeneca vaccine may be superior to the Pfizer-BioNTech vaccine in this cohort. These findings highlight the need for novel immunogenic vaccine formulations and schedules in these highest risk patients as well as continued public healthy safety measures to protect the most vulnerable members of our society.

As mutations in SARS-CoV-2 virus accumulate rapidly, novel primers that amplify this virus sensitively and specifically are in demand. We have developed a webserver named CoVrimer by which users can search for and align existing or newly designed conserved / degenerate primer pair sequences against the viral genome and assess the mutation load of both primers and amplicons. CoVrimer uses mutation data obtained from an online platform established by NGDC-CNCB (12 May 2021) to identify genomic regions, either conserved or with low levels of mutations, from which potential primer pairs are designed and provided to the user for filtering based on generalized and SARS-CoV-2 specific parameters. Alignments of primers and probes can be visualized with respect to the reference genome, indicating variant details and the level of conservation. Consequently, CoVrimer is likely to help researchers with the challenges posed by viral evolution and is freely available at http://konulabapps.bilkent.edu.tr:3838/CoVrimer/.

Rural areas of the United States have been disproportionately impacted by the opioid epidemic, exacerbated by COVID-19-related economic upheavals. While polysubstance use is an important determinant of overdose risk, variability in polysubstance use as a result of numerous factors (e.g., access, preference) has yet to be described, particularly among rural persons with opioid use disorder (PWOUD). Survey data on past-month use of prescription and illicit opioids and 12 non-opioid psychoactive drug classes were analyzed from a national sample of rural (n = 3872) and urban (n = 8153) residents entering treatment for OUD from 2012 to 2019. Trend analyses for opioid and stimulant use were compared between rural and urban PWOUD. Latent class analyses assessed substance use trends through identified typologies of rural/urban PWOUD, which then underwent comparative analyses. By 2019, prescription opioid use remained greater in rural versus urban PWOUD, and methamphetamine use showed greater growth in rural, compared to urban areas. Latent class analyses identified variability in polysubstance use, with five identical subgroups in rural/urban PWOD: high polysubstance, polyprescription, prescription opioid-focused, prescription opioid-focused with polysubstance use, and illicit opioid-focused. Polyprescription was highest in rural areas, with illicit opioid-focused use highest in urban areas. Demographic characteristics, co-morbid conditions and healthcare coverage were all associated with between-group differences. There is significant variability in polysubstance use that may identify specific prevention and treatment needs for subpopulations of OUD patients: interventions focused on reducing opioid prescriptions, early engagement with mental health resources, wider distribution of naloxone, and screening/treatment plans that take into account the use of multiple substances.

The coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has taken the world by surprise. To date, a worldwide approved treatment remains lacking and hence in the context of rapid viral spread and the growing need for rapid action, drug repurposing has emerged as one of the frontline strategies in the battle against SARS-CoV2. Repurposed drugs currently being evaluated against COVID-19 either tackle the replication and spread of SARS-CoV2 or they aim at controlling hyper-inflammation and the rampaged immune response in severe disease. In both cases, the target for such drugs resides in the lungs, at least during the period where treatment could still provide substantial clinical benefit to the patient. Yet, most of these drugs are administered systemically, questioning the percentage of administered drug that actually reaches the lung and as a consequence, the distribution of the remainder of the dose to off target sites. Inhalation therapy should allow higher concentrations of the drug in the lungs and lower concentrations systemically, hence providing a stronger, more localized action, with reduced adverse effects. Therefore, the nano-reformulation of the repurposed drugs for inhalation is a promising approach for targeted drug delivery to lungs. In this review, we critically analyze, what nanomedicine could and ought to do in the battle against SARS-CoV2. We start by a brief description of SARS-CoV2 structure and pathogenicity and move on to discuss the current limitations of repurposed antiviral and immune-modulating drugs that are being clinically investigated against COVID-19. This account focuses on how nanomedicine could address limitations of current therapeutics, enhancing the efficacy, specificity and safety of such drugs. With the appearance of new variants of SARS-CoV2 and the potential implication on the efficacy of vaccines and diagnostics, the presence of an effective therapeutic solution is inevitable and could be potentially achieved via nano-reformulation. The presence of an inhaled nano-platform capable of delivering antiviral or immunomodulatory drugs should be available as part of the repertoire in the fight against current and future outbreaks.