A Comprehensive Review of COVID-19–Associated Endocrine Manifestations

Coronavirus disease 2019 (COVID-19) has played a significant part in systematic damage, affecting lives and leading to significant mortality. The endocrine system is one of the systems affected by this pandemic outbreak. The relationship between them has been identified in previous and ongoing research. The mechanism through which severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can achieve this is similar to that for organs that express angiotensin-converting enzyme 2 receptors, which is the primary binding site of the virus. Endocrine cells widely express angiotensin-converting enzyme 2 receptors and transmembrane serine protease 2, the primary mediators initiating the acute phase of the disease. This review aimed to identify and discuss the endocrine complications of COVID-19. This primary focus is on presenting thyroid disorders or newly diagnosed diabetes mellitus (DM). Thyroid dysfunction with subacute thyroiditis, Graves' disease, and hypothyroidism caused by primary autoimmune thyroiditis has been reported. Pancreatic damage leads to type 1 DM because of the autoimmune nature of the disease and type 2 DM because of postinflammatory insulin resistance. Because follow-up data on COVID-19 on the endocrine glands are limited, long-term investigations are needed to assess specific effects.

A Comprehensive Review of COVID-19-Associated Endocrine Manifestations.

Coronavirus disease 2019 (COVID-19) has played a significant part in systematic damage, affecting lives and leading to significant mortality. The endocrine system is one of the systems affected by this pandemic outbreak. The relationship between them has been identified in previous and ongoing research. The mechanism through which severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can achieve this is similar to that for organs that express angiotensin-converting enzyme 2 receptors, which is the primary binding site of the virus. Endocrine cells widely express angiotensin-converting enzyme 2 receptors and transmembrane serine protease 2, the primary mediators initiating the acute phase of the disease. This review aimed to identify and discuss the endocrine complications of COVID-19. This primary focus is on presenting thyroid disorders or newly diagnosed diabetes mellitus (DM). Thyroid dysfunction with subacute thyroiditis, Graves' disease, and hypothyroidism caused by primary autoimmune thyroiditis has been reported. Pancreatic damage leads to type 1 DM because of the autoimmune nature of the disease and type 2 DM because of postinflammatory insulin resistance. Because follow-up data on COVID-19 on the endocrine glands are limited, long-term investigations are needed to assess specific effects.

The Impact of COVID-19 on the Behaviors and Attitudes of Children and Adolescents: A Cross-Sectional Study.

Background and objective Over the past few decades, new infectious diseases have emerged, and these have played a key role in changing behavior and lifestyle in all age groups. More recently, with the emergence of the coronavirus disease 2019 (COVID-19) pandemic, governments around the world have made unprecedented efforts to contain the epidemic by implementing quarantine measures, social distancing, and isolating infected individuals. Social behavioral adaptations (e.g., social distancing, isolation, etc.) impact children's and adolescents' lifestyle activities and lead to increased incidence of psychosocial problems, worsening of preexisting mental illness, and fears of infection, uncertainty, isolation, and stress. In light of this, this study aimed to assess the impact of COVID-19 on the behaviors and lifestyles of the children and adolescent population of Pakistan. Methodology A cross-sectional study was conducted involving 323 children and adolescents by targeting parents of children and adolescents in the age group of 4-18 years living in Pakistan. The study was conducted from April 2021 to September 2021. A well-designed structured questionnaire was used to collect data about the sociodemographic profile, attitudes, and behavioral factors impacted by COVID-19 in children and adolescents. SPSS Statistics version 23 (IBM, Armonk, NY) was used to enter and analyze data. Results Parents or caregivers of a total of 189 male and 134 female children aged between four and 18 years took part in this study. During COVID-19, the consumption of fast food and fried foods by children and adolescents increased significantly. In this study, out of 323 participants, almost all (289, 89.5%) had increased their screen time significantly. Nearly half of the total individuals experienced the feeling of depression and loneliness during the pandemic. Additionally, some children and adolescents felt fearful when leaving home. COVID-19 lockdowns have led to many changes in children's and adolescents' lifestyle habits. They reduced physical contact with others due to the fear of transmission of COVID-19. Based on our findings, the pandemic and its containment strategies have adversely affected the behaviors, lifestyles, and attitudes of children and adolescents. Conclusion Governments around the world have imposed social distancing during the COVID-19 pandemic, leading to adverse short-term and long-term negative mental health issues such as unhappiness, fear, worry, irritability, depressive symptoms, anxiety, and post-traumatic stress disorder (PTSD). Interventions are needed to focus on building resilience in children and adolescents, addressing their fears and concerns through better communication, encouraging routine and physical activity, and taking measures to alleviate loneliness.

Increased Levels of Autoantibodies against ROS-Modified Proteins in Depressed Individuals with Decrease in Antibodies against SARS-CoV-2 Antigen (S1-RBD).

Coronavirus 2019 (COVID-19) disease management is highly dependent on the immune status of the infected individual. An increase in the incidence of depression has been observed during the ongoing COVID-19 pandemic. Autoantibodies against in vitro reactive oxygen species (ROS) modified BSA and Lys as well as antibodies against receptor binding domain subunit S1 (S1-RBD) (S1-RBD-Abs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were estimated using direct binding and competition ELISA. Serum samples were also tested for fasting blood glucose (FBG), malondialdehyde (MDA), carbonyl content (CC), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Significant structural changes were observed in ROS modified BSA and Lys. Female depressed subjects who were also smokers (F-D-S) showed the highest levels of oxidative stress (MDA and CC levels). Similarly, increased levels of autoantibodies against ROS modified proteins were detected in F-D-S subjects, in males who were depressed and in smokers (M-D-S) compared to the other subjects from the rest of the groups. However, contrary to this observation, levels of S1-RBD-Abs were found to be lowest in the F-D-S and M-D-S groups. During the pandemic, large numbers of individuals have experienced depression, which may induce excessive oxidative stress, causing modifications in circulatory proteins. Thus, the formation of neo-antigens is induced, which lead to the generation of autoantibodies. The concomitant effect of increased autoantibodies with elevated levels of IFN-γ and TNF-α possibly tilt the immune balance toward autoantibody generation rather than the formation of S1-RBD-Abs. Thus, it is important to identify individuals who are at risk of depression to determine immune status and facilitate the better management of COVID-19.

SARS-CoV-2 origins: zoonotic Rhinolophus vs contemporary models.

The question of the origin of coronavirus spread like wildfire ever since it wreaked havoc among humankind, and ever since the scientific community has worked tirelessly to trace the history of the virus. In this review, we have tried to compile relevant literature pertaining to the different theories of origin of SARS-CoV-2, hopefully without any bias, and we strongly support the zoonotic origin of the infamous SARS-CoV-2 in bats and its transfer to human beings through the most probable evolutionary hosts, pangolins and minks. We also support the contemporary 'Circulation Model' that simply mirrors the concept of evolution to explain the origin of the virus which, the authors believe, is the most rational school of thought. The most recent variant of SARS-CoV-2, Omicron, has been taken as an example to clarify the concept. We recommend the community to refer to this model for further understanding and delving deep into this mystery of the origin of SARS-CoV-2.

Pharmacological Profile of Nigella sativa Seeds in Combating COVID-19 through In-Vitro and Molecular Docking Studies

COVID-19 infection is associated with elevated oxidative stress, systemic hyper-inflammatory responses, endothelial dysfunction, and red blood cell membrane deformability. Nigella sativa extract is widely used in alternative and complementary medicine systems in a large population, due to its highly therapeutic, economic, natural, and safe nature. The aim of this study was to evaluate the effect of N. sativa extract on oxidative stress, hemolysis, proteolysis, and glycation through in vitro studies, as well as to find out its anti-viral potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using in silico studies. N. sativa seed extract (at 600 µg/mL) displayed 67.33% scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, and 70.28% hydrogen peroxide reducing activity. N. sativa exhibited anti-proteolytic activity by decreasing heat-induced denaturation of bovine serum albumin (BSA) and egg albumin by 63.14% and 57.95%, respectively, and exhibited anti-proteinase potential of 66.28% at 600 μg/mL. In addition, heat-induced hemolysis and hypersalinity-induced hemolysis were inhibited by 57.86% and 61.7%, respectively, by the N. sativa seeds. N. sativa also inhibited browning intensity by 56.38%, and percent aggregation index by 51.38%, amyloid structure by 48.28%, and AGE-specific fluorescence by 52.18%, thereby protecting the native structure of BSA from glycation. The binding interactions between bioactive molecules of N. sativa seed with SARS-CoV-2 spike glycoprotein were proven by using in silico molecular docking tools. The functional amino acids involved in the interactions are Asp467, Thr108, Thr114, Ile468, Asn234, Gln155, Glu465, Arg466, Gly232, and Ile233, indicating the inhibiting property of N. sativa on SARS-CoV-2. Finally, we may infer that phytoconstituents of N. sativa seeds have the potential to protect against the spike protein of SARS-CoV-2. Studies on N. sativa seeds might act as a path to develop a potent alternative therapy against viral infections, especially COVID-19 infection, in the future. However, the limitations linked with the use of natural products are also needed to be considered in this regard.

VacSIM: Learning effective strategies for COVID-19 vaccine distribution using reinforcement learning.

A COVID-19 vaccine is our best bet for mitigating the ongoing onslaught of the pandemic. However, vaccine is also expected to be a limited resource. An optimal allocation strategy, especially in countries with access inequities and temporal separation of hot-spots, might be an effective way of halting the disease spread. We approach this problem by proposing a novel pipeline VacSIM that dovetails Deep Reinforcement Learning models into a Contextual Bandits approach for optimizing the distribution of COVID-19 vaccine. Whereas the Reinforcement Learning models suggest better actions and rewards, Contextual Bandits allow online modifications that may need to be implemented on a day-to-day basis in the real world scenario. We evaluate this framework against a naive allocation approach of distributing vaccine proportional to the incidence of COVID-19 cases in five different States across India (Assam, Delhi, Jharkhand, Maharashtra and Nagaland) and demonstrate up to 9039 potential infections prevented and a significant increase in the efficacy of limiting the spread over a period of 45 days through the VacSIM approach. Our models and the platform are extensible to all states of India and potentially across the globe. We also propose novel evaluation strategies including standard compartmental model-based projections and a causality-preserving evaluation of our model. Since all models carry assumptions that may need to be tested in various contexts, we open source our model VacSIM and contribute a new reinforcement learning environment compatible with OpenAI gym to make it extensible for real-world applications across the globe.

An extended motif in the SARS-CoV-2 spike modulates binding and release of host coatomer in retrograde trafficking.

ß-Coronaviruses such as SARS-CoV-2 hijack coatomer protein-I (COPI) for spike protein retrograde trafficking to the progeny assembly site in endoplasmic reticulum-Golgi intermediate compartment (ERGIC). However, limited residue-level details are available into how the spike interacts with COPI. Here we identify an extended COPI binding motif in the spike that encompasses the canonical K-x-H dibasic sequence. This motif demonstrates selectivity for αCOPI subunit. Guided by an in silico analysis of dibasic motifs in the human proteome, we employ mutagenesis and binding assays to show that the spike motif terminal residues are critical modulators of complex dissociation, which is essential for spike release in ERGIC. αCOPI residues critical for spike motif binding are elucidated by mutagenesis and crystallography and found to be conserved in the zoonotic reservoirs, bats, pangolins, camels, and in humans. Collectively, our investigation on the spike motif identifies key COPI binding determinants with implications for retrograde trafficking.

Electrospun Nanofiber-Based Viroblock/ZnO/PAN Hybrid Antiviral Nanocomposite for Personal Protective Applications.

Designing novel antiviral personal protective equipment (PPE) is crucial for preventing viral infections such as COVID-19 in humans. Here, we fabricate an electrospun nanofiber-based Viroblock (VB)-loaded polyacrylonitrile (PAN)/zinc oxide (ZnO) hybrid nanocomposite for PPE applications. Five different concentrations of Viroblock (0.5%, 1.5%, 2.5%, 3.5%, and 5%) were added to PAN/ZnO solution and loaded for electrospinning. The developed samples reflected antibacterial activity of 92.59% and 88.64% against Staphylococcus aureus and Pseudomonas aeruginosa bacteria, respectively, with 5% VB loading. Moreover, a significant reduction in virus titer (37%) was observed with the 5% VB/PAN/ZnO nanofiber sheet. Hence, VB-loaded PAN/ZnO nanofibers have great potential to kill enveloped viruses such as influenzas and coronaviruses and could be the ideal candidate for the development of nanofiber-based PPE, such as facemasks and surgical gowns, which can play a key role in the protection of frontline health workers and the general public in the COVID-19 pandemic.