Antiphospholipid antibodies in patients with stroke during COVID-19: A role in the signaling pathway leading to platelet activation.

Background: Several viral and bacterial infections, including COVID-19, may lead to both thrombotic and hemorrhagic complications. Previously, it has been demonstrated an "in vitro" pathogenic effect of "antiphospholipid" antibodies (aPLs), which are able to activate a proinflammatory and procoagulant phenotype in monocytes, endothelial cells and platelets. This study analyzed the occurrence of aPL IgG in patients with acute ischemic stroke (AIS) during COVID-19, evaluating the effect of Ig fractions from these patients on signaling and functional activation of platelets. Materials and methods: Sera from 10 patients with AIS during COVID-19, 10 non-COVID-19 stroke patients, 20 COVID-19 and 30 healthy donors (HD) were analyzed for anti-cardiolipin, anti-ß2-GPI, anti-phosphatidylserine/prothrombin and anti-vimentin/CL antibodies by ELISA. Platelets from healthy donors were incubated with Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG and analyzed for phospho-ERK and phospho-p38 by western blot. Platelet secretion by ATP release dosage was also evaluated. Results: We demonstrated the presence of aPLs IgG in sera of patients with AIS during COVID-19. Treatment with the Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG induced a significant increase of phospho-ERK and phospho-p38 expression. In the same vein, platelet activation was supported by the increase of adenyl nucleotides release induced by Ig fractions. Conclusions: This study demonstrates the presence of aPLs in a subgroup of COVID-19 patients who presented AIS, suggesting a role in the mechanisms contributing to hypercoagulable state in these patients. Detecting these antibodies as a serological marker to check and monitor COVID-19 may contribute to improve the risk stratification of thromboembolic manifestations in these patients.

Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents.

Mucormycosis is a fungal infection which got worsens with time if not diagnosed and treated. The current COVID-19 pandemic has association with fungal infection specifically with mucormycosis. Already immunocompromised patients are easy target for COVID-19 and mucormycosis as well. COVID-19 infection imparts in weak immune system so chances of infection is comparatively high in COVID-19 patients. Furthermore, diabetes, corticosteroid medicines, and a weakened immune system are the most prevalent risk factors for this infection as we discussed in case studies here. The steroid therapy for COVID-19 patients sometimes have negative impact on the patient health and this state encounters many infections including mucormycosis. There are treatments available but less promising and less effective. So, researchers are focusing on the promising agents against mucormycosis. It is reported that early treatment with liposomal amphotericin B (AmB), manogepix, echinocandins isavuconazole, posacanazole and other promising therapeutic agents have overcome the burden of mucormycosis. Lipid formulations of AmB have become the standard treatment for mucormycosis due to their greater safety and efficacy. In this review article, we have discussed case studies with the infection of mucormycosis in COVID-19 patients. Furthermore, we focused on anti-mucormycosis agents with mechanism of action of various therapeutics, including coverage of new antifungal agents being investigated as part of the urgent global response to control and combat this lethal infection, especially those with established risk factors.

Estimating the Genuine Progress Indicator before and during the COVID pandemic in Australia

In the efforts to ensure the health of the Australian population during the COVID pandemic, social, economic, and environmental aspects of people's life were impacted. In addressing the pandemic risks, a number of governments prioritized people's health and well-being over GDP growth. The Genuine Progress Indicator (GPI) is used to account for factors that influence well-being. We used the GPI to assess the pandemic's impact on well-being and we examined our results in relation to the GDP. We estimated the GPI for the first 6 months of 2019 and the same period in 2020, during which the first stages of the COVID pandemic and the first nationwide lockdown in Australia took place. We examined two scenarios, in the first we found that in Q1 the GDP growth (1.4%) was accompanied by a significant GPI growth (5.3%), showing a positive relation to the GDP;but in Q2 the significant drop (-6.3%) in the GDP was not followed by the GPI, instead the GPI growth remained almost steady with even a relatively small increase (0.33%), indicating a negative relation to the GDP growth. Whereas in the second scenario, the GPI growths (7.12%) in Q1 and (-2.60%) Q2 were positively related to the GDP growths (4.6%) in Q1 and (−0.25%) Q2.We discuss the reasons for the divergence between the two indicators and one of the limitations of the GPI as a measure of well-being. Lastly, we discuss the behavioural and policy lessons of the lockdown and their relevance to what is proposed by degrowth economists. © 2022 The Author(s)

Big Data Management Activities for Sustainable Business Performance During the COVID-19 Pandemic: Evidence from the Indian Pharmaceutical Sector

Grounded on resource-based view and dynamic capability perspectives, this research aims to explore linkages between the firm's big data management activities (BDMA), green manufacturing (GM) practices, and sustainable business performance (SBP). The research model was empirically evaluated using data collected from 248 pharmaceutical manufacturers in India during the COVID-19 pandemic. The analysis was performed using a covariance-based structural equation modeling using AMOS 20. The results indicate that GM activities impact SBP directly. Further results imply the mediating role of GM practices on the relationship between BDMA and SBP. The analysis reveals that senior management's resource commitment in pharmaceutical firms is a moderating mechanism in strengthening the association between BDMA and GM practices. This study is significant as it provides key theoretical and managerial implications for pharmaceutical sectors during emergent situations.

Containing the spread of COVID-19 virus facing to its high mutation rate: approach to intervention using a nonspecific way of blocking its entry into the cells.

Viruses have multiple mutation rates that are higher than any other member of the kingdom of life. This gives them the ability to evolve, even within the course of a single infection, and to evade multiple host defenses, thereby impacting pathogenesis. Additionally, there are also interplays between mutation and recombination and the high multiplicity of infection (MOI) that enhance viral adaptability and increase levels of recombination leading to complex and conflicting effects on genome selection, and the net results is difficult to predict. Recently, the outbreak of COVID-19 virus represents a pandemic threat that has been declared a public health emergency of international concern. Up to present, however, due to the high mutation rate of COVID-19 virus, there are no effective procedures to contain the spread of this virus across the globe. For such a purpose, there is then an urgent need to explore new approaches. As an opinion, the present approach emphasizes on (a) the use of a nonspecific way of blocking the entry of COVID-19 virus as well as its variants into the cells via a therapeutic biocompatible compound (ideally, "in a pill") targeting its spike (S) glycoprotein; and (b) the construction of expression vectors via the glycosyl-phosphatidylinositol, GPI, anchor for studying intermolecular interactions between the spike S of COVID-19 virus as well as its variants and the angiotensin-converting enzyme 2 (ACE2) of its host receptor for checking the efficacy of any therapeutic biocompatible compound of the nonspecific way of blocking. Such antiviral drug would be safer than the ACE1 and ACE2 inhibitors/angiotensin receptor blockers, and recombinant human ACE2 as well as nucleoside analogs or protease inhibitors used for fighting the spread of the virus inside the cells, and it would also be used as a universal one for any eventual future pandemic related to viruses, especially the RNA viruses with high mutation rates.

Targeting of neutrophil activation in the early phase of the disease for prevention of Coronavirus disease-19 severity.

The prevention of the disease severity seems critical for reducing the mortality of Coronavirus (CoV) disease-19. The neutrophils play a key role in the induction of severity. It is proposed here that inhibition of neutrophil activation and/or cascade reactions of complement, leading to this cell activation at the early phase of the disease, is a potential tool to inhibit aggravation of the disease. The need for appropriate timing in intervention is emphasized as follows. (1) Intervention at the very early stage of severe acute respiratory syndrome-CoV-2 infection may harm the defensive host response to the infection because of the critical function of neutrophils in this response, and (2) intervention at too late a stage will not stop the infiltration of fully activated neutrophils that produce large amounts of toxic substances.

Problems associated with antiviral drugs and vaccines development for COVID-19: approach to intervention using expression vectors via GPI anchor.

The outbreak of a novel coronavirus responsible for the severe acquired respiratory syndrome: SARS-CoV-2, also known as coronavirus disease 2019: COVID-19, represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for diagnostic, development of antibodies, entry inhibitors, and vaccines. COVID-19 also recognizes angiotensin-converting enzyme 2 (ACE2) as its host receptor binding to viral S protein. Several antiviral drugs and vaccines have been evaluated for the treatment and prevention of the infection by the virus. To facilitate medical countermeasure development, the problems associated with antiviral drugs and vaccines development for containing the spread of COVID-19 are discussed. There is an urgent need to study deeply on the structure, mutations, and function of COVID-19 as well as its pathophysiology from a large population. Construction of expression vectors for any protein targeting to the cell plasma membrane via the glycosyl-phosphatidylinositol, GPI, anchor for studying intermolecular interactions, as described in Ref. # 62 (Nguyen, K. V., Naviaux, R. K., Nyhan, W. L. Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP). Nucleosides Nucleotides Nucleic Acids 2020, 39, 905-922), between the S protein of COVID-19 as well as its variants and ACE2 could be useful in antiviral drugs and vaccines development.