Narrative review on century of respiratory pandemics from Spanish flu to COVID-19 and impact of nanotechnology on COVID-19 diagnosis and immune system boosting.

The rise of the highly lethal severe acute respiratory syndrome-2 (SARS-2) as corona virus 2019 (COVID-19) reminded us of the history of other pandemics that happened in the last century (Spanish flu) and stayed in the current century, which include Severe-Acute-Respiratory-Syndrome (SARS), Middle-East-Respiratory-Syndrome (MERS), Corona Virus 2019 (COVID-19). We review in this report the newest findings and data on the origin of pandemic respiratory viral diseases, reservoirs, and transmission modes. We analyzed viral adaption needed for host switch and determinants of pathogenicity, causative factors of pandemic viruses, and symptoms and clinical manifestations. After that, we concluded the host factors associated with pandemics morbidity and mortality (immune responses and immunopathology, ages, and effect of pandemics on pregnancy). Additionally, we focused on the burdens of COVID-19, non-pharmaceutical interventions (quarantine, mass gatherings, facemasks, and hygiene), and medical interventions (antiviral therapies and vaccines). Finally, we investigated the nanotechnology between COVID-19 analysis and immune system boosting (Nanoparticles (NPs), antimicrobial NPs as antivirals and immune cytokines). This review presents insights about using nanomaterials to treat COVID-19, improve the bioavailability of the abused drugs, diminish their toxicity, and improve their performance.

Clinical and chest computed tomography features of patients suffering from mild and severe COVID-19 at Fayoum University Hospital in Egypt.

BACKGROUND: In pandemic COVID-19 (coronavirus disease 2019), the prognosis of patients has been determined using clinical data and CT (computed tomography) scans, but it is still unclear whether chest CT characteristics are correlated to COVID-19 severity. AIM: To explore the potential association between clinical data and 25-point CT score and investigate their predictive significance in COVID-19-positive patients at Fayoum University Hospital in Egypt. METHODS: This study was conducted on 252 Egyptian COVID-19 patients at Fayoum University Hospital in Egypt. The patients were classified into two groups: a mild group (174 patients) and a severe group (78 patients). The results of clinical laboratory data, and CT scans of severe and mild patients, were collected, analyzed, and compared. RESULTS: The severe group show high significance levels of CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, ferritin, lactate dehydrogenase (LDH), neutrophil percent, and heart rate (HR) than the mild group. Lymphopenia, hypoalbuminemia, hypocalcemia, and decreased oxygen saturation (SpO2) were the most observed abnormalities in severe COVID-19 patients. Lymphopenia, low SpO2 and albumin levels, elevated serum LDH, ferritin, urea, and CRP levels were found to be significantly correlated with severity CT score (P<0.0001). CONCLUSION: The clinical severity of COVID-19 and the CT score are highly correlated. Our findings indicate that the CT scoring system can help to predict COVID-19 disease outcomes and has a strong correlation with clinical laboratory testing.

The Mutational Landscape of SARS-CoV-2 Variants of Concern Recovered From Egyptian Patients in 2021.

In December 2019, a mysterious viral pneumonia first developed in Wuhan, China, resulting in a huge number of fatal cases. This pneumonia, which was named COVID-19, was attributed to a novel coronavirus, SARS-CoV-2. The emerging SARS-CoV-2 mutations pose the greatest risk to human health because they could result in an increase in the COVID-19 severity or the failure of current vaccines. One of these notable mutations is the SARS-CoV-2 Delta variant (B.1.617) that was first detected in India and has rapidly expanded to 115 countries worldwide. Consequently, in this study, we performed next-generation sequencing and phylogenetic analysis of SARS-CoV-2 during the third wave of the pandemic to determine the SARS-CoV-2 variants of concern (VOC) prevalence in Egypt. We observed several mutational patterns, revealing that SARS-CoV-2 evolution has expanded in Egypt with a considerable increase in the number of VOC. Therefore, the Egyptian authorities should take an appropriate approach to investigate the compatibility of already employed vaccines with this VOC and to examine the efficacy of the existing therapeutic regimen against new SARS-CoV-2 variants.

Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra05268c

Six compounds namely, tanshinone IIA (1), carnosic acid (2), rosmarinic acid (3), salvianolic acid B (4), baicalein (5), and glycyrrhetinic acid (6) were screened for their anti-SARS-CoV-2 activities against both the spike (S) and main protease (Mpro) receptors using molecular docking studies. Molecular docking recommended the superior affinities of both salvianolic acid B (4) and glycyrrhetinic acid (6) as the common results from the previously published computational articles. On the other hand, their actual anti-SARS-CoV-2 activities were tested in vitro using plaque reduction assay to calculate their IC50 values after measuring their CC50 values using MTT assay on Vero E6 cells. Surprisingly, tanshinone IIA (1) was the most promising member with IC50 equals 4.08 ng μl−1. Also, both carnosic acid (2) and rosmarinic acid (3) showed promising IC50 values of 15.37 and 25.47 ng μl−1, respectively. However, salvianolic acid (4) showed a weak anti-SARS-CoV-2 activity with an IC50 value equals 58.29 ng μl−1. Furthermore, molecular dynamics simulations for 100 ns were performed for the most active compound from the computational point of view (salvianolic acid 4), besides, the most active one biologically (tanshinone IIA 1) on both the S and Mpro complexes of them (four different molecular dynamics processes) to confirm the docking results and give more insights regarding the stability of both compounds inside the SARS-CoV-2 mentioned receptors, respectively. Also, to understand the mechanism of action for the tested compounds towards SARS-CoV-2 inhibition it was necessary to examine the mode of action for the most two promising compounds, tanshinone IIA (1) and carnosic acid (2). Both compounds (1 and 2) showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication. This recommended the predicted activity of the two compounds against the S protein of SARS-CoV-2 rather than its Mpro protein. Our results could be very promising to rearrange the previously mentioned compounds based on their actual inhibitory activities towards SARS-CoV-2 and to search for the reasons behind the great differences between their in silico and in vitro results against SARS-CoV-2. Finally, we recommend further advanced preclinical and clinical studies especially for tanshinone IIA (1) to be rapidly applied in COVID-19 management either alone or in combination with carnosic acid (2), rosmarinic acid (3), and/or salvianolic acid (4). Tanshinone IIA shows the most promising anti-SARS-CoV-2 biological activity: molecular docking, molecular dynamics, in vitro, and SAR studies.

Correction: Clinical characteristics of Egyptian male patients with COVID-19 acute respiratory distress syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0249346.].

Biogenic and biocompatible silver nanoparticles for an apoptotic anti-ovarian activity and as polydopamine-functionalized antibiotic carrier for an augmented antibiofilm activity.

Silver nanoparticles (AgNPs) could be employed in the combat against COVID-19, yet are associated with toxicities. In this study, biogenic and biocompatible AgNPs using the agro-waste, non-edible Hibiscus sabdariffa stem were synthesized. Under optimized reaction conditions, synthesized green AgNPs were crystalline, face cubic centered, spherical with a diameter of around 17 nm and a surface charge of -20 mV. Their murine lethal dose 50 (LD50) was 4 folds higher than the chemical AgNPs. Furthermore, they were more murine hepato- and nephro-tolerated than chemical counterparts due to activation of Nrf-2 and HO-1 pathway. They exerted an apoptotic anti-ovarian cancer activity with IC50 value 6 times more than the normal cell line. Being functionalized with polydopamine and conjugated to either moxifloxacin or gatifloxacin, the conjugates exerted an augmented antibiofilm activity against Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii biofilms that was significantly higher than antibiotic alone or functionalized AgNPs suggesting a synergistic activity. In conclusion, this study introduced a facile one-pot synthesis of biogenic and biocompatible AgNPs with preferential anti-cancer activity and could be utilized as antibiotic delivery system for a successful eradication of Gram-negative biofilms.

Global dynamics of SARS-CoV-2 clades and their relation to COVID-19 epidemiology.

Expansion of COVID-19 worldwide increases interest in unraveling genomic variations of novel SARS-CoV-2 virus. Metadata of 408,493 SARS-CoV-2 genomes submitted to GISAID database were analyzed with respect to genomic clades and their geographic, age, and gender distributions. Of the currently known SARS-CoV-2 clades, clade GR was the most prevalent worldwide followed by GV then GH. Chronological analysis revealed expansion in SARS-CoV-2 clades carrying D614G mutations with the predominance of the newest clade, GV, in the last three months. D614G clades prevail in countries with more COVID-19 cases. Of them, the clades GH and GR were more frequently recovered from severe or deceased COVID-19 cases. In contrast, G and GV clades showed a significantly higher prevalence among asymptomatic patients or those with mild disease. Metadata analysis showed higher (p < 0.05) prevalence of severe/deceased cases among males than females and predominance of GR clade in female patients. Furthermore, severe disease/death was more prevalent (p < 0.05) in elderly than in adults/children. Higher prevalence of the GV clade in children compared to other age groups was also evident. These findings uniquely provide a statistical evidence on the adaptation-driven evolution of SARS-CoV-2 leading to altered infectivity, virulence, and mortality.

Clinical characteristics of Egyptian male patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.

Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks.

Coronaviruses (CoVs) are RNA viruses that have become a major public health concern since the Severe Acute Respiratory Syndrome-CoV (SARS-CoV) outbreak in 2002. The continuous evolution of coronaviruses was further highlighted with the emergence of the Middle East Respiratory Syndrome-CoV (MERS-CoV) outbreak in 2012. Currently, the world is concerned about the 2019 novel CoV (SARS-CoV-2) that was initially identified in the city of Wuhan, China in December 2019. Patients presented with severe viral pneumonia and respiratory illness. The number of cases has been mounting since then. As of late February 2020, tens of thousands of cases and several thousand deaths have been reported in China alone, in addition to thousands of cases in other countries. Although the fatality rate of SARS-CoV-2 is currently lower than SARS-CoV, the virus seems to be highly contagious based on the number of infected cases to date. In this review, we discuss structure, genome organization, entry of CoVs into target cells, and provide insights into past and present outbreaks. The future of human CoV outbreaks will not only depend on how the viruses will evolve, but will also depend on how we develop efficient prevention and treatment strategies to deal with this continuous threat.