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.

Seroprevalence of Anti-S1-RBD Antibodies in Pre-pandemic and Pandemic Subjects From Hail Region, KSA.

Background: Two years into the pandemic, yet the threat of new SARS-CoV-2 variants continues to loom large. Sustained efforts are required to fully understand the infection in asymptomatic individuals and those with complications. Identification, containment, care, and preventative strategies rely on understanding the varied humoral immune responses. Methods: An in-house ELISA was developed and standardized to screen for serum IgG antibodies against the SARS-CoV-2 S1-RBD protein as an antigen. This study aims to investigate the seroprevalence of serum antibodies against S1-RBD antigen in pre-pandemic (n = 120) and during the early pandemic period (n = 120) in subjects from the Hail region, KSA and to correlate it with clinical and demographic factors. Results: Samples collected from both male (n = 60) and female (n = 60) subjects during the pandemic in the age groups of 20-40 (0.31 ± 0.029 and 0.29 ± 0.024, respectively) and 41-60 years (0.35 ± 0.026 and 0.30 ± 0.025, respectively) showed significantly higher levels of serum antibodies against S-RBD antigen than the age-matched pre-pandemic samples [male (n = 60) and female (n = 60)]. Pandemic subjects exhibited significantly (p < 0.01) higher inhibition (80-88%) than age-matched pre-pandemic subjects (32-39%). Antibodies against S1-RBD antigen were detected in approximately 10% of the total pre-pandemic population (males and females). However, subjects > 60 years did not show antibodies. Conclusion: Antibody levels increased in samples collected during the pandemic, even though these subjects were not clinically COVID-19 positive. A small number of pre-pandemic subjects showed serum antibodies, suggesting prior exposure to other coronaviruses in the region. With dwindling neutralizing antibody levels and reduced vaccine efficacy against newer variants, it remains crucial to develop better assays for surveillance, management, and future research.

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.

Cytokine Response in SARS-CoV-2 Infection in the Elderly.

The last few months of 2019 witnessed the emergence, rise and rapid spread of a novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing an acute respiratory disease called coronavirus disease 2019 or Covid-19. Severe pathological manifestations of the disease in the infected population with comorbidities are linked to acute respiratory distress syndrome (ARDS), associated with an exaggerated synthesis and expression of cytokines, leading to a systemic inflammatory response also known as a cytokine storm (CS). Elderly patients (>60 years of age) showed more deaths in Covid-19 infection. Age-related immune imbalance increases patient susceptibility to CS. In acute Covid-19 infection, it is difficult to minimize or control the overproduction of cytokines; hence, limited medical treatments are effective. This review aims to provide an overview of the current knowledge of involvement of cytokines in SARS-CoV-2 infection, susceptibility factors for the accompanying cytokine storm in severe Covid-19 cases and possible treatment strategies.