Association between the expression of toll-like receptors, cytokines, and homeostatic chemokines in SARS-CoV-2 infection and COVID-19 severity.

The recent identification of the involvement of the immune system response in the severity and mortality of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the importance of cytokines and chemokines as important factors in the clinical outcomes of COVID-19. However, the impact and roles of the BAFF/APRIL cytokine system, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), as well as Toll-like receptor (TLR)-3/4 in COVID-19, have not been investigated. We sought to assess the expression levels and roles of TLR3/4, BAFF, APRIL, IFN-ß, homeostatic chemokines (CXCL12, CXCL13, CCL19, and CCL21), SARS-CoV-2 IgG and IgM antibodies in patients with critical (ICU) and non-ICU (mild) COVID-19 and their association with mortality and disease severity. Significant high levels of TLR-4 mRNA, IFN-ß, APRIL, CXCL13, and IgM and IgG antibodies were observed in ICU patients with severe COVID-19 compared to non-ICU COVID-19 patients and healthy controls. On the other hand, BAFF and CCL21 expression were significantly upregulated in non-ICU patients with COVID-19 compared with that in critical COVID-19 patients. The two groups did not differ in TLR-3, CXCL12, and CCL19 levels. Our findings show high expression levels of some inflammatory chemokines in ICU patients with COVID-19. These findings highlight the potential utility of chemokine antagonists as an immune-based treatment for the severe form of COVID-19. We also believe that selective targeting of TLR/spike protein interactions might lead to the development of a new COVID-19 therapy.

Durability of SARS-CoV-2 Specific IgG Antibody Responses Following Two Doses of Match and Mixed COVID-19 Vaccines Regimens in Saudi Population.

Background: SARS-CoV-2 pandemic continues to threaten the human population with millions of infections and deaths worldwide. Vaccination campaigns undertaken by several countries have resulted in a notable decrease in hospitalization and deaths. However, with the emergence of new virus variants, it is critical to determine the longevity and the protection efficiency provided by the current authorized vaccines. Aim: The aims of this study are to provide data about the magnitude of immune responses in individuals fully vaccinated against COVID-19 in Riyadh province of Saudi Arabia. Also, to evaluate the continuity of specific IgG levels and compare the titers in individuals who have been received two doses of the matched and mixed vaccines, including Pfizer and AstraZeneca against SARS-CoV-2 during the period of three to six months. Moreover, we analyze the current state of immune response in terms of antibody responses in thepopulation postvaccination using homogenous or hetrogenous vaccine regimen. Methods: A total of 141 healthy volunteers were recruited to our study; blood (n=63) and the saliva samples (n=78) and were collected from fully vaccinated individuals in Riyadh city. We employed a specific ELISA assay in plasma and saliva of fully vaccinated individuals. Results: IgG levels varied with age groups with the highest concentration in the age group 19-29 years, but the age group (≥50) had the lowest IgG concentration. The IgG levels in both serum and saliva were higher after three months and start to wane after six months. Individuals who received mixed types of vaccines had significantly better response than Pfizer vaccine alone. Conclusion: The current study investigates the status of humoral responses in different age groups, in terms of antibody measurements. These data will help to evaluate the need for further COVID-19 vaccine doses and to what extent a two-dose regimen will protect vaccinated individuals.

Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality.

COVID-19 severity due to innate immunity dysregulation accounts for prolonged hospitalization, critical complications, and mortality. Severe SARS-CoV-2 infections involve the complement pathway activation for cytokine storm development. Nevertheless, the role of complement in COVID-19 immunopathology, complement-modulating treatment strategies against COVID-19, and the complement and SARS-CoV-2 interaction with clinical disease outcomes remain elusive. This study investigated the potential changes in complement signaling, and the associated inflammatory mediators, in mild-to-critical COVID-19 patients and their clinical outcomes. A total of 53 patients infected with SARS-CoV-2 were enrolled in the study (26 critical and 27 mild cases), and additional 18 healthy control patients were also included. Complement proteins and inflammatory cytokines and chemokines were measured in the sera of patients with COVID-19 as well as healthy controls by specific enzyme-linked immunosorbent assay. C3a, C5a, and factor P (properdin), as well as interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IgM antibody levels, were higher in critical COVID-19 patients compared to mild COVID-19 patients. Additionally, compared to the mild COVID-19 patients, factor I and C4-BP levels were significantly decreased in the critical COVID-19 patients. Meanwhile, RANTES levels were significantly higher in the mild patients compared to critical patients. Furthermore, the critical COVID-19 intra-group analysis showed significantly higher C5a, C3a, and factor P levels in the critical COVID-19 non-survival group than in the survival group. Additionally, IL-1ß, IL-6, and IL-8 were significantly upregulated in the critical COVID-19 non-survival group compared to the survival group. Finally, C5a, C3a, factor P, and serum IL-1ß, IL-6, and IL-8 levels positively correlated with critical COVID-19 in-hospital deaths. These findings highlight the potential prognostic utility of the complement system for predicting COVID-19 severity and mortality while suggesting that complement anaphylatoxins and inflammatory cytokines are potential treatment targets against COVID-19.

Clinical characteristics and predictors of mortality among COVID-19 patients in Saudi Arabia.

BACKGROUND: The new coronavirus disease (COVID-19) has caused more than 1.8 million deaths, with a fatality rate of 2.5% in more than 200 countries as of January 4, 2021. Analysis of COVID-19 clinical features can help predict disease severity and risk of mortality, early identification of high-risk patients, and provide knowledge to inform clinical interventions. OBJECTIVE: The purpose of this study is to investigate the clinical characteristics and possible predictors associated with mortality in patients with COVID-19 admitted to King Fahad (KFH), Ohood, and Miqat hospitals in Madina, Saudi Arabia. METHODS: This retrospective observational study to investigate the clinical characteristic and possible predictors associated with mortality for those 119 mild, moderate, or critically ill patients confirmed by laboratory results to have COVID-19 who were admitted to three hospitals in Madina, Saudi Arabia, from March 25, 2020, to July 30, 2020. Data were collected from December 1, 2020, to December 14, 2020. RESULTS: Of the 119 patients included in the study, the mean age was 54.2 (±15.7) years, with 78.2% survivors and 21.8% non-survivors. The demographic analysis indicated that the likelihood of mortality for patients in the older age group (i.e., ≥65 years) was five times higher than those in the younger age group (OR = 5.34, 95% CI 1.71-16.68, p = 0.004). The results also indicated those patients who admitted to the intensive care unit (ICU) was approximately seven times higher odds of mortality compare with those who were not admitted (OR = 6.48, 95% CI 2.52-16.63, p < 0.001). In addition, six laboratory parameters were positively associated with the odds of mortality: white blood cell count (OR = 1.11, 95% CI 1.02-1.21, p = 0.018), neutrophil (OR = 1.11, 95% CI 1.02-1.22, p = 0.020), creatine kinase myocardial band (OR = 1.02, 95% CI 1.00-1.03, p = 0.030), C-reactive protein (OR = 1.01, 95% CI 1.00-1.01, p = 0.002), urea (OR = 1.06, 95% CI 1.01-1.11, p = 0.026), and lactate dehydrogenase (OR = 1.00, 95% CI 1.00-1.01, p = 0.020). CONCLUSIONS: In this cohort, COVID-19 patients within the older age group (≥65 years) admitted to the ICU with increased C-reactive protein levels in particular, were associated with increased odds of mortality. Further clinical observations are warranted to support these findings and enhance the mapping and control of this pandemic.

The pivotal roles of the host immune response in the fine-tuning the infection and the development of the vaccines for SARS-CoV-2.

SARS-CoV2 infection induces various degrees of infections ranging from asymptomatic to severe cases and death. Virus/host interplay contributes substantially to these outcomes. This highlights the potential roles of the host immune system in fighting virus infections. SARS-CoV-2. We highlighted the potential roles of host immune response in the modulation of the outcomes of SARS-CoV infections. The newly emerged SARS-CoV-2 mutants complicated the control and mitigation strategies measures. We are highlighting the current progress of some already deployed vaccines worldwide as well as those still in the pipelines. Recent studies from the large ongoing global vaccination campaign are showing promising results in reducing the hospitality rates as well as the number of severe SARS-CoV-2 infected patients. Careful monitoring of the genetic changes of the virus should be practiced. This is to prepare some highly sensitive diagnostic assays as well as to prepare some homologous vaccines matching the circulating strains in the future.

SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis.

The human population is currently facing the third and possibly the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China, on 31 December 2019 and spread within a short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt to many point mutation and recombination events; particularly in the spike gene, which enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. Both animal reservoir and intermediate host for SARS-CoV-2 are still unresolved and necessitate further investigation. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed, including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that the SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from natural reservoirs is a priority.