Viral immunology最新文献

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

Aging is physiologically associated with a decline in the function of the immune system and subsequent susceptibility to infections. Interferon-gamma (IFN-γ), a key element in the activation of cellular immunity, plays an important role in defense against virus infections. Decreased levels of IFN-γ in the elderly may explain their increased risk for viral infectious diseases such as COVID-19. There is accumulating evidence that ascorbic acid (vitamin C [VitC]) and α-tocopherol together help improve the function of the immune system in the elderly, control infections, and decrease the treatment duration. A SARS-CoV-2 strain was isolated from a patient and then cultured in the Vero cell line. The isolated and propagated virus was then inactivated using formalin and purified by the column chromatography. The inactivated SARS-CoV-2 was formulated in the Alum adjuvant combined with VitC or α-tocopherol and/or both of them. The vaccines were injected twice to young and aged C57BL/6 mice. Two weeks later, IFN-γ, IL-4, and IL-2 cytokines were assessed using ELISA Kits. Specific IgG and IgG1/IgG2a were assessed by an in-house ELISA. In addition, the expression of PD1 and TERT genes in the spleen tissue of the mice was measured using real-time PCR. IL-4 and IFN-γ cytokines showed a significant increase in both aged and young mice compared with the Alum-based vaccine. In addition, our results exhibited a significant decrease and increase in specific total IgG and the IgG2a/IgG1 ratio, respectively. Furthermore, the vaccine formulated in α-tocopherol + VitC led to decreased PD1 and increased TERT gene expression levels. In conclusion, our results demonstrated that α-tocopherol + VitC formulated in the inactivated SARS-CoV-2 vaccine led to a shift toward Th1, which may be due to their effect on the physiology of cells, especially aged ones and changing their phenotype toward young cells.

The widespread use of efficient vaccines against infectious diseases is regarded as one of the most significant advancements in public health and techniques for preventing and protecting against infectious diseases and cancer. Because the purpose of vaccination is to elicit an appropriate, powerful, and long-lasting immune response against the pathogen, compounds such as adjuvants must be used to enhance these responses. Adjuvants have been widely used since their discovery to boost immune responses, prevent diseases, and activate protective immunity. Today, several types of adjuvants with varying properties are available for specific applications. Adjuvants are supramolecular substances or complexes that strengthen and prolong the immune response to antigens. These compounds have long-term immunological effects and are low in toxicity. They also lower the amount of antigen or the number of immunogenic reactions needed to improve vaccine efficacy and are used in specific populations. This article provides an overview of the adjuvants commonly used in the vaccination industry, their respective mechanisms of action, and discusses how they function to stimulate the immune system. Understanding the mechanisms of action of adjuvants is crucial for the development of effective and safe vaccines.

Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

The enduring impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease manifestation, COVID-19, on public health remains significant. Postacute sequelae of SARS-CoV-2 infection (PASC) affect a considerable number of patients, impairing their quality of life. While the role of the cytokine storm in acute COVID-19 is well established, its contribution to the pathophysiology of PASC is not fully understood. This study aimed to analyze the cytokine profile of patients with PASC following in vitro stimulation of Toll-like receptor (TLR) pathways, comparing them with a healthy control group. From October 2020 till March 2021, Brugmann University Hospital's clinical research unit included patients with PASC in the study. Whole blood samples were collected from 50 patients and 25 healthy volunteers. After in vitro stimulation under five different conditions, cytokine levels were measured using a multiplex method. Significantly decreased cytokine levels were observed in patients with PASC compared with healthy volunteers, particularly after TLR4 (interleukin [IL]-1α, IL-1β, IL-2, IL-10, interferon (IFN)α, IFNγ, IFNω, and tumor necrosis factor (TNF)α) and TLR7/8 (IL-1α, IL-1β, IFNα, IFNω, IFNγ, and TNFα) pathway stimulation. Principal component analysis identified two distinct clusters, suggesting a likely dysregulation of immunity involving TLR4 and TLR7/8 pathways in patients with PASC. Our study suggests that TLR4 and TLR7/8 pathways play a role in the pathophysiology of PASC. Continuous basal activation of immunity could explain the high basal concentrations of cytokines described in these patients and the decreased amplitude of response of these signaling pathways following specific stimulation.

The current study investigates COVID-19 infection likelihood using data from 5,819 respondents in Vietnam and Indonesia (December 10, 2022, to March 27, 2023) through binary logistic regressions. Descriptive statistics highlight the significance of vaccination status, with almost half of unvaccinated respondents contracting the infection. The second vaccine dose showed the lowest infection percentages, suggesting a potential dose-dependent effect. Those receiving mRNA vaccines consistently had reduced infection likelihood across the first four doses, with an unexpected reversal for the fifth dose. Vaccinated individuals, especially with mRNA vaccines, had faster recovery times, and variability in recovery times and milder symptoms were observed in mRNA vaccine recipients. Regression results from Model 1 reveal a substantial impact of vaccination, with vaccinated respondents having ∼48.1% lower odds than the unvaccinated. Model 2 underscores a dose-dependent protective effect, with each additional dose associated with a notable 6.6% reduction in infection likelihood. Beyond vaccination, gender, family size, marital status, employment, urban residence, and nationality influenced infection likelihood. Males, larger families, single marital status, unemployment, rural residence, and Indonesian nationality increased the likelihood of infection. Surprisingly, respondents with infected family members exhibited a lower infection likelihood, suggesting potential protective measures within households. These findings highlight COVID-19 dynamics, and ongoing research refines comprehension.

The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).

It is difficult to differentiate between coronavirus disease 2019 (COVID-19) and influenza based on the symptoms. In the present study, a newly developed antigen rapid diagnostic test (Ag-RDT) called Panbio™ COVID-19/Flu A&B that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B virus was evaluated. Its accuracy was evaluated using 235 pairs of nasopharyngeal samples collected from patients with respiratory symptoms and fever (>37.5°C). Reverse transcription polymerase chain reaction was used as a reference method to evaluate the accuracy of the SARS-CoV-2 detection. We confirmed the accuracy of the developed Ag-RDT against the Omicron variant where the sensitivity and specificity were 94.8% and 100%, respectively. In addition, to identify the influenza A virus, a noninferiority test was conducted using a commercial Ag-RDT, which has a sensitivity and specificity in comparison with viral culture of 94.8% and 98.4%, respectively. The positive and negative predictive values for influenza A virus were 98.5% and 98.1%, respectively, for the Panbio COVID-19/Flu A&B test. The evaluation of this newly developed Ag-RDT using clinical samples suggests that it has a high efficacy in clinical settings.