Evaluating SARS-CoV-2 antibody reactivity to natural exposure and inactivated vaccination with peptide microarrays.

Objective: Vaccination is effective tool for preventing and controlling SARS-CoV-2 infections, and inactivated vaccines are the most widely used type of vaccine. In order to identify antibody-binding peptide epitopes that can distinguish between individuals who have been vaccinated and those who have been infected, this study aimed to compare the immune responses of vaccinated and infected individuals. Methods: SARS-CoV-2 peptide microarrays were used to assess the differences between 44 volunteers inoculated with the inactivated virus vaccine BBIBP-CorV and 61 patients who were infected with SARS-CoV-2. Clustered heatmaps were used to identify differences between the two groups in antibody responses to peptides such as M1, N24, S15, S64, S82, S104, and S115. Receiver operating characteristic curve analysis was used to determine whether a combined diagnosis with S15, S64, and S104 could effectively distinguish infected patients from vaccinated individuals. Results: Our findings showed that the specific antibody responses against S15, S64, and S104 peptides were stronger in vaccinators than in infected persons, while responses to M1, N24, S82, and S115 were weaker in asymptomatic patients than in symptomatic patients. Additionally, two peptides (N24 and S115) were found to correlate with the levels of neutralizing antibodies. Conclusion: Our results suggest that antibody profiles specific to SARS-CoV-2 can be used to distinguish between vaccinated individuals and those who are infected. The combined diagnosis with S15, S64, and S104 was found to be more effective in distinguishing infected patients from those who have been vaccinated than the diagnosis using individual peptides. Moreover, the specific antibody responses against the N24 and S115 peptides were found to be consistent with the changing trend of neutralizing antibodies.

Clinical Application of Antibody Immunity Against SARS-CoV-2: Comprehensive Review on Immunoassay and Immunotherapy.

The current COVID-19 global pandemic poses immense challenges to global health, largely due to the difficulty to detect infection in the early stages of the disease, as well as the current lack of effective antiviral therapy. Research and understanding of the human immune system can provide important theoretical and technical support for the clinical diagnosis and treatment of COVID-19, the clinical implementations of which include immunoassays and immunotherapy, which play a crucial role in the fight against the pandemic. This review consolidates the current scientific evidence for immunoassay, which includes multiple methods of detecting antigen and antibody against SARS-CoV-2. We compared the characteristics, advantages and disadvantages, and clinical applications of these three detection techniques. In addition to detecting viral infections, knowledge on the body's immunity against the virus is desirable; thus, the immunotherapy-based neutralizing antibody (nAb) detection methods were discussed. We also gave a brief introduction to the new immunoassay technology such as biosensing. This was followed by an in-depth and extensive review on a variety of immunotherapy methods. It includes convalescent plasma therapy, neutralizing antibody-based treatments targeting different regions of SARS-CoV-2, immunotherapy targeted on the host cell including inhibiting the host cell receptor and cytokine storm, as well as cocktail antibodies, cross-neutralizing antibodies, and immunotherapy based on cross-reactivity between viral epitopes and autoepitopes and autoantibody. Despite the development of various immunological testing methods and antibody therapies, the current global situation of COVID-19 is still tense. We need more efficient detection methods and more reliable antibody therapies. The up-to-date knowledge on therapeutic strategies will likely help clinicians worldwide to protect patients from life-threatening viral infections.

SARS-CoV-2 omicron variant: the black swan of microbiology.

The sudden emergence of the SARS-CoV-2 Omicron variant is causing major global concern due to its high number of mutations compared to previous variants, which is a relatively rare but significant event that can change the course of viral evolution, the occurrence of which might have huge consequences for the natural evolution of species in general, prompting us to rethink our knowledge on evolution.

Effect of a Functional Phospholipid Metabolome-Protein Association Pathway on the Mechanism of COVID-19 Disease Progression.

This study aimed to explore the clinical practice of phospholipid metabolic pathways in COVID-19. In this study, 48 COVID-19 patients and 17 healthy controls were included. Patients were divided into mild (n=40) and severe (n=8) according to their severity. Phospholipid metabolites, TCA circulating metabolites, eicosanoid metabolites, and closely associated enzymes and transfer proteins were detected in the plasma of all individuals using metabolomics and proteomics assays, respectively. 30 of the 33 metabolites found differed significantly (P<0.05) between patients and healthy controls (P<0.05), with D-dimmer significantly correlated with all of the lysophospholipid metabolites (LysoPE, LysoPC, LysoPI and LPA). In particular, we found that phosphatidylinositol (PI) and phosphatidylcholine (PC) could identify patients from healthy controls (AUC 0.771 and 0.745, respectively) and that the severity of the patients could be determined (AUC 0.663 and 0.809, respectively). The last measurement before discharge also revealed significant changes in both PI and PC. For the first time, our study explores the significance of the phospholipid metabolic system in COVID-19 patients. Based on molecular pathway mechanisms, three important phospholipid pathways related to Ceramide-Malate acid (Cer-SM), Lysophospholipid (LPs), and membrane function were established. Clinical values discovered included the role of Cer in maintaining the inflammatory internal environment, the modulation of procoagulant LPA by upstream fibrinolytic metabolites, and the role of PI and PC in predicting disease aggravation.

Investigation of Antibody Levels During Three Doses of Sinopharm/BBIBP Vaccine Inoculation.

Levels of neutralizing antibodies (NAb) after vaccine against coronavirus disease 2019 (COVID-19) can be detected using a variety of methods. A critical challenge is how to apply simple and accurate methods to assess vaccine effect. In a population inoculated with three doses of the inactivated Sinopharm/BBIBP vaccine, we assessed the performance of chemiluminescent immunoassay (CLIA) in its implementation to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies, as well as the antibody kinetics of healthcare workers throughout the course of vaccination. The antibody levels of NAb, the receptor-binding-domain (RBD) antibodies and IgG peaked one month after the second and remained at a relatively high level for over three months after the booster injection, while IgM and IgA levels remained consistently low throughout the course of vaccination. The production of high-level neutralizing antibodies is more likely when the inoculation interval between the first two doses is within the range of one to two months, and that between the first and booster dose is within 230 days. CLIA showed excellent consistency and correlation between NAb, RBD, and IgG antibodies with the cytopathic effect (CPE) conventional virus neutralization test (VNT). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off levels of NAb, RBD and IgG were 61.77 AU/ml, 37.86 AU/ml and 4.64 AU/ml, with sensitivity of 0.833, 0.796 and 0.944, and specificity of 0.768, 0.750 and 0.625, respectively, which can be utilized as reliable indicators of COVID-19 vaccination immunity detection.

Immunoassay and mass cytometry revealed immunological profiles induced by inactivated BBIBP COVID-19 vaccine.

With the global prevalence of COVID-19 and the constant emergence of viral variants, boosters for COVID-19 vaccines to enhance antibody titers in human bodies will become an inevitable trend. However, there is a lack of data on antibody levels and the protective effects of booster injections. This study monitored and analyzed the antibody potency and the antibody responses induced by the booster injection in the subjects who received three vaccine doses. The study was conducted in a multicenter collaboration and recruited 360 healthy adults aged 20-74. Participants received the first, second, and booster doses of inactivated Sinopharm/BBIBP COVID-19 vaccine at 0, 1, and 7 months. Vaccine-induced virus-specific antibody levels (SARS-COV-2-IgA/IgM/IgG) were monitored at multiple time points, surrogate virus neutralization test (sVNT), and the spatial distribution and proportion of immune cells and markers were analyzed using the CyTOF method before vaccination and a month after the second dose. The titers of SARS-CoV-2-IgA/IgM/IgG and neutralizing antibodies increased to a high level in the first month after receiving the second dose of vaccine and declined slowly after that. The antibody levels of SARS-CoV-2-IgG and sVNT were significantly increased at 0.5 months after the induction of the booster (p < 0.05). Despite a downward trend, the antibody levels were still high in the following 6 months. The B cell concentration (in humoral sample) a month after the second injection was significantly reduced compared to that before the vaccine injection (p < 0.05). The proportion of the C01 cell cluster was significantly decreased compared with that before vaccine injection (p < 0.05). Individual cell surface markers showed distinctions in spatial distribution but were not significantly different. This study has shown that serum antibody titer levels will decrease with time by monitoring and analyzing the antibody efficacy and the antibody reaction caused by the booster injection of healthy people who received the whole vaccination (completed three injections). Still, the significant peak of the antibody titer levels after booster highlights the recall immune response. It can maintain a high concentration of antibody levels for a long time, which signifies that the protection ability has been enhanced following the injection of booster immunization. Additionally, CyTOF data shows the active production of antibodies and the change in the immunity environment.

Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization.

BACKGROUND: The inactivated Sinopharm/BBIBP COVID-19 vaccine has been widely used in the world and has joined the COVAX vaccine supply program for developing countries. It is also well adapted for usage in low- and middle-income nations due to their low storage requirements. OBJECTIVE: This study aims to report on the kinetics, durability, and neutralizing ability of the induced immunity of the BBIBP vaccine, and the intensified antibody response elicited by the booster. METHODS: A total of 353 healthy adult participants, aged 20-74 years, were recruited in this multicenter study. A standard dose of the BBIBP vaccine was administered (Month 0), followed by a second standard dose (Month 1), and a booster dose (after Month 7). Vaccine-induced virus-specific antibody levels (SARS-CoV-2-IgA/IgM/IgG), conventional virus neutralization test (cVNT), pseudovirus neutralization test (pVNT), and surrogate virus neutralization test (sVNT) were monitored over multiple time points. RESULTS: Neutralizing titers induced by the two doses of inactivated vaccine for COVID-19 peaked at Month 2 and declined to 33.89% at Month 6. Following the booster dose, elevated levels of antibodies were induced for IgA, IgG, and neutralizing antibodies, with neutralizing titer reaching 13.2 times that of before the booster. CONCLUSION: By monitoring the antibody titer levels postvaccination, this study has shown that serum antibody levels will decrease over time, but a notable spike in antibody levels postbooster highlights the anamnestic immune response. This signifies that the protection capability has increased following the injection of booster immunization.

The molecular mechanism of SARS-CoV-2 evading host antiviral innate immunity.

The newly identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a global health emergency (COVID-19) because of its rapid spread and high mortality. Since the virus epidemic, many pathogenic mechanisms have been revealed, and virus-related vaccines have been successfully developed and applied in clinical practice. However, the pandemic is still developing, and new mutations are still emerging. Virus pathogenicity is closely related to the immune status of the host. As innate immunity is the body's first defense against viruses, understanding the inhibitory effect of SARS-CoV-2 on innate immunity is of great significance for determining the target of antiviral intervention. This review summarizes the molecular mechanism by which SARS-CoV-2 escapes the host immune system, including suppressing innate immune production and blocking adaptive immune priming. Here, on the one hand, we devoted ourselves to summarizing the combined action of innate immune cells, cytokines, and chemokines to fine-tune the outcome of SARS-CoV-2 infection and the related immunopathogenesis. On the other hand, we focused on the effects of the SARS-CoV-2 on innate immunity, including enhancing viral adhesion, increasing the rate of virus invasion, inhibiting the transcription and translation of immune-related mRNA, increasing cellular mRNA degradation, and inhibiting protein transmembrane transport. This review on the underlying mechanism should provide theoretical support for developing future molecular targeted drugs against SARS-CoV-2. Nevertheless, SARS-CoV-2 is a completely new virus, and people's understanding of it is in the process of rapid growth, and various new studies are also being carried out. Although we strive to make our review as inclusive as possible, there may still be incompleteness.

Identifying COVID-19 Infections From a Vaccinated Population Using Specific IgA Antibody Test.

We analyzed the serum from COVID-19 patients and vaccinated subjects, and found that the specific IgA titer level could be used to assist COVID-19 diagnosis, especially in China.

Rapid Antigen Test Combine with Nucleic Acid Detection: A Better Strategy for COVID-19 Screening at Points of Entry.

The coronavirus disease 2019 (COVID-19) pandemic has imposed an enormous disease burden worldwide, and the Delta variant now has become dominant in 53 countries. Recently published studies have shown that during periods of high viral load, rapid antigen tests (RAT) yield similar results to reverse transcriptase-polymerase chain reaction (RT-PCR) tests, and when used in serial screening (e.g., every three days), it has a high sensitivity. In this perspective, we recommend RT-PCR combined with RAT at points of entry: (i) RAT can be added to the detection phase at ports of entry to detect asymptomatic infections as early as possible; (ii) RAT can be added to post-entry quarantine every three days or less to reduce the rate of missed detection in later quarantine; (iii) Adding regular RAT to regular PCR testing for key airport personnel to prevent cross-infection and conduct closed-off management. In the face of sporadic Delta variant outbreaks, the combination of the two could help rapid triage and management of suspected populations at an early stage and thus contain the outbreak more quickly and effectively. We also discuss the issue whether the current antigen detection reagents can cope with various SARS-CoV-2 variants.

COVID-19: Look to the Future, Learn from the Past.

There is a current pandemic of a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of confirmed infected cases has been rapidly increasing. This paper analyzes the characteristics of SARS-CoV-2 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. COVID-19 is similar to the diseases caused by SARS-CoV and MERS-CoV virologically and etiologically, but closer to influenza in epidemiology and virulence. The comparison provides a new perspective for the future of the disease control, and offers some ideas in the prevention and control management strategy. The large number of infectious people from the origin, and the highly infectious and occult nature have been two major problems, making the virus difficult to eradicate. We thus need to contemplate the possibility of long-term co-existence with COVID-19.

2019 Novel coronavirus: where we are and what we know.

There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.