scholarly journals Immune response against SARS-CoV-2 variants: the role of neutralization assays

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Alicja Maria Chmielewska ◽  
Anna Czarnota ◽  
Krystyna Bieńkowska-Szewczyk ◽  
Katarzyna Grzyb

AbstractSince the emergence of the novel coronavirus SARS-CoV-2 in late 2019, the COVID-19 pandemic has hindered social life and global economic activity. As of July 2021, SARS-CoV-2 has caused over four million deaths. The rapid spread and high mortality of the disease demanded the international scientific community to develop effective vaccines in a matter of months. However, unease about vaccine efficacy has arisen with the spread of the SARS-CoV-2 variants of concern (VOCs). Time- and cost-efficient in vitro neutralization assays are widely used to measure neutralizing antibody responses against VOCs. However, the extent to which in vitro neutralization reflects protection from infection remains unclear. Here, we describe common neutralization assays based on infectious and pseudotyped viruses and evaluate their role in testing neutralizing responses against new SARS-CoV-2 variants. Additionally, we briefly review the recent findings on the immune response elicited by available vaccines against major SARS-CoV-2 variants, including Alpha, Beta, Gamma, and Delta.

2020 ◽  
Author(s):  
Daniel L. Rosenfeld

At the state level within the United States, did political ideology predict the outbreak of the novel coronavirus (COVID-19)? Throughout March 2020, the United States became the epicenter of the COVID-19 pandemic, recording the most cases of any country worldwide. The current research found that, at the state level within the United States, more conservative political ideology predicted delayed implementation of stay-at-home orders and more rapid spread of COVID-19. Effects were significant across two distinct operationalizations of political ideology and held over and above relevant covariates, suggesting a potentially unique role of political ideology in the United States’ COVID-19 outbreak. Considering political ideological factors may offer valuable insights into epidemiological processes surrounding COVID-19.


2020 ◽  
Vol 10 (5) ◽  
pp. 6444-6459 ◽  

The rapid spread of the novel coronavirus (SARS-CoV-2) as a serious threat to the world public health is in dire need of finding potential therapeutic agents. Chinese have tested several antiviral and antimalarial drugs as potent inhibitors for the novel virus, such as remdesivir, chloroquine, hydroxychloroquine, umifenovir and favipiravir. In this study, we used the molecular docking models to study the binding interactions between these pharmaceuticals, as well as our proposed remdesivir analogue (AZCV-20) with the 3CLpro and RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2, using MEO and Autodock4 methods. Our study provides insight into the possible role of structural flexibility and efficacy during interactions between 3CLpro, RdRp and the drugs.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 93 ◽  
Author(s):  
Jan K. Nowak ◽  
Jarosław Walkowiak

The current rapid spread of the novel coronavirus (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify six in vitro studies reporting on the influence of lithium on coronaviral infections. We propose mechanistic investigation of the influence of lithium – alone and with chloroquine – on the SARS-CoV-2 infection.


Author(s):  
Joe Alcock ◽  
Alix Masters

Abstract Since the identification of severe illness caused by the novel coronavirus SARS-CoV-2, the role of the host immune system in causing disease has attracted widespread attention, along with intense interest in medical interventions that target the host immune response. A wide variety of agents have been proposed to treat a cytokine storm in COVID-19, but so far, only one class of medications, corticosteroids, has proved useful. In recent decades, experimental therapies for cytokine storms have been tried and mostly failed to help patients with severe sepsis and other infections. We summarize this history in order to frame expectations for novel interventions in COVID-19 and to bring an evolutionary medicine perspective to the concept of cytokine storms and their treatment.


2021 ◽  
Author(s):  
Adam-Nicolas Pelletier ◽  
Gabriela Pacheco Sanchez ◽  
Mark Watson ◽  
Abdullah Izmirly ◽  
Tiziana Di Pucchio ◽  
...  

Development of fully protective dengue virus (DV) vaccines has been problematic as infection with DV requires a broad antibody immune response that targets all 4 possible serotypes. Herein, we used an integrated systems vaccinology approach to identify prevaccination features that allow the development of fully protective DV-specific antibody responses. This approach allowed us to identify a transcription network in a subset of monocytes defined by the expression of CD68 and downstream of specific pro- and anti-inflammatory cytokines. Moreover, we identified metabolites as drivers of an immune response that induced neutralizing antibodies to the 4 DV serotypes. Specifically, PC/PE drove the production of TGF-B in CD68 low monocytes, which was a positive correlate of the protective antibody response. In contrast, primary and secondary bile acids triggered a proinflammatory response downstream of TGR5 signaling and inflammasome activation in CD68 high monocytes, which was associated to a non-protective antibody response. These features were validated in vitro in primary myeloid cells. Our results highlight the role of cell and systemic metabolism as regulators of protective immune responses to vaccination, and that systems vaccinology is a key tool to identify such mechanisms.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 93 ◽  
Author(s):  
Jan K. Nowak ◽  
Jarosław Walkowiak

The current rapid spread of the novel coronavirus (2019-nCoV) originating from Wuhan, China, calls for a rapid response from the research community. Lithium is widely used to treat bipolar disorder, but has been shown to exhibit antiviral activity. This brief review took a systematic approach to identify five in vitro studies reporting on the influence of lithium on coronaviral infections. We propose that in the case of urgent need, lithium be explored as a potential treatment or prophylaxis for the novel Wuhan coronavirus (2019-nCoV).


Author(s):  
Ibrahim Y. Hachim ◽  
Mahmood Y. Hachim ◽  
Iman Mamdouh Talaat ◽  
Vanessa M. López-Ozuna ◽  
Narjes Saheb Sharif-Askari ◽  
...  

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.


Author(s):  
Sultan Saghir ◽  
Naif AlGabri ◽  
Mahmoud Alagawany ◽  
Youssef Attia ◽  
Salem Alailay ◽  
...  

In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected more than 56 million individuals worldwide and accounted for more than 1.344.000 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for HIV and HCV, the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. This review article provides a comprehensive overview of the CQ/HCQ regimen. It summarizes the evaluating data from in vitro studies and clinical studies either for the protection or the treatment against SARS-CoV-2. There is a sharp difference of opinion about the role of CQ/HCQ regimen in treatment of COVID-19. The literature data are controversial and contradictory due to the diverse study design, population selection, dosage, regimen, and outcome measures. Current evidence from the two largest randomized-controlled trials (recovery and solidarity) suggests that the HCQ regimen does not decrease COVID-19 patients’ mortality. However, conflicting data were published from observational studies showing that the drug might be sufficient. Therefore, more investigations are needed to emphasize these findings.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fabian Bohländer ◽  
Dennis Riehl ◽  
Sabrina Weißmüller ◽  
Marcus Gutscher ◽  
Jörg Schüttrumpf ◽  
...  

The rapid spread of SARS-CoV-2 has induced a global pandemic. Severe forms of COVID-19 are characterized by dysregulated immune response and “cytokine storm”. The role of IgG and IgM antibodies in COVID-19 pathology is reasonably well studied, whereas IgA is neglected. To improve clinical outcome of patients, immune modulatory drugs appear to be beneficial. Such drugs include intravenous immunoglobulin preparations, which were successfully tested in severe COVID-19 patients. Here we established a versatile in vitro model to study inflammatory as well as anti-inflammatory processes by therapeutic human immunoglobulins. We dissect the inflammatory activation on neutrophil-like HL60 cells, using an immune complex consisting of latex beads coated with spike protein of SARS-CoV-2 and opsonized with specific immunoglobulins from convalescent plasma. Our data clarifies the role of Fc-receptor-dependent phagocytosis via IgA-FcαRI and IgG-FcγR for COVID-19 disease followed by cytokine release. We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.


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