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Advancing climate change increases the risk of future infectious disease outbreaks, particularly of zoonotic diseases, by affecting the abundance and spread of viral vectors. Concerningly, there are currently no approved drugs for some relevant diseases, such as the arboviral diseases chikungunya, dengue or zika. The development of novel inhibitors takes 10–15 years to reach the market and faces critical challenges in preclinical and clinical trials, with approximately 30% of trials failing due to side effects. As an early response to emerging infectious diseases, CavitOmiX allows for a rapid computational screening of databases containing 3D point-clouds representing binding sites of approved drugs to identify candidates for off-label use. This process, known as drug repurposing, reduces the time and cost of regulatory approval. Here, we present potential approved drug candidates for off-label use, targeting the ADP-ribose binding site of Alphavirus chikungunya non-structural protein 3. Additionally, we demonstrate a novel in silico drug design approach, considering potential side effects at the earliest stages of drug development. We use a genetic algorithm to iteratively refine potential inhibitors for (i) reduced off-target activity and (ii) improved binding to different viral variants or across related viral species, to provide broad-spectrum and safe antivirals for the future. [ABSTRACT FROM AUTHOR]

AbstractNew therapies and vaccines changed the management of COVID-19. The aim of this retrospective study was to describe characteristics, in-hospital mortality and its predictors in patients with moderate/severe COVID-19, considering the 4 different pandemic waves and viral variants’ prevalence from February 2020 to January 2022. Among 1135 patients included, 873 (77%) had at least one comorbidity, 177 (16%) were immunocompromised. From waves 1 to 4, patients with severe respiratory failure and ICU admission decreased over time (p < 0.001), like the length of in-hospital stay (p < 0.001). Despite a reduction of in-hospital mortality from 19% to 11%, increased risk of death was related to older age and immunocompromising conditions, especially during the 4th wave (HR = 5.07 and HR = 10.86, p < 0.001 respectively) while remdesivir treatment in the 3rd wave (HR = 0.41, p = 0.010) and positive serology (aHR = 0.66, p = 0.027) were protective for survival. These data support the need for tailoring vaccine campaign for future COVID-19 waves. [ABSTRACT FROM AUTHOR]

COVID‐19 induces re‐circulating long‐lived memory B cells (MBC) that, upon re‐encounter with the pathogen, are induced to mount immunoglobulin responses. During convalescence, antibodies are subjected to affinity maturation, which enhances the antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single‐cell RNA sequencing analysis of spike‐specific B cells from a SARS‐CoV‐2 convalescent subject. After COVID‐19 vaccination, matured infection‐induced MBC underwent recall and differentiated into plasmablasts. Furthermore, the transcriptomic profiles of newly activated B cells transiently shifted toward the ones of atypical and CXCR3+ B cells and several B‐cell clonotypes massively expanded. We expressed monoclonal antibodies (mAbs) from all B‐cell clones from the largest clonotype that used the VH3‐53 gene segment. The in vitro analysis revealed that some somatic hypermutations enhanced the neutralization breadth of mAbs in a putatively stochastic manner. Thus, somatic hypermutation of B‐cell clonotypes generates an anticipatory memory that can neutralize new virus variants. [ABSTRACT FROM AUTHOR]

Abstract Virus mutations give rise to new variants that cause multiple waves of pandemics and escalate the infected number of individuals. In this paper, we develop both a simple random network that we define as a synthesized human interaction network and an epidemiological model based on the microscopic process of disease spreading to describe the epidemic process with three variants in a population with some features of social structure. The features of social structure we take into account in the model are the average number of degrees and the frequency of contacts. This paper shows many computational results from several scenarios both in varying network structures and epidemiological parameters that cannot be obtained numerically by using the compartmental model.

Introduction Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease. Areas covered This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines. Expert Opinion The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection.

Even with its endemic transition, the COVID-19 pandemic remains a public health threat, particularly in the light of emerging variants of concern (VoCs) and the need for pandemic preparedness in the future. In November 2021, the SARS-CoV-2 VoC Omicron emerged and its subvariants BA.1, BA.2 and BA.5 became predominant. Although the protease inhibitor Paxlovid® and the polymerase inhibitors Molnupiravir and Remdesivir were approved as specific antiviral treatment options for COVID-19 patients in the early stages after infection, effective prophylactically acting substances without adverse effects are not available yet. In a recent study, we demonstrated that iota-carrageenan, a sulfated polysaccharide extracted from red seaweed, efficiently inhibits the replication of the SARS-CoV-2 Wuhan Type and the VoCs Alpha, Beta, Gamma and Delta. Now, we extended this study by investigating the antiviral effects of iota-, lambda- and kappa-carrageenans on the VoC Omicron subvariants BA.1, BA.2 and BA.5. Using a VoC Omicron BA.1 spike pseudotyped murine leukemia virus (BA.1 MLVOMVLP) as well as patient-derived SARS-CoV-2 Omicron isolates BA.1, BA.2 and BA.5 (SARS-CoV-2OM BA.1, SARS-CoV-2OM BA.2 and SARS-CoV-2OM BA.5), we demonstrate that iota-carrageenan exhibits similar antiviral activity against all analyzed Omicron subvariants. As with other VoCs shown before, the biologically inert iota-carrageenan was more efficient than kappa- and lambda-carrageenan. Altogether, these results confirm that, independent of the current and potential future variants, the physical barrier provided by iota-carrageenan might be applicable for prophylaxis and early treatment of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study is to examine the chronological development of hospitalized oncology and COVID-19 patients, and compare effects on oncology sub-disciplines for pre-pandemic (2017–19) and pandemic (2020–21) years in the setting of a German university maximum care provider. Methods: Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with oncological main (nOnco) and COVID-19 secondary diagnosis (nCOVID-19). Data analysis is based on descriptive statistical assessment. Results: The oncology patient collective (nOnco = 27,919) shows a decrease of hospitalized patients for the whole pandemic (− 4% for 2020 and − 2,5% for 2021 to 2019). The number of hospitalized COVID-19 patients increases from first to second pandemic year by + 106.71% (nCOVID-19 = 868). Maximum decline in monthly hospitalized oncology patients amounts to − 19% (May 2020) during the first and − 21% (December 2020) during the second lockdown. Relative monthly hospitalization levels of oncology patients reverted to pre-pandemic levels from February 2021 onwards. Conclusion: The results confirm a decline in hospitalized oncology patients for the entire pandemic in the setting of a maximum care provider. Imposed lockdown and contact restrictions, rising COVID-19 case numbers, as well as discovery of new virus variants have a negative impact on hospitalized treated oncological patients. [ABSTRACT FROM AUTHOR]

Several epidemiological models have been proposed to study the evolution of COVID-19 pandemic. In this paper, we propose an extension of the SUIHTER model, to analyse the COVID-19 spreading in Italy, which accounts for the vaccination campaign and the presence of new variants when they become dominant. In particular, the specific features of the variants (e.g. their increased transmission rate) and vaccines (e.g. their efficacy to prevent transmission, hospitalization and death) are modeled, based on clinical evidence. The new model is validated comparing its near-future forecast capabilities with other epidemiological models and exploring different scenario analyses.

Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease. This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines. The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection. [ABSTRACT FROM AUTHOR]

Porcine Reproductive and Respiratory Syndrome (PRRS) is the most devastating and economically challenging disease to the swine industry worldwide due to reproductive failure. The main objective of the current study was to evaluate the sensitivity and accuracy of Real-Time RT-PCR method in the detection of PRRS virus and also estimation of the pathogen load in samples with clinical signs. The primers used for the detection of PRRS virus were represented by primers with a specific sequence for the ORF7 gene of the PRRS virus. More important, the primers attachment process was influenced by punctual mutations of the viral strand belonging to the ORF7 gene. 114 samples were tested to identify the presence of PRRS virus, genotype I and 14 of them were found to be positive, using OneStep PCR. Those samples were used to test the specificity of the TaqMan probe and robustness of Real-Time RT-PCR reaction. According to the results, only the samples which presented some specific punctual mutations (4 in total, all from one particular region of Romania) at the genome level of ORF7, were positive, due to primer sequence specificity and complementarity. The Real-Time RT-PCR method has been increasingly adopted by swine producers and veterinarian laboratories as one of the most trustful techniques, combining rapidity, specificity and efficiency for detecting and monitoring the spread of PRRS virus.

The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-pharmaceutical interventions (e.g. lockdowns) to control the epidemic, making it difficult to estimate the relative transmissibility of variants. In this paper, we model the spatial spread of these variants in England using a meta-population agent-based model which correctly characterizes the regional variation in cases and distribution of variants. As a test of robustness, we additionally estimated the relative transmissibility of multiple variants using a statistical model based on the renewal equation, which simultaneously estimates the effective reproduction number R. Relative to earlier variants, the transmissibility of B.1.177 is estimated to have increased by 1.14 (1.12-1.16) and that of Alpha by 1.71 (1.65-1.77). The vaccination programme starting in December 2020 is also modelled. Counterfactual simulations demonstrate that the vaccination programme was essential for reopening in March 2021, and that if the January lockdown had started one month earlier, up to 30 k (24 k-38 k) deaths could have been prevented. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'. [ABSTRACT FROM AUTHOR]

Students often struggle with visualizing protein structures when working with two-dimensional textbook and lecture materials, so introducing them to 3D visualization software developed by and for structural biologists offers them a unique opportunity to work with authentic data while furthering their spatial reasoning skills and understanding of molecular structure and function. This article presents an active learning virtual laboratory in which students use authentic structural biology data to investigate the effects of both hypothetical and real-world SARS-CoV-2 mutations on the virus's ability to bind to human ACE2 receptors and infect a host, causing COVID-19. Through this activity, introductory-level college students or advanced high school students gain a better understanding of applied biology, such as how vaccines and treatments are designed, as well as strengthening their understanding of core disciplinary concepts, such as the relationship between protein structure and function and the central dogma of molecular biology. While there were challenges during the pilot phase of activity development due to COVID-19 restrictions, students in the pilot groups came away from the activity with deeper understanding of the relationship between proteins and amino acid sequences and a new appreciation for the ways researchers design treatments for and study viruses. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 Mu variant emerged in Colombia in 2021 and spread globally. In 49 serum samples from vaccinees and COVID-19 survivors in Colombia, neutralization was significantly lower (p<0.0001) for Mu than a parental strain and variants of concern. Only the Omicron variant of concern demonstrated higher immune evasion. [ABSTRACT FROM AUTHOR]

Our previous paper showed that microRNAs (miRNAs) present within human placental or mesenchymal stem cell-derived extracellular vesicles (EVs) directly interacted with the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibiting viral replication. In this paper, we analyzed whether these miRNAs could exert antiviral activity against other variants of SARS-CoV-2. We downloaded compete SARS-CoV-2 genome data submitted to the National Center for Biotechnology Information for each SARS-CoV-2 variant, aligned the data to the reference SARS-CoV-2 genome sequence, and then confirmed the presence of 3′ untranslated region (UTR) mutations. We identified one type of 3′ UTR mutation in the Alpha variant, four in the Beta variant, four in the Gamma variant, three in the Delta variant, and none in the Omicron variant. Our findings indicate that 3′ UTR mutations rarely occur as persistent mutations. Interestingly, we further confirmed that this phenomenon could suppress virus replication in the same manner as the previously discovered interaction of placental-EV-derived miRNA with 3′ UTRs of SARS-CoV-2. Because the 3′ UTR of the SARS-CoV-2 RNA genome has almost no mutations, it is expected to be an effective therapeutic target regardless of future variants. Thus, a therapeutic strategy targeting the 3′ UTR of SARS-CoV-2 is likely to be extremely valuable, and such an approach is also expected to be applied to all RNA-based virus therapeutics. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study. [ABSTRACT FROM AUTHOR]

Several epidemiological models have been proposed to study the evolution of COVID-19 pandemic. In this paper, we propose an extension of the SUIHTER model, to analyse the COVID-19 spreading in Italy, which accounts for the vaccination campaign and the presence of new variants when they become dominant. In particular, the specific features of the variants (e.g. their increased transmission rate) and vaccines (e.g. their efficacy to prevent transmission, hospitalization and death) are modeled, based on clinical evidence. The new model is validated comparing its near-future forecast capabilities with other epidemiological models and exploring different scenario analyses. [ABSTRACT FROM AUTHOR]

Maria Teresa Mascellino, Federica Di Timoteo, Massimiliano De Angelis, Alessandra Oliva Department of Public Health and Infectious Diseases, Sapienza University, Rome, Lazio, ItalyCorrespondence: Maria Teresa MascellinoDepartment of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, Rome, 00185, ItalyTel +39 06 49970880Fax +39 06 49972628Email mariateresa.mascellino@uniroma1.itAbstract: This review takes into consideration the principal vaccines developed against the SARS-CoV-2 in this unprecedented period of Covid-19 pandemic. We evaluated the mechanism of action of each vaccine as well as the efficacy, the safety and the storage temperature. In addition, the problem of the dose units, the vaccinal strategy, the activity of alternative compounds such as the monoclonal antibodies and especially the issue of the virus variants were also described in detail. Four vaccines are currently used in Italy: Pfizer-BioNTech mRNA BNT162b2 (Comirnaty) (USA), Moderna mRNA 1273 (USA), Astra-Zeneca ChAdOx1-S (recombinant) viral vector adenovirus belonging to Oxford (UK) and Pomezia (Italy), Janssen (two recombinant viral vector adenoviruses) belonging to Johnson & Johnson (USA). The efficacy of Pfizer and Moderna for preventing disease or severe disease results 95– 87.5% and 94.5– 100%, respectively. The efficacy of Astra-Zeneca and Janssen is about 70% and 65%, respectively; in the case of Janssen, it depends on the geographical area ranging from 72% to 57%. The problem of the administrated doses (one dose, two doses from the same vaccine or from different vaccines, half dose) is also discussed. The vaccination strategy based on the age group remains the simplest, most transparent and fair criterion. This strategy is also based on accelerating the administration of the vaccines, so that as many subjects as possible can be vaccinated quickly for achieving the “herd immunity”. The monoclonal antibodies appeared to be a valid solution for the treatment of Covid-19 disease. Two antibodies (bamlanivimab and etesevimab) have just been approved by the FDA. They could also be used for the infection by virus variants which represent a big problem due to their higher transmissibility and virulence and to their lower response to the vaccines.Keywords: Covid-19 vaccines, vaccinal strategy, dose units, monoclonal antibodies, virus variants, vaccinal platforms

Background: The world faces the challenge posed by the interaction between hosts and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) with potential role for arthropod vectors, and the effect of SARS-CoV-2 variants on acquired immunity, vaccine efficacy and coronavirus disease-19 (COVID-19) pandemic control. Proposal: The characterization of the role played by animal hosts and host-virus interactions is essential to address this challenge. Zoonotic (animal-to-human) and reverse zoonotic (human-to-animal) routes may be involved in virus transmission with a possible still unconfirmed role for arthropod vectors. Herein we propose to consider the risks posed by the possible role of arthropod vectors in COVID-19 and that immunity against SARS-CoV-2 may increase the risk for zoonotic virus transmission. These risks should be considered when evaluating vaccine efficacy and monitoring animal SARS-CoV-2 variants. Conclusion: Virus surveillance, epidemiology, sequencing and evaluation of susceptibility to antibodies and other protective immune mechanisms from vaccinated individuals should be improved. A One Health approach such as the one applied by our group SaBio is necessary for a more effective control of COVID-19 and prevention of future pandemics.

Our previous paper showed that microRNAs (miRNAs) present within human placental or mesenchymal stem cell-derived extracellular vesicles (EVs) directly interacted with the RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), inhibiting viral replication. In this paper, we analyzed whether these miRNAs could exert antiviral activity against other variants of SARS-CoV-2. We downloaded compete SARS-CoV-2 genome data submitted to the National Center for Biotechnology Information for each SARS-CoV-2 variant, aligned the data to the reference SARS-CoV-2 genome sequence, and then confirmed the presence of 3′ untranslated region (UTR) mutations. We identified one type of 3′ UTR mutation in the Alpha variant, four in the Beta variant, four in the Gamma variant, three in the Delta variant, and none in the Omicron variant. Our findings indicate that 3′ UTR mutations rarely occur as persistent mutations. Interestingly, we further confirmed that this phenomenon could suppress virus replication in the same manner as the previously discovered interaction of placental-EV-derived miRNA with 3′ UTRs of SARS-CoV-2. Because the 3′ UTR of the SARS-CoV-2 RNA genome has almost no mutations, it is expected to be an effective therapeutic target regardless of future variants. Thus, a therapeutic strategy targeting the 3′ UTR of SARS-CoV-2 is likely to be extremely valuable, and such an approach is also expected to be applied to all RNA-based virus therapeutics.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2), we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, as well as after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally oriented regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and the possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates and broadly support the investigation of agents with adequate penetration into relevant regions of the CNS. [ABSTRACT FROM AUTHOR]

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The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants.

Since the discovery of hepatitis B virus (HBV) over five decades ago, there have been many independent studies showing presence of HBV genomes in cells of the immune system. However, the nature of HBV lymphotropism and its significance with respect to HBV biology, persistence and the pathogenesis of liver and extrahepatic disorders remains underappreciated. This is in contrast to studies of other viral pathogens in which the capability to infect immune cells is an area of active investigation. Indeed, in some viral infections, lymphotropism may be essential, and even a primary mechanism of viral persistence, and a major contributor to disease pathogenesis. Nevertheless, there are advances in understanding of HBV lymphotropism in recent years due to cumulative evidence showing that: (i) lymphoid cells are a reservoir of replicating HBV, (ii) are a site of HBV-host DNA integration and (iii) virus genomic diversification leading to pathogenic variants, and (iv) they play a role in HBV resistance to antiviral therapy and (v) likely contribute to reactivation of hepatitis B. Further support for HBV lymphotropic nature is provided by studies in a model infection with the closely related woodchuck hepatitis virus (WHV) naturally infecting susceptible marmots. This animal model faithfully reproduces many aspects of HBV biology, including its replication scheme, tissue tropism, and induction of both symptomatic and silent infections, immunological processes accompanying infection, and progressing liver disease culminating in hepatocellular carcinoma. The most robust evidence came from the ability of WHV to establish persistent infection of the immune system that may not engage the liver when small quantities of virus are experimentally administered or naturally transmitted into virus-naïve animals. Although the concept of HBV lymphotropism is not new, it remains controversial and not accepted by conventional HBV researchers. This review summarizes research advances on HBV and hepadnaviral lymphotropism including the role of immune cells infection in viral persistence and the pathogenesis of HBV-induced liver and extrahepatic diseases. Finally, we discuss the role of immune cells in HBV diagnosis and assessment of antiviral therapy efficacy.

We present a case of SARS-CoV-2 B.1. 525 infection in a healthcare worker despite the presence of highly neutralizing, multivariant-specific antibodies 7 weeks after full vaccination with the mRNA vaccine BNT162b2. We show that the virus replicated to high levels in the upper respiratory tract over the course of several days in the presence of strong antibody responses. The virus was readily propagatable in vitro, demonstrating the potential to transmit to others, bolstered by the fact that several household members were equally infected. This highlights the importance of protective measures even in vaccinated individuals.

Since the discovery of hepatitis B virus (HBV) over five decades ago, there have been many independent studies showing presence of HBV genomes in cells of the immune system. However, the nature of HBV lymphotropism and its significance with respect to HBV biology, persistence and the pathogenesis of liver and extrahepatic disorders remains underappreciated. This is in contrast to studies of other viral pathogens in which the capability to infect immune cells is an area of active investigation. Indeed, in some viral infections, lymphotropism may be essential, and even a primary mechanism of viral persistence, and a major contributor to disease pathogenesis. Nevertheless, there are advances in understanding of HBV lymphotropism in recent years due to cumulative evidence showing that: (i) lymphoid cells are a reservoir of replicating HBV, (ii) are a site of HBV-host DNA integration and (iii) virus genomic diversification leading to pathogenic variants, and (iv) they play a role in HBV resistance to antiviral therapy and (v) likely contribute to reactivation of hepatitis B. Further support for HBV lymphotropic nature is provided by studies in a model infection with the closely related woodchuck hepatitis virus (WHV) naturally infecting susceptible marmots. This animal model faithfully reproduces many aspects of HBV biology, including its replication scheme, tissue tropism, and induction of both symptomatic and silent infections, immunological processes accompanying infection, and progressing liver disease culminating in hepatocellular carcinoma. The most robust evidence came from the ability of WHV to establish persistent infection of the immune system that may not engage the liver when small quantities of virus are experimentally administered or naturally transmitted into virus-naïve animals. Although the concept of HBV lymphotropism is not new, it remains controversial and not accepted by conventional HBV researchers. This review summarizes research advances on HBV and hepadnaviral lymphotropism including the role of immune cells infection in viral persistence and the pathogenesis of HBV-induced liver and extrahepatic diseases. Finally, we discuss the role of immune cells in HBV diagnosis and assessment of antiviral therapy efficacy. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study.

The COVID-19 pandemic started by the SARS-CoV-2 virus from China hit different parts of the world and caused till now the first, second and third waves at different time periods from March 2020 to December 2021. Virus variants emerged to cause these waves with altered behaviour and severity of the disease and difficulty in the management of the pandemic. An unexpected upsurge happened during these waves due to social reasons and policies. In this article, we discuss the variations in the waves from a few geographic locations which will give us a better understanding of regional effects and precautions needed for the future. [ABSTRACT FROM AUTHOR]

Interactions between SARS-CoV-2 and the immune system during infection are complex. However, understanding the within-host SARS-CoV-2 dynamics is of enormous importance for clinical and public health outcomes. Current mathematical models focus on describing the within-host SARS-CoV-2 dynamics during the acute infection phase. Thereby they ignore important long-term post-acute infection effects. We present a mathematical model, which not only describes the SARS-CoV-2 infection dynamics during the acute infection phase, but extends current approaches by also recapitulating clinically observed long-term post-acute infection effects, such as the recovery of the number of susceptible epithelial cells to an initial pre-infection homeostatic level, a permanent and full clearance of the infection within the individual, immune waning, and the formation of long-term immune capacity levels after infection. Finally, we used our model and its description of the long-term post-acute infection dynamics to explore reinfection scenarios differentiating between distinct variant-specific properties of the reinfecting virus. Together, the model's ability to describe not only the acute but also the long-term post-acute infection dynamics provides a more realistic description of key outcomes and allows for its application in clinical and public health scenarios., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Few studies highlight the stratification of COVID-19 vaccine effectiveness on MIS-C according to vaccine status, types and SARS-COV-2 variants. A web-based analysis was conducted through searches of PubMed, Web of Science and Medline databases from January 1, 2020, to May 16, 2023. The search terms used were (multisystem inflammatory syndrome in children OR MIS-C OR PIMS OR PIMS-TS) AND (COVID-19 OR SARS-CoV-2) AND (vaccine OR vaccination) AND (children OR adolescents OR pediatric). 6701 children from 13 studies met the MIS-C definition. 92.1 % (1332/1446) of MIS-C cases were unvaccinated, whereas partial vaccination and full vaccination were 3.7 % (54/1446) and 4.2 % (60/1446)respectively. In the two studies encompassing 41 vaccinated MIS-C cases, 34 (82.9 %) received BNT162b2, 2 (4.9 %) received mRNA-1273, 4 (9.8 %) received Sinovac vaccine, and only one received a heterologous primary-boost regimen. Among 838 vaccinated MIS-C cases with different SARS-COV-2 variants, 23（2.8 %） were infected by the Wild-type, 80（9.5 %） by the Alpha variant, 521（62.2 %） by the Delta variant, and 214（25.5 %） by the Omicron variant. A significant difference was observed in vaccination rates among MIS-C cases across different variant pandemics (χ2 = 37.79, P < 0.001). The highest vaccination rate (26.3 %) occurred in the Alpha predominant period, thereafter dropped to 5.0 % in the Delta predominant period, and then increased to 12.6 % in the Omicron predominant period. Heterologous vaccination might provide a slightly more protective effect than homologous manner for MIS-C. As the virus mutates over time, its pathogenicity to MIS-C degrades among vaccinated individuals. [ABSTRACT FROM AUTHOR]

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

This paper proposes MAGE — A Malware Antigen Generating Evolutionary algorithm that is capable of generating unseen variants of a given source malware. MAGE evolves malware variants by employing code transformation functions as mutation operators and intra-population Jaccard similarity metric as fitness function. By virtue of these design choices, MAGE is capable of generating active malware variants with diverse code structure variations while retaining the maliciousness of the source malware. These malware variants (similar to biological antigens) generated throughout the run of MAGE forms a potential dataset of malware variants. The dataset can be used to train an adaptive Antivirus engine to learn the code structure variations that make up the space of malware variants. This could augment the engines ability to detect unseen malware variants, thus preventing attacks from the same. The efficacy of MAGE has been demonstrated with two malware viz. Timid , a COM infector and Intruder , an EXE infector. The simulation experiments demonstrate the potential and versatility of MAGE towards generating diverse malware variants. • This paper proposes a malware antigen generating evolutionary algorithm (MAGE). • MAGE is capable of generating variants of a given malware as Antigens for antivirus. • The evolved malware successfully evade detection by over 97 • MAGE evolves diverse non-trivial assembly code structure variations from source. • The evolved variants retain their original malicious characteristics. • The variants evolved can be fed to adaptive antivirus engines to prevent infection. [ABSTRACT FROM AUTHOR]

Accumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infect in vitro two closely related but functionally distinct immune cell types, CD4+ and CD8+ T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4+ or CD8+ T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4+ than in CD8+ T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4+ and CD8+ cells at estimated mean levels ± standard errors of the means of 6.7 × 10² ± 3.8 × 102 and 1.2 × 102 ± 0.8 × 102 copies/+g RNA, respectively (P + 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4+ and in 1.2% of CD8+ T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4+ and CD8+ cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients. IMPORTANCE Although the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicates in vitro in two closely related but functionally distinct types of T lymphocytes, CD4+ and CD8+ cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4+ and CD8+ T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C. [ABSTRACT FROM AUTHOR]

Background Despite continuing research efforts, determinants of mumps virus virulence are still largely unknown. One of consequences of this is difficulty in striking a balance between efficacy and safety of live attenuated mumps vaccines. Among mumps vaccine strains associated with occurrence of postvaccinal aseptic meningitis is L-Zagreb, developed by further attenuation of vaccine strain L-3. Starting from an archived L-Zagreb sample with suboptimal neuroattenuation score, we isolated different viral variants and compared their genetic and phenotypic properties, in investigation of neurovirulence markers. Methods Six different L-Zagreb variants were isolated by plaque purification. Their neurovirulent status was determined by rat-based neurovirulence test; population structure was determined by deep sequencing. Results We isolated one well neuroattenuated viral variant, two marginally neuroattenuated, and three insufficiently neuroattenuated. No genetic markers of neurovirulence could be identified. None of variants had detectable amounts of defective interfering particles. Two characteristics set insufficiently neuroattenuated variants apart from less-neurovirulent ones: elevated variability level in regions 1293−3314, 5363−7773 and 9382−11657, and/or elevated number of mutations present in frequencies ≥1%. The most neurovirulent variants possessed both of these features. Conclusions Distinctive heterogeneity profiles were obtained for insufficiently neuroattenuated L-Zagreb variants. No markers that would discriminate between marginally and well neuroattenuated variants were identified. The findings of this study may serve as a guideline during development of an improved L3/L-Zagreb vaccine strain. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) has been a global public health concern for almost three years, and the transmission characteristics vary among different virus variants. Previous studies have investigated the relationship between air pollutants and COVID-19 infection caused by the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether individuals might be more susceptible to COVID-19 due to exposure to air pollutants, with the SARS-CoV-2 mutating faster and faster. This study aimed to explore the relationship between air pollutants and COVID-19 infection caused by three major SARS-CoV-2 strains (the original strain, Delta variant, and Omicron variant) in China. A generalized additive model was applied to investigate the associations of COVID-19 infection with six air pollutants (PM 2.5 , PM 10 , SO 2 , CO, NO 2 , and O 3 ). A positive correlation might be indicated between air pollutants (PM 2.5 , PM 10 , and NO 2 ) and confirmed cases of COVID-19 caused by different SARS-CoV-2 strains. It also suggested that the mutant variants appear to be more closely associated with air pollutants than the original strain. This study could provide valuable insight into control strategies that limit the concentration of air pollutants at lower levels and would better control the spread of COVID-19 even as the virus continues to mutate.

Porcine Reproductive and Respiratory Syndrome (PRRS) is the most devastating and economically challenging disease to the swine industry worldwide due to reproductive failure. The main objective of the current study was to evaluate the sensitivity and accuracy of Real-Time RT-PCR method in the detection of PRRS virus and also estimation of the pathogen load in samples with clinical signs. The primers used for the detection of PRRS virus were represented by primers with a specific sequence for the ORF7 gene of the PRRS virus. More important, the primers attachment process was influenced by punctual mutations of the viral strand belonging to the ORF7 gene. 114 samples were tested to identify the presence of PRRS virus, genotype I and 14 of them were found to be positive, using OneStep PCR. Those samples were used to test the specificity of the TaqMan probe and robustness of Real-Time RT-PCR reaction. According to the results, only the samples which presented some specific punctual mutations (4 in total, all from one particular region of Romania) at the genome level of ORF7, were positive, due to primer sequence specificity and complementarity. The Real-Time RT-PCR method has been increasingly adopted by swine producers and veterinarian laboratories as one of the most trustful techniques, combining rapidity, specificity and efficiency for detecting and monitoring the spread of PRRS virus. [ABSTRACT FROM AUTHOR]

Highlights: [•] The live RSV vaccine virus was primarily detected in young children post dose 1. [•] About half of the shed vaccine viruses (13/24) contained sequence changes. [•] These sequence changes may result in lower RSVF protein expression. [•] These changes may have been selected during replication in humans. [•] The presence of vaccine variants may be associated with lower RSVF sero-responses. [ABSTRACT FROM AUTHOR]

Early on, scientists have pointed out that coronavirus disease 2019 is most likely here to stay, although its course and development are uncertain. This requires a long-term strategy of living with the virus. However, the urgency of new waves of infection and the emergence of new variants have invoked an approach of acute crisis management over and over, hindering the design of a structural approach for the long term. Exploratory scenarios can provide scientific strategic guidance to policy processes to be better prepared in this situation of fundamental uncertainty. We have therefore developed five scenarios, which describe the possible long-term development of the pandemic from an epidemiological, virological, and broader societal perspective. These scenarios are based on four driving forces that are both important and uncertain: immunity, vaccination, mutations, and human behavior. The scenarios are (1) return to normal, (2) flu+, (3) external threat, (4) continuous struggle, and (5) worst case. Working with scenarios is crucial for appropriate public communication and provides guidance for anticipating the various conceivable possibilities for the further course of the pandemic., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC50 values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants. [ABSTRACT FROM AUTHOR]

Objective: The hepatitis B virus X (HBx) protein plays an important role in the pathogenesis of hepatocellular carcinoma (HCC). One potential mechanism by which HBx can cause liver cancer may involve intracellular distribution and consecutively modulation of the proliferative important STAT/SOCS signaling with upregulation of STAT3. Methods: 153 Vietnamese HBV-infected patients, including 48 patients with HCC, were analyzed. HBx sequences were determined by sequencing and subcloned for functional experiments. Intracellular localization of HBx mutants was determined by immunofluorescence assays. The impact of HBx mutants on JAK/STAT/SOCS signaling was investigated using Western blot and PCR analyses. Results: In 4/48 HCC patients, truncated HBx together with full-length mutated HBx proteins were observed. Expression of HBx mutant proteins demonstrated an atypical nuclear and perinuclear localization. Functional experiments to determine the effect of HBx mutants on STAT/SOCS signaling demonstrated a significantly increased upregulation of STAT3 activation (p > 0.001) in comparison to wild-type (wt)-HBx. STAT1 was not activated either by wt-HBx or HBx mutants. Interestingly, SOCS1 and SOCS3 expression was not activated by wt-HBx and HBx mutants. Conclusions: Our results suggest that atypical nuclear/perinuclear localization of HBx mutants might be responsible for an enhanced activation of STAT3, inhibition of STAT1 and silencing of SOCS1/SOCS3 expression. This observation points to an active role of HBx mutants in hepatocarcinogenesis that involves dysregulation of STAT/SOCS signaling. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response. [ABSTRACT FROM AUTHOR]

Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enhance the spread and the infectiousness and decrease the protective effect of antibodies present after infection, vaccination or antibody treatment. The alpha variant (B.1.1.7), first seen in Kent/United Kingdom, has increased the R‑value and therefore the infectiousness by 75%; however, the effectiveness of the vaccines against SARS-CoV‑2 available in Germany seems to be only slightly impaired by these mutations. In the case of the beta variant (B.1.351), first described in South Africa, the neutralization ability of antibodies towards SARS-CoV‑2 is decreased. The monoclonal antibodies bamlanivimab and etesivimab, which are used therapeutically, are ineffective. The AstraZeneca vaccine offers almost no protection against mild or moderate disease caused by the beta variant. The gamma variant (P.1 or B.1.1.28.1), which was first found in Brazil, is probably 1.7-2.6 times more transmissible than previous virus strains circulating in Brazil. In addition to the infectiousness, the mortality risk of the gamma variant also seems to be increased between 1.2 and 1.9-fold in adults and between 5 and 8-fold in young persons. The delta variant (B.1.617), first described in India, is now dominant in most countries. It is 50% more infectious than the alpha variant, and the protective effect of vaccinations against symptomatic disease can be decreased (Biontech: delta variant 88%, alpha variant 93.7%; AstraZeneca: delta variant 67%, alpha variant 74.5%). Furthermore, the course of the disease with the delta variant is often more severe than with the wild type. Disease courses with the delta variant are less severe in vaccinated than in nonvaccinated persons, and fatal outcomes are substantially rarer. A high vaccination rate is essential in order to approach herd immunity and to bring the pandemic under control. Even where the protective effect towards mild or moderate disease is decreased, as a rule, vaccination still offers excellent protection against life-threatening and fatal disease courses., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)