The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India1–5. Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries6. The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2—also termed the Delta variant—is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein. The SARS-CoV-2 Delta variant partially evades neutralization by several monoclonal antibodies and by sera from individuals who have had COVID-19, but two doses of anti-COVID-19 vaccines still generate a strong neutralizing response.

/pdf/reduced-sensitivity-of-sars-cov-2-variant-delta-to-antibody-4vfjtit4rl.pdf

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.

The unprecedented public health and economic impact of the COVID-19 pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been met with an equally unprecedented scientific response. Much of this response has focused, appropriately, on the mechanisms of SARS-CoV-2 entry into host cells, and in particular the binding of the spike (S) protein to its receptor, angiotensin-converting enzyme 2 (ACE2), and subsequent membrane fusion. This Review provides the structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the S protein with ACE2, engagement of the receptor-binding domain of the S protein with ACE2, proteolytic activation of the S protein, endocytosis and membrane fusion. We define the roles of furin-like proteases, transmembrane protease, serine 2 (TMPRSS2) and cathepsin L in these processes, and delineate the features of ACE2 orthologues in reservoir animal species and S protein adaptations that facilitate efficient human transmission. We also examine the utility of vaccines, antibodies and other potential therapeutics targeting SARS-CoV-2 entry mechanisms. Finally, we present key outstanding questions associated with this critical process.

/pdf/mechanisms-of-sars-cov-2-entry-into-cells-57gdww9ak6.pdf

Mechanisms of SARS-CoV-2 entry into cells.

The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research.

/pdf/the-biological-and-clinical-significance-of-emerging-sars-4cwn3ih835.pdf

The biological and clinical significance of emerging SARS-CoV-2 variants.

Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: A narrative review.

http://manuscript.elsevier.com/S1198743X21006042/pdf/S1198743X21006042.pdf

Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review

Neutralizing Activity against SARS-CoV-2 Variants Among samples obtained from persons who had received the mRNA-1273 or BNT162b2 vaccines, neutralizing antibody titers against the B.1.617.1 variant...

https://www.nejm.org/doi/pdf/10.1056/NEJMc2107799

Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants.

The scale and magnitude of the current SARS-CoV2 or COVID-19 pandemic caused enormous burden to healthcare in addition to the socioeconomics of people and countries. The diagnosis is a key part of the strategies to prevent further spread of the infection and patient treatment. The viral infection can be detected by RT-PCR or by antibody testing for specific IgM. The chest X-ray and CT scan often diagnose the COVID-19 earlier than the laboratory tests. However, when radiologists are overburdened with too many cases it is very difficult to review them accurately and timely. The artificial intelligence (AI) based tools can assist at this step with faster detection of abnormality with comparable accuracy. The AI using neural-network-based models can distinguish COVID-19 from other pneumonia, based on the presence of ground glass opacity (GGO) and other features in X-ray and CT scan images. In addition to the interpretation of the radiological data, AI technology can also help with the optimization of data acquisition, preprocessing of initial slices, restructuring of a 3D image, and augmentation. Combining radiological information with the clinical symptoms and other vital measurements can increase the speed and accuracy of COVID-19 diagnosis. Based on the success of AI tools, we predict that the AI-based diagnostic will soon come bundled with the X-ray and CT operating software. In addition to radiology, the AI can be applied to other related data types from simple PCR data to complex high-dimensional cytometry data for automation and extraction of relevant information.

Malaya K. Sahoo

Papers

Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants.

Artificial Intelligence-Mediated Medical Diagnosis of COVID-19