Background The emerging SARS-CoV-2 variant of concern (VOC) B.1.6.17.2 (Delta) quickly displaced the B.1.1.7 (Alpha) and is associated with increases in COVID-19 cases nationally. The Delta variant has been associated with greater transmissibility and higher viral RNA loads in both unvaccinated and fully vaccinated individuals. Data is lacking regarding the infectious virus load in Delta infected individuals and how that compares to individuals infected with other SARS-CoV-2 lineages. Methods Whole genome sequencing of 2,785 clinical isolates was used to characterize the prevalence of SARS-CoV-2 lineages circulating in the National Capital Region between January and July 2021. Clinical chart reviews were performed for the Delta, Alpha, and B.1.2 (a control predominant lineage prior to both VOCs) variants to evaluate disease severity and outcome and Cycle threshold values (Cts) were compared. The presence of infectious virus was determined using Vero-TMPRSS2 cells and anti-SARS-CoV-2 IgG levels were determined from upper respiratory specimen. An analysis of infection in unvaccinated and fully vaccinated populations was performed. Results The Delta variant displaced the Alpha variant to constitute 88.2% of the circulating lineages in the National Capital Region by July, 2021. The Delta variant associated with increased breakthrough infections in fully vaccinated individuals that were mostly symptomatic when compared to the Alpha breakthrough infections, though it is important to note there was a significantly longer period of time between vaccination and infection with Delta infections. The recovery of infectious virus on cell culture was significantly higher with the Delta variant compared to Alpha in both vaccinated and unvaccinated groups. The impact of vaccination on reducing the recovery of infectious virus from clinical samples was only observed with Alpha variant infections but was strongly associated with low localized SARS-CoV-2 IgG for both variants. A comparison of Ct values showed a significant decrease in the Delta compared to Alpha with no significant differences between unvaccinated and vaccinated groups. Conclusions Our data indicate that the Delta variant is associated with increased infectious virus loads when compared to the Alpha variant and decreased upper respiratory antiviral IgG levels. Measures to reduce transmission in addition to increasing vaccinations rates have to be implemented to reduce Delta variant spread. Funding NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N2772201400007C, Johns Hopkins University, Maryland department of health, Centers for Disease Control and Prevention contract 75D30121C11061.

Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Infectious Virus Loads Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals

Summary Newly arising variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now a threat to global public health and are creating COVID-19 surges in different countries. At the same time, there is limited knowledge about these emerging variants. Even if research data are available, it is varyingly scattered. In this review, we have discussed the appearance of significant alarming SARS-CoV-2 variants in the entire world. The study also discusses the properties of the substantial variant of concern (VOC) variants such as B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427 (Epsilon) and B.1.429 (Epsilon). At the same time, the characteristic properties of some significant variant of interest (VOI) variants like B.1.525 (Eta), B.1.526 (Iota) (sublineage B.1.526.1), B.1.617 (sublineages B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3), P.2 (Zeta), P.3 (Theta), B.1.616 and B.1.427 have also been discussed. Here, we have explained some essential mutations for the VOC and VOI variants such as K417T/N, L452R, E484K, N501Y, D614G and P681R. Consecutively, we also highlighted the crucial clinical characteristics of the variants, such as transmissibility, infectivity, re-infectivity, immune escape, vaccine activity and vaccine escape. Our comprehensive review will provide updated information on the newly appearing variants of SARS-CoV-2 and help the researchers to formulate strategies to curtail the COVID-19 pandemic.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/rmv.2270

Present variants of concern and variants of interest of severe acute respiratory syndrome coronavirus 2: Their significant mutations in S-glycoprotein, infectivity, re-infectivity, immune escape and vaccines activity

Since the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to > 233 million infections and > 4.7 million deaths as of Sept. 28th, 2021. SARS-CoV-2, Spike (S) protein binds to host cells by recognizing human angiotensin-converting enzyme 2 (hACE2) receptor. The viral S protein contains S1 and S2 domains that constitute the binding and fusion machinery, respectively. Structural analysis of viral S protein reveals that the virus undergoes conformational flexibility and dynamicity to interact with the hACE2 receptor. The SARS-CoV-2 variants and mutations might be associated with affecting the conformational plasticity of S protein, potentially linked to its altered affinity, infectivity, and immunogenicity. This review focuses on the current circulating variants of SARS-CoV-2 and the structure–function analysis of key S protein mutations linked with increased affinity, higher infectivity, enhanced transmission rates, and immune escape against this infection.

/pdf/structural-and-functional-insights-into-the-spike-protein-42m54imk7a.pdf

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants.

Background SARS-CoV-2 Variants concerning for enhanced transmission, evasion of immune responses, or associated with severe disease have motivated the global increase in genomic surveillance. In this study, large scale whole genome sequencing was performed between November 2020 and end of March 2021 to provide a phylodynamic analysis of circulating variants over-time. In addition, we compared the viral genomic features of March 2020 and March 2021. Methods A total of 1,600 complete SARS-CoV-2 genomes were analyzed. Genomic analysis was associated with laboratory diagnostic volumes and positivity rates in addition to an analysis of the association of selected variants of concern/ interest with disease severity and outcomes. Our real-time surveillance features a cohort of specimens from patients who tested positive after the completion of vaccination. Results Our data showed genomic diversity over-time that was not limited to the Spike sequence. A significant increase in the B.1.1.7 lineage (alpha variant) in March 2021 as well as a transient circulation of regional variants that carried both the concerning S: E484K and S: P681H substitutions were noted. Lineage B.1.243 was significantly associated with ICU admission and mortality. Genomes recovered from fully-vaccinated individuals represented the predominant lineages circulating at specimen collection time, and those infections recovered with no hospitalizations. Conclusions Our results emphasize the importance of genomic surveillance coupled with laboratory, clinical, and metadata analysis for a better understanding of the dynamics of viral spread and evolution.

/pdf/an-update-on-sars-cov-2-diversity-in-the-united-states-2c3xabcn8t.pdf

An Update on SARS-CoV-2 Diversity in the United States National Capital Region: Evolution of Novel and Variants of Concern.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus’s transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.

/pdf/biological-properties-of-sars-cov-2-variants-epidemiological-2bdvy5o0.pdf

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences

In late January 2021, a clinical laboratory notified the Maryland Department of Health (MDH) that the SARS-CoV-2 variant of concern B.1.351 had been identified in a specimen collected from a Maryland resident with COVID-19 (1). The SARS-CoV-2 B.1.351 lineage was first identified in South Africa (2) and might be neutralized less effectively by antibodies produced after vaccination or natural infection with other strains (3-6). To limit SARS-CoV-2 chains of transmission associated with this index patient, MDH used contact tracing to identify the source of infection and any linked infections among other persons. The investigation identified two linked clusters of SARS-CoV-2 infection that included 17 patients. Three additional specimens from these clusters were sequenced; all three had the B.1.351 variant and all sequences were closely related to the sequence from the index patient's specimen. Among the 17 patients identified, none reported recent international travel or contact with international travelers. Two patients, including the index patient, had received the first of a 2-dose COVID-19 vaccination series in the 2 weeks before their likely exposure; one additional patient had a confirmed SARS-CoV-2 infection 5 months before exposure. Two patients were hospitalized with COVID-19, and one died. These first identified linked clusters of B.1.351 infections in the United States with no apparent link to international travel highlight the importance of expanding the scope and volume of genetic surveillance programs to identify variants, completing contact investigations for SARS-CoV-2 infections, and using universal prevention strategies, including vaccination, masking, and physical distancing, to control the spread of variants of concern.

/pdf/linked-clusters-of-sars-cov-2-variant-b-1-351-maryland-32et8wqx20.pdf

Alessandra Rivera-Colon

Papers

Linked Clusters of SARS-CoV-2 Variant B.1.351 - Maryland, January-February 2021.