Potential intervariant and intravariant recombination of Delta and Omicron variants.

Among numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns, Omicron is more infectious and immune-escaping, while Delta is more pathogenic. Here, we provide evidence for both intervariant and intravariant recombination of the rapidly evolving new SARS-CoV-2 genomes, including XD/XE/XF and BA.3, raising concerns of potential more infectious, immune-escaping, and disease-causing Omicron and Delta-Omicron variants.

The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant.

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.

Ready for new waves: optimizing SARS-CoV-2 variants monitoring in pooled samples with droplet digital PCR.

Introduction: The declaration of the end of the Public Health Emergency for COVID-19 on May 11th, 2023, has shifted the global focus led by WHO and CDC towards monitoring the evolution of SARS-CoV-2. Augmenting these international endeavors with local initiatives becomes crucial to not only track the emergence of new variants but also to understand their spread. We present a cost-effective digital PCR-based pooled sample testing methodology tailored for early variant surveillance. Methods: Using 1200 retrospective SARS-CoV-2 positive samples, either negative or positive for Delta or Omicron, we assessed the sensitivity and specificity of our detection strategy employing commercial TaqMan variant probes in a 1:9 ratio of variant-positive to variant-negative samples. Results: The study achieved 100% sensitivity and 99% specificity in 10-sample pools, with an Area Under the Curve (AUC) exceeding 0.998 in ROC curves, using distinct commercial TaqMan variant probes. Discussion: The employment of two separate TaqMan probes for both Delta and Omicron establishes dual validation routes, emphasizing the method's robustness. Although we used known samples to model realistic emergence scenarios of the Delta and Omicron variants, our main objective is to demonstrate the versatility of this strategy to identify future variant appearances. The utilization of two divergent variants and distinct probes for each confirms the method's independence from specific variants and probes. This flexibility ensures it can be tailored to recognize any subsequent variant emergence, given the availability of its sequence and a specific probe. Consequently, our approach stands as a robust tool for tracking and managing any new variant outbreak, reinforcing our global readiness against possible future SARS-CoV-2 waves.

Genomic analysis of SARS-CoV-2 Circulating during Second and Third Wave of COVID-19 in Nepal.

BACKGROUND: In Nepal, since the first detection of COVID-19 case in January 2020, the total cases have rose to almost a million with more than 12,000 deaths. Till now, WHO has classified 5 variants of SARS-Cov2 as variant of concerns at different time points causing many waves in different countries and regions at different time points. Nepal had also faced three distinct waves of COVID-19 caused by different variant of COVID 19. The objective of this study was to perform whole-genome sequencing of SARS-CoV-2 circulating in different waves of COVID-19 in Nepal and investigate its variant or lineage. METHODS: In this study, samples from 49 SARS-CoV-2 infected subjects from May 2021 to January 2022, were investigated. The methodology followed RNA extraction, real-time PCR for confirmation and whole-genome sequencing. The consensus genomes were interpreted with appropriate bioinformatics tools and databases. RESULTS: Sequence analysis of 49 genomes revealed to be of Delta (n=27) and Omicron Variant (n=22). The mutations in the consensus genomes contained the defining mutations of the respective lineages/variants. There were 20 genomes of Omicron sub-lineage BA.2, 1 of BA.1.1 and 1 of B.1.1.529. CONCLUSIONS: This study provides concise genomic evidence of presence of Delta and Omicron variant of COVID-19 in Nepal. Delta and Omicron variants were driving the second wave and the third wave of COVID-19 respectively in Nepal. Therefore, the genomic surveillance must be increased to clearly map out the pandemic and strategize vaccination approaches in the country.

PCR Test Positivity and Viral Loads during Three SARS-CoV-2 Viral Waves in Mumbai, India.

SARS-CoV-2 polymerase chain reaction (PCR) tests generally report only binary (positive or negative) outcomes. Quantitative PCR tests can provide epidemiological information on viral transmission patterns in populations. SARS-CoV-2 transmission patterns during India's SARS-CoV-2 viral waves remain largely undocumented. We analyzed 2.7 million real-time PCR testing records collected in Mumbai, a bellwether for other Indian cities. We used the inverse of cycle threshold (Ct) values to determine the community-level viral load. We quantified wave-specific differences by age, sex, and slum population density. Overall, PCR positivity was 3.4% during non-outbreak periods, rising to 23.2% and 42.8% during the original (June-November 2020) and Omicron waves (January 2022), respectively, but was a surprisingly low 9.9% during the Delta wave (March-June 2021; which had the largest increase in COVID deaths). The community-level median Ct values fell and rose ~7-14 days prior to PCR positivity rates. Viral loads were four-fold higher during the Delta and Omicron waves than during non-outbreak months. The Delta wave had high viral loads at older ages, in women, and in areas of higher slum density. During the Omicron wave, differences in viral load by sex and slum density had disappeared, but older adults continued to show a higher viral load. Mumbai's viral waves had markedly high viral loads representing an early signal of the pandemic trajectory. Ct values are practicable monitoring tools.

Pre-Existing Population Immunity and severe acute respiratory syndrome coronavirus 2 Variant Establishment and Dominance Dynamics in the United States: An Ecological Study.

We conducted an ecological analysis of the dynamics of Delta and Omicron establishment and dominance in US states. Omicron became the dominant circulating variant later in states with higher population-level immunity. By contrast, population immunity did not impact the maximum rate of takeover by Delta or Omicron from prior variants.