The Principles of SARS-CoV-2 Intervariant Competition Are Exemplified in the Pre-Omicron Era of the Colombian Epidemic.

The first 18 months of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Colombia were characterized by three epidemic waves. During the third wave, from March through August 2021, intervariant competition resulted in Mu replacing Alpha and Gamma. We employed Bayesian phylodynamic inference and epidemiological modeling to characterize the variants in the country during this period of competition. Phylogeographic analysis indicated that Mu did not emerge in Colombia but acquired increased fitness there through local transmission and diversification, contributing to its export to North America and Europe. Despite not having the highest transmissibility, Mu's genetic composition and ability to evade preexisting immunity facilitated its domination of the Colombian epidemic landscape. Our results support previous modeling studies demonstrating that both intrinsic factors (transmissibility and genetic diversity) and extrinsic factors (time of introduction and acquired immunity) influence the outcome of intervariant competition. This analysis will help set practical expectations about the inevitable emergences of new variants and their trajectories. IMPORTANCE Before the appearance of the Omicron variant in late 2021, numerous SARS-CoV-2 variants emerged, were established, and declined, often with different outcomes in different geographic areas. In this study, we considered the trajectory of the Mu variant, which only successfully dominated the epidemic landscape of a single country: Colombia. We demonstrate that Mu competed successfully there due to its early and opportune introduction time in late 2020, combined with its ability to evade immunity granted by prior infection or the first generation of vaccines. Mu likely did not effectively spread outside of Colombia because other immune-evading variants, such as Delta, had arrived in those locales and established themselves first. On the other hand, Mu's early spread within Colombia may have prevented the successful establishment of Delta there. Our analysis highlights the geographic heterogeneity of early SARS-CoV-2 variant spread and helps to reframe the expectations for the competition behaviors of future variants.

The early SARS-CoV-2 epidemic in Senegal was driven by the local emergence of B.1.416 and the introduction of B.1.1.420 from Europe.

Molecular surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is growing in west Africa, especially in the Republic of Senegal. Here, we present a molecular epidemiology study of the early waves of SARS-CoV-2 infections in this country based on Bayesian phylogeographic approaches. Whereas the first wave in mid-2020 was characterized by a significant diversification of lineages and predominance of B.1.416, the second wave in late 2020 was composed primarily of B.1.1.420. Our results indicate that B.1.416 originated in Senegal and was exported mainly to Europe. In contrast, B.1.1.420 was introduced from Italy, gained fitness in Senegal, and then spread worldwide. Since both B.1.416 and B.1.1.420 lineages carry several positive selected mutations in the spike and nucleocapsid genes, each of which may explain their local dominance, their mutation profiles should be carefully monitored. As the pandemic continues to evolve, molecular surveillance in all regions of Africa will play a key role in stemming its spread.

Development of the RealTime SARS-CoV-2 quantitative Laboratory Developed Test and correlation with viral culture as a measure of infectivity.

While diagnosis of COVID-19 relies on qualitative molecular testing for the absence or presence of SARS-CoV-2 RNA, quantitative viral load determination for SARS-CoV-2 has many potential applications in antiviral therapy and vaccine trials as well as implications for public health and quarantine guidance. To date, no quantitative SARS-CoV-2 viral load tests have been authorized for clinical use by the FDA. In this study, we modified the FDA emergency use authorized qualitative RealTime SARS-CoV-2 assay into a quantitative SARS-CoV-2 Laboratory Developed Test (LDT) using newly developed Abbott SARS-CoV-2 calibration standards. Both analytical and clinical performance of this SARS-CoV-2 quantitative LDT was evaluated using nasopharyngeal swabs (NPS). We further assessed the correlation between Ct and the ability to culture virus on Vero CCL81 cells. The SARS-CoV-2 quantitative LDT demonstrated high linearity with R2 value of 0.992, high inter- and intra-assay reproducibility across the dynamic range (SDs ± 0.08-0.14 log10 copies/mL for inter-assay reproducibility and ± 0.09 to 0.19 log10 copies/mL for intra-assay reproducibility). Lower limit of detection was determined as 1.90 log10 copies/mL. The highest Ct at which CPE was detected ranged between 28.21-28.49, corresponding to approximately 4.2 log10 copies/mL. Quantitative tests, validated against viral culture capacity, may allow more accurate identification of individuals with and without infectious viral shedding from the respiratory tract.

Tergitol-15-S-9 inactivates SARS-CoV-2 and boosts immunoassay signals.

Inactivation of SARS-CoV-2 virus is necessary to mitigate risk but may interfere with diagnostic assay performance. We examined the effect of heat inactivation on a prototype SARS-CoV-2 antigen immunoassay run on the ARCHITECT automated analyzer. Recombinant full-length SARS-CoV-2 nucleocapsid protein and virus lysate detection was reduced by 66 and 31%, respectively. Several nonionic detergents were assessed as inactivation alternatives based on infectivity in cultured Vero CCL81 cells. Incubation of SARS-CoV-2 in 0.1% Tergitol 15-S-9 for 10 min significantly reduced infectivity and increased the immunoassay signal for cultured lysate and patient specimens. Tergitol 15-S-9 can inactivate SARS-CoV-2 while preserving epitopes on the nucleocapsid protein for enhanced detection by immunoassay antibodies.