Emergence and spread of SARS-CoV-2 variants of concern in Canada: a retrospective analysis from clinical and wastewater data.

BACKGROUND: The spread of SARS-CoV-2 has been studied at unprecedented levels worldwide. In jurisdictions where molecular analysis was performed on large scales, the emergence and competition of numerous SARS-CoV-2lineages have been observed in near real-time. Lineage identification, traditionally performed from clinical samples, can also be determined by sampling wastewater from sewersheds serving populations of interest. Variants of concern (VOCs) and SARS-CoV-2 lineages associated with increased transmissibility and/or severity are of particular interest. METHOD: Here, we consider clinical and wastewater data sources to assess the emergence and spread of VOCs in Canada retrospectively. RESULTS: We show that, overall, wastewater-based VOC identification provides similar insights to the surveillance based on clinical samples. Based on clinical data, we observed synchrony in VOC introduction as well as similar emergence speeds across most Canadian provinces despite the large geographical size of the country and differences in provincial public health measures. CONCLUSION: In particular, it took approximately four months for VOC Alpha and Delta to contribute to half of the incidence. In contrast, VOC Omicron achieved the same contribution in less than one month. This study provides significant benchmarks to enhance planning for future VOCs, and to some extent for future pandemics caused by other pathogens, by quantifying the rate of SARS-CoV-2 VOCs invasion in Canada.

Near complete genome sequences from Southern Vietnam revealed local features of genetic diversity and intergenerational changes in SARS- CoV-2 variants in 2020-2021.

BACKGROUND: Since its beginnings in 2019, the COVID-19 pandemic is still a problem of global medical concern. Southern Vietnam is one of the country's vast regions, including 20 provinces and the densely populated metropolis Ho Chi Minh City. A randomized retrospective study was performed to investigate the epidemiology and genetic diversity of COVID-19. Whole-genome sequencing of 126 SARS-CoV-2 samples collected from Southern Vietnam between January 2020 and December 2021 revealed the main circulating variants and their distribution. METHODS: Epidemiological data were obtained from the Department of Preventive Medicine of the Vietnamese Ministry of Health. To identify circulating variants, RNA, extracted from 126 nasopharyngeal swabs of patients with suspected COVID-19 were sequenced on Illunina MiSeq to obtain near complete genomes SARS-CoV-2. RESULTS: Due to the effectiveness of restrictive measures in Vietnam, it was possible to keep incidence at a low level. The partial relaxation of restrictive measures, and the spread of Delta lineages, contributed to the beginning of a logarithmic increase in incidence. Lineages 20A-H circulated in Southern Vietnam during 2020. Spread of the Delta lineage in Southern Vietnam began in March 2021, causing a logarithmic rise in the number of COVID-19 cases. CONCLUSIONS: Pandemic dynamics in Southern Vietnam feature specific variations in incidence, and these reflect the success of the restrictive measures put in place during the early stages of the pandemic.

The dominance of co-circulating SARS-CoV-2 variants in wastewater.

SARS-CoV-2 remains one of the biggest global health problems, which has already reached our wastewater through fecal shedding by COVID-19 patients. While the development of vaccines has mitigated the threats of the COVID-19 pandemic, the evolutionary dynamics of SARS-CoV-2 in wastewater lack monitoring and understanding. In this study, SARS-CoV-2 variants in wastewater were identified by analyzing 8511 wastewater-derived genome sequences from 9 countries from March 2020 to May 2023. The dominance of co-circulating variants was observed, namely B.1 in 2020, Alpha and Delta in 2021, then superseded by Omicron lineages in 2022 with a three-times increase. Mutations were also profiled, revealing nearly 5031 unique amino acid substitutions occurring approximately 371,591 times, some of which were associated with enhanced viral transmission and fitness. This study provided the first long-term multi-country overview of the prevalence of co-circulating SARS-CoV-2 lineages and mutations in wastewater and showed its comparison with conventional epidemiological surveillance. The results highlight the ability of wastewater-based genome monitoring to supplement clinical surveillance efforts in rapidly detecting viruses up to the strain level to keep track of their potential transmission routes and evolutionary dynamics.

SARS-CoV-2: Air pollution highly correlated to the increase in mortality. The case of Guadalajara, Jalisco, México.

Objectives: To determine whether air pollution or changes in SARS-CoV-2 lineages lead to an increase in mortality. Methods: Descriptive statistics were used to calculate rates of infection (2020-2021). RT-PCR was used to compare viral loads from October 2020 to February 2021. Next-generation sequencing (NGS) (n = 92) was used to examine and phylogenetically map SARS-CoV-2 lineages. A correlative "air pollution/temperature" index (I) was developed using regression analysis. PM2.5, PM10, O3, NO2, SO2, and CO concentrations were analyzed and compared to the mortality. Results: The mortality rate during the last year was ∼32%. Relative SARS-CoV-2 viral loads increased in December 2020 and January 2021. NGS revealed that approximately 80% of SARS-CoV-2 linages were B.1.243 (33.7%), B1.1.222 (11.2%), B.1.1 (9%), B.1 (7%), B.1.1.159 (7%), and B.1.2 (7%). Two periods were analyzed, the prehigh- and high-mortality periods and no significant lineage differences or new lineages were found. Positive correlations of air pollution/temperature index values with mortality were found for IPM2.5 and IPM10. INO2. ISO2, and ICO but not for O3. Using ICO, we developed a model to predict mortality with an estimated variation of ∼±5 deaths per day. Conclusion: The mortality rate in the MZG was highly correlated with air pollution indices and not with SARS-CoV-2 lineage.

SARS-CoV-2 laboratory surveillance during the first year of the COVID-19 pandemic in southern Brazil

ABSTRACT Background: Brazil has one of the highest numbers of COVID-19 cases and deaths. Rio Grande do Sul (RS) in southern Brazil is one of the leading states in terms of case numbers. As part of the national public health network, the State Central Laboratory (LACEN-RS) changed its routine in 2020 to focus on the diagnosis of COVID-19. This study evaluated the laboratory surveillance of COVID-19 suspected cases analyzed at the LACEN-RS in 2020. Methods: Viral detection was performed using RT-qPCR in samples from patients with respiratory infection who met the study criteria. Viral RNA was isolated using commercial manual kits or automated extractors, and SARS-CoV-2 RT-qPCR was performed using the Bio-Manguinhos/Rio de Janeiro, IBMP/Paraná, or Allplex 2019-nCoV assay. In total, 360 representative SARS-CoV-2 samples were sequenced using the Illumina platform. Results: In total, 31,197 of 107,578 (positivity rate = 29%) tested positive for SARS-CoV-2. The number of RT-qPCR tests performed per month followed the COVID-19 epidemic curve observed for the state, with peaks in July-August and December. Females accounted for 63% of the samples, whereas the positivity rate was higher among males (33.1% males vs. 26.5% females). The positivity rate was higher in adults aged 50-79 years compared to the overall positivity rate. The majority of cases were observed in the capital, Porto Alegre, and the metropolitan region. Ten distinct lineages were identified, with B.1.1.28, B.1.1.33, and P.2 being the most frequent. Conclusions: Here, we describe laboratory surveillance of COVID-19 to identify priorities for epidemiological surveillance actions in RS.

Clinical and Virological Features of Patients Hospitalized with Different Types of COVID-19 Vaccination in Mexico City.

Coronavirus disease 2019 (COVID-19) vaccines effectively protect against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity remain poorly understood. This work aimed to compare COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in Mexico City. From March to September 2021, clinical, demographic characteristics, and viral variants were obtained from 1014 individuals with a documented SARS-CoV-2 infection. We compared unvaccinated, partially vaccinated, and fully vaccinated patients, stratifying by age groups. We also fitted multivariate statistical models to evaluate the impact of vaccination status, SARS-CoV-2 lineages, vaccine types, and clinical parameters. Most hospitalized patients were unvaccinated. In patients over 61 years old, mortality was significantly higher in unvaccinated compared to fully vaccinated individuals. In patients aged 31 to 60 years, vaccinated patients were more likely to be outpatients (46%) than unvaccinated individuals (6.1%). We found immune disease and age above 61 years old to be risk factors, while full vaccination was found to be the most protective factor against in-hospital death. This study suggests that vaccination is essential to reduce mortality in a comorbid population such as that of Mexico.

Genome sequencing and analysis of genomic diversity in the locally transmitted SARS-CoV-2 in Pakistan.

Surveillance of genetic diversity of the SARS-CoV-2 is extremely important to detect the emergence of more infectious and deadly strains of the virus. In this study, we evaluated mutational events in the SARS-CoV-2 genomes through whole genome sequencing. The samples were collected from COVID-19 patients in different major cities of Pakistan during the four waves of the pandemic (May 2020 to July 2021) and subjected to whole genome sequencing. Using in silico and machine learning tools, the viral mutational events were analyzed, and variants of concern and of interest were identified during each of the four waves. The overall mutation frequency (mutations per genome) increased during the course of the pandemic from 12.19 to 23.63, 31.03, and 41.22 in the first, second, third, and fourth waves, respectively. We determined that the viral strains rose to higher frequencies in local transmission. The first wave had three most common strains B.1.36, B.1.160, and B.1.255, the second wave comprised B.1.36 and B.1.247 strains, the third wave had B.1.1.7 (Alpha variant) and B.1.36 strains, and the fourth waves comprised B.1.617.2 (Delta). Intriguingly, the B.1.36 variants were found in all the waves of the infection indicating their survival fitness. Through phylogenetic analysis, the probable routes of transmission of various strains in the country were determined. Collectively, our study provided an insight into the evolution of SARS-CoV-2 lineages in the spatiotemporal local transmission during different waves of the pandemic, which aided the state institutions in implementing adequate preventive measures.

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study.

Since its advent, the pandemic has caused havoc in multiple waves due partly to amplified transmissibility and immune escape to vaccines. Delhi, India also witnessed brutal multiple peaks causing exponential rise in cases. Here we had retrospectively investigated clade variation, emergence of new lineages and varied clinical characteristics during those three peaks in order to understand the trajectory of the ongoing pandemic. In this study, a total of 123,378 samples were collected for a time span of 14 months (1 June 2020 to 3 August 2021) encompassing three different peaks in Delhi. A subset of 747 samples was processed for sequencing. Complete clinical and demographic details of all the enrolled cases were also collected. We detected 26 lineages across three peaks nonuniformly from 612 quality passed samples. The first peak was driven by diverse early variants, while the second one by B.1.36 and B.1.617.2, unlike third peak caused entirely by B.1.617.2. A total of 18,316 mutations with median of 34 were reported. Majority of mutations were present in less than 1% of samples. Differences in clinical characteristics across three peaks was also reported. To be ahead of the frequently changing course of the ongoing pandemic, it is of utmost importance that novel lineages be tracked continuously. Prioritized sequencing of sudden local outburst and community hot spots must be done to swiftly detect a novel mutation/lineage of potential clinical importance. IMPORTANCE Genome surveillance of the Delhi data provides a more detailed picture of diverse circulating lineages. The added value that the current study provides by clinical details of the patients is of importance. We looked at the shifting patterns of lineages, clinical characteristics and mutation types and mutation load during each successive infection surge in Delhi. The importance of widespread genomic surveillance cannot be stressed enough to timely detect new variants so that appropriate policies can be immediately implemented upon to help control the infection spread. The entire idea of genomic surveillance is to arm us with the clues as to how the novel mutations and/or variants can prove to be more transmissible and/or fatal. In India, the densely populated cities have an added concern of the huge burden that even the milder variants of the virus combined with co-morbidity can have on the community/primary health care centers.

Reduced levels of convalescent neutralizing antibodies against SARS-CoV-2 B.1+L249S+E484K lineage.

The E484K mutation at the SARS-CoV-2 Spike protein emerged independently in different variants around the world and has been widely associated with immune escape from neutralizing antibodies generated during previous infection or vaccination. In this work, the B.1 + L249S+E484K lineage was isolated along with A.1, B.1.420, and B.1.111 SARS-CoV-2 lineages without the E484K mutation and the neutralizing titer of convalescent sera was compared using microneutralization assays. While no significant differences in the neutralizing antibody titers were found between A.1 and B.lineages without the E484K mutation, the neutralizing titers against B.1 + L249S+E484K were 1.5, 1.9, 2.1, and 1.3-fold lower than against A.1, B.1.420, B.1.111-I, and B.1.111-II, respectively. However, molecular epidemiological data indicate that there is no increase in the transmissibility rate associated with this new lineage. This study supports the capability of new variants with the E484K mutation to be resistant to neutralization by humoral immunity, and therefore the need to intensify surveillance programs to determine if these lineages represent a risk for public health.

Comparative structural analyses of selected spike protein-RBD mutations in SARS-CoV-2 lineages.

The severity of COVID-19 has been observed throughout the world as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally claimed more than 2 million lives and left a devastating impact worldwide. Recently several virulent mutant strains of this virus, such as the B.1.1.7, B.1.351, and P1 lineages, have emerged with initial predominance in UK, South Africa, and Brazil. Another extremely pathogenic B.1.617 lineage and its sub-lineages, first detected in India, are now affecting some countries at notably stronger spread-rates. The present paper computationally examines the time-based structures of B.1.1.7, B.1.351, and P1 lineages with selected spike protein mutations. The mutations in the more recently found B.1.617 lineage and its sub-lineages are explored, and the implications for multiple point mutations of the spike protein's receptor-binding domain (RBD) are described. The selected S1 mutations within the highly contagious B.1.617.2 sub-lineage, also known as the delta variant, are examined as well.

The Evolving Faces of the SARS-CoV-2 Genome.

Surveillance of the evolving SARS-CoV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for 'bioinformatics surveillance' of the pandemic, with strong odds regarding visualization, intuitive perception and 'personalization' of the mutational patterns of the virus genomes.

Phylogeography of 27,000 SARS-CoV-2 Genomes: Europe as the Major Source of the COVID-19 Pandemic.

The novel coronavirus SARS-CoV-2 emerged from a zoonotic transmission in China towards the end of 2019, rapidly leading to a global pandemic on a scale not seen for a century. In order to cast fresh light on the spread of the virus and on the effectiveness of the containment measures adopted globally, we used 26,869 SARS-CoV-2 genomes to build a phylogeny with 20,247 mutation events and adopted a phylogeographic approach. We confirmed that the phylogeny pinpoints China as the origin of the pandemic with major founders worldwide, mainly during January 2020. However, a single specific East Asian founder underwent massive radiation in Europe and became the main actor of the subsequent spread worldwide during March 2020. This lineage accounts for the great majority of cases detected globally and even spread back to the source in East Asia. Despite an East Asian source, therefore, the global pandemic was mainly fueled by its expansion across and out of Europe. It seems likely that travel bans established throughout the world in the second half of March helped to decrease the number of intercontinental exchanges, particularly from mainland China, but were less effective between Europe and North America where exchanges in both directions are visible up to April, long after bans were imposed.