SARS-CoV-2 variants in immunocompromised COVID-19 patients: The underlying causes and the way forward

Bansal, Nalini; Raturi, Manish; Bansal, Yashik

doi:10.1016/j.tracli.2021.12.006

“…Even in the presence of VOC with mutations that alter vaccine efficacy, full vaccination is effective against severe COVID-19 caused by non-Omicron variants [ 192 ], resulting in a milder and shorter course of COVID-19, while booster doses have proven to improve neutralization against Omicron [ 175 ]. Furthermore, intra-host viral evolution during persistent infections leading to SARS-CoV-2 mutations identified in immune escape variants has been observed in immunocompromised patients [ 193 , 194 ]. In spring 2022, the mandatory use of face masks was repealed in Spain [ 195 ].…”

Section: Discussionmentioning

confidence: 99%

Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins

Troyano-Hernáez

¹

,

Reinosa

²

,

Holguín

³

2022

IJMS

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Monitoring SARS-CoV-2’s genetic diversity and emerging mutations in this ongoing pandemic is crucial to understanding its evolution and ensuring the performance of COVID-19 diagnostic tests, vaccines, and therapies. Spain has been one of the main epicenters of COVID-19, reaching the highest number of cases and deaths per 100,000 population in Europe at the beginning of the pandemic. This study aims to investigate the epidemiology of SARS-CoV-2 in Spain and its 18 Autonomous Communities across the six epidemic waves established from February 2020 to January 2022. We report on the circulating SARS-CoV-2 variants in each epidemic wave and Spanish region and analyze the mutation frequency, amino acid (aa) conservation, and most frequent aa changes across each structural/non-structural/accessory viral protein among the Spanish sequences deposited in the GISAID database during the study period. The overall SARS-CoV-2 mutation frequency was 1.24 × 10−5. The aa conservation was >99% in the three types of protein, being non-structural the most conserved. Accessory proteins had more variable positions, while structural proteins presented more aa changes per sequence. Six main lineages spread successfully in Spain from 2020 to 2022. The presented data provide an insight into the SARS-CoV-2 circulation and genetic variability in Spain during the first two years of the pandemic.

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“…Finally, given reports that have suggested evolution of complexed populations of SARS-CoV-2 in immunocompromised people [44][45][46][47], we were interested to compare infections between IM+ and IM-individuals. While normalizing for overall complexity by comparing infections that occurred within time-similar cohorts, we did not observe increased numbers of iSNVs in IMpatients.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, given published reports of extensive SARS-CoV-2 sequence diversity in association with infected immunocompromised (IM-) individuals [44][45][46][47], we have evaluated the complexity of SARS-CoV-2 sequence in the context of the immunological conditions of the infected individuals in our study. Because the infections studied included asymptomatic individuals and those who receive primary care outside the VA Northeast Ohio Healthcare System, it was not possible to conduct a complete association study on this focus.…”

Section: Association Between Immunological Competence and Sars-cov-2 ...mentioning

confidence: 99%

COVID-19 Infection and Transmission Includes Complex Sequence Diversity

Chan

¹

,

Jones

²

,

Linger

³

et al. 2022

Preprint

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SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta; requiring ≥ 80% genome coverage and ≥100X read depth). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report at least 79% of the observed sequence variation. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics involving both immunocompetent and immunocompromised patients. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.AUTHOR SUMMARYEvolution of the virus causing COVID-19 (SARS-CoV-2) has been associated with significant transmission surges. With evolution of SARS-CoV-2, evidence has accumulated regarding increased transmissibility of lineages, varying severity of illness, evasion of vaccines and diagnostic tests. Continuous tracking of SARS-CoV-2 lineage evolution distills very large and complex viral sequence data sets down to consensus sequences that report the majority nucleotide at each of over 29,000 positions in the SARS-CoV-2 genome. We observe that this eliminates considerable sequence variation and leads to a significant underestimation of SARS-CoV-2 infection diversity and transmission complexity. Additionally, concentration on the majority consensus sequence diverts attention from genetic variation that may contribute significantly to the continuing evolution of the COVID-19 pandemic.

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“…Finally, given published reports of extensive SARS-CoV-2 sequence diversity in association with infected immunocompromised (IM-) individuals [41][42][43][44], we have evaluated the complexity of SARS-CoV-2 sequence in the context of the immunological conditions of the infected individuals in our study. Because the infections studied included asymptomatic individuals and those who receive primary care outside the VA Northeast Ohio Healthcare System, it was not possible to conduct a complete association study on this focus and represents a limitation of our study.…”

Section: Association Between Immunological Competence and Sars-cov-2 ...mentioning

confidence: 99%

“…Finally, given reports that have suggested evolution of complexed populations of SARS-CoV-2 in immunocompromised people [41][42][43][44], we were interested to compare infections between IM+ and IM-individuals. While normalizing for overall complexity by comparing infections that occurred within time-similar cohorts, we did not observe increased numbers of iSNVs in IM-patients.…”

Section: Plos Geneticsmentioning

confidence: 99%

COVID-19 infection and transmission includes complex sequence diversity

Chan

¹

,

Jones

²

,

Linger

³

et al. 2022

View full text Add to dashboard Cite

SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report sequence variation in all samples tested. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.

show abstract

SARS-CoV-2 variants in immunocompromised COVID-19 patients: The underlying causes and the way forward

Cited by 6 publications

References 26 publications

Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins

Evolution of SARS-CoV-2 in Spain during the First Two Years of the Pandemic: Circulating Variants, Amino Acid Conservation, and Genetic Variability in Structural, Non-Structural, and Accessory Proteins

COVID-19 Infection and Transmission Includes Complex Sequence Diversity

COVID-19 infection and transmission includes complex sequence diversity

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