COVID-19-Related Age Profiles for SARS-CoV-2 Variants in England and Wales and States of the USA (2020 to 2022): Impact on All-Cause Mortality

Jones, Rodney P.; Ponomarenko, Andrey

doi:10.3390/idr15050058

Cited by 4 publications

(31 citation statements)

References 121 publications

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“…For instance, an increased viral load was observed primarily in the younger population with Delta infections [46]. The association of higher viral loads with a younger age group raises intriguing questions about age-related susceptibility and immune responses, both for specific variants and for SARS-CoV-2 in general, as discussed in [50]. Alternatively, inconsistent results in various studies may arise from using data on different sub-lineages of SARS-CoV-2, for example those belonging to the Delta variant (e.g., B.1.617.2 and AY).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections

Li,

Chaguza,

Stamp

et al. 2024

Preprint

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Variations in viral loads generated during SARS-CoV-2 infections can influence COVID-19 disease progression and the likelihood of onward transmission. However, the host and virus factors that may impact viral loads and infection dynamics are not fully understood. Here, we conducted virus whole genome sequencing and measured viral copies using RT-qPCR from 9,902 SARS-CoV-2 infections over a 2-year period to examine the relative impact of host factors and virus genetic variation on changes in viral copies. We first used statistical regression models to show that host age and SARS-CoV-2 variant significantly impact viral copies, but vaccination status does not. Then, using a genome-wide association study (GWAS) approach, we identified multiple nucleotide substitutions corresponding to amino acid changes in the SARS-CoV-2 genome associated with variations in viral copies. In particular, we analyzed the temporal patterns and found that SNPs associated with higher viral copies were predominantly observed in Omicron BA.2/BA.4/BA.5/XBB infections, whereas those associated with decreased viral copies were mostly observed in infections with Delta and Omicron BA.1 variants. Our work showcases how GWAS can be a useful tool for probing phenotypes related to SNPs in viral genomes, which can be used to characterize emerging variants and monitor therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections

Li,

Chaguza,

Stamp

et al. 2024

Preprint

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“…At that time, the Delta (B.1.617.2 and AY lineages) SARS-CoV-2 variant predominated in Croatia (data were taken from the ECDC database on SARS-CoV-2 variants) [21]. The delta SARS-CoV-2 variant was shown to cause more severe disease and an excessive number of younger people dying despite receiving vaccinations [22,23]. Eighty patients with COVID-19 were included, and these patients have not been reported in previous studies.…”

Section: Study Design and Patientsmentioning

confidence: 99%

Association of Immune Semaphorins with COVID-19 Severity and Outcomes

Vargovic,

Papic,

Samadan

et al. 2023

Biomedicines

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Semaphorins have recently been recognized as crucial modulators of immune responses. In the pathogenesis of COVID-19, the activation of immune responses is the key factor in the development of severe disease. This study aimed to determine the association of serum semaphorin concentrations with COVID-19 severity and outcomes. Serum semaphorin concentrations (SEMA3A, -3C, -3F, -4D, -7A) were measured in 80 hospitalized adult patients with COVID-19 (moderate (n = 24), severe (n = 32), critical, (n = 24)) and 40 healthy controls. While SEMA3C, SEMA3F and SEMA7A serum concentrations were significantly higher in patients with COVID-19, SEMA3A was significantly lower. Furthermore, SEMA3A and SEMA3C decreased with COVID-19 severity, while SEMA3F and SEMA7A increased. SEMA4D showed no correlation with disease severity. Serum semaphorin levels show better predictive values than CRP, IL-6 and LDH for differentiating critical from moderate/severe COVID-19. SEMA3F and SEMA7A serum concentrations were associated with the time to recovery, requirement of invasive mechanical ventilation, development of pulmonary thrombosis and nosocomial infections, as well as with in-hospital mortality. In conclusion, we provide the first evidence that SEMA3A, SEMA3C, SEMA3F and SEMA7A can be considered as new biomarkers of COVID-19 severity.

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“…Influenza and SARS-CoV-2 are among the class of RNA pathogens showing high mutation rates [21][22][23][24]. Each new clade of antigen mutations leads to a unique age profile for each variant which is also associated with the generation of specific miRNAs, further nuances of pathogen interference and epigenetic modifications [25]. In the UK, the COVID-19 pandemic commenced somewhere in early 2020 with the first laboratory-confirmed death occurring on 2 March 2020 [26].…”

Section: Introductionmentioning

confidence: 99%

“…The timing for the approval of COVID-19 vaccines (listed above) meant that the English population (mainly oldest first) only began to be vaccinated during an outbreak of the Alpha variant [25], and with first dose still being delivered to some people into 2022 and 2023 during the outbreak of the Omicron variant [37]. Ample opportunities for suboptimum time-based outcomes are therefore present.…”

Section: Introductionmentioning

confidence: 99%

“…The all-cause mortality data set used in this study is very large and covers all residents of England who are registered with a GP and were residents in England at the 2011 census [40]. This allows detailed analysis of 944 000 deaths over a 29-month period by gender, over 7 age bands, and by various stages of vaccination split by less than 21 days, and greater than 21 days post vaccination, and at monthly intervalswhich can be grouped by SARS-CoV-2 variant [25].…”

Section: Introductionmentioning

confidence: 99%

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The nonspecific effects of COVID-19 vaccination upon non-COVID-19 all-cause mortality (NCACM) in the population of England: Effects of age, sex, COVID-19 variant, vaccination history, and time in a real-world study from Jan-21 to May-23

Jones,

Ponomarenko

2024

Preprint

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All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

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COVID-19-Related Age Profiles for SARS-CoV-2 Variants in England and Wales and States of the USA (2020 to 2022): Impact on All-Cause Mortality

Cited by 4 publications

References 121 publications

Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections

Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections

Association of Immune Semaphorins with COVID-19 Severity and Outcomes

The nonspecific effects of COVID-19 vaccination upon non-COVID-19 all-cause mortality (NCACM) in the population of England: Effects of age, sex, COVID-19 variant, vaccination history, and time in a real-world study from Jan-21 to May-23

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