Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent

Pascall, David; Vink, Elen; Blacow, Rachel; Bulteel, Naomi; Campbell, Alasdair; Campbell, Robyn; Clifford, Sarah; Davis, Chris; Filipe, Ana da Silva; Sakka, Noha El; Fjodorova, Ludmila; Forrest, Ruth; Goldstein, Emily; Gunson, Rory; Haughney, John; Holden, Matthew T. G.; Honour, Patrick; Hughes, Joseph; James, Edward; Lewis, Tim; MacLean, Oscar A; McHugh, M.; Mollett, Guy; Nyberg, Tommy; Onishi, Yusuke; Parcell, Ben; Ray, Surajit; Robertson, David L.; Seaman, Shaun R.; Shabaan, Sharif; Shepherd, James G.; Smollett, Katherine; Templeton, Kate; Wastnedge, Elizabeth; Wilkie, Craig; Williams, Thomas C; Thomson, Emma C.

doi:10.1016/j.jinf.2023.05.019

Cited by 16 publications

(8 citation statements)

References 46 publications

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“…As demonstrated by the recent study, the directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent. It has increased continuously from the early lineages, through the Alpha variant to the Delta lineage, to decrease substantially in the case of BA.1 Omicron and even further when BA.2 emerged [ 89 ]. This contradicts the notion that SARS-CoV-2’s transmissibility can only be enhanced at the expense of its pathogenicity, since the Delta variant, infection with which was characterized by increased severity, was significantly more transmissible than preceding lineages [ 90 ].…”

Section: Future Viral Variants May Not Always Cause Milder Diseasementioning

confidence: 99%

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review

Rzymski,

Pokorska-Śpiewak,

Jackowska

et al. 2023

Vaccines

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The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

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Section: Future Viral Variants May Not Always Cause Milder Diseasementioning

confidence: 99%

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review

Rzymski,

Pokorska-Śpiewak,

Jackowska

et al. 2023

Vaccines

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“…This strengthened the premise that seasonality was not the strongest factor for the increase in SARS-CoV-2 cases since waves of infection emerged at different times of the year ( Figure 1 and Figure 2 ) [ 24 , 106 , 107 ]. Moreover, the generation of new waves of infection was more dependent on the emergence of new, more infectious variants with different antigenic profiles than the currently circulating variants [ 14 , 108 , 109 ]. In fact, similar to the fifth wave, the USA was identified both as an origin location for Omicron 5 and as comprising the majority of imports along with the UK ( Figure 9 , Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Yet, despite Omicron’s higher infectivity and spread, it has led to relatively fewer hospitalizations and deaths in contrast to other variants, such as Delta [ 99 , 113 , 114 , 115 ]. The lower virulence of Omicron does not constitute a reason for complacency since, with its exceptionally high variability, the emergence of a variant that shares its infectivity but has a higher virulence is entirely possible [ 108 ]. After all, this scenario occurred in the past with Alpha and Delta [ 108 ].…”

Section: Discussionmentioning

confidence: 99%

“…The lower virulence of Omicron does not constitute a reason for complacency since, with its exceptionally high variability, the emergence of a variant that shares its infectivity but has a higher virulence is entirely possible [ 108 ]. After all, this scenario occurred in the past with Alpha and Delta [ 108 ]. Omicron was also reported to have been associated with reduced vaccine effectiveness, and natural immunity could not provide adequate protection, even when the individual was previously infected with non-Omicron variants [ 116 , 117 ].…”

Section: Discussionmentioning

confidence: 99%

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Unraveling the Dynamics of Omicron (BA.1, BA.2, and BA.5) Waves and Emergence of the Deltacron Variant: Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus (Oct 2021–Oct 2022)

Chrysostomou,

Vrancken,

Haralambous

et al. 2023

Viruses

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Commencing in December 2019 with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three years of the coronavirus disease 2019 (COVID-19) pandemic have transpired. The virus has consistently demonstrated a tendency for evolutionary adaptation, resulting in mutations that impact both immune evasion and transmissibility. This ongoing process has led to successive waves of infections. This study offers a comprehensive assessment spanning genetic, phylogenetic, phylodynamic, and phylogeographic dimensions, focused on the trajectory of the SARS-CoV-2 epidemic in Cyprus. Based on a dataset comprising 4700 viral genomic sequences obtained from affected individuals between October 2021 and October 2022, our analysis is presented. Over this timeframe, a total of 167 distinct lineages and sublineages emerged, including variants such as Delta and Omicron (1, 2, and 5). Notably, during the fifth wave of infections, Omicron subvariants 1 and 2 gained prominence, followed by the ascendancy of Omicron 5 in the subsequent sixth wave. Additionally, during the fifth wave (December 2021–January 2022), a unique set of Delta sequences with genetic mutations associated with Omicron variant 1, dubbed “Deltacron”, was identified. The emergence of this phenomenon initially evoked skepticism, characterized by concerns primarily centered around contamination or coinfection as plausible etiological contributors. These hypotheses were predominantly disseminated through unsubstantiated assertions within the realms of social and mass media, lacking concurrent scientific evidence to validate their claims. Nevertheless, the exhaustive molecular analyses presented in this study have demonstrated that such occurrences would likely lead to a frameshift mutation—a genetic aberration conspicuously absent in our provided sequences. This substantiates the accuracy of our initial assertion while refuting contamination or coinfection as potential etiologies. Comparable observations on a global scale dispelled doubt, eventually leading to the recognition of Delta-Omicron variants by the scientific community and their subsequent monitoring by the World Health Organization (WHO). As our investigation delved deeper into the intricate dynamics of the SARS-CoV-2 epidemic in Cyprus, a discernible pattern emerged, highlighting the major role of international connections in shaping the virus’s local trajectory. Notably, the United States and the United Kingdom were the central conduits governing the entry and exit of the virus to and from Cyprus. Moreover, notable migratory routes included nations such as Greece, South Korea, France, Germany, Brazil, Spain, Australia, Denmark, Sweden, and Italy. These empirical findings underscore that the spread of SARS-CoV-2 within Cyprus was markedly influenced by the influx of new, highly transmissible variants, triggering successive waves of infection. This investigation elucidates the emergence of new waves of infection subsequent to the advent of highly contagious and transmissible viral variants, notably characterized by an abundance of mutations localized within the spike protein. Notably, this discovery decisively contradicts the hitherto hypothesis of seasonal fluctuations in the virus’s epidemiological dynamics. This study emphasizes the importance of meticulously examining molecular genetics alongside virus migration patterns within a specific region. Past experiences also emphasize the substantial evolutionary potential of viruses such as SARS-CoV-2, underscoring the need for sustained vigilance. However, as the pandemic’s dynamics continue to evolve, a balanced approach between caution and resilience becomes paramount. This ethos encourages an approach founded on informed prudence and self-preservation, guided by public health authorities, rather than enduring apprehension. Such an approach empowers societies to adapt and progress, fostering a poised confidence rooted in well-founded adaptation.

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“…Third, the intrinsic severity of SARS-CoV-2 variants is understudied. Despite the reduced risk of hospitalization and death among unvaccinated cases during the delta-to-omicron transition, 16 the fluctuating intrinsic severity of successive variants 17 highlights the risk posed by future immune-evasive pathogens, especially when the mainstream vaccine has low efficacy against symptomatic infection of past strains. 18 Fourth, work based on structured responses of a predefined scope of symptoms might underestimate the prevalence and diversity of symptoms.…”

Section: Research Gapsmentioning

confidence: 99%

Comparative analysis of symptom profile and risk of death associated with infection by SARS‐CoV‐2 and its variants in Hong Kong

Kwok,

Wei,

Mcneil

et al. 2024

Journal of Medical Virology

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The recurrent multiwave nature of coronavirus disease 2019 (COVID‐19) necessitates updating its symptomatology. We characterize the effect of variants on symptom presentation, identify the symptoms predictive and protective of death, and quantify the effect of vaccination on symptom development. With the COVID‐19 cases reported up to August 25, 2022 in Hong Kong, an iterative multitier text‐matching algorithm was developed to identify symptoms from free text. Multivariate regression was used to measure associations between variants, symptom development, death, and vaccination status. A least absolute shrinkage and selection operator technique was used to identify a parsimonious set of symptoms jointly associated with death. Overall, 70.9% (54 450/76 762) of cases were symptomatic with 102 symptoms identified. Intrinsically, the wild‐type and delta variant caused similar symptoms among unvaccinated symptomatic cases, whereas the wild‐type and omicron BA.2 subvariant had heterogeneous patterns, with seven symptoms (fatigue, fever, chest pain, runny nose, sputum production, nausea/vomiting, and sore throat) more frequent in the BA.2 cohort. With ≥2 vaccine doses, BA.2 was more likely than delta to cause fever among symptomatic cases. Fever, blocked nose, pneumonia, and shortness of breath remained jointly predictive of death among unvaccinated symptomatic elderly in the wild‐type‐to‐omicron transition. Number of vaccine doses required for reducing occurrence varied by symptoms. We substantiate that omicron has a different clinical presentation compared to previous variants. Syndromic surveillance can be bettered with reduced reliance on symptom‐based case identification, increased weighing on symptoms predictive of death in outcome prediction, individual‐based risk assessment in care homes, and incorporating free‐text symptom reporting.

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Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent

Cited by 16 publications

References 46 publications

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review

Unraveling the Dynamics of Omicron (BA.1, BA.2, and BA.5) Waves and Emergence of the Deltacron Variant: Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus (Oct 2021–Oct 2022)

Comparative analysis of symptom profile and risk of death associated with infection by SARS‐CoV‐2 and its variants in Hong Kong

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