key: cord-0031960-uw69bkj6
authors: Dennehy, John J; Gupta, Ravindra K; Hanage, William P; Johnson, Marc C; Peacock, Thomas P
title: Where is the next SARS-CoV-2 variant of concern?
date: 2022-05-19
journal: Lancet
DOI: 10.1016/s0140-6736(22)00743-7
sha: 2b057b18e15f82004d3ad02e77cc750842f459ac
doc_id: 31960
cord_uid: uw69bkj6

nan

readily seen to be highly divergent from its nearest common ancestor, having accumulated a constellation of mutations with worrisome properties more rapidly than the rest of the virus population. 1 The omicron (B.1.1.529) variant arose under similar circumstances and had about 45 mutations that separated it from its ancestor at a time when the distantly related delta (B.1.617.2) variant was dominant. 1 The beta (B.1.351) and gamma (P.1) variants are similarly divergent from their closest relatives, consistent with comparable origins. 1 The possibility of SARS-CoV-2 evolving resistance to existing therapies during such infections is real. 5 Hence, curing COVID-19 infections in immunocompromised individuals is of crucial importance as it is possible that an existing patient might harbour the next variant, a highly transmissible new variant of concern that challenges immunity and existing therapeutics. RKG reports consulting fees from ViiV Healthcare and has received honoraria for educational events from Janssen, Moderna, and GlaxoSmithKline. WPH is a member of the scientific advisory board of Biobot Analytics, has received payment for contributing expert witness testimony on the expected course of the pandemic, and has received stock options in Biobot Analytics. All other authors declare no competing interests. Where is the next SARS-CoV-2 variant of concern?

The COVID-19 pandemic has been characterised by successive waves of new variants of concern sweeping the population. The ultimate source of these variants is not known with certainty, but preliminary evidence suggests at least some have emerged from long-term SARS-CoV-2 infections, such as those observed in immunocompromised patients. 1 As a result, it is of the utmost urgency that those with long-term infections should be able to access quality health care and be prioritised for curative therapy because a failure to properly manage these infections poses a risk to the individual and to public health. Immunocompromised patients, such as those infected with HIV or recipients of organ transplants, can have difficulty eliminating SARS-CoV-2 infections. 2 Preliminary data suggest that infections often persist for many months with viruses acquiring new mutations over time 3 as they presumably evade immunemediated neutralisation 4 and hone their ability to infect human cells. Because the virus population size within persistent infections is not limited by bottlenecks at transmission, the rate of mutation is accelerated in comparison with the population at large, so these infections typically generate considerable genetic novelty. Although the evolutionary pressures on a virus within an individual host might be different from the adaptation to transmit between hosts, it is reasonable to assume that the next variant of concern could arise from a virus population with a high degree of genetic diversity and containing mutations allowing infection of resistant individuals.

The alpha (B.1.1.7) variant arose during a period of intense surveillance in the UK and was to those who died and their families but are also of enormous practical use to explain the widespread variation in COVID-19 infection that preliminary data have revealed, and its consequences. 9 Mortality data would help evaluate vaccination and other public health efforts. Counting the global COVID-19 dead will help the living. PJ precancer, albeit data only being available for women up to age 25 years. 3 The positive implications of changing the natural history of this disease were not anticipated or addressed. 3, 4 It is inevitable that the death and morbidity trade-offs will change from benefits towards harms, especially given the known lifelong risks of prematurity in the offspring of women with surgically damaged cervices. 5 

Screening can cause harm (eg, anxiety, further tests, diagnostic labels, costs, morbidity, and death). Sometimes, a screening programme can bring net benefits when the Wilson and Jungner criteria are applied. 1 Screening can detect problems too early, leading to overdiagnosis and overtreatment, resulting in high financial costs, morbidity, and death. Screening healthy people should be considered a medical failure, a second-rate and burdensome approach, and at best should be a temporary, contingent stopgap between the real successes of prevention and cure. Screening (of healthy people) and early diagnosis (with speedy management of symptomatic patients) are ethically and scientifically distinct, but often wrongly elided. 2 The UK National Health Service, policy makers, and the general public need to understand that programmes should be continuously interrogated and dismantled as they become redundant to release funds for something more effective and to liberate people from the constant anxiety of routine check-ups and self-checking. The preliminary observational data about the effects of England's national human papillomavirus (HPV) vaccination programme from Milena Falcaro and colleagues' study 1 show that the programme has almost eliminated cervical cancer and

Milena Falcaro and colleagues 1 reported that cervical cancer and grade 3 cervical intraepithelial neoplasia (CIN3) were prevented by a bivalent vaccine

Recurrent SARS-CoV-2 mutations in immunodeficient patients

SARS-CoV-2 variants, spike mutations and immune escape

Resistance mutations in SARS-CoV-2 delta variant after sotrovimab use