CDC Nowcast - The Dominance of Delta
#16,150
Three months ago `UK' B1.1.1.7 (Alpha) variant seemed in complete control in the United States and appeared poised for eventual world domination. But at the same time, the the Delta variant - first detected in India - was making serious inroads in the UK, and we were beginning to see evidence that Delta might produce more severe illness.
UK PHE Update, Technical Briefing & Revised Risk Assessment On COVID Variant B.1.617.2 (Delta) - June 3rd, 2021
Although several studies have suggested an increased risk of hospitalization with Delta over Alpha - and infection with the `wild type' COVID of 2020 - case fatality rates have continued to fall, suggesting that Delta cases were being better managed than previous cases.
This makes some sense, as we have more than a year of experience dealing with hospitalized cases - and between increasing vaccine uptake, monoclonal antibody treatments, and the growing rejection of unproven therapies (see WHO Solidarity Therapeutics Trial) - survival rates have improved.
Of course, many survivors must still deal with `Long COVID' or other sequelae (see CMAJ: Even Mild COVID-19 May Have Long-term Brain Impacts) - and the long-term health impacts of COVID infection are largely unknown. But fatal outcomes - at least in regions able to provide modern medical care - have declined.
With the `mixed signals' of increased hospitalizations - but lower deaths - researchers are trying to quantify the actual risks of infection with the Delta variant vs. older COVID strains. Yesterday The Lancet published the following open access study, which suggests - as we've seen previously - that Delta patients are more than twice as likely to be hospitalized as Alpha patients.
This is a lengthy, detailed, and impressive analysis of more than 40,000 COVID Cases occurring the UK between March 29, 2021 and May 17, 2021, all sequencing-confirmed with either Alpha or Delta infections.
You'll want to follow the link to read the study in full, as I've only reproduced some excerpts from the Abstract and Discussion. After the break I'll have a link to some expert commentary on the Science Media Centre website.
Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study
Katherine A Twohig, MPH *, Tommy Nyberg, PhD *, Asad Zaidi, MSc, Simon Thelwall, PhD,
Mary A Sinnathamby, MPH Shirin Aliabadi, PhD,et al.s
Published:August 27, 2021 DOI:https://doi.org/10.1016/S1473-3099(21)00475-8
Summary
Background
The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.
(SNIP)Findings
Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]).
Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.
InterpretationThis large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.FundingMedical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.
(SNIP)
Discussion
New SARS-CoV-2 infections in England are increasingly caused by the delta variant. Although the proportion of cases caused by the delta variant was 20% overall during the study period, this increased to 74% of new sequenced cases in the week starting May 31, 2021.
To our knowledge, this study provides the largest whole-genome-sequencing dataset for SARS-CoV-2 in a high-income country to date, enabling the assessment of hospitalisation risk for the delta variant compared with the alpha variant using linked administrative data.
The results suggest that patients with the delta variant had more than two times the risk of hospital admission compared with patients with the alpha variant. Emergency care attendance combined with hospital admission was also higher for patients with the delta variant, showing increased use of emergency care services as well as inpatient hospitalisation.
Similar results were observed for the subgroup of unvaccinated patients when comparing risks of both hospital care outcomes between the two variants. In the subgroup of patients who had received at least one vaccine dose (≥21 days since their first dose), the precision was too low to determine whether the risks of the outcomes were higher or similar for patients with the delta variant compared with patients with the alpha variant. It has previously been reported that vaccination leads to a similar relative reduction in the risk of hospitalisation for patients with the delta variant or the alpha variant.
This is consistent with the findings in the present study: overall, the number of hospital attendances were low in the vaccinated subgroup resulting in low-precision relative risk estimates.
You'll find several expert reactions available on the SMC website, including:
AUGUST 27, 2021
Expert reaction to study looking at risk of hospitalisation from the delta variant compared with alpha
A study published in The Lancet Infectious Diseases looks at hospital admission and emergency care attendance risk for SARS-CoV-2 variants of concern, delta (B.1.617.2) and alpha (B.1.1.7).
Dr Zania Stamataki, Viral Immunologist, University of Birmingham, said:
“The delta variant was responsible for the uptick in covid cases this summer in the UK, and many of us have heard of even vaccinated people that became infected. This study measures hospitalisations as a surrogate marker of severe disease, and the findings are clear: the delta variant increases hospitalisations compared to the alpha variant previously prevalent in the UK. The majority of cases (74%) were unvaccinated, and 24% were partially vaccinated, with nearly 2% double-vaccinated hospitalised with covid. Taken together with previous studies showing that delta is 50% more infectious than alpha, evidence mounts that we are dealing with a very dangerous variant. Both vaccine doses are needed for maximum protection.”
Dr David Strain, Senior Clinical Lecturer, University of Exeter, said:
“These data confirm what we are seeing in clinical practice, namely that, in addition to the Delta variant being more infectious than the original or the Alpha variants, it is also causing more severe illness, in populations that previously would have had only mild infections. It highlights the need for a comprehensive vaccine program in younger adults and it clearly demonstrates the pre-conception that they do not get severe covid is no longer true.
“This is not a surprise, as the two things that make the Delta variant more infectious will also have a role in the disease severity. Firstly the Delta variant produces up to a 1000 times more copies when it is replicating. This is not just pertinent when it comes to transmission between individuals, but also when it comes to spreading the virus throughout the body of the person who is infected. Secondly, the modification to the spike protein – the key, as it were, to the cellular lock – makes it easier for the virus to enter the cell thus making the move from viral carrier to infected person much quicker. This combination of more viral copies and better cellular penetration makes it more likely that the cells, tissues and organs will become overwhelmed before the immune system, particularly that of an unvaccinated individual, has had chance to mount a defence.”
Although it is hard to see past the 99% dominance of Delta in the United States right now, the inevitable question is what happens next? Once Delta has run its course, and community immunity (via infection or, preferably, vaccination) lessens its impact, will it become endemic like the flu? Or will another antigenically different, and potentially more dangerous, variant take its place?
At this point, no one really knows.
But the history of COVID has been one of escalating viral threats, with the D614G mutation upping the ante over the original Wuhan strain in early 2020 - only to be followed by Alpha, and then Delta - both of which have significantly increased the transmissibility and severity of the virus.
We are unfortunately, still in uncharted territory. Stay tuned.
