The Delta variant has continued to grab everyone's attention for a long time now. Researchers from Public Health England and Cambridge University recently published a study through whole-genome sequencing that analysed a two-fold increased risk of hospitalisation from Delta versus Alpha variant infections.

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The research

The researchers analysed 43,338 COVID-19 cases by virus genome sequencing which is the most accurate way to determine the virus variant. The study published online on 27 August 2021 in The Lancet Infectious Diseases also revealed that the risk of emergency care visits was also 1.5 times higher for people infected with the Delta variant compared to the Alpha variant.

The outbreaks of the Delta variant may lead to a greater burden on health services than the Alpha variant, particularly in unvaccinated people and other vulnerable populations. Around one in 50 patients were admitted to the hospital within 14 days of their first positive COVID-19 test (2.2% Alpha cases, 764/34,656; 2.3% Delta cases, 196/8,682).

After accounting for factors that are known to affect susceptibility to severe illness from COVID-19, including age, ethnicity, and vaccination status, the researchers found the risk of being admitted to the hospital was more than doubled with the Delta variant compared with the Alpha variant (2.26-fold increase in risk).

Since unvaccinated or partially vaccinated individuals made up the majority of cases in the study, the findings primarily reflect the increased risk of hospitalisation in these groups.

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Initial observations on VOC

Researchers initially detected one of the first Viruses of Concern (VOCs), Alpha (B.1.1.7), in England in November 2020. Alpha had increased transmissibility compared to the previous wild-type lineage, and rapidly became the predominant lineage accounting for 95% of cases in England by early February 2021. Researchers have identified it in 154 countries and were until recently the most prevalent lineage in Europe and North America.

Researchers first detected the SARS-CoV-2 Delta (B.1.617.2) variant in England in March 2021. Since then it has rapidly become the predominant lineage, owing to its high transmissibility. They suspected that the Delta variant is associated with a more severe disease than the previously dominant Alpha (B.1.1.7) variant. Their objective was to characterise the severity of the Delta variant compared to the Alpha variant by determining the relative risk of hospital attendance outcomes.

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Study methods

They accessed detailed individual-level data on these patients linked to routine healthcare datasets on vaccination, emergency care attendance, hospital admission, and mortality. These data were available from Public Health England’s Second Generation Surveillance System and COVID-19-associated deaths dataset. The National Immunisation Management System and NHS Digital Secondary Uses Services and Emergency Care Data Set.

They compared the risk of hospital admission and emergency care attendance between patients with sequencing-confirmed Delta and Alpha variants for the whole cohort and by vaccination status subgroups. They used appropriate statistical methods to adjust for age, sex, ethnicity, deprivation, and recent international travel, area of residence, calendar week, and vaccination status.

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Search for early studies

When the researchers searched, the literature from December 1, 2020, with no language bar they could locate only one relevant study. Based on record linkage of data on 7723 Delta and 11820 Alpha variant COVID-19 cases between April 1 and June 6, 2021, with routine healthcare data, a study in Scotland reported a 1.85 times higher risk of hospital admission within 14 days for patients with the Delta variant compared to the Alpha variant. The patients had been tested through PCR tests and variant status was determined based on S-gene positivity, a proxy test for the SARS-CoV-2 variant.

The present Lancet ID study is unique as it included data on 8682 patients with the Delta variant and 34656 patients with the Alpha variant, confirmed by whole-genome-sequencing. According to the researchers, it is the largest study to date to report on hospitalisation risk for the Delta variant compared with the Alpha variant, and the first to do so based on sequencing-confirmed variants. The Hazard Ratio (HR) of hospital admission within 14 days was 2·26. Researchers also believe that this study is the first to estimate risk for emergency care attendance or hospital admission within 14 days. The adjusted Hazard Ratio (HR) was 1·45.

The researchers highlighted the implications of the study in a Lancet press release:

"The evidence from these two studies in Scotland and England consistently suggest that patients with COVID-19 who are infected with the Delta variant have approximately two times the risk of hospital admission compared with patients with the Alpha variant. These findings should be considered for resource and policy planning in secondary care, particularly in areas where the Delta variant is increasing and is likely to become the dominant circulating SARS-CoV-2 variant."

The press release quoted Dr Gavin Dabrera, one of the study’s lead authors and a consultant epidemiologist at the National Infection Service, Public Health England, as stating that this study confirms previous findings that people infected with Delta are significantly more likely to require hospitalisation than those with Alpha, although most cases included in the analysis were unvaccinated.

Dr Dabrera added:

"We already know that vaccination offers excellent protection against Delta and as this variant accounts for over 98% of COVID-19 cases in the UK, it is vital that those who have not received two doses of vaccine do so as soon as possible. It is still important that if you have COVID-19 symptoms, stay home and get a PCR test as soon as possible."

Researchers reported the Delta variant in India in December 2020 and initial studies found it to be up to 50% more transmissible than the variant of COVID-19 that had previously gained dominance worldwide, known as the Alpha variant, first identified in Kent, UK.

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Early study

A preliminary study from Scotland reported previously a doubling in risk of hospitalisation with the Delta variant compared with the Alpha variant and it is suspected that Delta is associated with more severe disease. The Scottish study used patients’ initial PCR test results and determined which variant they had by testing for a specific gene that is more common in the Delta variant.

In the present study, researchers analysed healthcare data from 43,338 positive COVID-19 cases in England between 29 March and 23 May 2021, including information on vaccination status, emergency care attendance, hospital admission, and other demographic characteristics. In all cases included in the study, samples of the virus taken from patients underwent a whole-genome sequencing to confirm which variant had caused the infection.

During the study period, there were 34,656 cases of the Alpha variant (80%) and 8,682 cases of the Delta variant (20%). While the proportion of Delta cases in the study period overall was 20%, it grew to account for around two-thirds of new COVID-19 cases in the week starting 17 may 2021 (65%, 3,973/6,090), indicating it had overtaken Alpha to become the dominant variant in England.

Dr Anne Presanis, one of the study’s lead authors and senior statistician at the MRC biostatistics unit, University of Cambridge cautioned in the Lancet press release:

"Our analysis highlights that in the absence of vaccination, any Delta outbreaks will impose a greater burden on healthcare than an Alpha epidemic. Getting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admission."

The authors noted several limitations to the study. Some demographic groups may be more likely to seek hospital care, which could have biased the results, and there may have been changes in hospital admission policy during the period of the study, although adjustment for demographics and calendar time should have minimised such bias. In addition, the authors did not have access to information about patients’ pre-existing health conditions, which are known to affect the risk of severe illness from COVID-19. They accounted for this indirectly using age, gender, ethnicity, and estimated level of socioeconomic deprivation.

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Expert reaction to the study

Dr Zania Stamataki, Viral Immunologist, University of Birmingham, noted that the Delta variant was responsible for the uptick in COVID cases this summer in the UK, and many of them have heard of even vaccinated people became infected.

"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 Stamataki cautioned in a press release from the Science Media Centre, London.

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." To him, the study 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 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" Dr David Strain adds.

He clarifies, "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.”

Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at Kings College, London examined among other questions like: How concerning is this data for the UK/ globally?

“As the UK is rapidly advancing its vaccination program to include the younger age population, and vaccines appear to retain protection against more severe disease (based on the PHE vaccine effectiveness reports published weekly), this data is less concerning for the UK than it may be for countries where vaccine coverage is significantly less, as New Zealand and Australia are now finding as new outbreaks of infection caused by the Delta variant take hold in their largely unvaccinated populations. It is comforting that hospitalisation rates and deaths are not rapidly climbing in the UK notwithstanding the apparently lower effectiveness of the vaccines against infection with the Delta variant. The information reiterates the more severe outcomes; particularly as increased population, mixing is likely to increase transmissions as we head into autumn," Prof. Penny Ward stated.

Prof Ward believes that additional work is needed to clarify the impact of vaccination on the patterns of illness found in subjects with breakthrough infection as this might inform efficient use of antiviral medications which are just starting to become available.

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How to face the Delta variant?

Every passing day shows we are in for a long haul tackling the virus. If Delta variant gets the upper hand, our public health resources will collapse.

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What is the way forward?

In the WHO's video-audio series, Science in 5- The conversation in science, episode number 45 (5 July 2021), it is lucidly summarised: What do we know about the Delta variant so far? How can we assess our risk? What strategies should we apply to protect ourselves whether we are in a low vaccination or high vaccination setting?: WHO's Dr Maria Van Kerkhove replies to Ms Vismita Gupta-Smith. [1]

Takeaways from the Science in 5 programme:

1. Delta variant spreads "between people more efficiently than even the Alpha variant that was first detected around December, January 2021. As of today, the Delta variant has been reported in 96 countries and we expect that the Delta variant will continue to spread."
2. The factors that contribute to the spread of COVID-19 are the variants of concern, including the Delta variant, increased social mixing and increased social mobility increasing the number of contacts between individuals, the relaxation or the inappropriate use of public health and social measures and the uneven and inequitable distribution of vaccines.
3. When it's your turn, get vaccinated ("Vaccines are incredibly effective of preventing severe disease and death"). Make sure that you get the full doses. ("If you are required to get two doses, make sure you go back for that second dose so that you could be fully protected against severe disease and death") .
4. "Too many people around the world are not yet vaccinated or have not yet received the full vaccination course. Therefore, people remain susceptible to infection and they may remain susceptible to severe disease and death. This is why we continue to recommend taking a comprehensive approach using all of the tools that we have at our disposal to prevent ourselves from being infected in the first place. In addition, if we are infected, to pass the virus to others. Now, we recommend continuing to adhere, to reinforce adherence to all of the measures that we have, all of the tools that we have at our disposal. Follow the local guidance that is issued in your area and make sure that you take control over what you do every day and reduce your opportunities for being infected. So remember, this is a dynamic situation and we are learning more every day about these variants of concern. So for the time being, do everything that you can to keep yourself safe and keep up with the latest information," Dr Maria Van Kerkhove concluded.
5. Responsible agencies are striving hard to vanquish the virus. Mark the recent record of 10 million doses per day. However, many of us are failing to follow collective, responsible, behaviour in wearing masks, avoiding crowds, practising hand sanitation among others. All said and done, only COVID appropriate behaviour can presently save everyone.

 

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A Ph. D. from the University of Leeds, UK, he is a medical physicist with specialisation in radiation safety and regulatory matters. He was a Research Associate at the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees.