What a Delhi Hospital Study Does and Doesn’t Tell Us About Covishield v. Delta

Sir Ganga Ram Hospital, New Delhi. Photo: Hospital website

The study focused on infection rates and severity of illness among the staff of Sir Ganga Ram Hospital, New Delhi.
There are two important issues with the data and how it is presented, which prevent us from applying them to the general population
The study has resulted in some misleading headlines and unwarranted concerns over the efficacy of vaccines.

A recent study from India said that a single dose of the Covishield vaccine offered little protection during the country’s second major COVID-19 outbreak, when the delta variant was dominant. News coverage of the study was of a piece with concerns that new variants of the novel coronavirus could render the existing crop of vaccines ineffective.

Let’s take a closer look at the study, at breakthrough infections more broadly and what these incidents mean for the future of the COVID-19 pandemic.

The study

The study, released a little over a week ago as a letter to the editor of the European Journal of Internal Medicine, focused on infection rates and severity of illness among the staff of Sir Ganga Ram Hospital, New Delhi. Most of them had received the Covishield vaccine and experienced the second wave between January and April, 2021. At the time, of their staff members, 2,716 had received both doses of the vaccine; 623 had received one dose; and 927 were unvaccinated.

A group of doctors at the hospital performed a multivariate analysis to understand the differences between the groups. They adjusted for confounding factors that could impact infection rates and severity, such as age, gender, previous infections, health worker status and underlying health issues (like diabetes and heart disease). Around 33 staff members from their centre also had their samples sequenced, with over half confirming that the infection-causing strain was the delta variant.

As expected, those who received both doses of Covishield had a significantly better disease course – compared to those who were unvaccinated. The incidence of symptomatic infections was 24% lower; that of moderate to severe disease was 65% lower; the need for oxygen supplementation was reduced by 75%; and the number of deaths was 97% lower – all in the vaccinated group.

There were two additional points of interest.

First, a prior COVID-19 infection was significantly better than vaccination at preventing symptomatic infections (93% v. 28%), preventing moderate to severe disease (89% v. 67%), and reducing the need for oxygen therapy (85% v. 75%). Although the authors draw attention to this fact, it is not surprising: with most infectious diseases, natural infection confers better immunity than vaccination.

Second, there was a very small difference between those who received one dose of the vaccine and those who were unvaccinated vis-à-vis the likelihood of developing symptomatic infections (18%) or developing moderate to severe disease (37%). Compared to those who were unvaccinated, the need for oxygen supplementation was reduced by 53% and the risk of death by 69%. These figures are both lower than the corresponding ones from the pre-delta-variant era. Recall that a single dose of Covishield was shown to reduce hospitalisation by 85% and death by 80%.

The doctors use this data to hypothesise that a single dose of Covishield is relatively ineffective against the delta variant, and a vaccination strategy that prioritises one dose for everyone before mobilising the second may not be advisable.

Also read: COVID-19: Herd Immunity Is Not Going To Happen, so What Next?

Issues with the data

There are two important issues with the data and how it is presented, which prevent us from applying them to the general population – but which is what the study’s authors have attempted to do.

First, although the total number of participants in the study was impressive (4,276), the sub-groups used for the analyses are quite small. For example, only six patients died (five unvaccinated and one vaccinated). Representing these as percentages – a single dose of vaccination reduced the likelihood of death by only 69% when compared to the unvaccinated group – is misleading. For context, the percentage of employees who were vaccinated and still died was 0.16%.

Second, this study is centered around employees of a hospital, where we know infection rates are higher because sick patients have higher viral loads and more comorbid illnesses, which then affect transmissibility – as opposed to exposure in the general public, which is likely to carry lower risk. This would explain why their results were at odds with other, larger studies, which have shown a single dose of Covishield was more efficacious (between 30% and 60%) at protecting against infection.

This study reiterates the fact that the delta variant is more transmissible and has a higher risk of causing ‘breakthrough infections’ – COVID-19 infections that occur in the fully vaccinated population. But the inference that the vaccines are ineffective overall against new variants is wrong, and the headlines associated with this point have been misleading.

It is also important to note that a single dose of vaccination was never supposed to confer significant protection against infection. The second dose is meant specifically to boost the immune response. The timing of the second dose of vaccination is also contentious. During the second wave, the interval between both doses had been increased from four to 12 weeks, probably more, as a way to deal with vaccine shortages instead of as a method to increase vaccine efficacy. With a marked improvement in vaccine availability in India and a policy change reverting to the four-week interval, the panic associated with the study’s findings is unwarranted.

In order to understand how the virus variants can affect the vaccinated population and what we can do to prevent this, let’s take a closer look at breakthrough infections.

Also read: What Next for the Delta Variant?

Breakthrough infections

The emergence of newer variants of SARS-CoV-2 has paralleled a rise in breakthrough infections after vaccination – but in absolute numbers, they are still uncommon. These infections are a result of the virus evading the immunity that vaccination confers, and can happen in several ways.

The delta variant can reportedly replicate up to a thousand-times faster than other variants. Such rapid increase of its population overwhelms the local immunity in the nose and throat of vaccinated individuals. The resulting higher viral load means more viral particles shed into the environment, infecting others.

The major concern remains those who are yet to be vaccinated – availability is still a major problem in many parts of the world – and those who can’t be vaccinated (e.g. immunocompromised individuals or those on therapies that suppress the immune system). Data shows that most people being hospitalised following a COVID-19 infection are unvaccinated.

Rather than risk individual patients being infected, this represents a more sobering reality: in the absence of vaccine equity, no one can be fully immune. As the developed world prepares for booster shots, estimates suggest that under 2% of the African population has been vaccinated. This harsh reality was reflected as the delta variant spread unchecked through Europe and the US just as they were preparing to lift local restrictions.

We know that SARS-CoV-2 will continue to mutate as time passes. The best-case scenario is arguably endemicity – where there are seasonal surges and variations, but no waves or health infrastructure collapses (hopefully). Until then, we must continue COVID-appropriate behaviour and vaccination, not only in our country but around the world. Only then can we all truly be safe.

Dr Narayana Subramaniam is a head and neck surgical oncologist at Sri Shankara Cancer Hospital and Research Centre, Bengaluru.

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