April 26, 2021

expert reaction to COVID-19 situation in India

A few journalists have asked about the ongoing COVID-19 situation in India, so here some comments from scientists in case useful.

Prof Ravi Gupta, Professor of Clinical Microbiology, University of Cambridge, said:

“The B.1.617 variant has spread rapidly in parts of India, apparently dominating over previously circulating viruses in some parts of the country.  B.1.1.7 (the ‘Kent’ variant) is dominating in some parts and B1.617 has become dominant in others, suggesting both may have an advantage over pre-existing strains.

“The L452R mutation present in B.1.617 is in a key area of spike that is recognised by antibodies we make following vaccination or infection.  The mutation E484K also has this effect though little is known about the change E484Q in the B.1.617 variant.  The worry is that the two may have additive effects in making the virus less sensitive to antibodies – this is just a possibility at this stage, we don’t have confirmation of it yet.  It is possible the P681R mutation may enhances the amount of processed spike protein on the virus which we postulate impacts the ability of B.1.617 to infect cells and possibly transmit (these mutations have arisen in other strains where lab experiments have shown some of these impacts); again this is just a hypothesis at this stage, we don’t know yet.  One hypothesis is that the P681R may be able to enhance virus infectiousness to compensate for the other spike mutations the virus acquires in order to avoid the immune system – this hypothesis is based on the premise that viruses often lose infectivity when they mutate to avoid the immune system; as P681 is near the cleavage site this is its likely role.  But at the moment we do not have solid lab evidence for these predictions and hypotheses – we should know more about whether this is the case or not in the next few weeks.  Also, some of the imported cases of B.1.617 in the UK don’t seem to have the E484Q mutation – we don’t yet know why that might be and understanding this phenomenon could teach us about virus evolution in the context of previously infected / vaccinated populations.

“Given that the first wave of COVID-19 in India infected up to 50% in urban areas (https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30467-8/fulltext), it is probable that the B.1.617 confers reduced susceptibility to antibodies generated by previous infection, and possibly to vaccine responses – however, we don’t know for sure yet.  As the first wave in India was more than 6 months ago, people who were infected could now be experiencing declining immune responses and greater chance of being re-infected with a virus that is less sensitive to immune responses.  Those with the worst disease are likely to be in high risk groups who are non-immune, in other words neither vaccinated nor previously infected, including immune suppressed individuals who respond poorly to vaccination.”

(previous comments on B.1.617 variant here: https://www.sciencemediacentre.org/expert-reaction-to-cases-of-variant-b-1-617-the-indian-variant-being-investigated-in-the-uk/)

Prof Martin Hibberd, Professor of Emerging Infectious Disease, London School of Hygiene & Tropical Medicine, said:

“India is suffering from a rapid increase in COVID-19 cases that has led to the overwhelming the health care system; a situation that every country has tried to avoid.  As with other countries where this has happened, most likely this is due to a range of factors coming together to create the situation.

“Firstly, there has not been enough surveillance to allow adequate warning of the increase in cases.  Early on in 20221 there seems to have been a reduction in the number of tests done, which meant that policy was made, blind to the changes that were occurring.

“Secondly, while new variants are circulating in India, this is not uncommon for many countries in the world at the moment – it may be that some of these variants have increased transmissibility but we don’t know yet.

“Thirdly, the social distancing and other measures to control the transmission that were in place, were not adequate to prevent the ‘R’ value from increasing, given the number of cases.

“Fourthly, while India is the world’s biggest producer of vaccines, it has not had the biggest roll out of vaccination, meaning that only a relatively small 9% of people are protected so far.

“Fifthly, the disease is exposing the weak healthcare system, that remains (despite some expansion) inadequate to cope with the stresses of widespread and increasing COVID-19 cases.

“With sufficient testing and surveillance together with responsive public health policies, this terrible situation could have been mitigated.”

Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“Essentially, the large numbers being seen in India are not that surprising given the base numbers of infecteds that they are starting out with, assuming:

initially no lockdown (so efficient social mixing), and any lockdown now will take several weeks to show any impact;

with an R~1.5 (as we saw earlier in the UK in Jan 2021), each infected is potentially infecting 1.5 others – or 2 infecteds are resulting in 3 others becoming infected;

and no mass vaccination programme to further limit the spread of viruses amongst the population after several generations of transmission – especially when lockdown restrictions are being eased or not complied with completely (very common everywhere).

“My take on this as a virologist is really what is driving the virus to infect people is: a lack of immunity, and social mixing.

“India has ‘only’ vaccinated about 117 million people according to this website:

https://ourworldindata.org/grapher/people-vaccinated-covid?tab=table&time=latest in a population of 1.39 billion – so only about 8.4%.  And these vaccinees may not be evenly distributed to dilute the numbers of susceptibles in the overall population – so the population is still largely non-immune.  Also, remember that vaccines are not 100% protective, especially with some new variants.

“Also, the total number of recorded natural COVID-19 cases (likely a gross underestimate) is ‘only’ about 17 million – which does not add much to this in terms of natural immunity:

https://ourworldindata.org/grapher/people-vaccinated-covid?tab=table&time=latest

“So let’s say that the overall level of combined vaccine and natural immunity in India is about 10% – or about 140 million people – which still leaves the vast majority, 90% of the population, susceptible to the virus.

“If you look at some of the data from Worldometer (https://www.worldometers.info/coronavirus/country/india/) at the beginning of March, the number of new daily case numbers were about 15,000, up to now 25 April, where they are about 350,000 per day.  So assuming an incubation period of 5-7 days, this is about 8-11 incubation periods, which fits with an R of about 1.5 – which is what we saw in the UK earlier in January 2021.  This gives a rise of daily case numbers as (i.e. with R=1.5, each infected gives rise to 1.5 new infecteds after 1 incubation period): 22.5/33.75/50.63/75.94/113.91/170.86/256.29/384.43K – after about 8 incubation periods – with a generation time (i.e. the interval between cases) of about 5-7 days (https://www.nature.com/articles/s41467-021-21710-6).

“So the rate of rise in the numbers of COVID-19 cases is not too dissimilar from what we saw in the UK in the January peak (https://www.gov.uk/guidance/the-r-value-and-growth-rate) but the UK healthcare system was more able to cope with this because although the rate of rise of these COVID-19 cases may have been similar in the UK and India, the absolute numbers of daily COVID-19 cases in India are far higher than they were in the UK in Jan 2021.

“Also: 1) the UK was then in lockdown (so no social mixing); 2) it had a rapid and ever-expanding mass COVID-19 vaccination programme (so an increasing level of immunity with a reducing number of susceptibles); 3) the available healthcare resources per person in the UK is much higher than in India.

“These three factors may be contributory factors to India’s current situation – I’m not sure how much the variants are contributing to this overall, when the numbers of people exposed/infected with the wildtype virus are also high and relatively unchecked.”

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“There is no doubt that a humanitarian emergency is unfolding in India right now.  The stories of a collapsing health system are numerous, with reports of a lack of oxygen for hospitalised patients and bodies burning on pyres in the streets.

“India has locally made vaccines, which are being rolled out, including the AstraZeneca vaccine.  But the proportion of the population that is immunised is still very low, and alas, there are more than enough susceptible people for the virus to keep spreading.

“The test positivity rate (the proportion of people tested for COVID that return a positive test) in India is high – around 18%.  This is well above the WHO threshold of 10%, suggesting that a lot of positive cases are being missed because of a lack of testing capacity and timely reporting.  Indeed, one of the key concerns is the lack of high-quality real-time data to give an informed picture of the scenarios that are unfolding in India.  The numbers of deaths are starting to rise on a steep trajectory, and that graph will surely soar further over the next few weeks.

“There has been a lot of focus on the B1617 variant, which was first detected in India.  There is still a lot to learn about this variant, such as whether it is more transmissible and thus contributing to an increased community transmission.  It is a plausible theory, but as yet unknown.

“But it is the mixing of susceptible populations that ultimately drives the transmission of respiratory infectious diseases.  There were bold declarations from senior political figures, with Health Minister, Harsh Vardhan, saying in early March that India was in “the pandemic end game”.  Since then, there have been mass gatherings in India.  In March and April, there were state-level elections across several Indian states, which comes with associated campaigning and population mixing.  Fans attended the international cricket matches between India and England, with full stadiums and few wearing masks.  And there have been several large religious festivals, such as the Kumbh Mela, an event that occurs once every 12 years and is attended by millions.  There are recent examples from China, Saudi Arabia and Israel where key religious calendar events have been cancelled or scaled-back, to reduce the mixing of infectious and susceptible people during the pandemic.  This includes the Hajj and Chinese New Year.  India may have scaled back on their celebrations a little, but millions have been gathering for Kumbh Mela across different sites, and thousands of new coronavirus cases are already confirmed in revellers.

“See more in my Conversation article at: https://theconversation.com/covid-19-in-india-an-unfolding-humanitarian-crisis-159654.”

Previously issued comments on this topic:

22/04/2021 High number of cases and reported new variant: https://www.sciencemediacentre.org/expert-reaction-to-high-number-of-cases-and-reported-new-variant-in-india/

19/04/2021 B.1.617 ‘Indian variant’ investigated in the UK: https://www.sciencemediacentre.org/expert-reaction-to-cases-of-variant-b-1-617-the-indian-variant-being-investigated-in-the-uk/

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Martin Hibberd: “I have no conflicts to declare.”

None others received.