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Covid-19 ‘Variants of Concern’ have Changed the Game – and Vaccines Alone May Not be Enough

Susan Michie, Chris Bullen, Jeffrey V Lazarus, John N Lavis,

John Thwaites, Liam Smith, Salim Abdool Karim, & Yanis Ben Amor

At the end of 2020, there was a strong hope that high levels of vaccination would see humanity finally gain the upper hand over SARS-CoV-2, the virus that causes Covid-19. In an ideal scenario, the virus would then be contained at very low levels without further societal disruption or significant numbers of deaths.

But since then, new “variants of concern” have emerged and spread worldwide, putting current pandemic control efforts, including vaccination, at risk of being derailed.

Put simply, the game has changed, and a successful global rollout of current vaccines by itself is no longer a guarantee of victory.

No one is truly safe from Covid-19 until everyone is safe. We are in a race against time to get global transmission rates low enough to prevent the emergence and spread of new variants. The danger is that variants will arise that can overcome the immunity conferred by vaccinations or prior infection.

What is more, many countries lack the capacity to track emerging variants via genomic surveillance. This means the situation may be even more serious than it appears.

As members of the Lancet Covid-19 Commission Taskforce on Public Health, we call for urgent action in response to the new variants. These new variants mean we cannot rely on the vaccines alone to provide protection but must maintain strong public health measures to reduce the risk from these variants. At the same time, we need to accelerate the vaccine program in all countries in an equitable way.

Together, these strategies will deliver “maximum suppression” of the virus.

‘Variants of concern’

Genetic mutations of viruses like SARS-CoV-2 emerge frequently, but some variants are labelled “variants of concern”, because they can reinfect people who have had a previous infection or vaccination, or are more transmissible or can lead to more severe disease.

There are currently at least three documented SARS-CoV-2 variants of concern:

• B.1.351, first reported in South Africa in December 2020
• B.1.1.7, first reported in the United Kingdom in December 2020
• P.1, first identified in Japan among travellers from Brazil in January 2021.

Similar mutations are arising in different countries simultaneously, meaning not even border controls and high vaccination rates can necessarily protect countries from home-grown variants, including variants of concern, where there is substantial community transmission.

If there are high transmission levels, and hence extensive replication of SARS-CoV-2, anywhere in the world, more variants of concern will inevitably arise and the more infectious variants will dominate. With international mobility, these variants will spread.

South Africa’s experience suggests that past infection with SARS-CoV-2 offers only partial protection against the B.1.351 variant, and it is about 50% more transmissible than pre-existing variants. The B.1.351 variant has already been detected in at least 48 countries as of March.

The impact of the new variants on the effectiveness of vaccines is still not clear. Recent real-world evidence from the UK suggests both the Pfizer and AstraZeneca vaccines provide significant protection against severe disease and hospitalisations from the B.1.1.7 variant.

On the other hand, the B.1.351 variant seems to reduce the efficacy of the AstraZeneca vaccine against mild to moderate illness. We do not yet have clear evidence on whether it also reduces effectiveness against severe disease.

For these reasons, reducing community transmission is vital. No single action is sufficient to prevent the virus’s spread. We must maintain strong public health measures in tandem with vaccination programs in every country.

‘Maximum suppression’ needed

Each time the virus replicates, there is an opportunity for a mutation to occur. And as we are already seeing around the world, some of the resulting variants risk eroding the effectiveness of vaccines.

That is why we have called for a global strategy of “maximum suppression”.

Public health leaders should focus on efforts that maximally suppress viral infection rates, thus helping to prevent the emergence of mutations that can become new variants of concern.

Prompt vaccine rollouts alone will not be enough to achieve this; continued public health measures, such as face masks and physical distancing, will be vital too. Ventilation of indoor spaces is important, some of which is under people’s control, some of which will require adjustments to buildings.

Fair vaccine access

Global equity in vaccine access is vital too. High-income countries should support multilateral mechanisms such as the COVAX facility, donate excess vaccines to low- and middle- income countries, and support increased vaccine production.

However, to prevent the emergence of viral variants of concern, it may be necessary to prioritise countries or regions with the highest disease prevalence and transmission levels, where the risk of such variants emerging is greatest.

Those with control over healthcare resources, services and systems should ensure support is available for health professionals to manage increased hospitalisations over shorter periods during surges without reducing care for non-Covid-19 patients.

Health systems must be better prepared against future variants. Suppression efforts should be accompanied by:

• genomic surveillance programs to identify and quickly characterise emerging variants in as many countries as possible around the world
• rapid large-scale “second-generation” vaccine programs and increased production capacity that can support equity in vaccine distribution
• studies of vaccine effectiveness on existing and new variants of concern
• adapting public health measures (such as double masking) and re-committing to health system arrangements (such as ensuring personal protective equipment for health staff)
• behavioural, environmental, social and systems interventions, such as enabling ventilation, distancing between people, and an effective find, test, trace, isolate and support system.

Covid-19 variants of concern have changed the game. We need to recognise and act on this if we as a global society are to avoid future waves of infections, yet more lockdowns and restrictions, and avoidable illness and death.

(Susan Michie is a Professor of Health Psychology and Director of the UCL Centre for Behaviour Change, UCL. Chris Bullen is a Professor of Public Health at the University of Auckland. Jeffrey V Lazarus is an Associate Research Professor at the Barcelona Institute for Global Health. John N Lavis is a Professor and Canada Research Chair in Evidence-Informed Health Systems at the McMaster University. John Thwaites is the Chair at Monash Sustainable Development Institute & ClimateWorks Australia and Liam Smith is the Director, BehaviourWorks, Monash Sustainable Development Institute at the Monash University. Salim Abdool Karim is the Director at the Centre for the AIDS Program of Research in South Africa. Yanis Ben Amor is an Assistant Professor of Global Health and Microbiological Sciences, Executive Director – Center for Sustainable Development (Earth Institute) at the Columbia University. Article courtesy: The Conversation.)

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Interview: Indians Shouldn’t Believe the Myth that the Country’s Covid-19 Mortality Rate Is Low

Govindraj Ethiraj

[As the global Covid-19 ground zero shifts to India, as The Wall Street Journal put it, with nearly 1,00,000 cases per day, we spoke to Ramanan Laxminarayan, founder and director of the Center for Disease Dynamics, Economics and Policy, a health think-tank, also a senior research scholar at Princeton University and an affiliate professor at the University of Washington, on what the second wave means for India and what India should do to control it.

Laxminarayan, who has been working on Covid-19 from the beginning of the pandemic in 2020, spoke about how Indians should not believe the myth of lower mortality from the disease in India and take the disease seriously.]

Excerpts from the interview:

Govindraj Ethiraj: Did you see the second wave coming and how is it different this time, particularly in India?

Ramanan Laxminarayan: The second wave was always going to happen. The question was the size of the second wave. You have to remember a few things: One, the size of a wave is only apparent to us through testing today. We are doing far more testing than we did one year ago so the wave appears to be bigger, it is not necessarily bigger.

Second, Covid-19 cases are going up quite fast and that is because a year ago the country was under a lockdown, so the rate of increase was much slower because the transmission was slower. Today it is uninhibited and so we get a taste of what Covid-19 looks like when there are no restrictions. We can imagine what the country would have looked like a year back had there been no restrictions.

You also have to remember that Covid-19 works with a 10-day lag for infections and then a 10-day to two-week lag post that for mortality. Everything that we see happening now was dictated by behaviour that happened two to three weeks ago and two to three weeks ago was when there was a feeling that Covid-19 was firmly in the rear-view mirror.

Although people say, well, there was not a huge change with respect to compliance in mask-wearing and so forth, there was. The virus responds to human dynamics and a couple of weeks ago there was a lot less care about Covid-19.

Lastly, from a purely theoretical understanding of the disease, the actual size of a wave and subsequent waves are determined by the strength of the lockdown. Countries in western Europe, which had very significant lockdowns, were effective in controlling the disease then because they have smaller populations, but they had multiple waves.

India probably had a much bigger wave in the first round with a lot more people infected and therefore it took a while for it to come down and for the second wave to pick up. It is hard to predict what will happen here because it is entirely going to be a function of what restrictions are in place. Any restrictions that are put in place today will not see any effect for at least another couple of weeks.

GE: Are you arguing for restrictions at this point?

RL: I think there should be restrictions that are highly localised. This is what I had argued for in March 2020, but I realised that the government had only one choice in the absence of evidence of where the disease was and what would happen without healthcare facilities or with doctors knowing what to do.

They chose a nationwide blanket restriction in the hope that that could sort of lay things and it did. It certainly had a huge impact and data show that comprehensively. At this point, I think local jurisdictions have much better information and as cases go up people will also protect themselves a lot better.

GE: We are at about 1,00,000 cases each day right now. How much worse could it get? If everything were to converge with our vaccination efforts, where do you think we could land, from a modelling point of view?

RL: From a modelling point of view, 1,00,000 reported cases are probably more like 20-lakh to 30-lakh actual cases per day.

Not everyone is getting tested and there is not even the testing capacity to take on all of these people. Vaccination is progressing at the best rate that it can be given the current constraints, which is about three million a day, because we had vaccines manufactured from October-November 2020.

India’s actual vaccine manufacturing capacity without accounting for exports is just over two million a day. Of this, 10%-20% is Covaxin. We are not going to be able to vaccinate three million people a day in the next month or two months because you just do not have enough vaccines.

It is only a matter of time before people who have paid for their vaccines are going to want their vaccines as well and that is going to run into some rough weather. At the rate of two million vaccines a day, it is going to take us two-and-a-half years to even get 70% of the population vaccinated with two doses.

I think vaccination is part of the strategy and it is eventually the final strategy but, in the short term, it is really going to have to be people taking precautions themselves. Visibility into the virus and its variants and the consequences of the disease are the most important. It is a myth that case fatality rates are lower in India.

Any systematic evidence that we have gathered, based on literally millions of contact tracing, shows that case fatality rates in India are no different, if calculated correctly, than of other countries. All these India exception myths are simply not the case and the damage that they do is telling people that this is not as serious as it may be in the US. We have to deal with this disease seriously.

GE: You are saying we should get it out of our heads that India is an exception in terms of Covid-19? That we are the same as anywhere else in the world?

RL: The only thing that makes a difference for us is that we are a much younger population – 65% of Indians are under the age of 35 years. That block of people does not develop severe disease in general. Once we account for that, the rest is exactly the same thing.

The other thing that works in our favour is that our people who are above the age of 75 years to 80 years tend to be, oddly enough, healthier than the 75-plus year-olds in other countries. This is because of what is called selection bias – in a country, where those who have made it to 75 years are generally healthier, to begin with, because otherwise, they would not have made it to that age.

But, we have a dangerous age group which is between 45 years to 75 years. In that age group, the case fatality rates in India are sharply higher than in countries like China, Brazil, Italy and the US. That is the age group that really worries me the most and that is because we know that comorbidities are the single biggest driver of severe diseases and mortality.

If you are not diabetic or hypertensive, you do not have COPD [Chronic Obstructive Pulmonary Disease], you are not obese, then your risk of severe disease comes down significantly. It is a trick –Covid-19 is an infectious disease but it is actually a disease that gets us for non-communicable disease conditions.

GE: Some people have opined that we should vaccinate young people first and I think Indonesia has done it and others have maybe thought about it. Should we have gone that way and is there still time to reverse that and change the course?

RL: I would not do that for the simple reason that the vaccines do not prevent transmission generally. As far as I am concerned, the biggest value of the Covid-19 vaccine is reducing severe disease and mortality.

You may still get milder forms of the disease but if you get the vaccine, it significantly lowers your chance of dying from the disease. That is the great value of the vaccine. Why would one waste that on the younger age group? Give it to everyone in the 45+ age group and focus on just that.

Control your transmission through other methods because we have no evidence that giving the vaccine to a 20-year-old is going to prevent the 60-year-old grandparent living with them from getting the disease.

GE: You had projected last year that, at one point, the country would likely see several million people being infected by the virus either symptomatically or asymptomatically. Are we looking at a repeat of that situation? Also, is there a case to be made that not as many were infected last time, as when a lot of people get infected, they do not get infected again?

RL: We probably did have a few hundred million infections.

In fact, the Indian Council of Medical Research’s own second seroprevalence survey estimates that we underestimated infections by a factor of at least 30. If that is the case and we saw about one crore cases, you are talking about at least 30 crore cases, if not more, in that first wave. My guess is that we had had an upward of 40 crore cases.

That said, 40 crore cases in a country the size of India, just short of 140 crore, means that a lot of people were not infected. I think the people that I am seeing infected in this round are people who are sort of wealthier and they managed to stay indoors during that first phase of lockdown and they all came out during this phase, either post-vaccination or even pre-vaccination, in the assumption that this is gone.

GE: Let us say that was one half of the population and this is the second half that is now going to face the brunt and is facing the brunt right now?

RL: Absolutely, and this will continue until this wave also passes. Now the variants are really the big unknown in this entire scenario.

Variants in some instances can be thought of as a completely different virus so it is all coronavirus but if the virus changes its spike protein, then we are dealing with something different. We are not sure at this stage if people who were infected last year can be reinfected this year by a variant – that still remains to be determined.

What we do know is that vaccines are not perfect protection. We have seen a number of people getting infected even though they have been vaccinated but no surprise there because vaccines are only 60%-70% efficacious at best. I think we will see a new set of people being infected but possibly some of the old set will also have infections because of potential new strains.

GE: I am presently in Mumbai and you are in Bengaluru. Mumbai and Maharashtra are going into a semi-lockdown, there is a curfew, weekends will be shut down and Delhi has now announced a night curfew. Maybe other states and cities may react similarly down the line. Do you see the progression of Covid-19 changing?

RL: It is hard to tell because it is not just the lockdowns, it is also to do with how people actively change behaviour. There is a lot of confusion – one day, cinema halls had opened in Karnataka, the next day they closed, then they had 50%.

There is a lot of knee-jerk reaction because the economy has opened back up and policymakers are reluctant to go back into the situation which could impede the economy. I do not expect the night curfews and the [isolated or piecemeal] measures to have a significant impact on the transmission of the virus.

The only real change that will come about right now is because people comply better with masking because they are scared of getting Covid-19 or, if people stay indoors. That is a much more powerful force on the virus than an imposed lockdown.

GE: The last time Covid-19 started spreading on the western coast and then moved towards central, eastern and north India. Is it likely to follow a similar path? And therefore we have obviously got many difficult days ahead or, could it be different?

RL: It could be entirely different because at that time it was not west to east, it was mostly international airports – Delhi, Mumbai, Kerala for Gulf returnees and Chennai.

Uttar Pradesh and Bihar do not have international airports so those were not the first places with infections. Punjab and Gujarat as well. In this particular round, the virus can show up from anywhere.

The so-called UK variant is quite prevalent in Punjab for instance, because of people moving back and forth. I do not think we will necessarily see the same kind of spatial spread or that it is even possible to predict what the spatial spread will really look like.

I would instead look for cases and variance in places that appear to have low levels of cases now and take proactive action rather than being reactive. It is just too late for Maharashtra at this point to respond with night curfews.

I know they have to be seen as being responsible or something but the time to do it would have been a few weeks ago. This is hard stuff – it is not as if epidemiologists also have a good handle on when it is going to come back and they could have told the Maharashtra government to be prepared.

We are learning about a new virus and learning as we go along and we really have no template for this. Hindsight is 20/20 but it is very hard to look forward. The big variant here, apart from the viral variant, is human behaviour.

GE: What do you think policymakers should be focusing on or, how should we be rallying our efforts to reduce Covid-19?

RL: I would look at the test positivity rates [the proportion of all tests that are positive for Covid-19]. Testing rates are higher today but test positivity rates are lower so we need to pay attention to genetic testing for variants to systematically track where those are and see if there is a correlation between that and the severity of the disease and the number of people in the hospitals and mortality.

If we find that going up, then it means that we are going to have to rethink our vaccine strategy because we know that some variants do not respond at all or are unaffected by the AstraZeneca and Serum Institute Covishield vaccine. We may have to switch to a different policy at a very short notice.

We would probably want to increase testing in places where there is not enough testing. I am often asked why Maharashtra has so many cases. It is very simple – Maharashtra has a lot of people and it is a large urban agglomeration.

The third reason is that Maharashtra does a lot of testing because it has a very good health system. We really do not want to get this out of control in places where we know there were not any big epidemics in the first round – Odisha, parts of Telangana, Madhya Pradesh, Rajasthan, UP, Bihar, where potentially not as many people have been infected in the first round.

I would also look at spatial spread and where it is spreading to get ahead of the Covid-19 virus. Lockdowns or any kind of restrictive measures are not very useful once the virus has started transmitting because then it is a two-week lag. We would want to impose the restrictions where Covid-19 will spread now rather than as a response to a spike in cases.

GE: We saw the peak in September 2020 and then it started going down from about a little over 90,000 cases. Now we have crossed that peak. What is the lesson from the rise and fall and then the subsequent rise of cases? If we are here today and assuming that cases would go down again, could they rise again and how do we even prepare for that?

RL: Remember the dynamics, in the first round, we were on a severe lockdown and the virus still continued to rise because you can not stop the transmission among the urban poor who are living in very close quarters.

It does take off and everyone who was within the striking range of the virus at that point got infected. The reason it started coming down is that everyone within the strike range was already infected and they were immune.

But the virus has not managed to reach either the rural areas in full force or the urban wealthier middle class, who are sitting in their homes and working on the laptop. The peak starts coming down until that point in time when this bunch also starts going outside. [Then] the virus finds new prey and starts coming back up, so this pattern is very much dependent on us.

Over time as vaccination picks up, people start taking precautions and immunity builds up in this population, Covid-19 cases will start going down. At this stage, the cost of measures, like stringent lockdowns, as a main way to bring the virus down are going to be extraordinarily expensive and will not be terribly effective.

The main way we can bring cases down is by advertising how severe the problem is so that people respond with their own behaviour. When people see their neighbours getting Covid-19, you do not need to tell them to not go out but they themselves will take that call.

(Article courtesy: IndiaSpend, a data-driven and public-interest journalism non-profit.)