Lockdown is not the ultimate solution to the pandemic related woes - Dr Digbijay Mahat
KATHMANDU, JUNE 19
At a time when the several South Asian nations including Nepal have been hardly hit by the second wave of coronavirus pandemic, government's lack of preparedness has been exposed as hospitals faced acute shortage of oxygen and other medical supplies, putting lives' of hundreds of Covid-patients at risk.
Even though the government has imposed a nationwide lockdown to curb the current situation, altering the modality now and then, the rate of infections and deaths has remained not decreased significantly.
In this regard, Mausam Shah 'Nepali' of The Himalayan Times talked with US-based Nepali cancer research scientist Dr Digbijay Raja Mahat, who was one of the members of COVID-19 researchers' team while developing the CRISPR kit/ technology to detect the coronavirus in the USA; and Dr Sargam Raja Mahat, who has been closely following all aspects of COVID-19 vaccine development, to know and understand about the deadly virus and the pandemic as a whole. Excerpt:
What do you make of the ongoing second wave of COVID-19 being more contagious and spreading at a rapid rate in comparison to the first wave in Nepal?
Although we do not have adequate sequencing data, all the available evidences indicate that the ongoing second wave is driven by new variants. Limited sequencing of SARS-CoV-2 genome from samples collected in Nepal clearly indicates the prevalence of new variants in our communities. The cases and mortality in our southern neighbor - where SARS-CoV-2 genome has been sequenced relatively widely - has been driven by new variants that are more contagious. Inevitably, those variants have made their way to Nepal.
Some key alterations in the genome of new variants, primarily in the spike protein, make them more efficient in binding, engaging, and entering the human cells. Increased efficiency in invasion into human cells enable them to proliferate more rapidly, thus altering the incubation time and clinical manifestation of the disease. Not only that, reports indicate that the variant may also have better ability to evade the antibodies generated by natural infection and vaccination.
These features make variants appear more deadly. However, increased deaths do not necessarily mean the variant is more lethal. A widely transmittable variant will infect more people and eventually result in higher deaths. For example, if non-mutated SARS-CoV-2 causes two deaths out of 100 infections, then a more contagious variant can result in four deaths by infecting 200 people, but the mortality rate in both cases is 2%. So far, we do not have a concrete evidence of increased lethality in the new variants circulating in our region.
There was a 'hypothesis' of sorts being floated earlier that 'Nepali immunity' factor was the reason behind low infection rate and corresponding deaths. But there is no evidence to support that assumption given the current situation. What are your thoughts on this particular premise?
When the virus was rampaging through other parts of the world in 2020, we were left unscathed. This apparent discrepancy fueled the speculation of pre-existing immunity in our population, attributed to previous exposures to related pathogens, which is also the central premise behind the "hygiene hypothesis." We also believed that this theory of previous exposures might have conferred cross protection to our population, which led to less severe cases and deaths. It was a feel-good narrative, which many of us wanted to believe.However, it has been disproven now. We were lucky to evade the first wave that engulfed much of the world. Currently, we are one of the most affected nations, and our regions is among the hardest hit.
The beauty of science lies in its ability to strip the false sense of security, serenity, or superiority. It is humbling to know that we are just as vulnerable as others to COVID-19, despite our perceived "advantage", which many "experts" believed was conferred by our unique terrain, herbs, and fond recollection of bravery.
"The only solution to the current pandemic is the vaccine." Dr Sargam Raja Mahat.
What is your take on the Nepal government halting the vaccination drive amid the pandemic? How could the authorities have systematised the inoculation process during the lockdown to ensure safer administration of the vaccines- as opposed to the consequantial mismanagement?
It is a no brainer that the authorities could have continued the vaccination, instead of halting it, in the middle of pandemic. In fact, the best tool we have in the fight against COVID-19 are the vaccines. Depriving the vulnerable population of vaccine is akin to asking them to go to a war without their best weapon.
We have seen images of orderly vaccination in countries of similar socio-economic status. Could the pause be driven by the dwindling stockpile of the Sinopharm vaccines that were administered during the onset of second wave? Government authorities and medical personnel in the grounds would know better.
People are really curious about the efficacy of various kinds of vaccines that are available worldwide. During the second wave, we have noted that many people that were infected earlier are getting re-infected, and even the people that were fully vaccinated are showing severe symptoms. What could the reason be? Is its because the vaccines are getting ineffective against the new variant?
No vaccines were advertised as being 100% efficacious. We were certain of breakthrough cases and we are seeing them. However, the overwhelming evidence indicates that these breakthrough cases are much less severe. Vaccinated people who get reinfected can largely avoid hospital stays. The important thing to understand here is: this is exactly how vaccines are supposed to work.
The immunity conferred by vaccines is much more effective at protecting from severe disease and death than preventing viral entry and infection. With heightened scrutiny on the pandemic and vaccines, we are excessively cognizant of incidences that defy our expectations, such as breakthrough cases.
Nevertheless, it is true that some vaccines are less efficacious at preventing mild to moderate infection caused by new variants, but almost all of them have over 95% efficacy at preventing severe disease and death.
It will serve us well to remember that the protection conferred by COVID-19 vaccines is better than vaccines against several other diseases, such as annual flu vaccines.
COVID-19 vaccines are remarkably efficient in protecting from SARS-CoV-2 variants too. When people talk about immune protection, they mostly think of antibodies, but our immune system is much more than just antibodies. We also have unsung heroesin this battle - T Cells - and vaccines elicit T cell response very well. Recent studies have shown that while some variants may evade antibodies generated by infection or vaccination, they still have negligible impact on T Cell recognition.
There is a lot of confusion regarding the use of plasma therapy for treatment of infected people with severe symptoms. While hospitals are using this method, many experts have shared that this is not really very useful while many countries have halted its use for Covid treatment. Your take?
Based on overwhelming available evidence, convalescent plasma therapy is ineffective against hospitalised people with severe symptoms. The main goal of using plasma therapy is to provide antibodies that can neutralise the virus and halt further replication. By the time patients get hospitalised with severe symptoms, virus has replicated enough, therefore, providing antibodies via convalescent plasma serves little to no purpose.
By that time, the enemy is not the virus but patient's own immune system. Having said that, plasma therapy could potentially work if high titer plasmais is used within 3-4days of symptom onset because the sooner you can neutralize the virus, less severe the symptoms will be and the recovery could be expedited. Timing is key when it comes to convalescent plasma therapy. This has also been proven by the monoclonal antibody cocktail treatments used in the USA.
Informed citizens and media have to play their constructive role rather than fueling unfounded conspiracy theories to deter vaccination.
Is there any scientific reason behind why USA wants to offload its 60 million stock of AstraZaneca vaccine?
US does not need AstraZeneca vaccines. FDA has approved three highly effective vaccines -- Moderna, Pfizer, and Johnson & Johnson.
Almost half of the US population has already received one dose. There are reports indicating the availability of more vaccines in the US than the number of people who want them. The supply pledged by the three companies exceed the demand, rendering AstraZeneca's 60 million vaccine surplus.
Dr. Anthony Fauci also recently opined that US may not be needing AstraZeneca's vaccines.There should be no confusion or qualms regarding the efficacy or safety of AstraZeneca vaccines and therefore, we don't see any reason to second guess USA's decision of donating them. Not only AstraZeneca, President Biden recently announced that US will be donating further 20 million doses of other FDA approved vaccines. It is an obvious and smart decision to donate them to needier nations because it is abundantly clear that no one is safe until everyone is safe.
Are the AstraZeneca jabs that the US has committed to provide to South Asian countries as effective as the other vaccines?
First of all, I would consider us lucky if we receive significant amount of vaccines from the US. There are many nations around the world lining up for these surplus vaccines.There is nothing wrong with those vaccines. It has the same formula as the Covishield that Nepal has used. High vaccination rate is the only way out of this pandemic.
Informed citizens and media have to play their constructive role rather than fueling unfounded conspiracy theories to deter vaccination. The best vaccine is the one that gets into our arms.
Where do you actually see the problem is in Nepal government in securing vaccines and effectively implementing the program? As you have been continuously putting in efforts to help the government procure vaccines from the US, what are the hurdles that the authorities here may have had to face?
The major hurdle in procuring vaccines by Nepal government is the availability of vaccines in the world market. We have tried our best to help Ministry of Health & Population and Nepal Government's diplomatic missions in their pursuit of vaccines. We connected with MoHP with Moderna's Senior VP Patrick Bergstedt who is responsible for vaccine allocation.
Patrick had a zoom call with the then MoHP spokesperson Dr Jageshwor Gautam and chief of the National Immunization Program Dr Jhalak Gautam.
We also connected MoHP with J&J's senior executives Sarthan Ranade and Jyotsna Ghosal who look after South Asia region, and Vice President of Global Vaccines Jonathan Collard. Both companies eventually declined Nepal Government's request of direct purchase and instead asked Nepal to go through COVAX.
Our status as a LMIC nation, subjugated voice in the world stage, and the lack of "dispensable resources" (many nations invested and paid for the vaccine development without certainty of return of their investment) prevented us from timely procurement of vaccines. Companies manufacturing vaccines have non-uniform pricing structure. For example, Moderna decides price based on country's GDP.
They would have to sell the same vaccines to Nepal at a lower price compared to, for example, Canada, which disincentivises companies to sell to countries like Nepal.
Do you think the virus will come back again in the form of third wave and how contagious it would be?
It is impossible to rule out another wave for two reasons. First, the majority of the world remains unvaccinated, and as we have learned in the past month, a new wave can emerge in one part of the world and swiftly spread to others. Second, the sustained level of infection is a perfect breeding ground for new variants. As we have learned, some of these variants are more contagious and more resistant to vaccines.
It is difficult to rule out the possibility of new variants that could be even more resistant to vaccines. In our opinion, another wave is possible if we fail to expedite equitable vaccination programs covering rich and poor nations equally. when majority of the population is left unvaccinated, virus continues to replicate and with each replication, probability of new variants emerging increases. Just by chance, some variants can be more transmissible or, even worse, more adept at evading antibodies generated by natural infection or vaccination.
Therefore, we should make every effort possible to procure vaccines as soon as possible and roll out a fool-proof plan to tackle vaccine hesitancy. Vaccines do not save lives, vaccination does. Even a 100% efficacious vaccine will have no effect if it does not get in the arms of people.
What does Nepal need to do in the coming days to deal with the pandemic?
The playbook to fight the pandemic is open to the world. Some nations have succeeded, and some have failed. We are not experts on public health, so we will defer to the recommendations of public health experts of Nepal in this matter.
Is the lockdown only way out to deal with the virus?
Lockdown is not a popular solution. However, it is the only effective control measure during this unprecedented surge. While there are mortality reducing therapies like dexamethasone and tocilizumab, they do not prevent transmission nor have any effects on viral replication.
They simply calm the cytokine storm that our immune system generates in the later part of the disease. Vaccines are the ultimate solution to get out of this pandemic, and there are studies to show that they can start working as early as 12 days after the first dose.
Unfortunately, we may not be getting enough vaccines to make meaningful impact for a few months at least. Until then, social distancing is the best way to slow transmission and unfortunately, lockdown is the ultimate resort to minimize transmission.
"Lockdown is not the permanent solution to the virus, however, adhering to the government safety standards would help to keep the infection rate low by the time vaccines are delivered." - Dr Digbijay Mahat
Some people have been saying that the vaccines have failed to shield people from getting infected. Your comments?
We have to understand the definition of end point to measure vaccine's success and failures. Vaccines were never designed to completely prevent infection so it is unfair to label vaccines as failure due to few cases of breakthrough infections.
However, data from vaccine trials show that they are highly efficacious at preventing severe illness, hospitalisation, and death. While we are observing and acknowledging breakthrough cases in the vaccinated population, some of which could result in severe symptoms, the chances remain very very low. We do not have clear data in case of Nepal, but USA's CDC routinely publishes these data.
As of May 10, there were 1359 breakthrough cases that led to hospitalizations or deaths out of 115 million fully vaccinated people. That is a 0.001% breakthrough rate amongst fully vaccinated population. If you consider that some of those deaths and hospitalizations (384) were unrelated to COVID-19, the probability drops down to 0.0008%.
That is a miniscule number compared to how many people have been protected. A recent report from India indicated that the Covishield's effectiveness against breakthrough infection in health care workers was 97% and the hospitalization rate was only 0.06%. Reports from Italy further reinforce the effectiveness of vaccines. Vaccines have been a resounding success.
In your opinion, how long would it take for science and technology to come up will full-proof solutions to entirely overcome the pandemic?
We don't want to speculate the length of this pandemic or the probability of a new wave. However, although we are in the midst of the deadliest phase of the pandemic in our country, there are good signs around the corner.
The vaccines are working. The production capacity of vaccine manufacturing companies have increased and more vaccines will be available in the world market. The COVAX program, hopefully together with world's rich nations, will deliver vaccines to countries in need. Even the citizens of rich nations, who are privileged to be vaccinated first, will realize the need for the entire world to be vaccinated for them to be safe and their advocacy for poor nations will amplify.
Scientists are already working on Pan-Coronavirus Vaccines that holds the promise to mitigate potential pandemic at its root. Similar preemptive work is ongoingin the discovery of Pan-Coronavirus monocolonal antibodies, which could be used to treat future corona virus caused diseases.
The issue of vaccine equity was overshadowed by the crisis, but let's hope it will gain momentum and the equitable vaccination becomes a reality. Once the dust settles, we will have time and motivation to ensure mechanisms to prevent such pandemic in future – both the origin and the management.
Read also: Of trials, errors, and eventual success