Thread by @vipintukur

How well are the current #Covid vaccines performing?

In all fairness, we can say they are offering high protection against severe disease & deaths; considerable protection against the symptomatic disease; but only modest protection ag. infections/transmission of the disease 1/

To put it another way, the vaccines are contributing little to our fight against the frequent surges of the #SARSCoV2 virus.

This leads to one pertinent question:

What ought to be the prime objective of the vaccination particularly amid an intense pandemic? 2/

To resist the ongoing outbreak or avoid hospitalizations and deaths?

A four-fold reduction in the hospitalisation & death rates is not much use if we just allow infections to reach four-fold the previous peak. 3/

If we dispassionately analyze the key edifices of public health & virus transmission dynamics, the prevention of serious disease that requires hospitalization & may culminate in death contributes little to the transmission of the virus in the human population. 4/

It also does not impact the evolution of the virus. The main selective force for virus evolution is transmission, little else matters. The aim of the virus is not to kill its host, but gain high transmissibility to survive, from one host to another 5/

virology.ws/2020/08/13/the…

Hence, prevention of severe disease/deaths has immense ‘individual’ health benefits, but as counterintuitive it may seem, in the context of community & viral transmission dynamics, these events are inconsequential & add little to our fight against the pandemic 6/

Another basic learning of public health informs us about the two broad interventions to manage an infectious disease: preventive and therapeutic. Vaccination comes under the first whereas drugs/antivirals employed to treat & prevent severe illness/death, comes under the second 7/

In case of a pandemic of a new virus, the prime objective of vaccination ought to be to halt the ongoing transmission of the virus. However, the current generation of #Covid vaccines is failing to provide any significant resistance to an ongoing viral transmission 8/

There are reports that the #SARSCoV2 virus can thrive in the airways of vaccinated people, even if they're asymptomatic. And there is no difference in the amount of virus present in the nasopharynx of a fully vaccinated and unvaccinated individual 9/
context-cdn.washingtonpost.com/notes/prod/def…

We needed the vaccines that could provide ‘#sterilizing immunity, i.e., block #transmission of the virus from one vaccinated person to another vaccinated/unvaccinated person. So, they are failing to perform their primary role 10/

Even the #WHO erred in deciding the primary ‘end points’ of the Covid vaccines trials. Their entire focus was on the prevention of ‘symptomatic disease’, rather than on prevention of the ‘asymptomatic disease’ & transmission in the vaccinated subjects. 11/

However, the vaccines that do not much affect the clinical course but reduce the #transmissibility of SARS-CoV-2, could still be a more valuable intervention on a population level. 12/

Assessment of the #efficacy of a vaccine is complex for many diseases but particularly so in the case of #SARSCoV2, where the fundamental understanding of the pathogen is evolving. 13/

The potential #endpoints of an efficacious vaccine include reduction of infection to an individual, mitigation of the severity of disease, or reduction in the degree of transmission within a population 14/

The #WHO put at least 50% protection against the #symptomatic disease as an essential, primary endpoint whereas the impact of immunization on rates of onward transmission is clubbed under non-essential, ‘indirect effects’ of vaccination. 15/
who.int/medicines/regu…

However, they fail to realize the true significance of vaccines’ impact on the transmission of the disease that should have taken precedence over other endpoints while assessing the utility of vaccines. 16/

In the case of ‘stable’ endemic diseases (like Hepatitis-A & B, Chickenpox), ‘individual protection’ alone can be justified, but amid a fierce pandemic of a new pathogen, the impact of vaccines on transmission dynamics of the virus must take precedence. 17/

Why did #WHO overlook this crucial aspect? There may be few explanations. First, probably, they were not confident of the success of a vaccine against a new #Coronavirus (no licensed vaccine against SARS-1 and MERS). 18/

Second, they chose protection against severe disease and mortality as the most important efficacy endpoint since no effective therapeutic intervention was available. 19/

And lastly, it is difficult and much more labour-intensive to detect and capture asymptomatic infection with serial sampling (like weekly ‘swabbing’ for virus detection) than identifying a symptomatic illness in a vaccinee 20/

Can we vaccinate our way out of the pandemic?

One of the key objectives of large-scale vaccination is to achieve ‘herd immunity' against the pathogen. But it seems improbable to achieve herd immunity with the current generation of covid vaccines against the #SARSCoV2 virus 21/

Till quite recently, 70% is quoted as the level of vaccination required for 'herd immunity'. It is now likely to be much higher 22/

Let us see why: the standard calculation for ‘Herd Immunity Threshold’ (HIT) is (1/E) x (1-1/Ro) where E is vaccine effectiveness in reducing transmission and Ro is ‘reproduction number’ 23/

If Ro is high (~6 with #delta variant) and vaccines are 85% effective in preventing transmission, we would need to vaccinate 98% [(1-1/6)/0.85 = 98%] of the population. Achieving such a high coverage cannot be accomplished by most nations. 24/

If vaccines are less effective (that may be the case with most 'less potent' vaccines like the ones we are employing here) & & ‘Ro’ is higher, then herd immunity would not be achievable. 25/

#Delta is not the last variant to have emerged. There is a realistic possibility that new strains with even higher transmissibility (Ro) than Delta, may emerge that could lead to more widespread severe dis or evade the impact of current vaccines. 26/
reuters.com/world/uk/covid…

The way out?
A daunting task to develop vaccines that can effectively block transmission, in other words, can provide ‘sterilizing immunity’. 27/

Still, there are two options available--either employ a combination of vaccines or invest in developing a universal coronavirus vaccine, which is scientifically feasible 28/
science.sciencemag.org/content/372/65…

For the former, a ‘cocktail' of mucosal vax (intranasal vaccines that stop the virus at the portal of entry), existing vax (to mitigate severity of disease), & old, live attenuated vax as BCG, MMR, Mw vaccines (to bolster innate immunity) can be employed to maximize immunity 29/

The option of developing a ‘universal coronavirus vaccine’ that are ‘variant proof’ and capable of blocking transmission, is eminently doable, but we're not giving it the priority. 30/
nature.com/articles/d4158…

The #SARSCoV2 evolution signals the importance of rational vaccine designs. This is not the last pandemic virus. We are going to have SARS-CoV-3 & SARSCoV4 31/
theatlantic.com/science/archiv…

To conclude: Our #covid19 vaccines are good, but they could have been much more beneficial had we recognised the key difference in approach to develop a vaccine against an endemic & a pandemic disease!
My views here in @thewire_in👇 32/end
science.thewire.in/health/covid-1…