Novel Corona virus: The Known and the Unknown

 

As India recorded more than 3.5 mn COVID- 19 cases by August end, climbing to the third position in the world after the US and Brazil, and perhaps, as Dr Ashish Jha, Director of Harvard’s Global Health Institute, commented, is on the path to record more cases than any other place in the world, there came some good news to cheer us up: at last the second phase of the clinical trial of the much-awaited University of Oxford COVID-19 vaccine commenced in Pune on 26 August. Two volunteers aged 32 and 48 were administered the first shots of the Covishield – 0.5 ml dose – at Bharati Vidyapeeth Medical College and Hospital at around 1pm and were discharged after half-an-hour of administering the vaccine. The hospital authorities also said that a second dose will be given to these two volunteers after 28 days. Then they will finally be examined after 180 days for ascertaining whether the vaccine is successful or not.

This is how a vaccine is usually evaluated during its development phase:  it should go through three phases of rigorous experimental testing on human beings, which are commonly known as clinical trials, to judge its safety and efficacy. Phase I is the first study of safety: it is carried out with an average sample size of less than 100 people to find the acceptable level of the dose of vaccine which will not cause serious side-effects. In Phase II, safety and efficacy are tested together with a sample size of a few hundred people.  Then the so identified effective and safe doses are passed on to Phase III testing. It is a detailed evaluation of effectiveness of vaccine in comparison with some existing treatment or in its absence, some such similar looking treatment having no effect, usually called Placebo, carried out on a few thousands of people. Once administered, these people are tracked over months to determine whether the people receiving vaccine get infected less than the people who were given placebo (control lot). This phase of study also affords scientists to check for side-effects if any that they could have missed to notice in the earlier phases involving small sample sizes. It is only after the Phase III trial that the vaccine, if found safe and effective, is recommended to regulatory authorities for release for massive use. It is against this background that scientists from the west including Sir Patrick Vallance of UK, Anthony Fauci of the US and even WHO repeatedly said that a vaccine is not expected before 12-18 months. 

In this context, it is also essential to bear in mind that RNA viruses are widely known for frequent mutations. It is reported that about 10 lineages or subtypes have already evolved from the original Wuhan virus type. As per the revised nomenclature, the prominent subtypes are identified as: 19A, 19B, 20A, 20B and 20C. A defining mutation of former A2a lineage was: D614G. It means that in the new lineage, D614G, there is an amino acid substitution at the 614^th position in the viral sequence from aspartic acid in the pre-existing lineage to glycine. This mutant is reported to be a super-rapid spreader. It is also reported that this mutant, transmitting itself very efficiently, outcompeted and replaced all other lineages in Europe and North America. It however, could not get such a hold in East Asia.

It is further reported that all the lineages evolved in 2020 – 20A, 20B, 20C – have this D614G mutation. These lineages are now reported to have become dominant across India. However, it is still not known if there is any impact of this mutation on the functional characteristics of the virus.  It is also reported that no credible evidence was noticed to say that these different lineages have any differences in their mortality rates. In fact, according to Dr Partha Majumder, President, Indian Academy of Sciences, “all of the lineages are roughly similar in their ability to cause death upon infecting a host [man].”

A similar view has been expressed by Dr Mishra, Director of Centre for Cellular and Molecular Biology, who says, “though Covid-19 virus is mutating, there is no evidence yet to show the mutant as “bad or worse” and hence “so far there has been no threat to vaccine making”.

As per Dr Majumdar, there is no credible data to show that temperature, humidity and other such environmental factors have any impact on transmissibility of the virus. He further added that he is not aware if any epidemiological study was carried out with large sample size that has provided evidence to the effect that the mortality rate in India is lower than in other large geographical regions. He however, agreed that prior exposure to other coronaviruses and related viruses can have an impact on lowering the infection rates but he is not sure if it has any impact on mortality.  It is perhaps, keeping all this in view that he said in an interview to The Hindu that to be successful in arresting the spread of novel Coronavirus, “a vaccine must be efficacious to protect the recipients against the entire diversity of the virus.”

Now coming back to the likely date when the vaccine will be available, it becomes clear from what the medical college and hospital in Pune that commenced the second phase of trail said that it may take six more months to know the final outcome. Here it would be worth recalling what Dr Mishra of CCMB said: it is not good to raise hopes of the people “too much” when the vaccine is months away and “we do not know if there is going to be one.”

Importantly, we all also must remember the categorical statement Dr Mishra made in the said virtual meet on RSTV: “For now, we have to manage the pandemic without drugs or vaccine. We do not yet fully understand how the virus affects the body, but we do know how it spreads from person to person” and hence for the present, “the effective vaccine continues to be social distancing, masks and hand hygiene” and he was hopeful that “we will win the war with these measures.”

There is yet another disturbing feature which was reported in June that merits our attention:  the antibodies of SARS- CoV-2 produced in the body of an infected person may last only for 2-3 months after infection. That means, the vaccine might also do the same thing. Recent reports also indicate that people are getting re-infected with the virus, may be of a different lineage. The very recent reports about a repeat infection from Hong Kong and the US is perhaps a silent pointer towards this phenomenon or infection of a mutant – sub-type (?).

So, let us remember what we know for sure and ardently practice it: wear a mask properly covering mouth and nose, maintain social distancing and practice good personal hygiene, particularly, hand hygiene. And that’s the only way to stay Sthiram and Sukham, for now, before a vaccine, if any, arrives!