On December 21, Public Health England published a technical briefing document on the new cases of SARS-CoV-2 infections in south England — the so-called ‘UK strain’ that we are so apprehensive about. The cases also came with SGTF or ‘spike gene target failure’. This means that the gold-standard diagnostic test followed worldwide, RT-PCR, was failing to detect spike, one of the genes that it tries to detect to confirm whether the person concerned is infected with SARS-CoV-2. This happened because a number of mutations acquired by the UK strain affected the spike protein.

What else was reported by the UK authorities, other than the information about arrival of this new strain? Let’s begin with the good news.

Mutations in such pathogens are very common as they make millions of copies of themselves within the infected host or as they pass from host to host. Replication of the pathogen involves copying the genetic material which randomly incorporates errors at each step. These are largely corrected by inherent proofreading mechanisms present in these organisms, but at times they fail and the error stays back, as mutations.

For a virus like SARS-CoV-2, with its genetic code being written on a molecule called RNA (that is the reason this is called a RNA virus), the chances of such errors are more, as the proofreading mechanisms are characteristically weaker. SARS-CoV-2 is thus also acquiring a series of mutations leading to genetic variants of the virus causing infections in different parts of the world.

Any new strain, which accumulates considerable numbers of mutations, has chances of changing its character so much that the disease caused by them can also change. Well, it can go both ways. But possibility of a more severe disease in response to SARS-CoV-2 is scary, as the world has already seen close to two million deaths.

The good news about the UK strain has been, as asserted by the UK authority and substantiated by data in a subsequent report as well, that the new strain is not really changing the character of the human disease to a great extent. In a comparative analysis among 2,700 cases, with 1,360 infected with the wild type virus and 1,360 with the variant one, 0.89 per cent vs 0.73 per cent deaths were recorded when followed up till 28 days, which was not at all a significant difference.

And, what about the bad news?

More than a year into the pandemic, now we know that spike is the most useful tool the virus has, as it helps it to get access to human cells. Spike can be thought of as the necessary passcode that is verified by the receptionist, a molecule called ACE2, which greets the virus at the doorsteps of the human world. Such molecular receptions are physically quite close, almost like a lock and key mechanism.

Epidemiological studies in the UK point to greater transmissibility of the virus on acquisition of these new mutations, almost eight of them on the spike protein. Three of these mutations are on the specific portion of the spike that actually gets in touch with the ACE2 while attacking a host cell. The greater rate of transmission may have to do with changes in this portion which make it more suitable to talk to ACE2.

It has been estimated that the basic reproductive ratio of this variant has increased by 0.4 — compared to the same parameter for the wild type virus of 2.5, it is almost 2.9. This parameter, simply put, gives you the number of people that on an average get infected by one infected individual. A more clear idea comes from this data — on tracing the contacts notified by the individuals infected by the UK variant, almost 15.1 per cent of the contacts were found to also have contracted the infection. The estimate of this so-called secondary attack rate for the wild type virus is 9.8 per cent.

What will be the implications of these when the variant comes to India? It seems it has already been detected in quite a few numbers in different parts of the country.

Diagnostic capabilities

First, let us take note of the issue with SGTF. Widespread use of RT-PCR was never part of the general laboratory medicine workflow in the country. As some of us had noted very early into the epidemic, if a single benefit should be pointed out of this epidemic for India it will be enhancement of its molecular diagnostic capabilities, which was really restricted to very few laboratory medicine set-ups in the country. Even if the necessary equipment were available, the essential expertise was not. In an unprecedented move, basic research institutes all over the country commissioned their equipment to enhance capability in the health sector.

Moreover, RT-PCR being an intricate molecular biology technique is notorious for reaction failures. Usually two genes of the virus are targeted for detection in each test so that the technical hitches can be covered and the test becomes more specific and sensitive. Now, in SGTF, the spike gene detection is failed. If in addition technical artefacts cause the other gene — most commonly used in India is the RdRp gene which is responsible for making multiple copies of the virus — to be left undetected as well, cases may erroneously be diagnosed to be non-infected.

A lot of technical artefacts sneak into the process due to lack of expertise or failure to maintain necessary cold chain, and is expected to happen in newly commissioned testing centres. And India has a lot of them.

Anyway, greater transmission will also increase on the one hand the number of cases that need active medical attention and may progress to a severe disease even if the variant does not cause a more severe disease by itself. On the other, it will make the healthcare workers more susceptible to contagion.

Especially after the long fight they fought over almost a year, fatigue and complacency are bound to sneak in. Thus it is no brainer to assess the risk of missing cases infected with a virus which has much greater ability for transmission. The infection will spread faster and can create the possibility of overwhelming the Covid management logistics. A very prompt decision has although been taken to ramp up India’s capability and coverage for sequencing the virus by commissioning the Indian SARS-CoV-2 Genomic Consortium (INSACOG), so that any outbreak of variant viruses can be detected. This will be great ammunition to prevent undetected and undeterred spread of infections throughout the country.

A major effort should perhaps also be instituted to add programmes on detailed clinical profiling of all patients who are found to be infected with a variant so that any change in the disease course and outcome can also be recorded promptly.

Finally, us the citizens should pay heed to these developments and brace ourselves for a collective fight which may outlast our expectations. And vaccines have arrived. It will also help the fight to great extent, as we hope so badly that the variants will not be able to outwit the vaccines.

The writer is a physician-scientist and immunologist in CSIR-Indian Institute of Chemical Biology, Kolkata, and is actively engaged with research on patients with Covid

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