Lt Col Dr Inam Danish Khan, Dr Shashi Sudhan
In an apparently improved Covid-19 situation worldwide with initiation of vaccination, 94% recovery rate and reduction of quarantine period to 10 days by US Centre for Disease Control, three new mutants have emerged in UK, South Africa and Denmark, triggering concerns of a wider outbreak and jeopardization of existing mitigation and control efforts worldwide.
The UK mutant named Variant Under Investigation or VUI-202012/01 lineage B.1.1.7 with up to 23 spike-protein and other mutations has been detected in Southeast England and has become dominant by Dec 2020 amounting to 60% infections in UK. This new UK mutant has N501Y and P681H mutations both of which increases transmissibility by 70% due to increase in reproductive number (R) 0.4 or more. That means that it can spread easily between people. In addition, this mutant has spike-deletion 69-70del which may potentially elude immune response. This mutant has rapidly acquired 23 mutations in a couple of months and is infecting young people as well as children and causing extensive lung disease, complications and deaths. Other than UK, this super-spreader mutant is causing infections in Netherlands, Belgium, Denmark, Germany, Iceland, Italy, UAE, Singapore, Australia and many other countries. The South African mutant 501Y.V2 having K417N and E484K mutations also has high transmissibility and has been found in the UK. The Denmark mutant known as Cluster 5 is a mink-associated mutant reported in Denmark, the Netherlands, Spain, Sweden, Italy, Greece and the United States of America.
UK has declared situation out of control and imposed Tier-4 restrictions. In a globally connected world with thousands of flights, trains and ships with millions of travellers, the spread of mutant Covid-19 coronavirus is very fast and beyond control. 20 Covid-19 positive patients in India have been found from UK flights and many more are suspected. 40 nations including the Netherlands, Belgium, Ireland, Germany, Austria, Italy, Bulgaria, Poland, Russia, Hong Kong, Morocco, Iran, Israel, Turkey and India have banned direct cross border movement from UK and imposed stricter quarantine for indirect movement. Guatemala has banned flights from UK and South Africa. Saudi Arabia, Kuwait and Oman have banned all international arrivals, in sync with global response. Thousands of cargo trucks have been stranded on UK and Europe borders due to complete ban on transborder movement.
Govt of India has enhanced surveillance of all people arriving from UK in past four weeks. International airports, Bureau of Immigration, all state Govts and Integrated Disease Surveillance Program (IDSP) have been notified for ensuring compulsory RTPCR of all travellers from UK. All co-travelllers seated in same row, three rows in front and behind along with all cabin crew will be tested once a traveller is RTPCR positive. All RTPCR positive travelers will undergo gene sequencing test to identify the mutation as RTPCR cannot detect the mutation. UK mutation positive patients will be isolated in hospital and monitored for 28 days. Their community contacts will also be tested to detect spread.
This situation is somewhat similar to Covid-19 uncertainty prevailing in Feb-Mar 2020, when the exact pathogenesis, outbreak potential, clinical complications, diagnosis and prevention were not known. So far, it is being purported that the new mutants are not necessarily more severe or lethal, and vaccines are likely to be effective against them. The right answers are wired on further clinical research.
Nevertheless, it emanates caution, as coronaviruses, being RNA viruses have high potential of mutations, evasion of immune response and predisposition to repeated infections. So far there have been 50000 mutations with 4000 mutations in the spike-protein, not all of them being significant to alter viral fitness (ability to survive and reproduce). Since Covid-19 coronavirus has jumped host barrier to circulate between bats, minks, snakes, pangolins, dogs, domestic cats, lions and tigers etc, as spill-overs and spill-backs, there are changes of genetic recombination leading to mutational events due to selection pressure. Denmark has killed 17 million minks and there has been a ban on mink farming till 2022. Covid-19 is undergoing extended periods of adaptive evolution and emerging with mutants in humans too, especially when there is prolonged infection in one patient.
The first D614G Covid-19 mutant emerged in China and became dominant worldwide, with index case in Sivaganga cluster in Tamil Nadu, had 3 to 9 times increased transmissibility. The Spanish 20A.EU1 mutant and H69/V70 mutants also have higher transmissibility. Coronaviruses escape immunity over longer time periods mandating continuous molecular and epidemiological surveillance to monitor mutations.
Viruses don’t respect sociopolitical borders. The 1918 H1N1 pandemic aka ‘Spanish flu’ or ‘Bombay fever’ reached remote islands within months long before the era of globalization resulting in possibly 100 million deaths worldwide and 18 million deaths in India. The advent of Covid-19 mutants will preclude containment strategies on three known fronts, Covid-19 detection, transmissibility and vaccination; nevertheless there are many unknowns.
Firstly, conventional Covid-19 RTPCR is a two gene-based test which may be test negative due to mutants. However, apex labs test 4-genes (E, RDRP, N and ORF) to ensure detection of mutants, which is otherwise a resource and time-intensive effort. Despite targetting four genes, only Covid-19 positive result will be obtained. Detection of mutation is done by gene sequencing which is only available at very few laboratories in India. UK has been able to detect the new mutant due to extensive genomic surveillance under a network of six public health agencies under the Covid-19 genomics UK consortium (COG-UK).
Secondly, transmission will be rampant in Indian scenario with unlock strategies, festivities, transportation and socioeconomic revival. The only way to control its high transmission is by time-tested practices of physical distancing, perosonal hygiene, universal masks, avoidance of overcrowding and containment strategies.
Lastly, when the world is embracing the first two messenger RNA (mRNA) vaccines, Pfizer-BioNTech and Moderna, which have been approved for human use in US, UK, Canada and Europe, and are in the process of being rolled worldwide, mutations have unfurled suspicion and concern worldwide. Both vaccines are using synthetic mRNA targeted on spike proteins, and so far are likely to be effective with the known mutants. UK has ongoing Covid-19 vaccination program with the new Pfizer-BioNTech Covid-19 vaccine. Germany, France, Austria, Italy, Singapore, Qatar, Oman are also initiating vaccination programs. India is also planning to roll out an Indian manufactured vaccine next month. However, as more mutations accumulate in Covid-19 coronavirus, owing to its high potential for mutations, vaccines may require routine updation to include vaccine-escape mutants like H1N1 influenza vaccine for optimizing mitigation and control of Covid-19.
(The authors are incharge Microbiology Department Command Hospital Udhampur and Principal GMC Jammu)
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