Surging Delta, Booster Shot, Vaccine Mixing and more
The column highlights the intertwining issues of the spread of the delta variant, the imminent third wave, the benefits of vaccinations, other COVID variants, booster vaccine and vaccine mixing strategies
Till date, according to WHO, the highly infectious delta variant has spread to 111 countries (India Today online, July 14, 2021). There was nearly 3 million new Covid cases globally last week, a 10 per cent increase in infections that was accompanied by a three per cent increase in number of deaths globally, reversing a nine-week trend of COVID-19 incidence globally. According to WHO, the highest number of new cases were reported from Brazil, India, Indonesia, and the UK. It says that still more transmissible COVID-19 variants could emerge. This combined with relaxation of public health measures, increased social mobility and mixing may lead to significantly higher number of cases, hospitalizations, and deaths especially in countries with low vaccination rates.
Third Wave: Hint from R Value?
Among all the Covid variants, delta is currently the globally predominant strain.
India now faces the twin dangers of low vaccination rate and rising effective R number. According to Dr V K Paul of Niti Aayog, the rate of fall of active COVID cases has come down in the last several weeks (news18.com/; last accessed, July 17, 2021). Daily fresh cases hit the lowest mark on July 12, 2021 with 32,906 cases but since then the number has been steadily going up. Daily confirmed cases have remained stable at the range of 40,000 cases for the last few days.
About 73 districts in India still show positivity rate of over 10% and 47 of these are in North East India.
The R value or the effective transmission rate signifies how fast the coronavirus spreads from person to person. This value in India was the lowest in May 2021 but is now increasing rapidly. According to Sitabhra Sinha, Institute of Mathematical Sciences, Chennai; India's R number came below 1, i.e. it was 0.98 around May 11, 2021 and since fell down to the lowest point, 0.78 around June 16, 2021 (the peak value was about 1.37 during March 9-April 11, 2021). But the R value subsequently started rising again in part due to easing of restrictions and lack of Covid-appropriate behaviour. It shot up from 0.78 to 0.88 between June 20 and July 7, 2021. The R number exhibited a new high of 0.95 on July 16 (ndtv.com). Though the average R value is sill below 1 across India, the concerning trend is that it has crossed this threshold value of 1 in some states, e.g. Kerala, 1.1; Tripura, 1.15, Arunachal Pradesh, 1.14, and Manipur, 1.07 etc.
As the R number is rising our vaccination rate is falling. This is the double trouble India will be facing, at least for the near future. As of today India has fully vaccinated only 5.9% of its population. Contrast this with some other countries that have fared much better: UK, 53.3%; US, 49%, Germany, 46%; Brazil, 15.9%. It's now amply clear that no vaccine is 100% effective to protect us against Covid infections. But data across the world have conclusively shown that vaccines are highly protective against hospitalizations and deaths, even from the globally surging delta variant. But many scientific studies have indicated that this beneficial protection would be most effective only after getting two jabs of the vaccine. Therefore, administering the first shot to all eligible population as quickly as possible, giving the 2nd jab to elderly and co-morbid individuals immediately, increasing the vaccine availability and approving more vaccines (besides the two currently used vaccines), and approving the use of a Children's vaccine soon would be required to prepare for an imminent third wave in India (and Manipur). In addition, public health measures such as masking, sanitization, social distancing and avoidance of crowding need to be strictly enforced for many more months to come.
Vaccines prevent hospitalizations and deaths
Several studies have indicated that vaccines (especially 2 doses) protect us from hospitalizations and deaths. One such study was conducted by Indian Council of Medical Research (ICMR) during the peak of the 2nd wave from April to June 2021. It included 677 cases that comprised of 592 individuals who had received 2 doses of vaccine and 85 individuals who got just 1 shot, who later got breakthrough Covid infections. It was found that hospitalizations were only 9.8% and deaths only 0.4% among the fully vaccinated people (Hindustan Times, July 17, 2021). Thus, it was shown beyond doubt that even though vaccinations may not prevent infections, the number of hospitalizations and deaths were much lower in people who have received both doses of the vaccine. However, it must be pointed out that the study has been as of now only published as a preprint and is yet to be peer-reviewed.
Another study was done by Niti Aayog on 1,17,525 police personnel in Tamil Nadu during the peak of the 2nd wave triggered by the delta variant. Of these, 17,059 received no vaccine (20 died in this group), 32,792 got a single shot (7 deaths were reported in this group) and 76,673 people received 2 jabs of the vaccine (only 4 deaths occurred in this category). Dr V K Paul, Niti Aayog member, claimed that one dose gave 82% protection from death while two doses gave 95% protection from deaths due to COVID-19 (HT, July 16, 2021). One more study was performed by National Institute of Virology, Pune to decode the reasons why people who got 1 or 2 vaccine shots still get infected with Covid-19. The study included 53 samples from Maharashtra, 181 from Karnataka and 10 from West Bengal which were subjected to genomic sequencing after getting post-vaccination infections. Delta variant was observed in the majority of the samples; the other variants found included alpha, kappa, delta AY.1 lineage (delta plus) and delta AY.2 lineage. It was shown that vaccination conferred more than 99% protection against death even in the presence of the virulent delta strain, according to Dr Yadav, a member of the research team (TOI, July 17, 2021). Fever was the most common symptom observed in these breakthrough infection cases (69%), followed by bodyache including headache and nausea (56%), cough (45%), and sore throat (37%).
All these studies described above demonstrate that vaccinations prevents severe disease, hospitalization and death. This beneficial correlation has also been amply observed in the UK, Canada, and Israel.
When is the third wave coming?
According to Dr Samiran Panda, a senior ICMR scientist, the third wave will hit India by the end of August 2021 (India Today TV, July 16, 2021). The country may log nearly 1 lakh cases of daily infections in this new wave. He says that, if the virus doesn't mutate to a more transmissible form, the situation will be similar to that of the first wave. If the virus mutates further, the scenario could be worse. Dr Panda, however, affirms that the third wave may not be as severe as the second wave. ICMR has also done modeling studies together with Imperial College London (ICL) that indicated that low vaccination rates and easing restrictions may trigger a possible surge in COVID-19 cases. The take-home message is that while vaccinations must be rapidly scaled up, we must closely monitor when and where public health restrictions could possibly be eased.
The study published in Indian Journal of Medical Research stressed the need for avoiding mass gatherings and wearing masks to contain the spread/severity of the third wave. It also hinted at the likely impact of the third wave due to low vaccination rates in India. There's the imperative need for ramping up vaccinations to mitigate the drastic impact of Covid infections. Dr Panda also hinted at the test positivity ratio as a guide for easing restrictions.
On the other hand, Dr Vipin Srivastava, physicist and former Pro VC, University of Hyderabad, is of the opinion that the third wave in India possibly began on July 4, 2021 (Business Standard, July 12, 2021). He made this conclusion based on his observations on the pattern of the number of cases and deaths in the past 463 days. He says that, whenever there is a transition from an increasing trend to a decreasing trend in daily deaths or vice versa, the daily death loads (DDL) fluctuate wildly. Such fluctuations were observed at the end of first week of Feb. 2021 (on the eve of the 2nd wave in India). He says, the same trend was observed on July 4, 2021 and it likely indicates the onset of the third COVID-19 wave in India.
The WHO Chief, Dr Tedros Ghebreyesus, also warned of an early stage of COVID third wave (news.un.org/; July 14, 2021). He delineated the major factors triggering a fresh wave of Covid infections globally that includes the dominating spread of the delta variant, the shocking vaccine inequity (parts of rich countries have fully vaccinated over 50% of their populations while poor nations, e,g., many African countries are yet to fully vaccinate even 1% of their populations), and lack of enforcement of public health measures.
Variants & vaccines
It's natural for viruses to mutate as they infect human cells and make copies of their genetic blueprints, during which small mistakes may occur in the copying process. Mutations are more common in viruses that use RNA as their genetic material. However, all mutations need not lead to variants with significant changes in their structure or physiological behaviour. Nonetheless, some mutations create variants with increased transmissibility or with potential to cause more severe disease or resist vaccines or treatments/tests.
There are 4 VOC till date: alpha (B.1.1.7), beta (B.1.251), gamma (P.1), and delta (B.1.617.1) (Indian Express, July 16, 2021).
Alpha has 23 mutations of which 8 are located in the spike protein. Of these 8 spike mutations, 3-N501Y, 69-70del, and P681H-have the greatest impact. The N501Y mutation allows the spike to attach more tightly to the human ACE2 receptor while the other two mutations increase transmissibility.
Beta has 8 mutations of which 3 are significant: N501Y, K417N, and E484K. As in alpha, N501Y enables the virus to bind more tightly to the ACE2 receptor and the other two mutations help the virus evade immunity more easily. Gamma has 11 mutations in the spike protein, of which N501Y and K417T help the virus bind to human cells more tightly and E484K mutation enables the virus to be more resistant to antibodies.
Delta is now the fastest spreading variant. It has several key mutations of which L452R and D614G help the virus to bind to human cells more tightly while the P681R mutation enables the coronavirus to evade immunity more easily.
Besides the 4 variants of concern (VOC), SARS-CoV-2 now has many variants of interest-eta, iota, kappa and lambda- and other variants that may become VOC and help trigger a fersh wave of COVID-19 infections in clusters of various regions of the world or even globally
Some countries think that a third dose (booster shot) of the vaccine may now be needed for certain groups of individuals such as transplant patients and other patients with weak immune systems (Hindustan Times, July 15, 2021). Israel has already started administering a booster shot of the Pfizer vaccine to immunocompromised patients.
France also approved a similar third-dose policy for the elderly and those with weak immune systems. However, there are as yet no comprehensive studies on whether a thord dose helps, and, if so, who needs a booster dose and when. The first large study on booster shot is currently underway in Norway.
There's also talk of the effectiveness of mixing vaccines, e.g. 1st shot of AstraZeneca vaccine followed by a 2nd dose of Moderna/Pfizer vaccine. Such mixing have been reported to trigger more potent immune responses. One such study was recently published in the leading science journal Nature (July 15, 2021).
Thailand, which has recently seen a surge due to delta variant, is now talking of a Sinovac (inactivated virus vaccine) combined with the AstraZeneca vaccine (viral vector vaccine). The Thai health officials believe that such mix-and-match strategies may help achieve the enhanced immune response of two doses in just 6 weeks instead of 12 weeks if you have to use 2 shots of either Sinovac or AstraZeneca vaccine.
However, WHO Chief Scientist, Soumya Swaminathan has sternly warned against booster shots and vaccine mixing. Her major concern is that there is limited data about the benefits of vaccine mixing. She says that we must wait for detailed studies on mixing various vaccines. While such data are awaited, individuals must not decide about mixing vaccines for themselves. Immunogenicity and safety of different combinations of vaccines need to be evaluated carefully before public health authorities approve such strategies on a wide scale.
As an editorial in the prestigious medical journal, The Lancet Microbe (Jan. 1, 2021) says, "Vaccines will be instrumental in the control of COVID-19, but their global distribution will be challenging and their effect won't be immediate." So, in the meantime, we must not let our guards down and we must still strictly observe the non-pharmaceutical interventions such as the major SOPs of the use of face masks, physical distancing, and hand hygiene and avoidance of 3 Cs: crowded places, close contact settings, and closed spaces (with poor ventilation). We must religiously follow the protocol of 'test, track, and treat' for months to come. If possible, the public health authorities must take steps to prevent large gatherings such as weddings and death ceremonies, music concerts, and large meetings. The 'hoi polloi' must voluntarily practice the 3 Ws (watch your distance, wear your masks, wash your hands frequently) and avoid the 3 Cs: crowded places, closed contact settings, and closed spaces.
Meanwhile, we must enhance the pace of vaccinations across India, including Manipur, in a big way.
Also Read: Possible measures for Manipur