New COVID-19 hotspots and probable models of third wave
Vaccine upgrades or altogether new vaccines may be required to face the challenges of new COVID surges triggered by variants.
It's now clear that the highly transmissible delta variant is going to become a globally predominant strain, unless a "fitter variant" arises which may displace it. The delta strain has now spread to at least 104 countries (Times of India, July 8, 2021). Though Covid cases are dipping in India, several countries across the globe are now struggling with a fresh surge in COVID infections, possibly triggered by the highly contagious delta variant. The rapid spread of the delta variant has compelled a growing number of countries in parts of Australia, Europe, Asia and South America to reimpose lockdowns and other public health restrictions. The worst-hit nations/regions include Indonesia, New South Wales, Australia; Myanmar, Bangladesh, South Korea, Portugal, Spain, and Germany etc. Even Iran is talking about an imminent 5th Covid wave. Even though the US is a highly vaccinated country, parts of it, especially South and Southwest US are now reporting a surge in cases. The surge in cases are mostly occurring among unvaccinated populations.
The delta variant is already the predominant strain in the UK. It's also fast becoming the dominant variant in the US, accounting for nearly 52 per cent of all new infections (USA Today, July 8, 2021). Cases and hospitalizations have risen by about 11 per cent and seven per cent respectively in the past week while deaths have declined by 13 per cent, according to the Centers for Disease Control and Prevention (CDC), US. The delta variant accounts for nearly 98 per cent, 93 per cent and 81 per cent of samples sequenced in UK, US, and India respectively (covidvariants.org/; last accessed, July 10, 2021).
As of July 7, 2021 (fortune.com/; last accessed, July 10, 2021), the World Health Organization (WHO) has listed four variants of concern (VOC) and four variants of interest (VOI). The VoC are alpha (B.1.1.7), beta (B.1.351), gamma (P.1) and delta (B.1.617.2). The VoI are eta (B.1.525), iota (B.1.526), kappa (B.1.617.1) and lambda (C.37).
Among these, delta is already known to trigger the alarming rise in infections across the world. Two other variants that may pose risks for a new wave of infections which the world is closely monitoring are the lambda and kappa variants. The lambda variant was first detected in Peru in August 2020 and is supposed to have triggered the deadly Covid pandemic there causing the alarming number of fatalities (Peru has the worst Covid fatality record in the world followed by Hungary).
The variant has since been found in at least 31 countries. As per GISAID data, 2,253 genome sequences of lambda lineage have been detected in various countries. This variant has been found in the UK, US, Israel, Spain, Germany, Italy, France, Switzerland, Turkey, Australia among others. Luckily, the lambda variant hasn't been detected in India so far. However, with easing of restrictions and opening of international flights, this variant may emerge in India in the near future.
Lambda accounts for 82 per cent of recent cases (May-June, 2021) in Peru, 32 per cent in Chile and 37 per cent in Argentina. The variant has also invaded other South American nations e.g. Argentina, Brazil, Columbia, Ecuador and Mexico. This variant has an unusual combination of 7 mutations in the spike protein. One of them, L452Q (similar to L452R in delta variant) may make the virus more infectious. There are other mutations that may make the variant to cause more severe infections or resist antibodies generated by infections or vaccines.
However, detailed studies are still needed to ascertain if this variant is indeed more transmissible or cause more severe infections or evade immune response. Studies in Chile and Peru which are yet to be peer-reviewed indicate that the lambda variant may be more infectious than other variants or more resistant to neutralization by antibodies. We need to closely watch the trajectory of this variant and its likely arrival/emergence in India and Manipur.
Two cases of kappa variant have been reported from UP (Indian Express, July 10, 2021). Out of 109 samples sequenced at King George Medical University, Lucknow; 107 was found to be the delta variant and the rest 2 to be the kappa variant. Kappa is a cousin of the delta variant. The health authorities, however, say that this variant is of no serious concern. It's less dangerous than the delta variant. Another concerning development is that of delta plus (AY.1) mutant; 138 cases of which were recently reported from Tripura, a state in NE India, which is also currently struggling with a surge in Covid cases (HT, July 10, 2021). We need to scale up genomic surveillance of Covid cases in Manipur, to ascertain if the continuing surge in our state is driven by delta, delta plus or another SARS-CoV-2 coronavirus variant.
None of the currently available vaccines is 100 per cent effective against infections. That doesn't mean that vaccines are not useful. The contrary is true: most vaccines are highly effective in preventing hospitalizations and deaths due to SARS-CoV-2 coronavirus including the currently surging delta variant. A new study has found that two doses of vaccines are highly effective in preventing hospitalizations triggered by the delta variant (Indian Express, July 6, 2021). The scientific analysis has been published by Public Health England (PHE). The study included 14,019 cases of the delta variant, of which 166 were hospitalized.
It was found that Pfizer vaccine's effectiveness in preventing hospitalization with delta was 94 per cent after the first dose and 96 per cent after two doses. The corresponding figures for the AstraZeneca vaccine (CoviShield in India) were 71 per cent after the first dose and 92 per cent after the second jab. The study also found no deaths among the vaccinated individuals. However, it must be pointed out that the study is yet to be peer-reviewed. AstraZeneca also claimed that data from PHE study suggests that vaccine effectiveness against milder symptomatic disease was lower-74 per cent against the alpha variant and 64 per cent against the delta variant.
Another factor which is highly significant is that the recent COVID surge in various countries and clusters of hotspots in some countries is quite correlated with the low rate of vaccinations among the affected populations. Therefore, to preclude the surge in infections by delta and other variants and also to prevent hospitalizations and deaths, it's very important to increase the pace of vaccinations to ensure that the majority of the population is fully vaccinated if possible, or partly vaccinated, if not; as soon as possible.
According to a new study by Yale University, the US vaccination program has prevented about 2,79,000 additional deaths and up to 1.25 million additional hospitalizations. Nearly 48 per cent of the US population has been fully vaccinated so far (USA Today, July 8, 2021). Another study by the famous Pasteur Institute in Paris published recently in the premier scientific journal Nature (July 8, 2021) emphasizes the importance of full vaccination to offer robust protection against the delta variant. It showed that a single dose of Pfizer or AstraZeneca vaccines "barely inhibited" the delta variant whereas a second dose "generated a neutralizing response in 95 per cent individuals", even though it was a little less potent that against earlier versions of the virus (Sunday Morning Herald, July 9, 2021). This study once again highlights the importance of full vaccination for protection against infectious variants such as delta strain.
The study also found that immune response in people who recovered from previous COVID infections was 4 times weaker against the delta variant. However, a single vaccine shot dramatically raised the antibody levels, conferring protection against delta and two other mutants. The take-home message is that Covid survivors must get vaccinated rather than relying on natural immunity.
Taking account of the less effectiveness of vaccines against variants such as delta especially in elderly and co-morbid individuals, Pfizer company has recently reported that its trials showed that a third dose (booster shot) of its vaccine is safe and highly effective and sought approval of its booster vaccine. However, the US FDA has decided that a booster shot is not needed yet and ruled out approval of a booster vaccine as of now. However, a booster (3rd jab) is likely to be used in several countries by the end of this year or early 2022. In case a more vaccine-resistant variant emerges, vaccine upgrades or altogether new vaccines may be required to face the challenges of new COVID surges triggered by variants.
Third wave scenarios
Many modeling studies are currently underway to predict the likelihood and severity of the third wave of COVID-19 in India. We may consider two such studies: the State Bank of India (SBI) study and the Sutra Model of IITs.
According to the SBI report (Hindustan Times [HT], July 5, 2021), India may see a third wave as early as August 2021 and it would peak in September 2021. It further said that the third wave could be "as severe as the second." However, the study claimed that the number of Covid fatalities would be less than the corresponding figures in the second wave.
On the other hand, the Sutra Model involving scientists in IITs and other Institutes, says that a third wave can peak in India in October-November, 2021 if Covid-appropriate behaviour is not followed (HT, July 4, 2021). The third wave may see half the number of daily cases during the second wave. However, Prof. Manindra Agarwal, a member of the Sutra Model panel, warned that if a new virulent variant emerges, the infection can spread faster during the third wave. This model delineated 3 scenarios: optimistic, intermediate and pessimistic scenarios. The optimistic case assumes that life goes back to normal by August 2021, and there is no new mutant. The intermediate scenario considers that vaccination is 20 per cent less effective in addition to optimistic scenario assumptions. The pessimistic case assumes that a new, 25 per cent more infectious mutant spreads in August 2021 (it's not delta plus).
He continued "If there is no significantly faster spreading mutant, the third wave will be a ripple. And if there is such a mutant, the third wave will be comparable to the first one. However, if there is an immune-escape mutant, all the above scenarios will be invalid !"
To prevent/postpone/mitigate/tackle a possible third wave, all of us must take care of a few things: adherence to masking/hand sanitization/social distancing, avoidance of crowds, religious/cultural/political/recreational gatherings, stepping up the pace of vaccinations and reinforcement of public health infrastructure etc.
Most of us wrongly assume that those who have "recovered" from COVID-19 are free from any further complications. But the truth is that a significant fraction of the so-called recovered people are likely to suffer from a variety of complications lasting from a few months to even a year. In other words, a subset of recovered individuals may take a long time to fully return to normal life. So there is a need to closely monitor the recovered people and also to create public health infrastructure to take care of them.
Besides lung fibrosis, brain fog, mucormycosis and multisystem inflammatory syndrome in children (MIS-C), we have recently come across some new post-Covid complications in India and across the world. We may now consider just two of them: avascular necrosis and gray matter loss.
Avascular necrosis(AVN) is also called osteonecrosis. In layman's terms, it's known as "Bone Death." Several cases have been reported in recovered patients in Mumbai and Pune. Osteonecrosis results from death of bone tissue due to lack of blood supply. It may mostly affect the hip bone but it can also affect other bones in the shoulder, knee, hand, and foot. Like mucormycosis, AVN is also associated with use of steroids during Covid treatment (HT, July 10, 2021).
Another concerning complication is loss of grey matter of the brain (The Hindu, June 24, 2021). This is probably associated with the loss of smell and taste found in many Covid patients. The coronavirus may affect regions of the brain associated with taste, smell, memory or emotions. If the virus causes loss of gray matter in memory-related regions of the brain, there is a higher risk of patients developing dementia in the longer term, say authors of the study based in Oxford University, Imperial College London, UK; and NIH, USA.
Apoorva Bhandari of Brown University, US says that the findings show a "significant though subtle grey matter loss" linked to COVID-19 infection. Thus, appropriate Post-COVID centres or clinics need to be set up to monitor symptoms in recovered patients such as breathlessness, damage in lungs or other vital organs, brain fog, anxiety. depression, memory loss, mucormycosis, MIS-C, Covid toes, bone death, and gray matter loss etc. and provide relevant therapeutic/medical interventions in time.
Certain measures would help prevent, ward off, or mitigate the third wave. One is to massively speed up vaccinations. Another is aggressive genomic surveillance to monitor the trajectory of delta and other COVID variants across the country to ascertain which variant is surging where and catch any new variant early before it leads to a deadly local outbreak. R. Sukumar, Editor-in-Chief, Hindustan Times has another two interesting suggestions (HT, June 3, 2021). One is to link the stringency of standard SOPs (3 Ms, 3 Ws, as mentioned in previous columns) in a district to the ratio of the population that has been vaccinated. Another is about deciding when and where to ease lockdowns; he suggests a possible benchmark: 5 per cent positivity rate or less for two weeks combined with vaccine coverage of a minimum of 20 per cent of eligible population (18 years and above) to permit easing of restrictions in any locality.
Possible measures for Manipur
We need to assume that there may be a third wave in Manipur too. Even if that may turn out to be a wrong anticipation, it's better to err on the side of caution. Accordingly, we must initiate measures to squarely face a possible third wave in our state. These may include:
1. Speeding up vaccinations in a big way.
2. Genomic sequencing of a subset of positive cases and surveillance of the variants including the delta variant: which COVID strains are there in Manipur, where are they, and where are they moving towards.
3. Boosting up healthcare provisions such as medical oxygen plants, tankers and cylinders; steroids, antifungal drugs, oxygen concentrators, ventilators, oximeters, masks, PPEs, sanitizers etc.
4. Strengthening of healthcare infrastructure such as construction of new COVID hospitals.
5. Provision of more COVID care centres (CCCs), more Covid beds and ICUs in existing hospitals
6. Constitution of a special taskforce for the third wave; a separate taskforce for pediatric COVID is also highly recommended.
7. Special provisions for kids such as pediatric hospitals, wards, and ICUs, pediatric oximeters, concentrators, and ventilators and strengthening of staff such as pediatricians and pediatric nurses and paramedical workers etc.