MOST drugs for COVID are re-purposed drugs, i.e. medicines developed for another disease and now used for treating Covid. For example, Remdesivir is an antiviral drug developed for treating Ebola but later re-purposed for COVID-19 (it's another matter that it would soon be dropped from the standard treatment protocol for critical COVID).
There has been so far no drugs specifically targeted against SARS-CoV-2. This was before the arrival of the monoclonal antibodies (mABs). What are these molecules? These are synthetic (man-made) Y-shaped antibody molecules that mimic the natural antibodies made inside the body after an infection. In fact, mABs are made in the Lab by isolating the most efficient WBCs (say, a B cell producing antibodies), making clones of such cells, culturing them and producing efficient antibodies that neutralize the pathogen, SARS-CoV-2 in this case.
On May 26, 2021, Mohabbat Singh, an 84-year-old man from Haryana became the first COVID patient in India to be injected with an mAb cocktail made by Roche company in Medanta Hospital, Delhi. The cocktail contains two mAb molecules-casirivimab and imdevimab-that targets different areas in the SARS-CoV-2 Coronavirus, preventing it from entering and replicating inside human cells. It's like two border patrol commandos preventing a militant intruding into a country's boundary by holding his arms by each of the commandos.
Who are to be given this medicine? Not all may be benefitted by this mAb 'miracle drug.' It's meant for mild-to-moderate patients who're in the first week of infection. It's advisable to be given to patients as soon as they get a COVID-positive result or, at least, within seven days of getting infected. This drug must not be used in hospitalized patients with severe COVID or those with supplemental oxygen therapy.
As per preliminary information from reliable sources, the following high-risk groups wil be most benefitted by the mAb therapy:
1. 65+ patients in early phase of infection
2. Covid patients with diabetes
3. Covid positive mild-to-moderate patients with other co-morbidities e.g. obesity, lung or kidney disease, cancer and transplant patients etc.
The cons of the treatment are availability of infusion centres e.g. OPD blocks (as the drug must be given in slow IV infusion lasting an hour or so, and the area mustn't pose risk to other patients, high cost (about Rs. 60,000 per dose), and possibility of anaphylaxis or other allergic reactions (so the administration of the drug must be dome under expert medical supervision).
This cocktail has been shown to work even against variants, including the B.1.617.2 strain. Other companies such as Eli Lilly and GSK have also come up with similar mAb cocktails. In India too, Zydus Cadila has requested regulatory approval for trial of its mAb drug, ZRC-3308.
We can hope that it gets approval soon and its drug enters the market soon (hopefully the Indian drug will be much more affordable and help prevent hospitalizations of many poor Covid patients in India especially Manipur).
After Medanta, several other hospitals e.g. Apollo, Delhi and other hospitals in Chennai and Indore have started using the mAb cocktail. There're no reports of adverse effects so far. The relevant public health authorities in Manipur may start exploring if the Roche drug (casirivimab + imdevimab) may be imported soon and administered to certain sections of Covid positive pateints to prevent their possible hospitalizations and deaths (at least to those patients who can afford the cost)! For those who cannot afford the expensive drug, we must work out possible mechanisms by which they may get access to this investigational drug.
Trajectory of Variants
According to an update given by WHO, the B.1.617 variant (double mutant), first detected in India, is now found in 53 countries globally (Business Standard, May 27, 2021). This lineage is now reported to have 3 sub-types: B.1.617.1, B.1.617.2, and B.1.617.3. The report says that the B.1.617.1 sub-variant has been found in 41 countries, B.1.617.2 in 54 and B.1.617.3 in 6. As per analyses in various sources, the B.1.617.2 sub-lineage seems most concerning.
The B.1.617.1 strain has been declared by WHO as a variant of concern (VoC), in addition to B.1.1.7 (UK variant), B.1.351 (South African mutant), and P.1 (Brazil lineage), which were earlier declared as VOC. The double mutant (B.1.617) has been called a VoC due to its proven increased transmissibility. Moreover, its potential for enhanced disease severity, higher risk for reinfection and increased resistance to neutralizing antibodies is currently under active investigation.
In a study of 69 healthcare workers in Apollo Hospital, Delhi, who have been vaccinated (fully or partially with CoviShield; 51 both doses, and 18 single dose), and became COVID positive post-vaccination, 48% were infected with the B.1.617 lineage, followed by other variants (Indian Express, May 27, 2021). This means that CoviShield (AstraZeneca) vaccine cannot fully protect an individual against the B.1.617 variant, even after receiving the full regimen of two jabs. However, the level of protection among various vaccines e.g. Spunik V, Pfizer, Moderna, JNJ may vary against this lineage or other lineages.
Public Health England has recently conducted a study in this regard, covering the period from April 5 to May 16, 2021 (preprint, not yet peer-reviewed) (see https://www.gov.uk/; last accessed May 29, 2021). It was found that:
- The Pfizer vaccine was 88% effective against symptomatic disease resulting from the B.1.617.2 variant, two weeks after the 2nd dose, compared to 93% effectiveness against the B.1.1.7 variant (formerly called Kent or UK variant).
- AstraZeneca (CoviShield in India) vaccine (2 doses) was 60% effective agaisnt symptomatic disease from the B.1.617.2 variant compared to 66% effectiveness against the B.1.1.7 variant.
- Both vaccines (single dose) were just 33% effective against symptomatic disease resulting from the B.1.617.2 variant, 3 weeks after the first dose, compared to 50% effectiveness against the B.1.1.7 strain.
The analysis included data of 1,054 people confirmed to be infected with the B.1.617.2 sub-type through genomic sequencing. This study probably indicates that the AstraZeneca vaccine possibly takes longer to reach maximum effectiveness as compared to the Pfizer Vaccine. It also clearly indicates the importance of the 2nd dose to ensure strongest possible protection SARS-CoV-2 and its variants.
Possible Need for Booster Vaccines?
We really don't know definitively how long the immunity against COVID-19 lasts, after infection or vaccination. So far, the duration of this protection was estimated as ranging from a few months to less than a year. However, two new reports give us the heartwarming news that immunity may last much longer, maybe one year or much longer (The Economic Times, May 29, 2021). Nonetheless, these developments much be taken with a few caveats.
Actually immunity against a pathogen e.g. SARS-CoV-2 has two arms: neutralizing antibodies produced by our immune system's B cells and cellular immunity mediated by activated T cells. Also, our immune system retains a memory of past infections and will mount prompt and more potent immune response upon subsequent infection by the same pathogen. This kind of immunological memory is mediated by the so-called 'memory B cells.'
Both the reports studied people who've been infected with the coronavirus about one year earlier. Memory B cells persist in the bone marrow and may elicit antibodies against SARS-CoV-2 whenever needed, according to an article published in the leading journal Nature (Turner et al. Nature, May 24, 2021; https://doi.org/10.1038/s41586-021-03647-4). This finding has also been corroborated by another study published in BioRxiv (Breton et al., Dec. 9, 2020, doi: https://doi.org/10.1101/2020.12.08.416636; under review for publication in Nature).
They found that memory B cells produced in response to infection with SARS-CoV-2 and further enhanced with vaccination are so potent that they may suppress even some coronavirus variants, according to Michael Nussenzweig, an immunologist at Rockefeller University, New York, who led the BioRxiv study.
The take-home message of these studies is that individuals who were infected with SARS-CoV-2 and later got vaccinated may not need a booster dose (3rd dose for two-dose vaccines, and 2nd dose for single-jab vaccines). This condition may not apply to people who are protected by vaccinations alone. That means individuals who have not been exposed to COVID-19 and have been vaccinated may eventually need a booster shot.
According to Ali Ellebedy, an immunologist at Washington University, St. Louis, Missouri, US, who led the Nature study, the waning levels of antibodies combined with emerging variants that may partly resist the protective effects of the vaccine, means that booster vaccines may be needed to effectively protect human populations against the coronavirus.
New COVID Tests
A rapid home testing (self testing) kit has been recently approved by ICMR, Govt. of India (The New Indian Express, May 22, 2021). The kit is called CoviSelf and is produced by Mylab, a Pune-based company. Now, anyone can collect his own nasal sample in the comfort of his own home and test it for presence of absence of SARS-CoV-2, the coronavirus that causes COVID-19. Each kit is priced at just Rs. 250 and the test results can be known within just 15 minutes. After the test is completed, the tube and swab are sealed in the biohazard bag, to be disposed as a biomedical waste. Though this kit seems promising, there're the issues of false negatives, and improper details sent to ICMR portal and difficulties in contact tracing etc. to be addressed.
One must wait for CoviSelf and Dipcovan to soon arrive in Indian markets in adequate amounts with bated breath.
Pediatric Covid Surge?
The jury is still out on the possible adverse impacts of third COVID wave in kids and young people. However, as current variants surge and maybe new variants also emerge and as more and more of the elderly population gets vaccinated, one can well imagine that kids and children will be a significant target for SARS-CoV-2 in the upcoming third wave. Remember that the evolution-driven dharma of the virus is "replicate, replicate and replicate" (Cf. "The Selfish Gene" by Dr Richard Dawkins). Viruses cannot reproduce on inanimate objects. They would need living hosts (host cells) to replicate. So, whenever the opportunity arises they would infect humans-old or young, healthy or morbid, even vaccinated or unvaccinated.
As kids may be hit hard in the third wave, we must make provisions such as the following:
- Dedicated Pediatric Covid Hospitals, if possible.
- Pediatric Covid wards in major hospitals.
- Pediatric Covid care centres.
- Pediatric ventilators/concentrators and other gadgets appropriate for children.
We must also explore the possibility of introducing a pediatric Covid vaccine (ages 12-15, 2-18, 12-18 etc.) and vaccinating children as soon as possible. Already a Pfizer vaccine for children has been approved in Canada and US. Moderna is also about to introduce its pediatric vaccine. Other vaccine makers are also having their children's vaccine in the pipeline including one by Zydus Cadila company, India.
Moreover, the parents of young kids must be given priority for receiving two shots of the vaccine as if their kids become seriously ill with COVID, the care of the kids cannot be left to the doctors and nurses alone, the parents need to stay in the hospital to help take care of their wards.
Preparations for Possible Third Wave
Whether a third COVID wave will emerge or not depends on human behaviour, speed of vaccination, and the trajectory of the virus especially the VoC across the globe. The opinion is divided about the imminent rise of a third wave. But as, Dr Bhramar Mukherjee who's an epidemiologist at the University of Michigan, US says, we better err on the side of caution and assume that a third wave is coming soon.
How do we prepare for an eventual third wave, whenever that would arrive? Can we actually prevent it? If not, can we at least blunt the attack of the COVID's third wave?
We probably need to tweak the strategy of "test-track-treat" strategy in view of the surge in certain parts of India including Manipur, the predominant spread of VoC especially the B.1.617 strain across the globe, the low testing rates in rural areas and lack of high-quality healthcare infrastructure in many non-metropolitan areas of India. Therefore, testing must be enhanced in areas where Covid is currently surging, possibly by adopting self-testing kits e.g. CoviSelf; tracking the contacts and isolating positive cases in COVID care centres (and not in home isolation, as far as feasible), preventing mild-and-moderate cases from hospitalizations and deaths using the new 'wonder drugs' such as casirivimab/imdevimab cocktail drug which has been approved in India recently, and meticulous treatment of severe cases in COVID hospitals through times oxygen therapy and judicious use of steroids and antibiotics (their overuse/misuse is implicated in the alarming rise of mucormycosis in several parts of India).
The most efficient way for preventing third wave, reducing the number of infections and deaths is the mass vaccination. We need to ramp up vaccination in a big way, both nationally and also in Manipur too. India has so far got about 15% of its population vaccinated with at least one dose of a COVID vaccine and about 3.1% fully vaccinated. We need to raise the level of fully vaccinated to at least 70% of the population (bout 97 crores). To be on the safe side, India needs to vaccinate at least 100 crore people but till today it has fully vaccinated just about 4.3 crores and partially vaccinated about 20.3 crores. How to inoculate the remaining more than 80 crore people in the next few months is a perplexing issue. The encouraging news is that the government has committed to inoculate the majority of Indian population by December 2021.
According to Dr Vincent Rajkumar, an oncologist at the Mayo Clinic, US, we need to quickly vaccinate 70-80% of the Indian population, boost up health resources such as medical oxygen supply and regulate the use of critical medicines such as steroids and antibiotics in order to adequately face the possible third wave in India (Business Standard, May 29, 2021).
One can also think of establishing dedicated COVID hospitals in anticipation of the third wave.
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 appropriate authorities must take steps to prevent large gatherings such as wedding and death ceremonies, music concerts, and large meetings. The 'hoi polloi' must voluntarily practice the 3 Ws (watch your distance, wear 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. In this intricate games of chess, humanity must be one step ahead of the wily virus!
(The views expressed are the writer's own)
