As we battle the next wave/peak of the pandemic, Dr. Purvish Parikh discusses about the dilemma on vaccine considerations for COVID-19, players involved, safety among vulnerable populations, and the international regulations, and logistical problems that present new challenges.

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With compliance fatigue and burnout setting in, normal sensible community precautions (like wearing masks, washing hands frequently and sanitising places), the COVID-19 pandemic is raising its ugly head in the form of a second wave or a second peak (don't want to split hairs on terminology). On the one hand, Center for Disease Control (CDC), USA wants to relax the quarantine period to 10 days (7 days if the person tests negative) and on the other, Hong Kong no longer allows more than 2 persons from gathering together.

There is also the concern about long term consequence of COVID-19 infection, even amongst people who had a mild course of the acute illness. This includes interstitial lung fibrosis, kidney impairment and diabetes mellitus. Estimates are that about 10% of the 1,500 such patients diagnosed in the civic hospitals of Greater Mumbai have required hospitalisation.

The good news is that December 1st, 2020 has become a major landmark in the fight against the COVID-19 pandemic - with the Pfizer vaccine getting emergency regulatory approval in the UK. (Remember, Sputnik V got regulatory approval in Russia on 11th August 2020 even though phase 3 data was not available). With a 95% success rate, 28 days after the first dose, it is the brightest ray of hope in the fight against COVID-19 (study included 43,661 people. Of the 170 confirmed COVID-19 cases, 162 were in the placebo arm and 8 in the vaccination arm). The company has pledged to produce 50 million doses in 2020 and about 1.3 billion doses by the end of next year.

Six other companies in the race with promising vaccines in the final phase of development have also promised to make available millions of vaccine doses. To look at this from another angle, the global airlines community is happy with this opportunity to get out of the red. They will need to gear up to transport 8000 Boeing 747 loads (of 110 tons each) - if the world is to receive the 1.4 billion doses of vaccine to end this pandemic. This would translate into regular flight shipments spanning the next two years.

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COVID-19 exposure = natural immunity: Should vaccines still be considered?

It is estimated that about 60 million people of the Indian subcontinent already carry protective antibody titers against COVID-19. Even if random testing (serosurvey) was sufficiently robust to allow accurate extrapolation to the entire population, antibody testing has its challenges. While a positive test confirms past exposure, several questions remain an enigma.

1. COVID-19 virus has several antigens on its surface as well as internally. Only four of these antigens have been selected to develop antibody kits - two types of spike proteins (S1 & S2), one nucleocapsid (N) and one receptor-binding domain (RBD). Thus antibodies detected by one kit will have a different implication as opposed to those detected by another technique for antibody detection.
2. Each antigen (and the corresponding antibody) has different parameters with respect to the time of appearance, time duration for circulation in the blood and rate of decay.
3. Antibody titer is only a surrogate because it does not have a linear correlation with the protective virus-neutralising function of the immunity. Routine testing for virus-neutralising antibodies is not permitted in diagnostic laboratories because it carries the risk of handling live virus (a task limited to only the most secure research labs).
4. When people who never developed COVID-19 symptoms or those who had only mild symptoms were tested, their antibody titers fell by 50% in a month. Studies also showed them becoming undetectable after a gap of two months in patients with proven infection.
5. Antibodies are not the only way our body's immune system works against viral infections. There could be cellular immunity, particularly that carried by memory lymphocytes, a process that is yet to be evaluated with respect to COVID-19.

These are the reasons why vaccination should still be considered for patients who have been previously infected with COVID-19. Why take a chance? Why worry when, as healthcare frontline workers, we continue to get exposed to varying strains of the virus? Why have the need to continue with precautions to protect against viral exposure (N95 masks, PPE, etc).

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The case for taking the COVID-19 vaccine

1. The Russian government has already vaccinated 100,000 individuals and also shown a 95% efficacy. They have 2 million doses already manufactured and have just announced that their plan is to do mass vaccination in their country.
2. The Japanese parliament has also passed a bill to ensure free vaccination to their citizens - with federal funding (ultimately and indirectly paid by taxpayers).
3. The UK government has agreements with vaccine manufacturers to procure 350 million doses (their population is only 67 million).

Are you (or the world ) willing to take the risk of leaving your future in the hands of nature?

The Scripps Research Institute, USA brainstormed about vaccine stimulated versus natural immunity against COVID-19. They are predicting that vaccine protection shall be superior and suggest that universal vaccination provides the best solution. (How they have reached this conclusion is beyond comprehension - especially since none of the vaccine trials have ever studied its effect, benefit or safety in any person below the age of 15 years).

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Are the COVID-19 vaccines safe?

In general, vaccines have been around for a long time. Common side effects of currently licensed vaccines include pain redness/itching at the site of injection, fever, chills, rigors, headache, bodyache, nausea and vomiting. They have been reported by 50% of recipients, are usually mild and subside within a few days without any pharmacological intervention. Having said that, we must be aware that hardly anything is known about the long term efficacy or safety of the vaccines that will hit the market soon.

Will it follow the influenza vaccine story and be required on an annual basis? Will it give partial protection against other corona viruses in the future? Only time will allow us to answer such questions with any certainty.

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Vulnerable populations

Vaccine availability is going to be limited and in phases. The health authorities have identified and triaged groups of individuals based on their vulnerability to COVID-19. Commonly this includes frontline workers, elderly population, those in assisted living and people of all ages with co-morbidities that make them at high risk for death in case they are infected by COVID-19.

Obviously, the government cannot make the vaccine available to everyone on day one. Projections vary from six months to two years and even more - as the time that will be required for completing the vaccination process in any country. So, it might be necessary to purchase the vaccine, even before becoming eligible for the free quota.

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Vaccine tourism

An extreme but realistic possibility of getting vaccinated early is to travel to a country that has made the vaccine available commercially. UK is likely to be the first country. Several travel agents in India are already offering packages (flights, hotel accommodation, meals) that can be appropriately labeled as vaccine tourism. Those who can afford, will not only have the opportunity to get vaccinated early but also spend a few days away from the pandemic routine; getting a break and recharging their batteries. They could also have freedom from the fear of COVID-19 infection.

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International air travel regulations

Currently, international air travel is restricted. Certain countries do not allow entry of anyone other than their citizens or permanent residents. At the other end of the spectrum are those that have no restrictions as long as the COVID-19 test is negative and the incoming passenger complies with quarantine regulations.

Today, India has a bilateral air-bubble with about 14 countries. International air travel is unlikely to be normalised in the immediate future, due to the fear of resurgence of COVID-19 in the concerned country. The availability of an effective vaccine would transform the scenario in a dramatic manner.

This reminds me of another vaccine - against yellow fever. WHO website states that "countries mandate yellow fever vaccine to prevent international spread of the disease by protecting countries from the risk of importing or spreading yellow fever virus." This could easily be extrapolated to COVID-19. Such discussions are currently being debated online across social media. I believe that international visa procurement, travel and immigration will be easier for those who are vaccinated against COVID-19.

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Logistics nightmare

Most countries have a structured and well-established universal vaccination program, usually for infants and children. India has done a fabulous job, as evident from the eradication of polio. This expertise, trained personnel and system shall be valuable in rolling out the COVID-19 vaccination program right up to the last mile.

Unfortunately, this vaccine raised unique logistic problems, the most important being transport and storage of huge quantities at very specific temperatures. The Pfizer vaccine requires the most extreme -70 degree C storage. So they had to innovate and claim to have developed temperature-controlled and GPS-enabled boxes that use dry ice to keep its vaccine at around -70 degree C for up to 10 days. Each of these boxes can carry 975 doses of the vaccine.

Common sense tells us that this would be possible only in the most stringent of conditions and only if the container is not opened during transit (time when box is open needs to be limited to less than one minute and can be done twice before the dry ice needs replenishment).

The effect of ambient temperature is also to be taken into consideration. When we talk about room temperature, it is commonly intended to mean 20 deg C (which is why such countries can serve red wine without being chilled). We know that several parts of India (and the world) will have local ambient temperature in excess of 40 deg C (e.g. Nagpur in summer). Whether the dry ice packed box still control temperature at -70 deg C is anyone's guess. No wonder CDC USA has had to develop a unique Vaccine Administration Management System (VAMS).

To understand the magnitude of the problem, let us begin from the first step - bulk procurement from the manufacturing facility (which could be thousands of miles away in another country). One 10 ml vial weighs 50 grams, and its tamper-proof, shock-proof packing weighs another 50 grams. This would make each COVID-19 vaccine's weight as 100 grams per vial dose. Assuming 500 doses are packed in a bigger box, its weight would be 75 kg (50 kg net weight plus 25 kg packing). Three hundred of such boxes shall make 150,000 doses, at a collective weight of 22,500 kg.

The weight of each regular empty 20 foot shipping container is 2300 kg and it can normally carry cargo weighing 25,000 kg. For shipments between 2 and 8 degree C, active shipping system is used with large, thermostatically controlled containers powered via internal batteries or an external electrical source coupled with large cooling fans. This increases the container tare (empty) weight to 4600 kg and reduces the load capacity reciprocally to 22,700 kg. So, one 20 foot container can carry 150,000 doses of the vaccine at 2 to 8 deg C. A Boeing 747-8F (like the one used by UPS for cargo shipments) can carry four such 20 foot containers. This would mean that one planeload will comprise of 600,000 vaccine doses.

But none of the shipping specialists (like DHL, Blue Dart or Fedex) detail commercial capability lower than 2 degree centigrade on their website. Two specialists for ultra low temperature shipment are Cryoport Inc and Germany-based va-Q-tec. Cyroport's capsule containers, which use dry vapour liquid nitrogen keep goods as cool as -150 degree C for up to 10 days (holding time: up to 10 days). But their capacity is only 75 vials of 2.0 ml or 22 vials of 10.0 ml each.

Let us assume that these companies have scaled up successfully. Assuming that this was 100 fold, it would mean 2200 vials of 10 ml each. Even this will be woefully inadequate to solve the shipment logistics. What solution these ultra low temperature shipment specialists have come up with remains hidden from public access and is probably patented.

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Fear of shipment theft

Organised crime will find a new kind of "liquid gold" by targeting vaccine shipments. Interpol is already geared up to monitor, share information and assist law enforcement agencies across the world to prevent this. Let us take the example of 800,000 doses of the Pfizer vaccine that are to be shipped from Belgium to UK next week. The price quoted by the company is USD 19.5 per dose. The retail price of this shipment will be a staggering 15.6 million USD. Let us assume shipping and handling cost of USD 1 million. That still leaves 14.6 million USD as the official price. Keeping in mind the demand in the grey market, such a shipment can easily yield four times the price, at just under 60 million USD.

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Fake vaccine bogey

There is a message circulating on WhatsApp that says that the fake vaccine manufacturers are ready with their "product copy" since the last three months. They are just waiting for the original to be launched so that they can roll in the moolah. But seriously, the World Health Organization (WHO) has stated that the global counterfeit medicine is $30 billion. It will therefore not be surprising if we are plagued with a flood of COVID-19 vaccines of questionable authenticity. Some of the fake medicines are packaged so sophistically that even the authorities have difficulty in separating the real from the copy.

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In conclusion, the long and short of the dilemma

Taking into consideration all the facts and uncertainty surrounding the COVID-19 vaccine, my wish of being vaccinated at the earliest opportunity (even if I have to pay for it) is to protect myself and my family from the risk of death during the ongoing pandemic. I hope that the vaccines that become available shall reduce infection, disease as well as its transmission. Until such a time as this vaccine protection becomes available to me, I shall continue following the currently recommended precautions (social distancing, N95 mask, frequent hand washing, PPE, etc.) as diligently as possible.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Purvish Parikh is a Precision & Medical Oncologist from Mumbai.