Whether we like it or not, the lack of implementation of proper measures to curb the transmission of Covid-19 in Bangladesh has now taken us down the herd immunity path. It is a risky path to be on because we do not have adequate data on the duration of immunity.
Bangladesh has one of the highest vaccination records in the world, and it is primarily because people are known to follow health directives without question or skepticism, unlike other countries such as the US.
This is a powerful factor which could have been harnessed to bring down transmission rates, had there been proper measures with wide-scale awareness campaigns and strong enforcement. At least, if there is a vaccine for Covid-19 and vaccination is mandated, anti-vaccination sentiment will not be an issue amongst the masses in Bangladesh.
Generalizations do not help
It is not very useful to make sweeping generalizations like the “Sweden Model” or the “China Strategy,” in terms of adopting and implementing any strategy for a country. What strategy a country implements successfully is heavily contingent on what kind of political regime they currently have.
In order to implement South Korea’s strategy, you would need educated citizens that trust the government, and a government that is efficient and believes in data transparency.
There are also cultural factors at play -- South East Asian countries have a “culture of compliance,” and are more technology-oriented in terms of solution implementation. So, when countries like the US and the UK attempted to adopt the same strategy without contextualizing, it was breaking apart at the seams due to the mismatch in political leadership and cultural differences in citizen behaviour.
Sweden declared from the very beginning that they would not adopt China’s lockdown strategy as they do not have the authoritarian regime to enforce it, and they do not wish to import such political elements. Instead, they implemented a democratic strategy that places trust in their educated citizens to implement health directives without having to impose it by force.
The majority of Sweden’s death toll is from nursing homes which were affected before the health directives came into practice, and that still remains the bulk of the death count.
In the long run, we will see how effective each strategy has been not only in controlling the pandemic situation, but also in affecting the political climate. It should be noted that even with no lockdown, seroprevalence in Sweden remains low as their conscientious citizens practise social distancing, and the population density is low.
Where Bangladesh stands
On the other end of the spectrum, we have Bangladesh, one of the most densely populated countries in the world, where instead of lockdowns we have had mockdowns, and the infection is more or less running free, with very little awareness on social distancing or virus related hygiene practices.
Given the death toll in other countries, ours has been comparatively low. There are a number of things to consider in this respect. For one, there is definitely underreporting, but even if we back-calculate by assuming official reports to be a fraction of the actual death toll, as official numbers are said to be 6% of actual numbers, the numbers are still low in comparison.
For one, we have a demographic advantage with a younger population with our median age in the 20s. We also do not have a large number of nursing homes or an elderly population, and there may be cross-protection from cold-causing coronaviruses. In other words, there is some “immunological dark matter” that has kept our death toll relatively lower than other countries.
The latest study published on July 2 in Cell, shows that the most prevalent form globally of SARS-CoV-2, the virus that causes Covid-19, has mutated to a variant that carries the spike protein amino acid change D614G. This variant is more infectious but less severe -- a probable contributing factor to lower death counts around the world.
Therefore, given how infectious the disease is, how densely populated the country is, with no measures in place to control transmission and no awareness regarding social distancing or virus protection protocols, it is only a matter of time before we have areal pockets where swathes of people have been infected and have recovered from it. A form of areal natural herd immunity.
It is unfortunate that due to political strategies that discount people’s lives, the term herd immunity itself has become politicized. But herd immunity is a scientific phenomenon, not a political strategy. Adopting it as a political strategy is up for debate, and that is a separate conversation.
For instance, the bout of chikungunya spreading through Dhaka like wildfire, with certain areas that had cluster transmission. The next year, during mosquito season, we did not have cluster transmission any more because chikungunya is self-limiting, in that if you get infected once you will be protected from getting infected again.
In other words, having been through the disease confers lifelong immunity, similar to diseases such as mumps, rubella, etc. Hence, the next year, when one person got chikungunya and people around that person had already recovered from the infection the year before, the virus could not transmit to the surrounding persons, and these were transmission dead ends.
It is very important for us to now have seroprevalence testing to see what percentage of the population has already recovered from Covid-19, in order to gauge where we are in terms of transmission dynamics.
Given that Dhaka is the most congested city, it will be the first city to have the largest population to have recovered from the infection, and therefore Dhaka will have more transmission dead ends. There will be no more community transmission, and infection rates will decline.
However, with Eid-ul-Azha coming up as another superspreader event, we will have the infection carried from Dhaka to other parts of the country. From the news, we can see that anyone travelling from Dhaka to another country is testing positive, which means Dhaka is the possible hub now. And while Dhaka becomes a transmission dead end, we will have areal hubs all over the country as the year progresses.
Therefore, it is not useful either, to say what the peak of the entire country is, as different geographical locations will have different peaks depending on transmission dynamics, population density, and contact with infected areas.
Immunity and Covid-19
However, it will never be a safe world for vulnerable people like the elderly or the immune-compromised, or those with co-morbidities, until there is a vaccine. Even coming across a single person carrying the virus is a high risk for them.
The key issue here is that we do not know the “duration” of immunity for Covid-19. Immunity has become another heavily politicized term because of countries lifting lockdowns. One thing to bear in mind is that countries that have had effective lockdowns will have low seroprevalence rates by virtue of the fact that the lockdown was successful in bringing down transmission, and therefore they have a high percentage of the population that never got infected and therefore never developed antibodies.
So, it is futile to talk of herd immunity in countries that are implementing strict lockdowns. The idea of the intermittent lockdown strategy is to open up when the transmission is low and then go back into lockdown when transmission flares up in an effort to support the health care system and prevent it from getting overwhelmed.
However, at what point any particular country can safely begin to lift its lockdown has become a heavily politicized issue.
As for immunity regarding Covid-19, a study published on June 18 in Nature Medicine on the decline of antibodies has been widely circulated due to the global politics of lifting lockdowns. The study conducted in China is a considerably small one, and not representative of the population.
More importantly, the study showed the decline of antibodies to one viral protein, while the antibody that neutralizes the spike protein, which neutralizes the virus and prevents reinfection, was still present. The preprint of a longitudinal study conducted in the UK also showed gradual decline of antibodies in seropositive individuals.
However, another study published on June 18 in the journal Nature shows that the antibody threshold required to develop temporary immunity to Covid-19 is comparatively low. In other words, low antibody titres are not a marker for lack of immunity, and even low levels of neutralizing antibodies provide protection against the virus.
While antibody decline needs to be taken into account for public health directives, in order to exercise caution when lifting lockdowns, it does not directly mean there is no temporary immunity. Antibodies are only one part of the immunity picture.
A study published on June 25 in Cell, shows that Covid-19 stimulates a robust and protective cellular immune response from cytotoxic and helper T-cells. Hence, even though the discussion on immunity centres on antibodies, there is also cell-mediated immunity conferred by immunological memory of T-cells localized in the lungs. Current endeavours for vaccine development are considering both humoral and cell-mediated immune responses for a robust vaccine.
No confirmed cases of reinfection
Most importantly, to date there has been no confirmed case of reinfection anywhere in the world, the only speculation. With countries lifting lockdowns, any news of reinfection would have precipitated in massive headlines across all news outlets, in an effort to caution those nations. Any incidence of reinfection would be followed by clusters of reinfection since it would signal immunity wearing off.
As published in the Journal of the American Medical Association (JAMA) and confirmed by Stanford researchers, there has been no reinfection to date. That is not to say reinfection cannot happen, it has not happened yet.
Given that the first incidence of infection in the world was in December, and there has been no confirmed reinfection yet, it provides evidence of some level of temporary immunity. At this point, we are not certain of the mechanism, or more importantly, the duration of immunity. However, current studies point to some level of immunity given the presence of antibodies as well as immunological memory of T-cells.
The news of reinfection in Bangladesh is improbable given that we have not seen the incidence of reinfection from other countries that have started the infection cycle a number of months before us, and have better testing and reporting facilities.
There has been speculation of reinfection in a small number of cases in South Korea, but these were found to be cases of false positives. Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) testing, although considered the gold standard, still has a margin of error inherent to its design.
One of the issues is that it does not differentiate between active and inactive virus material. So, patients who had recovered from Covid-19 but still had “dead” virus material in their system tested positive for it, ie, a false positive. There is also a study on a macaque animal model for Covid-19 published in Science, that has shown no reinfection when rechallenged with the virus after the first infection -- data that is key for vaccine development.
Many people claim that the news said there is “no immunity” to Covid-19 after recovery. The news, based on WHO’s statement, said “no evidence of immunity,” not “no immunity.” There is a significant difference between the two statements. “No evidence” of immunity does not mean no immunity. It simply means we’re so early in the lifecycle of the virus that we don’t have data yet on the “duration of immunity.”
Viruses trigger an immune response when they infect us. Our immune system can fend off viruses through humoral immunity -- produce antibodies specific to that virus to neutralize it. And through cell-mediated immunity such as cytotoxic T lymphocytes that recognize and kill viruses and contribute to immunological memory.
The duration of immunity depends on how long the antibodies remain in the blood along with immunological memory. Assuming someone is not immuno-compromised, every time they recover from a viral infection they develop immunity to it for a given period of time-based on how long the antibodies remain in the blood along with cell-mediated immunity.
For some viruses, the duration of immunity can be lifelong (mumps, each strain of dengue, etc), for some a few years (SARS), and for some a few months or less (cold-causing viruses).
The statement on “no evidence of immunity” for Covid-19 is tied to the politics of countries lifting lockdowns. Since we do not know the duration of immunity of the SARS-CoV-2 virus, we are not being able to predict when immunity will wear off and there will be a resurgence.
The path to a vaccine
If there is no immunity, then how are we even developing a vaccine? A vaccine is essentially a modulated induction of an immune response to a particular antigen. Just as when we get infected by a virus we develop natural immunity, similarly, vaccines are a controlled way of triggering a similar immune response for protection against future infection.
If the duration of immunity is only a few years, then we will have to take booster shots whenever that time period of immunity is over. If there was no immunity, then there would be no basis for a vaccine.
Viruses are not studied in a vacuum of information; the studies are informed by decades of research on other viruses of the same class. As for predicting the post-Covid-19 duration of immunity, the current data-models are informed by data from other beta-coronaviruses of zoonotic origin -- one model from Harvard University published in Science draws on the cold-causing coronaviruses (HCoV-OC43 and HCoV-HKU1), the SARS coronavirus (SARS-CoV-1), and the MERS coronavirus.
The closest genetic virus to SARS-CoV-2, is SARS-COV-1 which causes SARS. The cold-causing coronaviruses have a duration of immunity of 40 weeks, for SARS the duration of immunity is 2 years. Therefore, that stands as the given range for predicting the post-Covid-19 duration of immunity, ie, as low as 40 weeks to about two years.
If Covid-19 follows the pattern of the cold-causing coronaviruses, then a winter-time resurgence is probable; however, given that the SARS virus is the closest genetically, there is a higher probability that the post-Covid-19 duration of immunity will be around two years.
There is also interesting evidence of cross-protection from cold-causing coronaviruses that can extend post-Covid immunity beyond the given range.
For countries like Bangladesh, with viral infections running rampant all year round, the masses might get milder Covid-19 infections due to cross-protection. However, city-dwellers living with air pollution and other toxins that are detrimental to the immune system can be more susceptible to severe infections. The vulnerable members of our population need to be protected until an effective vaccine becomes available.
Importance of serosurveillance
At this point, it is imperative for us to undertake serosurveillance measures with serology (antibody) testing to study the seroprevalence levels of Covid-19 in Bangladesh. It is important to carry out community-level sero-surveys in order to understand the spread of the infection in various geographical locations, the scale of the spread, and the percentage of the population that have already recovered and are seropositive.
It will also help determine the percentage of the population that remains uninfected and formulate community-based health directives in accordance to the data. Sero-surveys can be done periodically, and provide information on the progress of the infection over time. Demographic and geographic patterns of sero-survey results can help determine which communities may have experienced higher infection rates and therefore may have higher rates of seropositivity along with transmission dead-ends.
Serology testing will not only help us in understanding the transmission dynamics of Covid-19, it will also help us identify and create a list of possible donors for convalescent plasma. Therefore, it is necessary to immediately commence sero-surveys to understand the epidemiology of Covid-19 in the general population, identify groups at higher risk for infection, and determine community-based levels of seropositivity.
Sources:
https://www.cell.com/cell/fulltext/S0092-8674(20)30820-5
https://www.nature.com/articles/s41591-020-0965-6.pdf
https://www.nature.com/articles/s41586-020-2456-9
https://www.sciencedirect.com/science/article/pii/S0092867420306103
https://jamanetwork.com/journals/jama/fullarticle/2766097
https://science.sciencemag.org/content/early/2020/05/19/science.abc4776
https://science.sciencemag.org/content/368/6493/860.full
Naira Khan is an Associate Professor, Department of Linguistics, DU, and Member, Health Alliance Bangladesh.