Since the beginning of the second wave of pandemic in early March, Bangladesh has witnessed a jump in the daily coronavirus infection at an alarming rate. Hospital beds and ICUs have been occupied within a short span of time. Death rates are skyrocketing. UK and South African strains have been detected in the samples from the travellers. Has UK or South African variant spread within the community? Why are we suddenly seeing the rapid surge of infection? These questions have no clear answers yet.
How mutation alters viruses?
Coronavirus, scientifically known as SARS-Cov-2, is an RNA virus that naturally changes its structure over times by mutations and gives birth to new strains or variants. The mutation often favours viruses for their fitness to survive and spread within the community more efficiently. Not all mutations are harmful for the host. The genomic location and the number of mutations dictate the nature of the new emergent variants.
Coronavirus docks with host cells by its surface Spike protein. The Spike protein has a tiny active region called the 'receptor binding domain (RBD)' which anchors with its corresponding receptor ACE2 on human cells and causes infection- a clinical condition known as COVID-19. Any alteration of the 'receptor-binding domain' can enhance virulence and transmissibility of the virus. Moreover, as the Spike protein is the target of most of the current vaccines, mutations on the Spike protein can potentially transform the new strains as vaccine resistant.
Current variants of concern pose a real global threat:
In September last year, the Public Health England (PHE) identified a new variant, B.1.1.7 in the South-East region of England. By December, this strain became dominant all over the UK, and was responsible for the worst second pandemic wave that took thousands of lives. The B.1.1.7 strain is characterised by a deletion in the Spike protein (HV60/70 del), a mutation at N501Y on the receptor binding domain and at the furin cleavage site P681H, together which enhances its transmissibility by 70 percent and capability of causing severe COVID by 30-40 percent. According to a recent Nature paper, this variant increases death from severe COVID by 61 percent. Indeed, two-third of all COVID-associated deaths in the UK occurs during the second wave.
Although the available vaccines, including Oxford/AstraZeneca, are effective on this strain, due to its extremely high transmissibility, this new strain poses a real threat towards global pandemic control. In fact, B.1.1.7 variant is believed to be responsible for the recent surge of infection in Europe, including Germany and France. According to the GISAID database, B.1.1.7 has spread to 109 countries including Bangladesh and India.
The second major 'variant of concern' is South African variant B.1.351. This variant has two key mutations on its Spike protein, namely N501Y and E484K, which has spread to 68 countries. Due to this dual mutation, B.1.351 has become an immune evader and resistant to vaccine in various extents. While Oxford/AstraZeneca vaccine has been reported to be ineffective against B.1.351 strain, other vaccines, like Pfizer and Jonson & Jonson partly lose their efficacies on this virus.
The Brazil variant P.1 has N501Y, E484K and K417T mutations on the Spike protein along with additional 14 other mutations. This variant has also spread to 36 countries and has a propensity for causing reinfections and rapid transmission. A recent surge in Brazil has been attributed to this highly contagious variant, which creates the biggest crisis in the region since the pandemic began.
New strains in Bangladesh, are we going to face a worse pandemic crisis?
According to the IEDCR, only 450 genome sequencing have been done in a scattered manner, among which 30 are of the UK variant (B.1.1.7), two are of the South African variant (B.1.351), and no Brazilian variant (P.1) has been detected. GISAID database, however, shows submission of only 9 UK variant and 5 South African variant on behalf of Bangladesh. So, there is a clear lag between detection of new strains and reporting it to the Global Consortium for nCov variant tracker.
Recently, a news published in several online and print media stating that the Bangladesh Council of Scientific and Industrial Research (BCSIR) conducted a genome sequencing on 120 samples, among which 70% were found to be the UK variant. This report has not been published yet, and there is no record of it in the GISAID repository; therefore, it is difficult to make any assumption on its implications. Nevertheless, if this is true, it is certainly a very alarming news. This level of high frequency of positive mutation detection is an indicator of wider spread.
The UK variant was first detected on January 6, 2021 from a 50-year-old symptomatic patient at Dhaka. A team at the icddr,b screened a total of 5,250 nasal swabs by RT-PCR and chose 191 samples for variant surveillance. One of these matched with the UK variant with a 99% similarity. This study was published in the journal 'Microbiology Resource Announcement' on February 25 this year, but the paper did not disclose if those samples were collected from travellers or from the community.
Amidst uncertainty of spread and extent of the new coronavirus strains in the community, Bangladesh saw the highest daily rise of cases with over five thousand positive cases daily in the last seven consecutive days, whereas over seven thousand cases were detected on April 4 with 23% positive rate, which is by far the highest number since pandemic began in Bangladesh. The test positivity rate jumps from 3% to 23% in just last four weeks. On March1 this year, when the second wave began, the infection detection was just over 550 cases, which increased by almost 13-fold in just 35 days. Over ninety thousand new cases have been added to the total pool in this period (1 March – 4 April). Whereas it took 3 and a half months to reach the ninety thousand mark during the beginning of the first wave of pandemic last year.
Around 850 people died of COVID since the beginning of the second wave, whereas the daily deaths jumped from 7 to 53 in last 35 days. Due to the ongoing rapid surge of widespread infection and hospital admissions with sever COVID, one can speculate to see 3-digit daily deaths by mid to late April. We must bear in mind that there is a two-week lag between infection surge and consequential fatalities from COVID.
According to the 'Our World in Data', the latest (1 April) reproduction rate (R0) of coronavirus infection in Bangladesh is 1.54, which is 88% higher than that during the month of February this year, when pandemic was under control. The R0 (R-not) implies how fast the infection is spreading in any given time. In simple term, R0 number tells us how many people are infected from one person. R0 is equal to 1 means spreading remains in steady state and is not increasing. If R0 is more than 1,it indicates spreading is increasing exponentially. And if R0 is less than 1, spreading is declining.
In Bangladesh, throughout February, the R0 was around 0.8, which rose to 1.21 on March 1. This is the magnitude of R0 that forced Britain to declare nationwide strict lockdown to curb the second wave on January 5 this year. By this measure, the UK managed to fully reverse the pandemic wave from up-slope to down-slope with a significant reduction of R0 number to 0.71 within one month. R0 is considered as one of the major epidemiological determinants for decision making on imposing or withdrawal of mitigation measures.
Considering the R0 values, Bangladesh should have imposed a strict mitigation measure in the first week of March. But instead, the gthe overnment put forward an 18-point directive in the last week of the month, which is self-conflicting and contains vaguely defined terms, that may have little impact on the current circumstances. This kind of mitigation measures may control transmission with an R0 number around 1. But evidently, this 18-point directive was not sufficient to put any effect on such skyrocketing surge of infection transmission. Finally, the government, however, called for a week-long countrywide lockdown, starting from Monday.
Although, the expertise of Bangladesh cannot be sure if the current infection surge is attributed to UK variant or not, by considering the dynamics of current spread of infection, inter-district transmission with over 10% positive rate, overwhelming hospital admissions, rise of young people infection and alarming increase of deaths, it can be speculated that the UK variant must have spread in the community, particularly in the urban areas. If this is true, which is more likely to be, the government should declare a 'health emergency' to alert all levels of health system and impose following mitigation and surveillance measures:
1. Countrywide strict lockdown: Although the government has called for a countrywide lockdown for a week, more likely it will not be sufficient to make any impact on the current course of infection. Ideally, it needs at least two to three weeks of lockdown to control the surge of infection of this kind. Apart from lockdown, a night-time curfew could be imposed to boost the benefit to curb the infection transmission. During the lockdown period, the poor and the day labourers will be the first victims of losing their jobs. How are they going to survive, and how will they feed their families? The government should ensure proper rationing and supply of food to all the first line victims. This is essential for the acceptance of lockdown from every corner of the society avoiding chaos.
2. Variant surveillance: It is now imperative to conduct a mutation surveillance in the community. The WHO has recently urged to all nations to conduct variant surveillance. This is important to assess viral transmission, fatality outlook and efficacy of vaccine. Genome sequencing is the gold standard technique for novel mutation detection and variant surveillance. However, this technique is expensive, time consuming and requires high level of skills and specialties, which obviously Bangladesh lacks. Alternatively, there is a very specific and effective -gene RT-PCR kit which can detect the UK variant (B.1.1.7) with an accuracy of 99% sensitivity. This kit is called 'TaqPath COVID-19 kit' and is made commercially available by the ThermoFisher company. This specific kit has been widely utilised by the Public Health England (PHE) in their three Lighthouse Laboratories on thousands of samples for B.1.1.7 variant detection. Later, this kit has been used in the United States for mutation surveillance in the community level. According to the published 'Technical briefing 2' by the PHE, the 'S-gene dropout of 3-gene RT-PCR test provides a good proxy for monitoring trends in the infection by UK variant.'
3. Serosurveillance: It has been more than a year now Bangladesh is hit by the pandemic. Over 6 lakh thirty thousand people have been detected positive for COVID-19. Vaccination programme is currently ongoing. This is the right time for serosurveillance. Without region-wise systematic serosurveillance, it is not possible to implement vaccination programme equally in every corner of the country to achieve herd immunity. This test will also help us screen if the vaccine can sufficiently elicit antibody response in our population. By natural infection and vaccination, herd immunity is achievable. According to a recent survey, in the UK, 57% of the population have developed antibody against coronavirus, which is due to natural infection and current vaccination that covers nearly half of the population to date. The UK is moving towards developing herd immunity against COVID-19.
(The writer is a Senior Research Associate, Sheffield University, UK)