Masked office workers in Singapore amid the COVID-19 pandemic (Image taken from Reuters)

Vaccines & Variants— Perspectives on COVID-19 from Singapore

Having received plaudits for its response to COVID-19, Singapore has nonetheless seen a resurgence in cases during recent days. Was our earlier success largely due to public policy, or could there be other biological factors involved, and what does this mean for us moving forward?

Since 2020, the COVID-19 pandemic has swept through the globe, infecting ~164 million people, and causing ~3.4 million deaths at the time of writing¹. As countries continue to grapple with the virus, these figures are unlikely to have peaked just yet. Barring the crisis in our foreign worker dormitories, my country, Singapore, has fared relatively well in handling COVID-19 within our borders. Recently, we pipped New Zealand to the top spot in Bloomberg’s COVID Resilience Ranking, due to “a combination of nailing the virus and rolling out vaccines at one of the fastest rates in Asia”². Indeed, most of us are thankful to have been spared the brunt of the pandemic here, with numerous measures introduced to attempt to curb the spread of COVID-19. Nonetheless, one interesting statistic behind this success has been the exceptionally low severity of our cases (31 deaths in 61,585 cases, a mortality rate of ~0.05%) as compared to the global average mortality rate of ~2.07%³. Our hospitals and Intensive Care Units (ICUs) were not overwhelmed despite the outbreaks amongst our foreign worker dormitories last April, where we saw surges of over 1,000 cases each day. This success in containing the situation has led to our gradual recovery right up until the past few days, where the detection of local clusters following months of minimal to no transmission has triggered a roll back of certain preventative measures. What is different this time, and what does this mean for Singapore as we enter a state of “Phase 2 (Heightened Alert)”?

Singapore’s approach of contact tracing, testing, quarantine, and lockdown (or ‘Circuit Breaker’, as we called it here) has been held up as an exemplary model for countries worldwide. However, much is now being said about COVID-19 ‘variants’, strains of the virus that have evolved differences in their key spike protein. The B.1.1.7, B.1.351 and B.1.617 strains are the names most commonly bandied around, sparking fears due to their increased transmissibility and virulence. In Singapore, the B.1.617 strains appears to be the major variant driving the current resurgence. However, what are ‘variants’ exactly, and why are they such a concern?

As a virus replicates, mistakes occasionally occur during the replication of its genetic information. These ‘mistakes’ are mutations, which change the genetic sequence of the virus. Sometimes, these changes confer new properties to the virus, for example, they may allow them to bind to cells more rapidly and efficiently. The more a virus replicates and is transmitted, the greater the chances for mutations to accumulate, eventually resulting in a ‘variant’ that has significant changes to its genetic code compared to the original. However, while mutations can make a virus ‘stronger’, they can also make it ‘weaker’. In Singapore, a variant with a 382-nucleotide deletion i.e. ‘missing’ (∆382) in the open reading frame 8 (ORF8) region of its genome was detected and the findings presented in the prestigious medical journal, The Lancet. In this study, 22% of individuals were found to predominantly be infected with this variant, while a further 8% showed a mix of both the ∆382 variant and the WT strain. Interestingly, the researchers found that infection with the ∆382 strain or a mix of both caused milder infections with lesser need for supplemental oxygen, as well as lower systemic release of pro-inflammatory signals and a stronger immune response as compared to infection with the WT strain alone. This raises an important point to consider, could such ‘weaker’ variants (possibly related to ∆382?) have contributed to the lower infection severity and mortality rate that we saw here in Singapore? Can our exceptionally high ratio of mild cases and low mortality rate (~42x lower than the rest of the world!) solely be attributed to factors such as public policy and the relatively young age of the affected patients, or were we lucky to avoid the more infectious and virulent variants currently spreading across the globe?

Indeed, the uptick in cases largely driven by the B.1.167 strain suggests that gaps did exist in our COVID-19 management strategy, and perhaps we were lucky to get away with it at some point. Another possibility would be complacency, a likely factor if you were to see what was really going on down here. It cannot be emphasized enough that there is still a lot we do not understand about COVID-19, and assuming we have it under control would be foolhardy. With only ~22.9% of our population fully vaccinated, it is way too early to assume that we have overcome this pandemic, notwithstanding the fact that the vaccine appears to have reduced efficacy against the B.1.167 variant.

Dear Singaporeans, this is not how you take precautions as we try to recover from the pandemic (Images taken from Zaobao SG and Mothership.com).

The recent cluster which started from Changi Airport is believed to have originated from an area receiving travellers from “high-risk countries”. Of course, questions need to be asked about how it eventually got out to the general public via the nearby canteen. Could the entire zone have been designated as a ‘bubble’ of sorts, given that they were dealing with passengers from heavily affected areas? Were there measures in place to continually ensure good practices with personal protective equipment(PPE)? Were the infected cleaning staff provided with additional PPE apart from their masks, given their job and proximity to potentially infected inbound travellers? Or was it complacency, believing that we were alright having kept cases down for a while? Whatever the situation, the implemented measures were insufficient, resulting in the virus spreading outside to the wider community. B.1.167 clearly appears to be more infectious than prior strains, and perhaps this was not taken into account when dealing with potentially infected individuals arriving into the country.

Another area for concern that has surfaced recently is the shortening of quarantine periods for individuals which test negative a few days into their isolation period. These individuals are assessed to be uninfected or previously infected and allowed to cut short the quarantine¹⁰. Notably, there were cases who were let out of quarantine in this manner, only to test positive for COVID-19 later on¹¹. As mentioned earlier, there is still much we do not know about COVID-19 and its newer variants. Would it not be prudent to err on the side of caution in this situation and request these individuals to serve out the full quarantine period, regardless of any negative test results? After all, it has already been noted multiple times that the incubation period of the virus may even extend up to 21 days in some cases. Can we say for sure that we can catch all possible infections, or that infected individuals will not test negative at first during the early stages of incubation? Otherwise, it will be too late once these individuals head out and come into contact with other members of the public. I reiterate that at this point in time, many aspects of COVID-19 are still being debated, and there is much left to understand. Take this recent report in the Proceedings of National Academy of Sciences (PNAS) journal, for example, controversially claiming that SARS-CoV-2 gene fragments are able to integrate into the genome of infected cells¹². The findings attempt to explain why many individuals continue to shed viral RNA long after they have recovered, and remain hotly debated for reasons beyond the scope of this article. This incomplete understanding of COVID-19 serves as a reminder for us not to let our guard down. The situation can change rapidly, and until we have been able establish a meaningful vaccination level globally, it will continue to be an issue.

COVID-19 is a global pandemic that affects everyone. This is not the time to point fingers, especially drawing boundaries along the lines of race (with talk of the ‘Indian variant’ and whatnot). Mistakes are to be expected, and there is nothing to be ashamed about for the odd slip. Rather than being defensive¹⁰, we need transparency and accountability while immediately moving to contain any spread. What we need is to constantly review and update our protective measures if necessary, all while aiming to achieve a high vaccination rate amongst the population. Instead of getting cocky and putting down other countries, we should be thankful that we were able to make it through the brunt of the pandemic so far.

To all of us with scientific backgrounds, we have to do our part to educate others on the virus. Inform others as best as you can, and help them to understand what is going on. With the rampant spread of rumours and misinformation, we need to contribute more to helping the layman understand why certain measures, especially vaccination, is necessary. On that note, vaccination remains our best option, and Singapore needs to step up its vaccination programme as quickly as possible in order for us to overcome COVID-19.

Disclaimer: The views expressed in this article are solely the personal views and opinions of the author.

References:

  1. COVID-19 Live Update, Worldometer, 2021. https://www.worldometers.info/coronavirus/
  2. The COVID Resilience Ranking — The Best and Worst Places to be During the Pandemic, Bloomberg, 2021. https://www.bloomberg.com/graphics/covid-resilience-ranking/
  3. All COVID-19 figures obtained from https://www.worldometers.info/coronavirus/
  4. Measures to Contain the COVID-19 Outbreak in Migrant Worker Dormitories, Ministry of Health, Singapore, 2020. https://www.moh.gov.sg/news-highlights/details/measures-to-contain-the-covid-19-outbreak-in-migrant-worker-dormitories
  5. Singapore begins month-long period of heightened alert to curb rising COVID-19 cases | Video, Channel News Asia, 2021. https://www.channelnewsasia.com/news/singapore/singapore-begins-month-long-period-of-heightened-alert-to-curb-14822196
  6. Additional Restrictions under Phase 2 (Heightened Alert) to minimise transmission, Gov.sg, 2021. https://www.gov.sg/article/additional-restrictions-under-phase-2--heightened-alert
  7. Tracking of Variants, Global Initiative on Sharing all Influenza Data (GISAID), 2021. https://www.gisaid.org/hcov19-variants/
  8. Young et al., Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study, The Lancet, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31757-8/fulltext
  9. Changi Airport Covid-19 cluster originated in zone that received travellers from higher-risk places, The Straits Times, 2021. https://www.straitstimes.com/singapore/health/changi-airport-cluster-originated-around-specific-zone-that-received-higher-risk
  10. Former DJ Jade Rasif’s account of maid with COVID-19 ‘inaccurate’, says MOM, Channel News Asia, 2021. https://www.channelnewsasia.com/news/singapore/jade-rasif-maid-mom-manpower-ministry-covid-19-quarantine-14829122
  11. New COVID-19 cluster in Singapore linked to imported case who was ‘probably reinfected’ in India, Channel News Asia, 2021. https://www.channelnewsasia.com/news/singapore/covid-19-cluster-reinfected-case-india-recovered-travellers-14659896
  12. Zhang et al., Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues, PNAS, 2021. https://www.pnas.org/content/118/21/e2105968118

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Ph.D. Student, writing about my interests in advances related to the biomedical sciences, molecular biology, and novel technologies

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Matthew Heng

Matthew Heng

Ph.D. Student, writing about my interests in advances related to the biomedical sciences, molecular biology, and novel technologies

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