COVID-19 in Asia - Tackling the 3rd wave and Vaccines
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February 2021
COVID-19 in Asia – Tackling the 3rd wave and Vaccines
Report from the HTAi Asia Policy Forum Digital Session, 4 February 2021
Welcome to the report of the second of three virtual meetings of HTAi’s Asia Policy Forum (APF). 2020 proved to be a
difficult year for all; however, some countries in the region fared better than others and members of the APF were keen
to share some of the lessons learned along the SARS-CoV-2 journey. The APF Chair, Professor Brendon Kearney
welcomed 51 attendees from around the region, from both HTA agencies and industry alike, to listen to two fascinating
plenaries from Dr Norhizan Ismail, Deputy Director (Medical) of the Malaysian Ministry of Health, and Professor Terry
Nolan, a vaccine specialist from the Peter Doherty Institute, Australia.
The Lowy Institute from Australia recently
released an interactive report that analyzed
publicly available data on how over 100 countries
managed the SARS-CoV-2 pandemic. A weighted
average of the rankings across the following
indicators was calculated for each country to
produce a score from 0 to 100:
• confirmed cases;
• confirmed deaths;
• confirmed cases per million people;
• confirmed deaths per million people;
• confirmed cases as a proportion of tests; and
• number of tests per thousand people.
Countries from around the region have fared well
in comparison to those in Europe or the Americas,
especially those ranked in the top 10: Vietnam,
Taiwan and Thailand. Regional experience with
previous epidemics, such as SARS and MERS may
have better prepared these countries to cope with
the onset of COVID-19.
The challenge for the region remains how to help
those countries that are struggling, and having
performed well during the initial phase of the
pandemic, to keep the momentum going in order
to tackle the 3rd wave of infection. Success in this
task will come from public health measures
combined with vaccine rollout, as outlined by both
of our eminent speakers’ presentations.
Source: AFP News Agency, adapted from the Lowy Institute
The Public Health Response to the 3rd COVID-19
measures that the Malaysian Government have taken
Wave in Asia - Dr Norhizan Ismail
to not only contain the spread of the virus, but to
The first case of COVID-19 was detected in mitigate and minimize the impact of the pandemic on
Wuhan, China in December 2019, and COVID-19 the population and the economy.
was declared a pandemic on 11 March 2020 by
COVID-19 was first detected in Malaysia in early January
the World Health Organization (WHO). Since that
2020, with the identification of 22 cases, almost half of
first case, countries in the Asia region have
which had a travel history to affected countries and
implemented several public health measures,
regions. During this time, there were minimal
including restrictions on population movement,
restrictions in place and Friday prayers continued as
in order to mitigate the transmission of the virus.
usual. A sudden upward swing in infections (the 2nd
In the early phase of the pandemic, many of
wave) that began in late February 2020 was attributed
these measures were successful in “flattening the
in part to a large religious gathering in Kuala Lumpur
curve”, as demonstrated by the following two
attended by up to 16,000 people, many of whom came
figures. The first figure reiterates the discussion
from other Southeast Asian countries.
above, that many countries in the region were
highly successful in limiting the spread of By March, new daily cases were had increased from an
infection compared to Europe and the Americas. average of 100 to greater than 200. This prompted the
Ministries of Health and Immigration to implement a
Movement Control Order (MCO) in mid-March, which
stayed in place until early May. The MCO put in place
travel restrictions, restricting overseas travel for
Malaysians, as well as mandatory 14-day quarantine of
incoming travelers. The MCO prohibited all foreign
visitors from entering Malaysia. Importantly the MCO
prohibited mass gatherings including religious services
and restricted travel across states and districts, which
was especially difficult to enforce due to Ramadan
falling in April. Employees were encouraged to work
However, the second figure clearly demonstrates from home, with only essential businesses permitted to
that by mid-2020, some countries in the region remain open. At the same time, the Department of
were experiencing a severe 2nd wave, and now, Health continued with messaging campaigns to
by the beginning of 2021, are battling a 3rd wave encourage social distancing, mask wearing (made
of even greater proportions. mandatory in public spaces on 1 August) and to practice
personal hygiene. In addition, in mid-April the contact
tracing app, MySejahtera, was launched.
As cases began to fall in early May, a Conditional MCO
with fewer restrictions was put in place, which
continued until early June when the number of new
daily cases was finally brought under control. The
CMCO allowed greater movement of people within
each state in Malaysia, and opened up the economy;
however large gatherings of people for sporting or
religious events were still prohibited. During this time
Malaysia’s laboratory capacity was scaled up in order to
The surge in the number of cases can be increase PCR testing capacity to 30,000 tests per day.
attributed to many reasons including: a lack of
social distancing, a reluctance to curtail travel In early June the Recovery MCO replaced the CMCO,
and religious practices, economic pressures, a again allowing greater freedom of movement with
lack of technical capacity to test, track and trace, interstate travel permitted, the resumption of many
and importantly, a lack of capacity and social, religious and business activities, as well as the re-
preparedness in the healthcare system. opening of markets. Schools gradually re-opened,
combining in-school and home-based learning. As of 1
Dr Norhizan described the impact that the August 2020, Malaysia had a total of 8,976 confirmed
COVID-19 pandemic has had on Malaysia, and the cases and 125 deaths, with 96% of cases recovered.
During the RCMO, the number of new cases • Reduce morbidity and mortality by
remained low but persistent, driven in large part • categorizing/triaging patients into high or low-risk
by incoming travelers and linked to known and quarantining low-risk Cat1 and Cat 2 patients in
clusters. However, in early September, a sudden large centers away from hospitals (Cat 3 and 4);
surge in cases was noted with a corresponding
• increasing hospital and ventilator capacity;
increase in the R number for COVID-19 from 1.0 to
1.78. This surge coincided with elections being • improving management of healthcare workers;
held, particularly in the state of Sabah, with • outsourcing of non-COVID cases to the private
increased movement of voters and politicians sector to free up hospital beds.
across states resulting in high levels of community Enhance diagnostics and surveillance by
transmission. Of concern was the number of • expanding laboratory capacity to enable 150,000
health-care workers infected while caring for tests per day;
COVID patients, and the high-level of transmission
• implementing an early warning system;
between these health-care workers with the
potential for community transmission. • increasing the use of rapid antigen testing and
genomic surveillance;
By mid-September it was clear that Malaysia had
• screening foreign workers; and
entered a 3rd COVID-19 wave and that action
needed to be taken. CMOs were reinstated in • mobile app to monitor low-risk patients at home.
several states, followed by nationwide Achieve herd immunity
implementation in early November. The MOH • vaccination plan: free vaccination for all adults,
activated the National Crisis Preparedness and aiming to vaccinate 70% of population in 1st year,
Response Centre (CPRC) and a comprehensive starting with frontline workers.
action plan was drafted to assess all aspects of the
• procurement arrangements with Pfizer vaccines,
pandemic to get the outbreak under control.
and negotiations with China’s Sinovac and CanSino
By early January 2021, forecasting predicted that Biologics, and Russia’s Sputnik V vaccine.
at the current R number, the number of new cases
Increase awareness and inculcate new norms
would be 8,000 per day. Urgent measures were
• reiterate COVID “normal” behaviors.
needed to flatten the curve and a state of
emergency was declared on 12 January. With
The Malaysian Government’s live COVID-19 dashboard
40,000 active cases every day, enormous strain publishes cumulative case numbers, new daily case
was placed on hospital resources, especially
numbers, test numbers, the current R number and
critical care beds. The surge in daily case numbers
state-by-state data. From a peak of 5,728 daily new
resulted in higher mortality, and undue stress was cases on January 30th, it reports that the emergency
put on the health system when 3,000 health- measures put in place are gradually slowing the rate of
workers were required to quarantine. COVID-19 transmission. On the 11th February, the R
number has reduced to below 1.0 to 0.90, and the
number of new daily cases has almost halved to 3,384.
A whole of society approach was put in place, with
5 over-arching strategies running concurrently:
Break the chain of transmission by
• increasing human resources;
• improving contact tracing;
• rollout of digital health technology – scanning
of QR codes and the MySejahtera app; and
• increased collaboration with private medical A timeline tracks the cumulative number of COVID-19 cases
in the region http://covid-19.moh.gov.my/
practitioners conducting COVID tests.
COVID vaccines update: turning the science into countries but at a major cost to the world’s economy.
public health reality – Professor Terry Nolan Despite hundreds of clinical trials, no therapeutic drug
Severe acute respiratory syndrome coronavirus-2 has been identified that can prevent hospital admission
(SARS-CoV-2), more commonly referred to as COVID-19, for COVID-19 patients. Recent results from clinical trials
is a novel, highly pathogenic virus that belongs to the have identified promising drugs, such as the recent
coronavirus family of RNA viruses. Uptake of the virus is RECOVERY trial, reported that a combination of
mediated by binding of the viral spike glycoproteins to Dexamethasone the monoclonal antibody, tocilizumab,
ACE2 receptors expressed on the surface of human reduces time spent in hospital, the need for mechanical
cells, especially those lining the respiratory tract. Once ventilation and reduces the risk of death or severity of
inside the cell, viral replication tales place with viral RNA disease. The focus has now shifted to the development
translated into proteins, which are then assembled and of vaccines to create broad, world-wide immunity
released as more virus particles. Infected individuals are against COVID-19.
often pre-symptomatic at this stage. Anti-viral vaccine candidates
The body’s innate immune system responds to the There are 3 types of candidates:
presence of the budding virus with antigen presenting • Gene-based that deliver gene sequences (mRNA or
cells engulfing the virus, and in so doing, activating T- DNA) that encode viral target protein antigens.
helper cells. This in turn mediates a further immune Antibodies are then produced against these
response from B cells, which make antibodies directed antigens.
at the virus, blocking the virus from infecting other cells. • Viral vectors – either whole inactivated virus
In addition, the T-helper cells tag the virus for (traditional approach), or recombinant adenoviral
destruction by cytotoxic T cells. Immunity to the virus vectors that express target antigen, preventing viral
comes from the long-lived memory T and B cells that replication.
continue to recognize the virus.
• Protein-based – using viral proteins manufactured
Why do we need a vaccine? in vitro, such as the spike protein or the ACE2
Since the global pandemic was declared by the WHO receptor binding domain to elicit an immune
in March 2020 the world has been searching for ways response.
in which to successfully treat and prevent COVID According to the WHO’s vaccine tracker, as of the 9th
infection. Simple public health preventative measures February 2021, there are 63 vaccines in clinical
such as frequent handwashing, social distancing and development and 179 in pre-clinical development. Of
the wearing of masks have been shown to reduce those in clinical testing, the majority are directed against
transmission. More drastic public health measures the protein subunit (32%), whilst 16% use a non-
such as lockdowns and quarantine have been replicating viral vector. Similar numbers are using DNA
successful in flattening the curve in many (13%), RNA (11%) or inactivated virus (14%.
Image: SARS-CoV-2 - the COVID-19 coronavirus Oxford Vaccine Group
Vaccines: the main players resulted in very different VEs. The relatively small UK
study (n=2,700) mistakenly deviated from protocol by
The leading vaccines as of early 2021, how they work,
using a low dose followed by a standard dose, with an
and their regulatory status are summarized below.
increased interval between doses. The VE of 90% was
When evaluating the performance of these vaccines, it is
thought to mimic the body’s natural immune response
important to consider not only the published vaccine
to infection by promoting a stronger immune response
efficacy (VE) against placebo, but also the primary
to the second dose. The larger Brazilian study (n=9,000)
endpoints of the clinical studies – was the study
using the standard protocol reported a significantly
designed to reduce infection or hospitalization, or
lower VE of 62%. A larger (n=30,000) Phase III trial that
prevent moderate/severe disease or death? In addition,
encompasses all age groups is ongoing in the US.
many of the clinical trials were conducted in specific age
Further results reported in the Lancet in February found
groups – few have been tested in the elderly, and none
that a single standard dose gave a VE of 76% giving
in children. Many regulatory agencies will not approve
protection against symptomatic COVID-19 in the first 90
use of these vaccines outside of those age groups where
days after vaccination, which allowed the UK to extend
safety and efficacy were proven.
the time between the first and second doses. The VE
rose from 54.9% after 2 standard doses given 12 weeks apart.
Much interest surrounded the Russian developed
Sputnik V vaccine, which is unique, using two different
adenoviruses to deliver 2 doses, 21 days apart. Little
was known about the performance of this hybrid
vaccine until early 2021 when the interim analysis of its
Phase III trial was published in the Lancet. Participants
(n=20,000) were allocated to the vaccine and placebo
arms of the trial in a 3:1 ratio. The overall VE was
91.6%, which remained consistent across all age groups,
including the 10% of participants aged >60 years.
Of great interest to countries in the region has been the
development of several vaccine candidates in China.
New York Times Vaccine Tracker Sinovac and Sinopharm have both produced inactivated
vaccines that have been given emergency authorization
Emergency use authorization by regulators in the UK in several countries including China, Brazil, Turkey and
and US for the Pfizer mRNA vaccine was based on a VE Indonesia. A study in Brazilian healthcare workers
of 94% from its Phase III trial of >36,000 participants. vaccinated with Sinovac resulted in78% and 100%
The vaccine requires 2 doses and much has been made protection against mild and severe to moderate COVID-
of the cold-chain requirement for to be stored at –70°C, 19 disease, respectively. The study conducted in Wuhan
which may impact on the roll-out of the Pfizer vaccine in that resulted in approval for the Sinopharm vaccine in
countries with limited infrastructure. China reported a VE of 86% against any COVID-19
disease and VE 100% against moderate and severe
The Moderna mRNA vaccine also requires 2 doses, given
disease.
4 weeks apart, but only needs refrigeration –20°C. An
overall VE of 94.1% was reported from its Phase III trial What about the variants?
of >30,000 participants; however, of note, is that no
RNA viruses like coronaviruses constantly mutate. Most
cases of severe disease were reported in the vaccine
mutations will not have a significant impact; however,
arm, compared to 30 cases in the placebo group.
some may result in increased transmissibility, and in so
Importantly each arm of the trial enrolled at least 3,500
doing, give the virus a selective advantage. Currently
participants aged ≥ 65 years with a VE of 86.4% reported
there are 3 variants of concern that affect the receptor
in this age group.
binding domain of the virus: the so-called UK, South
The AstraZeneca vaccine, often referred to as the Oxford African and Brazilian variants. Concern is growing that
vaccine, is the only approved product that uses a these variants may be capable of evading the body's
genetically engineered adenovirus derived from immune system by decreasing the ability of antibodies
chimpanzees. Interestingly, although results from 2 to recognize and neutralize the virus, and as such, the
Phase II/III trials conducted in the UK and Brazil real-world effectiveness of vaccines have been
produced an overall VE of 70%, the 2 studies had questioned.
different dosage regimens and populations, which
The first interim analysis of a large UK trial (n=15,000 How did we get here so fast (and is it safe?)
aged between 18-84 years of age), the protein-
Firstly, a lot of the “basic science” had already been
based vaccine, NovaVax, reported a VE of 89%. Only
conducted investigating vaccines against MERS and
62 PCR-confirmed symptomatic cases were
Ebola. During the rapid development of the H1N1
detected during the trial; however, the
influenza vaccine, it was recognized that novel
increasingly prevalent UK variant strain accounted
development-and-manufacturing platforms were
for 50% of these cases. Based on PCR performed
needed that could rapidly adapt to new pathogens.
on strains from 56 of the 62 cases, VE by strain
Non-government organizations such as the Coalition
was calculated to be 96% against the original
for Epidemic Preparedness Innovation (CEPI)
COVID-19 strain and 86% against the UK variant.
supported the development of platform
Efficacy of the vaccine reported from a trial in
technologies, including RNA and DNA platforms, to
South Africa was lower at 60% but this may be due
prepare for the emergence of new pathogens such
to the high prevalence of the variant in circulation,
as COVID-19 that would facilitate development from
with 92.6% of cases detected in the trial being the
viral sequencing to clinical trials in less than 16
South African variant.
weeks and be suitable for large-scale
Of great interest is a trial that commenced in early manufacturing.
January that combines vaccination with the
Secondly, in the wake of the pandemic being
AstraZeneca and Sputnik V vaccines in order to boost
declared, government funding, such as the US
the efficacy of the Oxford-AstraZeneca vaccine.
Government’s Operation Warp Speed, was critical
The vaccine platforms have been demonstrated to to mitigate the risk that companies were exposed to
be flexible and, although the emergence of variants during vaccine development.
has prompted the modification of existing vaccines,
Most important of all; however, overlapping the phases
it is still challenging.
of development significantly shortens development
time. Traditional vaccine development tends to follow
a linear sequence of steps, with pauses for data analysis
between each phase (see diagram).
Lurie et al NEJM 2020; 382:1969-1973 DOI: 10.1056/NEJMp2005630
Small-scale manufacture of any candidate vaccine would As you can see from this diagram, South America, Asia,
only take place once clinical efficacy had been Africa and Oceania have minimal access to vaccination.
demonstrated in small clinical studies. Only after large Countries such as Canada and Australia must ensure that
clinical trials and evaluation of the date would large- excess doses of vaccines be contributed to the COVAX
scale manufacture of the vaccine take place. initiative for distribution to low- and middle-income
countries that encompass one fifth of the world’s
The new “pandemic paradigm” of vaccine development
population. As evidenced by our first plenary today,
saw many of the sequential steps run in parallel,
countries like Malaysia that are gripped by a 3rd wave of
elevating financial risk if the vaccine fails, but
COVID-19 are relying heavily on equity of access to
accelerating the time to validation. For many of the
vaccines to enable mass vaccination of their population.
COVID-19 vaccines currently being rolled out, the
greatest risk of all was to commence large-scale
manufacturing before safety and efficacy data had been
fully evaluated.
Another positive to note, is that the rapid development
of a vaccine against an RNA virus has opened the door
to the development of vaccines against other diseases.
Vaccine roll-out. Is it a level playing field?
Overwhelmingly, high-income countries have purchased
vast numbers of vaccine doses compared to low- and
middle-income countries, highlighting persistent Questions that still need to be addressed
inequality. A recent study found that, as of mid-January
2021, a small group of high-income countries - • Do the vaccines prevent transmission of COVID?
comprising just 16% of the world's population - had • Vaccination of children and young adults?
purchased 60% of the global vaccine supply. • Vaccination of pregnant women?
• Will we need seasonal vaccination against COVID?
• Herd immunity?
• Elimination or suppression?
• Vaccination “passports” to allow travel?
• More variants?
A global pandemic
To combat this, the COVAX initiative, co-led by Gavi,
requires a global solution
CEPI and the WHO, aims to guarantee fair and equitable
access to COVID-19 for every country in the world.
COVAX is aiming to provide two billion doses by the end
of 2021; however, the number of doses secured by
COVAX remain low in comparison to some countries
that have ordered excess doses per head of population.
Coming up next, Thursday March 25th 2021:
After our focus on public health measures and the role of vaccines in curtailing the impact of
the SARS-CoV-2 pandemic, the 3rd virtual meeting of the Asia Policy Forum will explore the
evolving approach to COVID-19 diagnostic testing and, looking to the future, therapeutics that
can mitigate severe illness and even death in those who still get infected.
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