Globally, there is an urgent need for continued collection of data related to COVID-19 and Indigenous populations, according to an article cited in the latest COVID-wrap.
The column from public health researcher Alison Barrett also sounds an alarm about the scaling back of important COVID-19 data surveillance in the United Kingdom, and profiles recommendations for improving global vaccine equity.
After reviewing recent studies on COVID vaccines, Barrett concludes that “a more concerted effort at widespread communication and public health education is required to encourage more people to have a third dose”.
COVID-19 vaccine effectiveness in NSW
Article: People are still dying from COVID. But who? And are they vaccinated?
Butt, C and Cunningham, M, The Sydney Morning Herald, 21 March 2022
An analysis by The Sydney Morning Herald of NSW COVID-19 data found that one in every 1,048 people who acquired COVID-19 during the Omicron wave died compared with one in every 128 COVID-19 infection during the Delta wave.
This is likely due to the Omicron variant being less severe than Delta variant and more people being vaccinated by the end of 2021 than during the Delta wave in mid-2021.
Because the actual case numbers are likely to be under-reported for the Omicron wave when it was difficult to get a PCR or rapid antigen test (RAT), it is likely that the death rate for the period is lower than one in 1,048.
Professor Robert Booy from University of Sydney told the SMH that he “estimates the death rate was closer to one in 3,000, not one in 1,000”.
The analysis found that between 26 November 2021 and 12 February 2022, the 20 to 29 year old group made up a higher proportion of positive cases than other groups.
As in other waves during the pandemic, the highest proportion of deaths occurred in people aged 80 years and older.
Indicating the disproportionately high number of unvaccinated people who have died with COVID-19, the analysis found that while unvaccinated people represented only 4.6 percent of COVID-19 cases in NSW, people who had not received any COVID-19 vaccine doses represented 22.8 percent of total deaths.
Only one percent of people aged between 80 and 89 years in NSW have had fewer than two doses. However, almost one-third of people in this group were admitted to ICU or died.
This is compared to 4.8 percent of those who had received two doses, and 2.2 percent who had received three doses.
Professor Peter Collignon from the Australian National University told the SMH: “Those over the age of 70 and the unvaccinated remain at highest risk of severe illness.”
It is important to note that the data should be interpreted with caution due to the under-reporting of cases during the Omicron wave and the circulation of both Delta and Omicron variants, particularly during the earlier period of the Omicron wave.
However, they provide an indication of the benefits of vaccination against severe symptoms of COVID-19.
As Professor Lesley Russell Wolpe points out in the tweet above, it is also important to gain a better understanding of the under-counted COVID-19 cases.
The Kirby Institute and National Centre for Immunisation Research and Surveillance are undertaking serosurveillance of donated blood samples to help better understand the extent of undetected COVID-19 infections in the community.
Researchers will analyse de-identified blood samples from Australian blood donors to test for specific antibodies called nucleocapsid produced during natural infection of SARS-CoV-2.
Among other benefits, more accurate prevalence data can help inform future vaccine strategies and strategies for managing long COVID.
COVID-19 data surveillance is vital for equitable pandemic management
In what is hopefully not an indication of what is to come in Australia, important COVID-19 data surveillance has recently been scaled back in the United Kingdom.
Widescale free PCR and RAT testing ended at the end of March in England and funding for the Real-time Assessment of Community Transmission (REACT) and ZOE COVID studies is being substantially reduced.
Both the REACT and ZOE studies have been integral throughout the pandemic in collecting and analysing real-time COVID-19 data.
“The withdrawal of funding for the ZOE coronavirus study and REACT is consistent with the government’s ongoing quest to convince us that things are ‘back to normal’ by removing the ability to properly track what’s happening with COVID,” University of Bath academic Dr Kit Yates wrote in the BMJ.
Wales, Scotland and Northern Ireland also plan to stop free PCR testing for most people in the coming months.
Some British people will continue to be eligible for free testing, but it is unclear exactly how the Government will determine who will be eligible, according to Yates.
Removal of free testing will be detrimental to continued surveillance and management of the pandemic.
The need for individuals to pay for their own COVID-19 tests will likely deter many from testing, particularly those with lower incomes who have been impacted disproportionately from the pandemic.
Data surveillance enables earlier identification of new variants and some prior warning for hospitals and healthcare systems to prepare for surges in cases and subsequent admissions to hospitals.
“A lack of knowledge about previous infection could also prove problematic for access to appropriate care for long COVID and could even affect disability claims after occupational exposure,” science correspondent Nicola Davis wrote in The Guardian UK.
Data matters for Indigenous populations
Researchers at University of Queensland’s Poche Centre for Indigenous Health have called for continued collection of data related to COVID-19 and Indigenous populations worldwide.
In this commentary, the authors outline some key reasons for continued COVID-19 data collection on Indigenous populations:
- Major gaps were identified in data collection and analysis of COVID-19 among Indigenous populations globally to date
- As Indigenous populations globally have fared poorly during the pandemic in relation to non-Indigenous populations, it is important to continue assessing their health and wellbeing
- Timely and accurate data should be urgently collated and reported due to the vulnerability of Indigenous people to more severe outcomes of COVID-19
- Provision of epidemiological data on Indigenous populations will enable justification vaccine prioritisation for Indigenous populations in some countries.
In conclusion, the authors wrote: “Informative, inclusive and participatory decision-making and policy creation is key to preventing and limiting the spread of SARS-CoV-2 among Indigenous populations who are at a greater risk of losing cultural phenomena and shared histories that belong to humankind.”
Perils of relying on market-based responses
Publication: COVID-19 vaccines and the Australian healthcare state
Gillespie, JA et al., Health Policy and Technology, 13 February 2022
An interesting analysis by Associate Professor James Gillespie at University of Sydney and colleagues was recently published highlighting the “leadership failure” that weakened Australia’s production and distribution of COVID-19 vaccines.
The paper also critiques the reliance of the pandemic response on the market for managing complex social and health problems.
Gillespie and colleagues used a concept of ‘health care state’ to show how interlocking elements of consumption, production, governance and statecraft created the conditions for Australia’s contradictory response to the [vaccine] crisis.”
Healthcare is one of the largest mechanisms of modern economies and three domains need to be considered for effective governance: technology, professional provision of services and collective consumption.
Australia’s healthcare state is a hybrid model of command and control, supply driven and corporatist, that has been “shaped by federalism,” Gillespie and colleagues wrote.
For example, the Federal Government’s powers are allocated by the Constitution, which restricts their responsibilities to funding medical services and a pharmaceutical benefits scheme, including vaccines and quarantine.
State and Territory Governments are responsible for public hospitals and public health including infectious disease control.
Because of an imbalance in cost and service delivery between the two entities, Australia’s vaccine policy led to blame shifting and “politics of cost”, according to Gillespie and colleagues.
In relation to the healthcare state, the authors outline some of the issues Australia’s vaccine policy had in technology and producing and procuring vaccines.
These include Australia’s strategy to rely on local development and production of vaccines, in particular the local production of the Oxford-AstraZeneca vaccine and University of Queensland-QSL’s vaccine candidate.
This decision was justified by “the chaos and nationalism that dominated early vaccine production in the US and Europe”, the authors wrote.
The Federal Government was slow to negotiate with international pharmaceutical companies BioNTech Pfizer and Moderna, resulting in an initial order of 10 million doses of Pfizer.
Doses of Moderna and Novavax vaccines were later ordered but would not be due to arrive in Australia until late 2021 for Moderna and early 2022 for Novavax.
The University of Queensland-QSL’s vaccine candidate was discarded in December 2020 when they found that fragments in the vaccine produced false positive reactions to HIV.
As such, Australia was heavily reliant on one vaccine, the Oxford-AstraZeneca, at the beginning of 2021, which was not approved for use by the Therapeutic Goods Administration (TGA) until March 2021.
Australia’s vaccine rollout began on 22 February 2021 with its first delivery of the Pfizer vaccine prioritised for residents and staff in aged and disability care, frontline healthcare workers and quarantine and border workers.
While the plan was that Australia would be able to produce sufficient AstraZeneca doses for all Australians, supply was disrupted when a rare but serious blood-clotting condition, thrombosis with thrombocytopenia syndrome (TTS), was discovered as a potential side-effect from the AstraZeneca vaccine.
Confusing and changing communications from health authorities and the Australian Technical Advisory Group on Immunisation (ATAGI) about AstraZeneca and TTS influenced vaccine hesitancy among the Australian public, slowing the uptake of COVID-19 vaccines.
However, according to Gillespie and colleagues, “the problem did not lie in population hesitancy to vaccination” but with issues in distribution (i.e. the vaccine “strollout”) and poor communication with priority populations, including culturally and linguistically diverse and Aboriginal and Torres Strait Islander people.
One of the biggest failures of Australia’s vaccine policy was in aged care.
“The Australian Government has not had recent experience of running health services on this level and scale, so the services relied on the newly created network of outsourced private suppliers. An early scandal showed the difficulties of managing these interventions [in aged care],” Gillespie and colleagues wrote.
Due to the frustratingly slow pace of the vaccine rollout, in April 2021, State and Territory Governments established large scale vaccination hubs, which immediately helped increase vaccination rates in Australia.
Initial delays with vaccine rollout were turned around as a result of public sector expertise from already established structures of the healthcare state, general practitioners, pharmacies and logistics management from the Australian military.
“By December 2021, Australia had become one of the world’s better performing nations in terms of adult population rates,” the authors wrote.
However, since then vaccine uptake has slowed with only 64 percent of the eligible population people aged 18 years and older having had their third dose.
Gillespie and colleagues wrote, “Australia’s experience with COVID-19 vaccines shows the importance of public sector leadership of public-private partnerships to manage the complexities of a modern health care state.”
According to the authors, the Federal Government’s issues largely arose when they outsourced critical services to commercial entities. The Government was also widely criticised for lacking leadership and shifting blame to State and Territory Governments.
One of the greatest challenges for the Federal Government is in managing “its complex articulation of public and private sectors”, requiring leadership that has “consistent capacity for agile stability” and “creative power-sharing”, Gillespie and colleagues wrote.
These qualities are present in some State and Territory public health systems and contributed substantially to the final success of the rollout of the primary vaccine course in adults.
In conclusion, Gillespie and colleagues wrote: “As the crisis unfolds it will be interesting to see if this capability is further developed or if political leaders, especially at national level, persist with experiments in placing great reliance on market (or commercial agents) to manage complex social and health problems for which to date they have proved entirely incapable of managing competently.”
Time to act on global vaccine inequity
Publication: It is not too late to achieve global COVID-19 vaccine equity
Yamey, G, et al. The British Medical Journal, 24 March 2022
Large disparities continue to exist in COVID-19 vaccine rates across the globe. Many people, particularly in African countries and Papua New Guinea, have yet to receive their first dose.
As of 3 April 2022, 73.6 percent of people in high income countries have had two doses of a COVID-19 vaccine compared to 11 percent of people in low income countries.
Professor Gavin Yamey from Duke Global Health Institute and colleagues call for an urgent commitment to global vaccine equity to help prevent new variants of the virus emerging and prevent so many severe disease and deaths.
COVID-19 vaccine inequity occurred as a result of high income countries’ capacity to pre-order huge quantities of doses from pharmaceutical companies before clinical trials were complete.
Vaccine companies in high income countries were also reluctant to share vaccine patents and technologies with low-middle income countries to help them manufacture their own vaccines.
Additionally, low-middle income countries lacked capacity to negotiate for vaccine doses and distribute vaccines among their residents.
“It is unjust that people in high income and middle income nations have been protected from illness, hospitalisation and death while those in low and lower middle income countries are left behind,” Yamey and colleagues wrote.
Yamey and colleagues recommend the following ways to improve vaccine equity:
- Empower countries to establish their own vaccine priorities and targets
- High income countries to donate more doses, well before they are due to expire
- Redistribute expected deliveries of doses from high income countries to low income countries
- Financial and operational support to low-middle income countries to support their vaccination programs
- For vaccine equity to become sustainable, it is important to support vaccine manufacturing in low-middle income countries by sharing vaccine technology. Cuba, China and India “have invested in their own COVID-19 vaccine development and production and have achieved impressive vaccination coverage”.
- Regional initiatives and unions, such as the Asia Pacific Vaccines Access Facilities, are important for increasing coverage in these regions
- Steps have to be implemented now for the fair and transparent global allocation of variant specific vaccines.
The authors conclude by stating that “prematurely “moving on” from the pandemic, however attractive the short term implications, would be a moral failure from which the world will not easily recover.”
Watch the video with Dr Maria Van Kerkove.
Effectiveness of a third dose of a COVID-19 vaccine
Publication: Safety and efficacy of a third dose of BNT162b2 COVID-19 vaccine
Moreira, E, et al., The New England Journal of Medicine, 23 March 2022
An ongoing randomised control trial of Pfizer’s BNT162b2 COVID-19 vaccine, involving 10,136 participants, found that a third dose of the vaccine was safe and effective against COVID-19 infection.
In a group of study participants who had not previously been infected with SARS-CoV-2, six people out of 4,695 in the vaccine group had a confirmed case of COVID-19 between a seven day and median of two-and-a-half month follow-up.
In comparison, 123 people out of 4,671 in the placebo group had confirmed COVID-19, which is a relative vaccine efficacy of 95.3 percent (with a 95% confidence interval, 89.3% to 98.6%).
Study participants were recruited from the United States, South Africa and Brazil, and had been participants in the pivotal trial of the vaccine.
Due to real-world observations of waning immunity after two doses and recommendations for additional doses in some countries, the placebo group were unblinded before the two-month interim analysis and allowed to receive a third dose.
Their data up to this point was still included, but with a shorter follow-up than participants who chose to stay in the trial.
The study also found that the third dose was safe – the most common adverse events reported were pain at the injection site, fatigue, fever and headaches. No cases of severe COVID-19 were reported during the trial.
In addition to the short follow-up of some participants in the placebo group, other limitations of the study include limiting the study to participants who received Pfizer vaccines in first two doses and not evaluating the incidence of asymptomatic infection.
Third dose matters
Publication: COVID-19 vaccine effectiveness against the Omicron (B.1.1.529) variant
Andrews, N. et al., The New England Journal of Medicine, 2 March 2022
A study in the United Kingdom has found that two doses of the Vaxzevria (AstraZeneca) or Pfizer BNT162b2 vaccines provide limited protection against symptomatic COVID-19 from the Omicron variant.
A third dose of either Pfizer or Moderna’s mRNA vaccine after either a primary course of Vaxzevria or Pfizer increased protection considerably, but the protection waned over time.
The English-based study estimated the effectiveness of the COVID-19 vaccines against symptomatic disease caused by Omicron and Delta variants between 27 November 2021 and 12 January 2022.
During the study period, 886,774 people with symptomatic COVID-19 were infected with Omicron variant and 204,154 with Delta variant. A control group was based on 1,572,621 people who had tested negative during the study period. Data from both PCR and rapid antigen tests were included.
Vaxzevria, Pfizer and Moderna vaccines were effective against symptomatic disease caused by the Delta variant.
For example, a primary course of Vaxzevria was 82.8 percent effective (95% CI, 74.5 to 88.4%) against Delta after two to four weeks from the second dose – this waned to 43.5 percent (95%, 42.4 to 44.5%) after 25 or more weeks.
Two doses of Pfizer was 90.9 percent effective against Delta two to four weeks after the second dose, and waned to 62.7 percent after 25 or more weeks.
The Moderna vaccine provided similar protection to Pfizer – 94.5 percent effective against Delta after two to four weeks after the second dose and waned to 80.4 percent after 25 or more weeks.
In comparison, vaccine effectiveness from the three vaccines was lower for Omicron variant than for Delta.
A primary course of Vaxzevria was 48.9 percent (95%CI, 39.2 to 57.1%) effective against Omicron at two to four weeks after the second dose, which waned to less than zero percent after 25 or more weeks (-2.7%, 95%CI, -4.2% to 1.2%).
A third dose with Pfizer brought protection for those with a primary course of Vaxzevria up to 62.4 percent at two to four weeks after the dose. However, this waned to 39.6 percent after ten or more weeks.
A third dose with Moderna increased protection to 70.1 percent at two to four weeks after the dose. Due to the Moderna third-dose program starting later, no data beyond nine weeks exists at this stage.
A third dose with Vaxzevria increased protection to 57.7 percent one week after the dose which waned to 46.7 percent between five and nine weeks after the dose. Similar to Moderna, no data beyond nine weeks exists for the third dose of Vaxzevria.
A primary course of Pfizer was found to be 65.5 percent effective against Omicron variant at two to four weeks after the second dose. This protection waned to 8.8 percent at 25 or more weeks after the second dose.
A third dose with Pfizer boosted protection against Omicron to 67.2 percent at two to four weeks after the dose, which waned to 45.7 percent (44.7-46.7%) at 10 or more weeks after the dose.
A primary course of Moderna’s mRNA vaccine was 75.1 percent effective against Omicron at two to four weeks after the second dose. This waned to 14.9 percent vaccine effectiveness at 25 or more weeks after.
A third dose with Pfizer increased this protection to 64.9 percent at two to four weeks after the third dose. Due to Moderna’s rollout beginning later than other vaccines, no data exists for the third dose beyond five weeks.
A third dose with Moderna increased protection to 68.1 percent one week after the dose, which waned to 66.3 percent (63.7-68.8%) at two to four weeks after. No additional data was reported beyond that.
While this was a rigorous study that included a large population sample, due to the relatively small timeframe since the Omicron variant emerged, this study did not have access to enough data to determine the effectiveness of the vaccines against severe outcomes from the disease.
Additionally, due to different populations receiving different types of vaccines for their primary course, the results should be viewed with some caveats.
For example, the Vaxzevria vaccine was initially the vaccine provided to people in aged care homes and immunocompromised people that may result in lowering levels of vaccine effectiveness.
On the other hand, the Pfizer vaccine was the primary vaccine in people younger than 40 years of age which may help to explain the high vaccine effectiveness of Pfizer against Omicron two to nine weeks after the second dose.
However, the researchers did all possible to adjust for confounders such as age and clinical risk factors.
Despite limitations in this study and Pfizer’s clinical trial on three doses, they add to a body of growing research about the effectiveness of a third vaccine dose against COVID-19, particularly against the Omicron variant.
More was written about this by Honorary Professor Stephen Duckett at The University of Melbourne and Senior Associate Linda Lin at the Grattan Institute at Croakey earlier this week.
Clearly a more concerted effort at widespread communication and public health education is required to encourage more people to have a third dose.
Victorian mRNA vaccine production
The new mRNA vaccine production facility in Victoria is commencing recruitment for its Phase 1 clinical trial of two vaccine candidates made in Melbourne.
The two vaccine candidates focus on the immune response on the receptor binding domain (RBD), which is on the tip of the SARS-CoV-2 spike protein.
Researchers are initially looking for 114 volunteers to participate who have had their third dose of a COVID-19 vaccine at least three months prior to the study.
Moderna mRNA vaccine for children under six years
Moderna announced by press release that its phase two and three trial of COVID-19 vaccine in children aged six months to five years was generally well tolerated and effective against COVID-19 infection.
They reported that most adverse reactions to the vaccine were not severe, and consistent with the mRNA vaccine in other groups, adverse reactions were more frequent after the second dose than the first dose.
High fever were reported in 17 percent of children between six months to under two years old, and in 14.6 percent of children between two years old and under six years old.
No deaths, myocarditis, pericarditis, multisystem inflammatory syndrome in children were reported during the study.
The vaccine was reported to have a vaccine efficacy of 43.7 percent in the group of children between six months and under two years old, and 37.5 percent in the group who were between two and six years old, which is similar to the vaccine efficacy of two doses of Moderna’s vaccine in adults against the Omicron variant.
While the results indicate protection from infection and severe COVID-19 disease in children six months to under six years old, the results have not yet been peer-reviewed and must be viewed with caution.
Additionally, the study group was relatively small and longer-term follow-up is required.
Moderna has requested authorisation from the US Food and Drug Administration for emergency use of the vaccine.
Vaccine safety in Australian children
Recent analysis of Australian vaccination safety data indicates that the Pfizer vaccine is generally well tolerated in children aged between five and 11.
The most common side effects reported included a local reaction at the injection site, fatigue, headache and muscle or joint pain.
Similar to the mRNA vaccines in adults, minor side-effects were more common after the second Pfizer dose than after the first dose (30 percent compared to 26 percent).
Three percent of children reported missing some study or routine duties after the first Pfizer dose and nine percent reported this impact on routine activities after the second dose.
Alison Barrett is a research assistant at University of South Australia, with interests in public health, rural health and health inequities; and science and public health communications. She is also an editor at Croakey.org and a member of Croakey Health Media. Follow on Twitter: @AlisonSBarrett. Croakey thanks her for providing this column as a probono service to our readers.
See previous editions of the COVID wrap.
