Women who have been vaccinated against COVID-19 had a slight but not clinically significant change in the length of their menstrual cycles compared to unvaccinated women, according to a new study published by researchers from Oregon Health & Science University in Portland in Obstetrics & Gynecology.

Specifically, vaccinated women experienced a less than one-day (0.71-day) unadjusted increase in the length of their menstrual cycle after their first shot and a less than one-day (0.91-day) after their second shot, the study found. 

The increase in cycle length, however, seemed to be driven by several hundred women in the study who received both shots during a single cycle. This subgroup experienced a two-day unadjusted mean cycle length increase. 

“Statistically significant differences existed between vaccination status groups, but the change in cycle length was less than one day, which is below the reportable difference in the menstrual cycle tracking application and is not clinically significant,” the authors stressed.

Reverted to normal

In all cases, the cycles reverted to their original length after two post-vaccine cycles. 

This is the first peer-reviewed research published on the matter through the US National Institute of Child Health and Human Development (NICH), which awarded five grants totaling $1.67 million in October to agencies to explore the link between COVID-19 vaccination and menstruation changes after tens of thousands of women worldwide reported changes in menstruation after receiving the jab. 

“Concerns about a possible association between coronavirus disease 2019 vaccination and abnormal menstrual cycles may lead to vaccine hesitancy,” the study’s authors wrote in their report. “Unfortunately, clinical trials of the current COVID-19 vaccines did not collect menstrual cycle outcomes post vaccine.”

Other NICH-funded research is still underway by teams from Boston University, Harvard Medical School, Johns Hopkins University and Michigan State University.

The study was a retrospective cohort analysis, leveraging data from the Natural Cycles digital fertility-awareness application between October 2020 and September 2021. Nearly 4,000 women – 2,403 vaccinated and 1,556 unvaccinated – between the ages of 18 and 45 who had regular cycles, were not pregnant or taking hormonal contraception were evaluated as part of the study. 

Participants were inoculated with Pfizer (55%), Moderna (35%) or Johnson and Johnson (7%). 

Six cycles were analysed for each participant – for those who were vaccinated, three cycles before the first shot and three cycles during and after.

Study limitations

Dr Itamar Netzer, a gynaecologist and a sub-district director for Clalit Healthcare Services in Israel, there were some challenges with the study, which were also noted by the research team. These included that it relied completely on Natural Cycles data and application users tend to be mostly white, college-educated and have lower BMIs than the average American woman. 

In addition, he said that because the study relies on self-reported data by women, it is possible that these women did not accurately record their number of bleeding days. 

“Women with underlying gynaecological disorders may experience greater differences,” according to Netzer, who noted that only healthy women were included in the study.

Menstrual cycle timing is regulated by the hypothalamic-pituitary-ovarian axis, the researchers explained, which can be affected by life, environment and health stressors. They hypothesised that because mRNA vaccines create a robust immune response or stressor this could temporarily affect this axis, which could be the cause of the slight shift in cycle length. 

Netzer said that the research shows that the vaccine is “probably safe for everyone” and especially menstruating women. He noted that separate studies have shown that the vaccine is safe for pregnant women and does not impact the rate of stillbirths or premature delivery.

“In contrast, we have seen the hazards of COVID-19 on pregnancy,” Netzer stressed. “A pregnant woman who catches COVID is two to five times more likely to be hooked up to a lung-heart machine than a non-pregnant woman.

“We are quite sure the vaccine is safe in pregnancy,” Netzer continued, “and we know the [COVID-19] disease is dangerous for pregnancy.”

John Nkengasong, Director of Africa Centers for Disease Control, in a press conference Thursday, 6 January

IBADAN – COVID-19 could become “endemic” in Africa if the continent is unable to fully vaccinate 70% of its population by the end of 2022, warned Africa Centers for Disease Control Director, Dr John Nkengasong in a press conference on Thursday. An endemic disease is a disease that is always present in a certain population or region. 

Speaking at the first Africa CDC briefing of 2022, Nkengasong noted that without achieving the vaccination goal, COVID-19 could become an additional disease that African countries would be forced to deal with perenially, in addition to malaria, HIV/AIDS and tuberculosis.

However, with more vaccine doses increasingly becoming available to African countries, he said efforts are underway to consolidate countries’ vaccination initiatives by providing support to enhance actual roll-out of the jabs.

“One is to enable us to acquire more vaccines to support member states. Second, is to support their vaccination efforts. And then thirdly, to support the manufacturing. All of these initiatives are progressing extremely well,” Nkengasong said.

More equitable sharing of COVID vaccines and treatments a precondition for exiting the pandemic 

Corroborating Nkengasong at a separate briefing in Geneva, World Health Organization Director General Dr Tedros Adhanom Ghebreyesus, declared that more rapid and fair sharing of the full range of tools that science has provided is a pre-condition for the world to exit the acute phase of the COVID-19 pandemic. And access needs to span the range of tools  — tests, vaccines, treatment options, prevention and control measures.

At the current pace of vaccine rollout, a total of 109 countries would miss out on fully vaccinating 70% of their populations by the start of July 2022, Tedros warned. In late December WHO said that some 98 countries, nearly half of them in Africa, would missed the WHO goal of vaccinating 40% of their population by end 2021.  

Now, while some countries even move toward vaccinating citizens a fourth time, others haven’t even had enough regular supply to vaccinate their health workers and those at most risk, Tedros added.  

“Booster after booster in a small number of countries will not end a pandemic while billions remain completely unprotected. But we can and must turn it around. In the short-term we can end the acute stage of this pandemic while preparing now for future ones,” the WHO DG said at the global press briefing. See related story:

Gloomy New Year Prognosis – WHO Experts Warn Omicron Could Also Spawn More Dangerous Variants

Supporting African countries on vaccine rollout – vaccine advocates, engaging military support

Nkengasong said in addition to the $1.5 billion partnership with the MasterCard Foundation to support vaccine rollout in Africa, Morocco and Rwanda are serving as centres of excellence for COVID vaccination to share experience with other African countries that are struggling to more efficiently administer available vaccines in their respective countries.

He added that implementation partners are also being engaged in various countries. 

“We’ve worked with the countries to develop their micro plan. So this year, we will actually swing into action,” he said. 

One aspect of the plan, he said, includes the identification and engagement of vaccine advocates – in addition to military officers supporting, advocating for and facilitating the transportation and roll out of COVID vaccines.

“The initiative is saving costs and saving lives. The program is progressing very well,” he told Health Policy Watch. 

Increasing confidence in rapid antigen tests – but…  

Nkengasong also told Health Policy Watch that as cases surge, he sees rapid test kids replacing PCR tests for diagnosis of COVID-19.

Even in rich countries, PCR tests have become increasingly laborious and expensive to administer as nations struggle with unprecedented rates of new infections. 

On Wednesday, the UK government announced that a confirmatory PCR test will no longer be required for people who receive positive test results for COVID-19 from rapid antigen tests based on a lateral flow device (LFD). It cites evidence that  for every 10,000 lateral flow tests carried out, “there are likely to be fewer than 3 false positive results.” 

“The new approach reflects similar changes made this time last year in January 2021, when there was also a high prevalence of infection meaning it was highly likely that a positive LFD COVID-19 result was a true positive. This meant confirmatory PCRs were temporarily paused and reintroduced in March 2021 following a reduction in prevalence,” the UK government stated.

“It is in line with what the Africa CDC has been advocating for a while, which is that we should actually begin to recognize the antigen tests as well, because they are almost as good as PCR tests,” Nkengasong told Health Policy Watch.

At the same time, a parallel debate is still raging about whether negative antigen tests results can be relied upon as an early measure of infection. One new preprint study found that among a group of high-risk individuals tested with both rapid antigen and PCRs, in parallel, most people were infectious for an average of three days before the rapid test picked up their virus.  

UK advice still recommends that people with symptoms get tested with PCRs. 

WHO press briefing – first of the new year sounds gloomy notes.

Mass Omicron infection could lead to the formation of new and potentially even more dangerous coronavirus variants, officials from the World Health Organization warned on Thursday.

That is despite the fact that the Omicron variant is proving less lethal than its SARS-CoV2 predecessors, such as Alpha, Beta and Delta – which swept through India and then the world beginning in the spring of 2021. 

“We are giving this virus plenty of opportunities to circulate and the more the virus circulates the more opportunity it has to change,” said Dr. Maria Van Kerkhove, WHO’s COVID-19 technical lead, speaking at the first global press briefing of 2022. 

“I think, unfortunately, this will not be the last variant you hear us address. It will not be the last variant of concern.”

Her comments followed on remarks by a WHO European Region Emergencies official, Catherine Smallwood, earlier in the day, who sounded an even more ominous note:  

”The more Omicron spreads, the more it transmits and the more it replicates, the more likely it is to throw out a new variant,” Smallwood told AFP, “Now Omicron is lethal, it can cause death, maybe a little bit less than Delta, but who’s to say what the next variant might throw out.”

At the WHO global briefing later in the day, Mike Ryan, executive director of WHO’s Health Emergencies Program, also recalled having discussions during the previous Delta wave with top scientists who said that the Delta variant was so adept at infecting and replicating, that they could not imagine it mutating much more.  

“Yet it did,” Ryan stressed, “and we have seen a further variant emerge that is even more transmissible than Delta, which was even more transmissible than its predecessors… We are not doing well enough globally to say with any degree of certainty that we can avoid the emergence of new variants.”

Spreading at an unprecedented rate 

Dr Tedros Adhanom Ghebreyesus, WHO Director General.

Omicron is spreading at an unprecedented pace worldwide. In the United States, it now makes up 95% of cases, the Centers for Disease Control and Prevention said. The United Kingdom has said that one in 15 people are infected with the virus, and Indian health officials said Thursday that the country logged more than 90,000 new COVID cases in a 24-hour period, with a positivity rate of more than 4%. 

Last week also saw record highs in the number of new COVID-19 cases to be reported since the beginning of the pandemic  – “and we know for sure this is an underestimate number of cases,” said WHO Director-General Dr. Tedros Adhanom Ghebreyesus.  He stressed that increased vaccine roll-out in underserved countries 

While Omicron does appear to be less severe compared to Delta, especially in those who are vaccinated, it should not be classified as mild, he warned. 

“Omicron is hospitalizing people and killing people,” Tedros said. “It is overwhelming health systems around the world.”

Moreover, the Delta variant is still dominant in some countries and is mutating too, Van Kerkhove added. 

“Omicron is very efficient, but Delta is evolving as well,” Van Kerkhove said. “There are about 30 sub-lineages of Delta that we are tracking.”

WHO Advice includes more of same: masking, social distancing, vaccination  

While the WHO officials sounded a gloomy prognosis on the massive infection wave underway – and what that could mean for future virus mutations  – there were few new measures that they could suggest. 

And certain thorny questions that countries are struggling with now, such as  whether rapid antigen tests could be a reliable go-to protocol for people that suspect they are infected, or want to be released from quarantine, were not addressed. 

Ryan stressed, however, the need to continue with quarantine policies –  even while in some countries as many as one in 15 people are infected with Omicron. He said that quarantines should remain in place for at least five days, while people are most infectious.   That is generally in line with the revised advice that has been issued by the United States Centers for Disease Control, to respond to the infection surge. 

Ryan added that one of the ways to temper longer periods of isolation is through regular testing.  But he didn’t enter the debate raging now in many countries about reliance on rapid antigen tests, as compared to PCRs, to determine COVID infection status, officially report on COVID cases, and send people to quarantine – or allowing them to exit.  

While positive results of rapid antigen tests, using lateral flow devices, are generally regarded as reliable, negative results are considered far less accurate.

One recent pre-print study found that rapid tests are particularly unreliable at detecting the early stages of infection – leaving many people to walk around infectious for an average of three days after a positive PCR test – before showing a positive antigen test result. See related story:

COVID-19 Could Become Endemic in Africa if 70% Vaccination Coverage is not Achieved by 2022 – Africa CDC

WHO officials reiterated well-worn advice on the value of masking, social distancing and vaccination. Tedros also stressed, once more, the importance of expanding vaccine drives in under-resourced developing countries, where even more variants could otherwise fester. 

“This is about making personal decisions,” Van Kerkhove said, “this is about distancing – keeping your distance from others – wearing a well-fitted, appropriately made mask… Make sure you spend more time in places where there is better ventilation… and stay home if you are unwell.”

Air pollution in Mashhad, Iran

Almost nine out of ten (86%) people living in urban areas across the globe, or 2.5 billion people, are exposed to unhealthy particulate matter levels, leading to the 1.8 million excess deaths in cities globally in 2019, in a study that examined urban air pollution and related mortality trends in over 13,000 cities globally. 

The first of two studies, both published today in The Lancet Planetary Health journal, found that 86% of urban inhabitants lived in areas that exceeded the 2005 World Health Organization (WHO) guidelines for annual PM2.5 exposure of 10 micrograms per cubic meter (μg/m3); in 2021 that safe air quality guideline was tightened even further to 5 μg/m3 of PM2.5.  

“The majority of the world’s urban population still live in areas with unhealthy levels of PM2.5,” said lead author of the study Veronica Southerland, of US-based George Washington University. 

Figure 3Change in population-weighted PM2·5 concentrations and PM2·5-attributable mortality rates between 2000 and 2019 for the top 250 most populated urban areas based on 2019 WorldPop estimates

Exposure to PM2.5 (fine particulate matter with a diameter of 2.5 micrometers or less) is a leading environmental risk factor for disease. 

Inhalation is known to increase the risk of premature death from health conditions such as cardiovascular disease, respiratory disease, lung cancer, and lower respiratory infection. 

Additionally, the second study, focusing on transport-related NO2 (nitrogen dioxide gas) pollution and paediatric asthma incidence, found that nearly two in three urban childhood asthma cases in 2019 were attributable to NO2 pollution, with nearly 2 million asthma cases found among children worldwide.  

Both studies highlight the urgent need to improve air quality in cities and reduce exposure to pollution, particularly among children and the elderly. 

PM2.5 concentration seven times WHO 2021 guidelines in first study 

The first study focused on PM2.5 concentrations and associated mortality trends in over 13,000 cities globally between 2000 – 2019. 

Average population-weighted PM2.5 concentration in 2019 across all urban areas globally was 35 micrograms per cubic meter – equivalent to seven times the new 2021 WHO guideline for annual average PM2.5 of five micrograms per cubic meter. 

Study authors estimate that 61 deaths per 100,000 inhabitants in urban areas were attributable to PM2.5 in 2019. 

A 2021 report by Greenpeace Southeast Asia and IQAir had also found the link between urban air pollution and attributed mortality, with exposure to PM2.5 responsible for the deaths of 160,000 in the world’s five biggest cities.  

Southeast Asia sees largest increase in PM2.5 concentration and attributable deaths 

urban
Pollution in Delhi peaks in late autumn when drifting emissions from crop burning exacerbate the usual urban household, traffic and industrial sources

While global average PM2.5 concentrations remained consistent over the 19-year period, there were large variations by regions.

Urban areas in Southeast Asia (including India) saw the largest regional increases, with a 27% increase in average population-weighted PM2.5 concentration between 2000 – 2019. Southeast Asian cities also saw the largest increase in PM2.5-attributable mortality during this period – 33% – from 63 to 84 deaths annually per 100,000 people. 

Trends in global urban mortality rates and PM2·5 concentrations, 2000 to 2019

However, higher or lower PM2.5 concentrations in some urban areas of Asia, Africa and elsewhere did not always yield correspondingly lower PM2.5-attributable death rates. That is because demographic factors, such as the age of the population, as well as baseline health conditions, also have a strong impact on pollution-related deaths. 

For instance, Guangzhou, China, had a decrease in population-weighted PM2·5 of 14% during the 19 year period, from 37 μg/m3 to 32 μg/m3. Howver, PM2·5-attributable mortality rates increased by 10%. In contrast, Luanda, Angola, saw a 38%  increase in PM2·5 population-weighted concentrations from 13 μg/m3 to 18 μg/m3. But attributable mortality decreased by 16%.

At the same time, decreases in PM2.5 concentrations had a comparatively larger impact on reducing PM2.5 attributable mortality in urban areas where pollution levels were already low, such as the Americas and Europe, the researchers found.

For instance, in European cities, a 20% reduction in contractions, from an average of 20 μg/m3 to 16 μg/m3 over the course of the 19 year period, resulted in a 23% decrease in PM2.5 attributable deaths despite an ageing population, the study found. That is because proportionally speaking, decreases in air pollution at relatively lower levels yield comparatively greater reductions in mortality.   

“Avoiding the large public health burden caused by air pollution will require strategies that not only reduce emissions but also improve overall public health to reduce vulnerability,” stated Sutherland. 

Second study finds two out of three new pediatric asthma cases in cities due to NO2 

The second study analyzed global concentrations of NO2 with population and baseline asthma rates in order to estimate the paediatric asthma incidence attributable to NO2 between 2000 – 2019 in 13,129 cities.

NO2 is an air pollutant mainly emitted by vehicles, power plants, industrial manufacturing, and agriculture.

Previous research has shown transport-related air pollution is associated with both asthma exacerbation and new onset of asthma in children. 

The study revealed that 1.85 million, or 8.5% of all new paediatric asthma cases reported in 2019 were attributed to NO2.  Two out of  three of these new cases occurred in the 13,129 urban areas covered in the study.  

In urban areas, NO2 was responsible for 16% of all new child asthma cases in 2019. 

“Our results demonstrate the important influence of combustion-related air pollution on children’s health in cities globally,” says Susan Anenberg of US-based George Washington University, who is co-first author on the NO2 study and corresponding author of both studies.

Anenberg pointed out that despite the downward trend of NO2 concentrations over several decades – the result of effective air quality management programs, NO2 continues to contribute to child asthma. 

“Current NO2 levels contribute substantially to pediatric asthma incidence, highlighting that mitigating air pollution should be a critical element of children’s public health strategies.”

Image Credits: Mohammad Hossein Taaghi, The Lancet, Planetary Health , Flickr, The Lancet, Planetary Health .

WHO trainers introduce a group of African health workers to COVID-19 vaccination protocols in April, 2021; Champions of the organization say it’s finance structure is “fundamentally rotten” – leaving it ill-equipped to meet global health challenges.

Big pre-holiday hopes that WHO member states might agree on a sweeping financial reforms to put the World Health Organization’s $3 billion annual budget on a more sustainable foundation now seem to be foundering in the New Year.

A report by the member state Working Group on Sustainable Financing, published on Tuesday, has stopped short of recommending that assessed contributions by WHO member states be scaled up gradually to meet 50% of the Organization’s core budget needs by 2028-29. 

The scale-up in assessed contributions has been viewed as the lynchpin measure in a series of broader reforms to WHO finances, proposed by a number of recent external reviews of WHO’s performance – and shortcomings –  during the COVID pandemic – among those the Independent Panel review co-chaired by Helen Clark and Ellen Johnson-Sirleaf, former heads of New Zealand and Liberia respectively. 

In the wake of those scathing reviews, reforming WHO’s finance has become a flagship cause for Germany, backed by a large bloc of European, African and other member states – who see  funding reform as critical to maintaining WHO’s central role in global health decision-making, post pandemic. 

While the Working Group impasse does not mean that the financing reform initiative is dead, it means that there is not, right now, any clear pathway to a formal decision on sweeping reforms in the lead-up to the WHO Executive Board meeting, scheduled for 24-29 January – where the Working Group’s deliberations will be reviewed.  

Leading holdouts on reform include US, handful of other rich countries and Russia, Brazil 

(left) World Health Organization Headquarters in Geneva (Photo: WHO/P. Virot). (right) White House in Washington, DC (Photo: LoC/Carol Highsmith)

In a series of extensive member state consultations that took place since March 2021, WHO’s entire Africa bloc, as well as most European Union and Eastern Mediterranean (Middle Eastern) member states spoke out strongly in favor of the financial reforms, the report states.  Of the 100 countries submitting written responses, some 90 supported an increase in the level of assessed contributions, which have stagnated for over a decade.  

But a handful of countries, including the United States, but also Russia and Brazil, have continued to hold back, diplomatic observers in Geneva told Health Policy Watch.  

Other holdouts include Japan, Monaco and Poland, observers say.  China, meanwhile, has remained on the fence, neither emphatically supportive or opposed.   

Their reluctance is summed up by a terse sentence in the 4 January report that states: “The Working Group did not reach consensus on the Recommendations of the report, given the limited time.”

On the face of it, that may seem odd  in the case of the United States – regularly the largest, or one of the largest, contributors to WHO overall.  However, notably most of the US contributions are  “voluntary” – meaning they can be packaged into a wide range of US offices and initiatives – from USAID and the Centers for Disease Control to the US Department of Health and Human Services.  

Regular, assessed US contributions to WHO have remained frozen for over a decade, while the majority of funding has been as “voluntary” contributions.

In contrast, getting US Congressional approval to a decision increasing the US proportion of required, assessed contributions would be a potentially difficult political move. And that is the case now  even for the WHO- sympathetic administration of US President Joe Biden, who is already facing increasingly tough opposition from his Republican opponents in Congress. 

And although the cumulative impact of the proposed 50% assessment move would only add up to about $600 million a year more in contributions from all WHO member states together, some countries may also be worried about the precedent the decision could set.   

In particular, they may fear that agreeing to  higher WHO assessments might lead to stiffer payments for the rest of the UN system – with much larger budgetary implications, sources said.  

“I think that is a key elephant in the room – what would the WHO Assessed Contribution increase mean for the entire UN system?” one observer told Health Policy Watch. “Are we opening up a Pandora’s box, so that if we are increasing the AC for WHO, wouldn’t we have to increase the AC for the UN overall, for UNDP, for everybody.”   

WHO member states are ‘minority shareholders’ in WHO’s budget  

Top contributors to WHO’s Budget (2018)

The current system, however, leaves  WHO member states as effectively minority shareholders in their own governance of WHO, critics say.  

In contrast, philanthropies like the Bill and Melinda Gates Foundation and Gavi, The Vaccine Alliance, rank among WHO’s top five largest contributors, and wield accordingly disproportionate influence.  

Currently, the regular, assessed contributions from member states generate only about $475 million a year – which is only about 16% of WHO’s $3 billion annual budget costs.

Along chronically budget shortfalls for key tasks, the reliance upon “voluntary” donations has been decried by WHO Director General Dr Tedros Adhanom Ghebreyesus as confounding more strategic planning of resource use. 

Voluntary donations are not only unpredictable, but they also too often come with hobbling strings attached – meaning that they have to be dedicated to a specific programme activity. This limits WHO’s ability to nimbly shift funding and respond to emergencies such as the recent COVID pandemic, another WHO review body, the Independent Oversight and Advisory Committee (IOAC), stated in its report, published in May.   

Going forward, there also are building concerns that if other new global health institutions are created under the auspices of a Pandemic Convention or a UN-sponsored Global Health Threats board, these could have the unintended consequences of weakening WHO. Conversely, a robust financial base would help ensure that WHO remains the pulsebeat of global health decision-making – even if new pandemic-specific offices or agencies spring up alongide it.

Budget system is ‘Fundamentally Rotten’ – but action may still take more time 

Björn Kümmel, Germany’s deputy head of global health in the Ministry of Health

In a mid-December appearance at Geneva’s Graduate Institute Global Health Centre, shortly before the last Working Group meeting, Germany’s Björn Kümmel, deputy head of global health in the Ministry of Health and head of the Sustainable Finance Working Group, made a spirited appeal for bold changes in WHO’s financing blueprint.

The current structure is “fundamentally rotten”, in its excessive dependence on just a handful of rich countries and a few private donors, he declared.   

“Practically, it’s not possible to come up with piecemeal reforms, but we need to change the way, substantively, how WHO is financed,” said Kümmel, currently Executive Board vice-chairman as well. 

It’s now very “disappointing” that member states have not seized upon the urgency of the  moment created by the pandemic to undertake bold reforms, says Olaf Wientzek, Director of Multilateral Dialogue at the Geneva office of Germany’s Konrad-Adenauer Foundation. 

He points out that the proposal to inch up contributions to the 50% benchmark does not even go as far as other outside reviews. The Independent Panel had, for instance, called for an increase in contributions to cover 66% of WHO’s base budget costs.  

 “I think it was quite a good compromise, because in the long-term it makes a big change, but it doesn’t do it too quickly, where you could argue that given the economic backlash the Corona crisis has created, it would be too tough for many countries,” said Wientzek. 

“And to be honest, if we talk about the massive recovery packages that countries have passed to address the pandemic, the sums involved regarding WHO are very limited. It’s not ambitious – it’s low-hanging fruit.”

Wientzek held out hope that the process of consensus-building over the reforms may simply take more time – as is often the case in laborious WHO debates where consensus is the norm. 

“The initiative may have more chances in May [at the World Health Assembly], or the following May,” he predicted.  “What I do know is that Germany remains very committed to this – and I don’t think that’s going to change with the new [German] government.”  

Image Credits: Wikimedia Commons, WHO/P. Virot & LoC/Carol Highsmith, Kaiser Family Foundation , WHO .

Israeli Prime Minister Naftal Bennett (right) is briefed about Sheba Medical Center's COVID-19 fourth shot trial on Tuesday, January 4, by hospital Director-General Prof. Yitshak Kreiss.
Israeli Prime Minister Naftal Bennett (right) is briefed about Sheba Medical Center’s COVID-19 fourth shot trial on Tuesday, January 4, by hospital Director-General Prof. Yitshak Kreiss.

A fourth shot of the Pfizer coronavirus vaccine administered to individuals who received their third shot nearly five months ago produces a five-fold increase in antibodies, according to preliminary results of a first-in-the-world trial being conducted in Israel.

The news comes on the same day that the country announced it would launch a trial to determine the effectiveness of receiving a fourth shot of the Moderna coronavirus vaccine beginning on Wednesday.

Both trials are being run out of Sheba Medical Center at Tel Hashomer and include around 150 medically personnel who received their third doses by August 2021, with a serology result below 700.

Participants in the Pfizer trial were inoculated a week ago. The hospital announced the preliminary results on Tuesday during a visit to the facility by Israeli Prime Minister Naftali Bennett. The data has not yet been published.

Fourth Pfizer shot increases antibodies five-fold

“I am pleased to announce … that the initial research indicates that within one week of receiving the fourth vaccine, there is a nearly fivefold increase in the number of antibodies in the blood,” Bennett said. “[A fourth booster] will probably provide a much higher level of protection than without the shot – a high level of protection for both infection and severe morbidity. In simple terms, the fourth vaccine is safe, it must be. The fourth vaccine is very likely to work.”

He added that in the two days since Israel opened up fourth doses, more than 100,000 Israelis registered to be vaccinated or have already been vaccinated.

Israel is the first country in the world to offer a fourth shot to all citizens over the age of 60 and medical workers who received their last doses at least four months prior.

Chile also announced last month that it would offer citizens a fourth coronavirus vaccine dose, also starting with those who are at highest risk of infection or developing severe disease, but those shots are not expected to begin until February and they are being given only after six months have passed from the previous jab.

Brazil also has approved a fourth shot, but only for the immunocompromised.

Researchers say fourth dose safety profile is as good as expected

Prof. Gili Regev-Yochay, director of the Infection Prevention and Control Unit at Sheba, is overseeing the trial. She stressed that the safety profile of the fourth shot appears similar to the profile in the previous doses.

“These initial findings join the preliminary results on potential side effects, which were obtained following the administration of the fourth dose, which also indicate the safety of the fourth dose,” said Regev-Yochay. “This study will yield more information in the coming days and weeks.”

The Moderna trial is being run in collaboration with Medison Pharma, a company that markets the Moderna vaccine in Israel. Participants will be medical workers who received three shots of Pfizer and will now receive a dose of Moderna. Researchers will be evaluating the degree of immunity and protection against the Omicron variant with this combination.

Both trials are being run on conjunction with Israel’s Health Ministry and with full approval of the Helsinki Committee.

Image Credits: Sheba Medical Center.

Influenza virus
Influenza virus

The world’s first case of “flurona” – a co-infection with both seasonal influenza and COVID-19 was reported in Israel last week, as the Omicron variant sweeps across the world. Since then, small numbers of people co-infected with both viruses have been identified in other European countries as well, a World Health Organization official in the European Regional Office confirmed.

“Small numbers of co-infections of influenza and SARS-CoV-2 have been seen elsewhere and have been reported internationally during the pandemic to date,” Dr. Dorit Nitzan, WHO European Regional Emergency Director, told Health Policy Watch. “Experience and understanding needs to build further whether there are clinical differences in the presentation, management and outcome of these cases.”

WHO so far has not provided any reports on the numbers.

Coronavirus
Coronavirus

Fears of a widespread flu and COVID twindemic did not materialize last year, as masking and social restrictions apparently kept flu cases unusually low.

There are fears that the European region and other parts of the northern hemisphere could now be vulnerable to a “Flurona” wave – as the highly infectious Omicron variant sweeps through the world. And at the same time, many vulnerable people also didn’t get a seasonal flu jab.

Although WHO’s Geneva Headquarters also said Tuesday that the current Omicron symptoms indeed appear much milder than previous waves, largely affecting the upper respiratory tract.

“We are seeing more and more studies pointing out that Omicron is infecting the upper part of the body. Unlike other ones, the lungs would be causing severe pneumonia,” WHO Incident Manager Abdi Mahamud said in a Geneva press briefing.

Seasonal Flu on rise

Already, the number of flu cases detected in the WHO European region was “above what we would normally expect to find in the population,” Nitzan said.

According to WHO European Region,, in any given year 5% to 15% of the population is affected by influenza – around 3 million to 5 million cases resulting in 650,000 deaths.

“With COVID-19 also in high transmission across our region, there is the risk that this so-called twindemic could put excessive pressure on already overstretched health systems,” the WHO website said.

The impact could be especially acute on the most vulnerable populations, such as the elderly or people with underlying medical conditions, explained Prof. Cyrille Cohen, head of the immunology lab at Bar-Ilan University, as both flu and COVID-19 on their own can be lethal for older people.

“One virus might weaken you and the second one could be the straw that breaks the camel’s back,” he said. “You might end up with the Omicron variant that is not so tough but then get the flu and that gives you a high fever and the combination could put your life at risk.”

First case of flurona reported in Israel

The first case reported by Israel was a young woman in her 38th week of pregnancy. The woman was treated with a drug combination that targets both coronavirus and flu, according to Dr. Arnon Wiznitzer, head of the Women’s Hospital at Beilinson Hospital in Petah Tikva, Israel. She and her baby were in stable condition on Monday.

“We did not have any kind of influenza all year last year,” Wiznitzer said, “but this year is different.”

He said that a significant number of pregnant women are presenting in the delivery room with flu-like symptoms and it is difficult to know whether they have influenza or COVID-19. As such, these women are put into special isolation rooms for labor and delivery, where they are tested for both viruses.

Until now, the majority of cases have turned out to be the flu, but he expects the balance will shift as COVID cases rise in the country. Israel is reporting more than 10,000 new cases per day and is expected to reach up to 50,000 – around the same number per capita as some of the hardest hit European countries, such as Denmark.

‘Flurona’ symptoms

When it comes to the symptoms of flu, COVID or flurona, it can be difficult to tell the difference, according to Dr. Richard Peabody, who leads the High-threat Pathogen team and the Surveillance and Laboratory pillar of the COVID-19 Incident Support Management Team at WHO/Europe.

In a WHO Q&A, he explained that “both viruses are highly infectious respiratory diseases and share many of the same symptoms, such as coughing, fever, shortness of breath, and/or loss of taste and smell. Because of the difficulty in distinguishing the diseases from symptoms alone, if you are symptomatic, you should isolate yourself from other people to reduce the risk of the infection spreading, particularly to vulnerable people, and get tested for COVID-19 as soon as possible.

“While both diseases can cause serious illness, COVID-19 is more likely to lead to health complications, admission to hospital and, in some cases, death – so getting tested is essential,” Peabody said.

Flu vaccines important – and so far vaccine rates in European Region appear lower than usual

It is also important to get vaccinated, Peabody stressed.

In Israel, where there are around 2,000 people hospitalized for flu, vaccination rates against influenza are down, in comparison to past years. And this is likely to be reflective of the broader situation in WHO’s European Region, Nitzan said – although WHO’s regional influenza vaccine uptake rates for the 2020/21 season are not yet available.

Until now, the region is mainly seeing three strains of influenza viruses, including: A(H3N2) viruses and some influenza A(H1N1)pdm09 or influenza B viruses, according to WHO’s European Regional Office.

“People at increased risk of severe disease from [flu] infection include older people, pregnant women, young children, immunocompromised people and people with chronic underlying medical conditions,” WHO said. ”These groups represent a sizable proportion of the population in the WHO European Region. Therefore, WHO/Europe recommends that everyone at risk of severe disease from infection with influenza, as well as health-care workers, be vaccinated.”

Although there is limited evidence about people who have received both the COVID-19 and the influenza vaccines at the same time, WHO said that doing so does not show any increase in adverse effects.

Wiznitzer said that in Israel these high-risk groups, especially pregnant women, are encouraged to get both shots, because flu and COVID can have adverse effects on mom and baby.

“Fighting both flu and COVID can be very dangerous,” he said. “I can ensure that both vaccinations are safe during pregnancy and on the baby.”

Image Credits: Flickr.

A child receives a vaccine through the Maccabi Health Fund in Israel in December 2021.
A child receives a vaccine through the Maccabi Health Fund in Israel in December 2021.

Two new large scale reviews of the effects of the two-dose Pfizer’s mRNA vaccine in children aged 5-11 shows fewer severe effects than in older groups.

Tuesday’s report, by the Israeli Health Fund Maccabi covering more than 20,000 children, comes on the heels of a similar US Centers for Disease Control and Prevention (CDC) study of some 42,504 children that found nearly all side effects have been mild as well.

The findings also coincide with a US Food and Drug Administration announcement that it has expanded its approval of booster vaccines to kids aged 12- to 15-years-old. It also said that it would allow some children aged five to 11 who are immunocompromised to get a third shot, such as those who have undergone organ transplants. A CDC expert group is meeting today to decide on implementation of the FDA authorization.

Children ages 5-11 did not experience any severe or unusual side effects after receiving a second dose of the Pfizer coronavirus vaccine, according to a report released Tuesday by Maccabi Health Services – one of Israel’s four national health funds.

No reports of heart inflammation

In the CDC study, there were 12 serious reports of seizure and 11 reports of myocarditis among the children enrolled in the CDC-FDA Vaccine Adverse Event Reporting System (VAERS) – none fatal. Two deaths reported in 5-year-olds with complicated health histories could not be directly linked to the vaccine.

Notably, in the Israeli study, there have been no reports of myocarditis – a rare heart inflammation condition that was found to affect most young men between the ages of 16 and 30 in previous studies of those age groups.

“There were no unusual side effects,” said Dr. Miri Mizrahi Reuveni, director of the Health Division at Maccabi Healthcare Services in a briefing.

According to the report, 70% of children experienced pain at the site of injection – the same percentage who experienced pain after their first jab.

In addition, a third (33%) of children experienced general side effects, such as fatigue, headaches and general achiness. Only 20% of children experienced similar side effects after the first shot.

“One in four (26%) of 11-year-olds vaccinated with a second coronavirus vaccine dose missed a school day or afternoon activity due to side effects,” Reuveni said.

Fewer side effects the younger the age group

She noted that there are fewer side effects the younger the children are. Only 11% of five-year-olds missed a school day or activity. Also, 18% of 11-year-olds experienced a headache, for example, compared to 8% of five-year-olds.

This is also the case when comparing vaccinated children to adults, the Maccabi data shows.

Israel approved vaccines for children 5-11 shortly in late November, shortly after the United States.

So far, around 9% of Israel’s 5-11-year-olds are fully vaccinated, meaning they have had two shots in the last six months, although much higher percentages of children have had their first dose.

Maccabi has vaccinated 44,300 children and another 34,000 have appointments for shots. Around 50% of children have received their second dose.

About one in five children in the US have gotten their first COVID vaccine, according to data by the CDC.

Image Credits: Maccabi Health Services.

First vaccinations of Israeli health workers and people over age 60 roll out on Monday.

JERUSALEM – Israel once again has placed itself in the middle of the global clinical debate on the medical benefits of a fourth Pfizer shot to slow the Omicron wave, when it became the first country to approve such an injection for all citizens over the age of 60 and healthcare workers.

Israeli Prime Minister Naftali Bennett announced the roll-out of the second booster during a press conference Sunday night, where he said that anyone over the age of 60, as well as  medical staff who had received their first booster four months ago or more, could get inoculated. 

“The decision was made after consulting with various experts,” Bennett said. “The significance is great; we will have a new layer of protection.”

He added that the country’s policy of booster shots has kept citizens healthy with per capita death rates among the world’s lowest – as compared to the United Kingdom, where the mortality rate is 50 times greater, Germany 100 times and in the United States, 130 times higher.

Israel was the first in the world to approve a third jab despite international criticism,  including from the World Health Organization, which has repeatedly  warned rich countries  against hoarding shots – saying that leaves variants to flourish in low-income countries, prolonging the pandemic.  

“We must not be complacent,” the prime minister warned. “Everyone who is entitled to a fourth dose, get vaccinated.”

In his own announcement, the country’s Healthy Ministry Director-General Nachman Ash said the move was made “in light of the increase in morbidity,” as new daily cases on Monday topped 6,500 and the prime minister warned of 50,000 new daily cases in the coming weeks. That would be a per capita rate about equal to Denmark, one of the European countries seeing exceptionally high COVID infection rates. 

Still no evidence of fourth dose preventing infection 

But local and international scientists and doctors were quick to highlight that there is still no evidence of the effectiveness of a fourth dose in preventing infection, serious disease or death. 

“The decision must be accompanied by a scientific evaluation by an independent body,” charged the Israeli Association of Public Health Physicians in a statement. “Resources must be directed first and foremost to [encourage the public] to complete their first, second and third vaccines whose benefit is clear and scientifically proven.”

Despite racing ahead of the world on vaccine roll-out, Israel’s overall vaccination rate for people who have received their first two doses now lags behind many other nations, with only 60% of the country vaccinated with two jabs within the last six months or three shots, and some 700,000 entirely unvaccinated.  

Other countries will be closely eyeing moves

As in other virus waves, Israel’s moves will be closely eyed by other countries that are anxious to blunt the full force of the new Omicron variant – which is far more infectious – even if it is also supposedly less deadly.  

That, in the face of mounting evidence from around the world that the degree of protection offered by mRNA vaccines against SARS-CoV2 in general, and against Omicron in particular, declines sharply four to six months after vaccination. Laboratory tests have, however, suggested that even lower levels of neutralizing antibodies, as well as continued T-cell immunity, may still provide protection against the development of serious disease. 

Chile also announced last month that it would offer citizens a fourth coronavirus vaccine dose, also starting with those who are at highest risk of infection or developing severe disease, those shots are not expected to begin until February and they are being given only after six months have passed from the previous jab.

Brazil also has approved a fourth shot, but only for the immunocompromised. 

Giant experiment on safety and efficacy 

Couple awaits their fourth vaccine at a Jerusalem health fund station.

Now Israel’s new campaign, which will be tracked by its  national digitized system of healthcare records, and research teams, is expected to provide real-time information on the efficacy of yet another booster against Omicron – in what amounts to a large-scale national clinical trial. 

There is also still no evidence as to the safety of a fourth shot – although most health experts believe that the mRNA vaccines will not cause any short- or long-term harm. 

Sheba Medical Center at Tel Hashomer last week launched a fourth shot trial in late December of around 150 healthcare workers to see how much an additional COVID shot raises a person’s antibody levels and if there are any negative effects, but no concrete data has been released yet.

On Sunday night, the hospital said that out of 154 people who received the jab, 80% reported mild reactions at the point of injection – similar to after the third dose. Some 45% of recipients experienced fever, weakness, muscle aches or headaches – symptoms that in most cases passed within 24 hours. 

“From these data, it appears at this stage that the fourth vaccine profile is as safe as the previous vaccine doses,” said Dr. Gili Regev-Yochay, director of the Infectious Disease Epidemiology Unit at the hospital who is running the new study. 

Local experts argued that pre-existing vaccine protection could decline to almost nil within another month 

The decision to move to a fourth jab was taken following a December 21 meeting of Israel’s national Pandemic Response Team, when experts warned that within a month’s time, Israel’s population would be as vulnerable to Omicron as they had been to the initial COVID-19 outbreak prior to any vaccination whatsoever.

Another team of researchers told the committee that a third booster shot was not even enough to halt Omicron as its effectiveness against the variant would decline from 75% to 25% after month four. 

The Ministry of Health team ultimately voted in favor of the fourth shot – just 10 days after it had shot down the move. But it took Ash another week and thousands more Omicron cases to give his final approval. 

Other critics still maintain, however, that the Pfizer vaccine was never intended to ward off infection, but to prevent severe disease and death. And it appears that the second dose, and certainly the third shot, does a decent job of that already – even in the face of Omicron. 

Moreover, the Omicron variant causes less serious disease in general than its Delta predecessor, according to all studies and predictions. 

Finally, the Omicron wave appears to be short-lived. Already this week, South African health officials announced that they believed the country had passed the peak of the wave, with new cases dropping by nearly 30%.

But until Sheba’s fourth dose trial is over or enough Israelis over the age of 60 get the jab, the decision to give a fourth dose is just a shot in the dark. 

“In the coming days, we will report preliminary findings regarding the initial increase in antibodies and immunity within a week of vaccination,” Regev-Yochay said. 

Image Credits: Clalit Health Fund , G. Ginsberg.

South African President Cyril Ramaphosa and Deputy President David Mabuza visit an Aspen Pharmacare facility in March 2021, a key partner in the country’s J&J vaccine drive.

A new South African study shows that a second Johnson & Johnson dose, administered 6-9 months after the initial single-dose vaccine provided 84% protection against hospitalization from the Omicron SARS-CoV2 variant – results that even outperformed those of an earlier South African study looking at effectiveness of the two-dose Pfizer regime in the face of Omicron.

The study, published in the medrxiv.org preprint server on Thursday,  measured the vaccine’s effectiveness in a group of some 227,000 health care workers, including 69,000 people who received the vaccine booster, between 8 November and 17 December – just as the Omicron variant was taking hold in the country.

The study found that vaccine efficiency against hospitalizations increased over time since the booster dose was administered from 63% in the first to weeks, to 85% post-boost.

“This data is important given the increased reliance on the Ad26.COV.2 [J&J] vaccine in Africa,” said the team of researchers, led by scientists at the South African Medical Research Council, the Desmond Tutu HIV Centre, and other prominent research centers.

Previous large-scale South African study on two Pfizer jabs yielded weaker results

A University of Michigan researcher administers the Johnson & Johnson COVID-19 vaccine candidate during phase 3 clinical trials in the US and seven other countries. The vaccine was authorized in February 2021 by the US FDA.

The study contrasts with a 14 December report on Pfizer vaccine efficacy in the face of Omicron by one of South Africa’s largest insurance providers.

The study by Discovery Health,  found that a two-dose Pfizer-BioNTech vaccine provided 70% protection against severe COVID cases, requiring hospitalizations, but only 33% protection against COVID infection during the current Omicron wave. The study examined some 211,000 COVID-19 test results obtained between 15 November and 7 December, 41% of which were from adult members who had received two-doses of the Pfizer vaccine.

Although the U.S. Food and Drug Administration was one of the first regulatory agencies to authorize the Johnson & Johnson/Janssen COVID-19 vaccine in February 2021, and following that, a booster shot, the vaccine had fallen from favour more recently in the United States. And that was following warnings from the US Centers for Disease Control and Prevention about rare but life-threatening blood clots that could be linked to the vaccine.

The South African Medical Association in November also had protested the exclusive arrangements between Johnson & Johnson and the government which led to health workers having only one booster option – a second J&J jab – while the company ran research on the results.

Latest South African results – turn earlier assumptions on head

Johnson & Johnson can ship vaccines standard cold chain technologies, because the temperature requirements are not as strict as for Pfizer’s and Moderna’s vaccines.

At the time, the South African Medical Association complained that the Pfizer jabs appeared to generate a more robust response – and should thus also be made available to highly exposed health workers.

Now, those assumptions may be turned on the head.

The J&J vaccine has been an anchor of the South African vaccine response from the beginning of vaccine rollouts – where the jab is also being produced in a collaboration with Aspen Pharmaceuticals for domestic use – as well as for the wider African market.

Along with stimulating a high degree of response with the first shot, the J&J vaccine can remain stable for up to three months at  2°C to 8°C, while the Pfizer and Moderna mRNA vaccines require cold chain storage at -28°C to 70°C.

The J&J vaccine uses a inactivated adenovirus  (cold virus) to deliver a genetic fragment of the SARS-CoV2 spike protein into the body, which in turn stimulates immune response.

In contrast, the Pfizer and Moderna vaccines deliver messenger RNA (mRNA) – a single strand genetic instruction making part of a SARS-CoV2 spike protein – into the body.  And that mRNA triggers and immune response.

Unexpectedly potent T Cell responses to Omicron Variant

In another a pre-print laboratory study published on 26 December, South African researchers also found that T-cells taken from people who received Johnson & Johnson vaccines recognized Omicron-infected cells almost as well as they recognized cells infected with other variants. That study is also significant as it suggests that even if antibody response to Omicron is not as robust in vaccinated individuals, the other critical factor in the body’s immune response remains more resilient.

“We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations,” wrote the authors, led by scientists at the University of Cape Town.

See here a video about how the four main categories of SARS-CoV2 actually work:

https://youtu.be/lFjIVIIcCvc

Image Credits: Johnson & Johnson, NBC News.