When reports emerged this week that six people in the US had developed a rare blood clotting condition after taking the Johnson & Johnson COVID-19 vaccine, for many, one detail appeared to stand out: all of the individuals affected were women.
The six cases, which include one fatality, represent a tiny fraction of the more than 6.8 million doses of the jab that have so far been administered throughout the US.
And public health officials have stressed that it is not clear if the blood clotting was caused by the vaccines themselves or whether women or any subgroup are more likely to be impacted.
Still unclear if women are more likely to be impacted
Dr William Schaffner, a professor of infectious diseases at the Vanderbilt University Medical Center, told Euronews that while the fact that all six reports of the rare blood clotting disorder following the Johnson & Johnson vaccine may stand out as a "striking feature," there is still simply not enough information to determine whether that means women could be more affected.
Noting that US health agencies have recommended that states pause the rollout of the Johnson & Johnson vaccine until more information can be gleaned, Dr Schaffner said officials are working to establish a "more clear picture about what the risks associated with the J&J vaccine might be".
"As you may know the [Centers for Disease Control and Prevention]'s advisory committee on immunisation practices met yesterday [Wednesday] to discuss that," he said.
"They have decided not to make a final vote on policy regarding the use of the J & J vaccine, but they have continued the pause in order to gather more data," he said.
Prof Neil Mabbott, Personal Chair of Immunopathology at the University of Edinburgh, doubled down on Dr Schaffner's comments, adding more research needed to be done to find out "is the vaccine in very, very rare instances triggering CVST (cerebral venous sinus thrombosis) in some recipients".
"What we do know is that CVST is more common in women than it is in men, but it's still a very, very rare disease," he added.
Vaccine benefits outweigh the risks
The US Food and Drug Administration (FDA) has stressed that these particular blood clots, CVST, are rare, with the agency noting that they are being observed in combination with low levels of blood platelets, with symptoms including headaches, blurred vision, fainting and seizures.
The cases of CVST among Johnson & Johnson vaccine recipients come after Europe’s drug regulator said it had identified a potential link between the AstraZeneca COVID-19 vaccine, with the rare blood clots also being observed in some adults who had received the jab.
As of April 4, the European Medicines Agency (EMA) said it had received 169 reports of cases of CVST, as well as 53 cases of splanchnic vein thrombosis (SVT), which sees clotting in the veins in the abdomen.
Most of the cases reported in Europe were found to have occurred among women under the age of 60. However, that data could lead to misleading assumptions, since both Germany and Britain have said more women have received the AstraZeneca jab than men. It is also important to note that the cases occurred out of 34 million AstraZeneca doses administered across Britain and the European Economic Area.
As health officials work to build a clearer picture of why these rare occurrences have taken place, Prof Mabbott said it should be kept in mind that "this is only impacting a very small amount of women".
He stressed that a definite link between the use of the vaccine and CVST hasn't yet been identified and all the medical regulators had been careful to communicate this.
"They have also stressed that for a majority of the population, the benefits of using the vaccines far outweigh any potential side effects the vaccines might cause," he added.
Dr Schaffner also emphasised the importance of keeping the data in perspective, as he reiterated guidance from health officials advising that those eligible to receive a jab do so.
"The risk of one in a million is not something you should be afraid of. You should be knowledgeable of it and be cautious and thoughtful," he said. However, the expert asserted, the reality is that "there is no drug that we use that is risk-free".
"I’m not diminishing the seriousness of this rare event - it is rare and it is potentially serious and that is why the advisory committee and all of us ... take it very seriously, but let’s keep it in perspective, particularly in comparison with the associated risks with COVID," he said. "We can’t think of it in isolation - you have to think of it in comparison to the risk of COVID-19".
But do women experience vaccines differently?
Despite their rarity, the fact that the blood clotting incidents have so far only been observed in women who received the Johnson & Johnson vaccine appears to have sparked broader discussion around the ways in which women are impacted by vaccines, including the COVID-19 vaccine compared to men.
In one preliminary study analysing early data from the CDC, researchers found that women were reporting more adverse reactions to vaccine doses than men - the most commonly reported symptoms were headaches, fatigue, and dizziness.
The study, which looked at data from the earliest vaccinations in the US in December, found that while women had received 61 per cent of vaccine doses, they made up 72 per cent of reports of side effects.
One possible explanation that has been put forward is that estrogen can produce a stronger immune response, which could heighten the impact of side effects.
‘Not at all surprised’
Sabra Klein, a microbiologist and immunologist at the Johns Hopkins Bloomberg School of Public Health, recently told The Times that she was “not at all surprised” by the study’s findings.
“This sex difference is completely consistent with past reports of other vaccines,” she said.
Indeed, in a 2013 study, researchers found that women were more likely to suffer negative reactions to the 2009 swine flu pandemic vaccine compared to men, even though more men received the jabs.
Meanwhile, a study analysing data from 1990 to 2016 found that women made up 80 per cent of all anaphylactic reactions to vaccines among adults.
There is a general proposition, stepping back from vaccines, that once you reach puberty - and this has been well established - women access medical care resources more than men do," Dr Schaffner said. "And when it comes to vaccines and just speaking about vaccines generally, women report more adverse events after receiving vaccines of all types than do men."
While he noted that it has been suggested that estrogen could play a role in impacting the way women experience side effects of vaccines, he said that ultimately the potential cultural and biological factors behind the phenomenon "really hasn't been well-studied".
Prof Mabbott said it is plausible that there could be differences between the sexes in the immune response that our bodies generate to the jabs, adding some of the studies looking at the immune response to the COVID-19 infection have shown subtle sex-related differences.
But he said when it comes to low-grade side effects, like the most common ones reported in the CDC study, it's important to bear in mind we all differ in our response to vaccines.
"Everybody varies in their response to these vaccines," Prof Mabbott said, with some getting flu-like symptoms, others getting soreness at the site of injection and others no symptoms at all.
"This is nothing to worry about, it is just our body's natural response to this type of vaccination."
Vaccines can change mammogram imaging
However, there are some ways in which vaccines can impact women that experts say are worth taking into consideration.
For example, coronavirus jabs can cause enlarged lymph nodes in the armpit, which could affect the way the nodes appear on mammograms.
This is normal and typically does not last for more than a few weeks. However, the Society of Breast Imaging (SBI) has recommended that patients reschedule routine mammograms before their first COVID-19 vaccine dose or at least a month after receiving the second dose, given that the swelling of lymph nodes can be mistaken as a rare sign of cancer.
“Breast radiologists look closely for any changes on your mammogram,” the SBI says in a fact sheet on COVID-19 guidance. “Swollen lymph nodes under one arm can be seen on a mammogram and can be a rare sign of breast cancer.”
Scheduling your mammogram around your vaccine dose, the society says, “reduces the chance that swollen lymph nodes from the vaccine will appear on your mammogram”.
Prof Mabbott added that all vaccines stimulate cells in the lymph nodes including the yearly flu shot, which might cause some swelling and tenderness in the week following the jab, as we are stimulating our immune system to respond.
"I would never advise anyone not to take up their coronavirus vaccine when asked to do so because they were about to attend a mammogram screening," he added.
Scheduling fertility treatments around doses
Likewise, the American Society for Reproductive Medicine has advised that fertility patients who plan to have procedures like egg retrieval do not schedule such procedures within close proximity to receiving the COVID-19 jab.
That is because some of the side effects of the jab, which can last up to a few days, can include fever or chills, which can also be signs of post-surgical infection, making it difficult for doctors to determine the cause of such symptoms.
"Those are serious considerations," said Dr Schaffner. "I know that has occurred to many people, in terms of adverse effects of the vaccine, [where they want to] plan a day after the vaccination where they’re not going to do anything particularly energetic or stressful because they might get a reaction to a vaccine that leaves them more tired, for example."
Can the jab impact the menstrual cycle?
Recently, there have been anecdotal reports of women experiencing changes to their menstrual cycles after receiving the coronavirus jab.
However, as it stands, there is no clear data on whether the vaccine may actually impact menstruation, with periods also known to be affected by a range of factors, including stress or thyroid dysfunction.
Prof Mabbott said he was not aware of any data to back these reports up, adding: "We have to remember that these kind of side effects are unlikely to be related to the coronavirus aspect of the vaccine and what we're talking about here are side effects linked to vaccines in general."
Ultimately, Dr Schaffner said that with the benefits of receiving the COVID-19 vaccine far outweighing the risks, those who are offered the opportunity to receive the jab should take it, with the expert also echoing advice from the World Health Organisation (WHO).
"Take whatever vaccine is made available to you first, even if you have already had COVID-19," WHO recommends on its website.
"It is important to be vaccinated as soon as possible once it’s your turn and not wait," it states, noting that "approved COVID-19 vaccines provide a high degree of protection against getting seriously ill and dying from the disease, although no vaccine is 100% protective".
"We must remember this (vaccination) is the safest, most efficient and cheapest way of getting all countries and the world out of this pandemic," Prof Mabbott said.
"The sooner we can get vaccines to a large amount of the population, the sooner we'll be able to protect everyone against the virus."