SINGAPORE - Early research findings, anecdotes, facts stitched together from various sources: The Covid-19 pandemic has unleashed a tsunami of information surrounding vaccine safety and efficacy. With so much material, discerning fact from fiction has certainly become tougher.
Lim Min Zhang and Clara Chong investigate four claims and lay out how valid each one is.
Claim 1: The mRNA vaccines can alter human DNA
An open letter penned by some doctors which was later retracted, called for children to be given traditional Covid-19 vaccines instead of mRNA ones.
Citing a study published in the prestigious US journal Proceedings Of The National Academy Of Sciences (PNAS) last month, the letter suggested evidence had been found that Sars-CoV-2 sequences can be integrated into the DNA of infected human cells in culture.
mRNA (messenger ribonucleic acid) is a molecule that instructs DNA (deoxyribonucleic acid) to make protein.
In general, RNA cannot be incorporated into DNA readily. Human DNA is housed in the nucleus of the cell and is separate from the rest of the cell. Movement of molecules in and out of the nucleus is strictly controlled.
Since mRNA vaccines only tell human cells to produce the Covid-19 virus' spike protein, which the body then mounts an immune response against, the vaccines themselves do not have any other part of the virus's genetic code and cannot make the entire virus itself.
"The mRNA of the spike protein alone is like the body of a car without the engine. It looks like a car but goes nowhere," says Professor Ooi Eng Eong, an expert on emerging infectious diseases at Duke-NUS Medical School.
There were also several limitations in the study that the doctors referenced, Prof Ooi pointed out.
First, the study used a DNA sequencing technique known as high throughput screening, in which multiple genes and even the entire genome can be sequenced simultaneously. This generates a lot of genetic material, and polymerase chain reactions were used to amplify this material. If errors are present, they will be amplified.
Experiments were also done in a the artificial environment of a cell line in a test tube, and not in patient tissues. Results from this do not always accurately replicate what occurs in animal or human cells.
"The proof of the pudding will be to find Sars-CoV-2 integrated into the genome of a Covid-19 patient. Despite the many genome level studies that have been done, such an event has not been found. The evidence that Sars-CoV-2 is able to insert its genome into the human genome is thus inconclusive at this stage," said Prof Ooi.
Claim 2: Taking the Covid-19 vaccines will weaken the body's natural immune system
Dr Geert Vanden Bossche, a Belgian who has a PhD in virology, has claimed that like with antibiotics, there is a risk of building up "vaccine resistance".
He theorises that because Covid-19 vaccines do not provide perfect protection, people can still get and transmit the coronavirus - allowing more mutations along the way. Eventually, a dangerous variant emerges that existing vaccines are ineffective against.
He also purports that the Covid-19 vaccines and public health measures are weakening the ability of the body's innate immune system to fight off the coronavirus. Some of his interviews on YouTube have spread on online forums here.
There is a theoretical possibility that a vaccine may induce the body to produce a low level of antibodies that may be insufficient to kill the virus if the person is infected with Sars-CoV-2, the virus which causes the Covid-19 disease. There is then the possibility that the virus may stay in the body and mutate.
But international data so far has shown that the coronavirus mutates slowly and if the vast majority of the global population is vaccinated, the chances of mutations happening will be small.
Vaccines, which train the body's immune system to fight off the virus in the event of a real infection, have been shown to be highly effective in reducing the number of Covid-19 infections and mortality rate.
As for whether the body's natural immunity after being infected could be better at fending off the virus than with the immunity conferred by vaccination, Professor Paul Tambyah, president of the Asia Pacific Society of Clinical Microbiology and Infection, said: "There is a theoretical possibility that natural infection gives better and more long lasting immunity than vaccination, but most people are not willing to take the risk."
He added that this idea is not new. In the past, there were those who advocated "chicken pox parties" when a child in the neighbourhood had chicken pox instead of having children vaccinated against the disease.
"When people realised that some children can get seriously ill from chicken pox and how safe the chicken pox vaccines are, that idea has gone out of the window," Prof Tambyah said.
Claim 3: Covid-19 mRNA vaccines could result in various side effects, some which may appear only years later
Heart inflammation concerns were raised after six individuals in Singapore were recently reported to have suffered myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) after getting an mRNA vaccine. Four of them were young men younger than 30.
Some have also worried about whether reports of heart attacks and strokes after vaccination could be linked to the jab.
Others have claimed that there might be risks to pregnancy, or long-term side effects of the vaccine months, years and decades after the jab.
A Telegram group called "SG Suspected Vaccine Injuries Channel", which allows anyone to submit suspected side effects from the Covid-19 vaccine, has gained traction in recent weeks, with more than 4,200 subscribers so far.
On heart attacks and strokes
When trying to determine whether an event was caused by a drug, some factors such as how biologically plausible the event is, the time frame after the dose was taken and if the effect was observed again after reintroduction, needs to be considered, Dr Danny Soon of the Consortium for Clinical Research and Innovation Singapore (Cris) said.
Associate Professor Hsu Li Yang, vice-dean of global health at the NUS Saw Swee Hock School of Public Health, said that baseline comparisons for side effects also need to be made to tell if there are higher incidents of these conditions after vaccination.
"For more common conditions like heart attacks and strokes that happen on a daily basis in Singapore, it is quite likely that one can have a stroke within a week after vaccination, but which is not actually triggered by the vaccine," Prof Hsu said.
Dr Soon added: "Families and loved ones are understandably distraught if their elderly relatives suffer from disability or death following a vaccination, and will seek answers. However, in the search for the truth, it is important that all parties concerned do not mistake the timing of an event with its actual cause."
Three independent bodies of medical experts in Singapore have reiterated that the risk of heart conditions associated with the Covid-19 mRNA vaccine is "very small", and have recommended that people still get the vaccines in the interest of public health.
Singapore's Health Sciences Authority said that in general, five to seven individuals per 100,000 people a year are hospitalised for myocarditis or pericarditis. The frequency of heart attacks and strokes in vaccinated people locally is within the background incidence rate, and there is no evidence currently that the vaccines can directly cause these events, HSA said. Doctors added that its exact prevalence of these heart conditions in Singapore is not known as milder cases often go unreported.
On risks to pregnancy
There is currently no evidence that Covid-19 vaccination causes any problems with pregnancy, including the development of the placenta and also no evidence that fertility problems are a side effect of any vaccine, including Covid-19 vaccines, the United States Centers for Disease Control and Prevention said.
During the Pfizer vaccine clinical trials, 23 women volunteers involved in the study became pregnant. Twelve received the vaccine, and 11 were given a placebo jab. The only one woman who had a miscarriage had not received the actual vaccine, but a placebo.
The College of Obstetricians and Gynaecologists Singapore and the Obstetrical and Gynaecological Society of Singapore released a joint statement on June 3 to address some of these concerns.
Real-world data of almost 4,000 women in the US, who self-identified as pregnant at the time of vaccination or shortly thereafter, has demonstrated safety of the Pfizer and Moderna vaccines, with no increased risks of adverse pregnancy outcomes, nor any obvious adverse events, it said.
On long-term side effects
The mRNA vaccine and the protein it triggers production of are both broken down by the human body after a few days. This makes it highly unlikely that there will be side effects that only occur years after.
"Imagine you get a common cold, usually caused by a rhinovirus, which is an RNA virus. This RNA virus also works by giving instructions to your cells to produce a whole set of viral proteins, in order to reproduce. Yet, we do not concern ourselves about the long term effects of getting the common cold," said Dr Soon.
The majority of vaccine side effects such as injection site pain and swelling, fever, and fatigue are predictable and happen within days of injection. Severe allergic reactions can also happen, but these are rare and for the majority of vaccines usually occur within hours of the injection.
Some unusual side effects have been observed weeks after Covid-19 vaccinations, like facial muscle weakness and bleeding. The health authorities are continuing to monitor for these nearer term side effects as vaccinations continue, Dr Soon added.
Some people have expressed wariness about the short timeframe of trials and actual use of the Covid-19 vaccines so far.
To this point, Dr Soon explains that medicines that are taken short-term may have shorter periods of study.
Medications for chronic illnesses such as hypertension or diabetes, which are taken long term or for life, studies of up to several years may be required to better understand efficacy and safety.
On the flip side, Dr Soon noted that how long a drug has been in use need not necessarily be correlated with how safe it is. "Paracetamol has been around for decades and available over the counter, but it has a narrow safety margin, and is one of the leading agents of drug overdose and liver failure," he said.
Claim 4: Ivermectin, a medication used to treat parasitic infections, is effective in treating or preventing Covid-19
An online petition targeting Singaporeans and residents here has gathered more than 2,200 signatures so far had called for ivermectin to be used as part of an outpatient treatment plan for Covid-19. It claims that ivermectin had strong evidence of efficacy against Covid-19, as well as being cheap, safe and effective and has been in use for decades, although it has been overlooked by the World Health Organisation (WHO) and other regulatory bodies.
Associate Professor Jenny Low, a senior consultant of infectious diseases from the Singapore General Hospital, said much of the controversy over ivermectin stems from the fact that its proponents have ignored the varying quality of trials testing this drug for Covid-19.
"If we remove the 'noise' of poor quality clinical trials and their reports, and just focus on the ones that are of at least decent quality, then the current evidence does not support the use of ivermectin. That's not to say that the drug definitely does not work. We can only say that with the best evidence out there till date, there is no strong evidence to support its use."
In March, WHO said current evidence on the use of ivermectin to treat Covid-19 patients was inconclusive, and it recommended that the drug be used only in clinical trials until more data was available.
A review by the United States' National Institutes of Health, a government medical research agency, has also found that while ivermectin has been shown to inhibit the replication of Sars-CoV-2 in cell cultures, studies suggest that achieving the plasma concentrations necessary for the antiviral efficacy detected in-vitro would require doses of up to 100-fold higher than those approved for use in humans.
The agency noted that while there were some published studies that showed some positive results, including lower mortality rates, there were several limitations with the studies. These included small sample sizes, patients receiving other medications in addition to ivermectin, and the studies being open-label, which means information was not withheld from trial participants, introducing possible bias towards the drug being tested.
A study done in Singapore in May last year did not find significant preventive benefits either. The study was done with more than 3,000 healthy migrant workers in dormitories, of whom 617 received ivermectin. The others received hydroxychloroquine, povidone-iodine throat sprays, or vitamin C. No statistically significant differences in Covid-19 infection rates were observed between those who took vitamin C versus ivermectin.
Prof Low also noted that even the drug's manufacturer, Merck, has advised against the use of ivermectin for Covid-19.
There was no scientific basis for a potential therapeutic effect against Covid-19 from pre-clinical studies, it said in February. There was also no meaningful evidence for clinical activity or clinical efficacy in patients with Covid-19, and a concerning lack of safety data in the majority of studies, it added.
Prof Low said: "To me, this says everything."