by Dr Seema P Upadhaye
While we have a lot of promising COVID-19 vaccine candidates ready to roll out in the earliest timeline possible, this is the first time that a vaccine for such a novel infection has been developed in such an accelerated manner. That also leaves space for a lot of trial errors and side effects we might be exposed to, once the vaccination drives start.
Experts pointed out that the lack of transparency in releasing crucial information and data could lead to stricter scrutiny by regulators in many countries and mistrust among people.
Vaccines, though they are designed to protect from disease, can cause side effects, just as any medication can. Most side effects from vaccination are mild, such as soreness, swelling, or redness at the injection site. Some vaccines are associated with fever, rash, and achiness. Serious side effects are rare, but may include seizure or life-threatening allergic reaction which can persist to next human generations as well.
The possible Moderate to Severe Problems of vaccination includes:
– Serious eye infection, or loss of vision, due to spread of vaccine virus to the eye.
– Rash on entire body (as many as 1 per 4,000).
– Severe rash on people with eczema (as many as 1 per 26,000).
– Encephalitis (severe brain reaction), which can lead to permanent brain damage (as many as 1 per 83,000).
– Severe infection beginning at the vaccination site (as many as 1 per 667,000, mostly in people with weakened immune systems).
– Death (1-2 per million, mostly in people with weakened immune systems).
Historical incidents of side effects of vaccines
– In 1955, some batches of polio vaccine given to the public contained live polio virus, even though they had passed required safety testing. Over 250 cases of polio were attributed to vaccines produced by one company: Cutter Laboratories.
– From 1955 to 1963, an estimated 10-30% of polio vaccines administered in the US were contaminated with simian virus 40 (SV40). The virus came from monkey kidney cell cultures used to make polio vaccines at that time. Most of the contamination was in the inactivated polio vaccine (IPV), but it was also found in oral polio vaccine (OPV).
– An increased risk of narcolepsy (a chronic sleep disorder) was found following vaccination with Pandemrix, a monovalent 2009 H1N1 influenza vaccine that was used in several European countries during the H1N1 influenza pandemic. This risk was initially found in Finland, and then some other European countries also detected an association. Pandemrix manufactured by GlaxoSmithKline in Europe was specifically produced for pandemic 2009 H1N1 influenza. Pandemrix was never licensed for use in the United States.
– In 1998, the FDA approved RotaShield vaccine, the first vaccine to prevent rotavirus gastroenteritis. Shortly after it was licensed, some infants developed intussusception (rare type of bowel obstruction that occurs when the bowel folds in on itself) after being vaccinated. The Advisory Committee on Immunization Practices (ACIP) withdrew its recommendation to vaccinate infants with RotaShield® vaccine, and the manufacturer voluntarily withdrew RotaShield from the market in October 1999.
What we know for current COVID-19 vaccine? Side effects and trial error
In case of COVID-19 vaccine, recent findings are coming from under trial vaccines. It is irrelevant to discuss about phases of trials here because the vaccine which had lost its charm are not in the race of COVID-19 cure. There are 3-4 front runners in the race against COVID-19 but these have also reported moderate to serious side effects. And where the numbers of participants are less as compared to other regular trial, it should not be neglected while vaccinating billions of people around the globe.
According to Moderna’s COVID-19 vaccine trial, involving some 23,000 volunteers most side effects reported during its clinical trials were mild to moderate, but some were classified as “Grade 3”, or severe. The independent board that conducted the interim analysis of Moderna’s huge trial found that severe side effects included fatigue in 9.7% of participants, muscle pain in 8.9%, joint pain in 5.2%, and headache in 4.5%. According to an article by Science magazine, a computational biologist Luke Hutchison who volunteered for a trial of Moderna’s COVID-19 vaccine after the second injection, his arm swelled up to the size of a “goose egg,” Hutchison says. He can’t be sure whether he got the vaccine or placebo, but within a few hours, Hutchison, who was healthy and 43, was beset by bone and muscle aches and a 38.9°C fever. “I started shaking. I had cold and hot rushes,” he says. “I was sitting by the phone all night long thinking: ‘Should I call 911?’”
In the Pfizer/BioNTech COVID-19 vaccine trial which involved 40,000 volunteers, severe side effects included fatigue (3.8%) and headache (2%). After Britain began administering the Pfizer/BioNTech vaccine, British health authorities said two patients had suffered adverse reactions. Four cases of Bell’s palsy – a facial paralysis that is often temporary – were observed among 18,000 volunteers over two months in the Pfizer/BioNTech trial. There were eight cases of appendicitis in those who were administered the vaccine, double the amount for those who received the placebo, but the FDA put this down to a statistical coincidence, unrelated to the vaccine. https://www.nst.com.my/world/world/2020/12/648984/what-we-know-about-covid-19-vaccines-and-side-effects
The Oxford/AstraZeneca COVID-19 vaccine trial was voluntarily put on hold at one stage to investigate why one participant – out of many thousands – had died. It restarted once it was clear it was not related to the vaccine. One patient who received the Oxford AstraZeneca jab had a “serious side effect possibly related” to the injection, according to the data in The Lancet. The patient suffered from transverse myelitis, a rare neurological condition that causes inflammation of the the spinal cord.
Jaseem (name changed to protect identity) from India said that he had a hard time getting back on his feet after he was diagnosed with ‘Acute Neuro Encephalopathy’ (means damage or disease that affects the brain), a sudden neurological dysfunction affecting the brain. According to his family, he could not recognise them, experienced mood swings and could not carry out daily work on his own. He claims it was the result of an extreme side-effect of the COVID-19 vaccine that he was administered on October 1 as part of the trial by the Pune-based pharmaceutical giant, Serum Institute of India Private Limited which is sponsoring Oxford/AstraZeneca COVID-19 vaccine trial in India. Responding to this volunteer’s allegations, the Serum Institute, in turn, threatened him with a Rs 100 crore suit to “safeguard the reputation of the company.
Also, during the clinical trials of AstraZeneca COVID-19 vaccine, some participants were mistakenly given half a dose rather than a full dose in their first round of shots, according to BBC News. Still, the trial continued and the researchers discovered those given the weaker dosage produced a better immune response. Some experts have criticized the fact that AstraZeneca combined the efficacy results from what’s essentially two different trials and say the company will need to conduct another trial properly evaluating the effectiveness of the half-dose full-dose regimen. Small mistakes are common, but giving thousands of participants the wrong dose unintentionally is not a common mistake. Time will tell whether this particular mistake leads to a discovery, but at this point in time there is a lot of uncertainty around the findings,” said Dr. Philip Smith, an assistant professor in the department of kinesiology and health at Miami University in Ohio. It has also come out that the trial participants, based on which the early results have been released, consisted of very few elderly individuals among whom the efficacy of the potential vaccine was found to be lower than other groups, but this information was not made public. https://www.newindianexpress.com/nation/2020/nov/26/covid-19-vaccine-by-astrazeneca-oxford-sparks-controversy-amidst-concerns-that-crucial-information-w-2228486.html
Vaccines generally work better in younger people, says Hunter. Neither AstraZeneca nor Oxford released full details of the age profiles of the volunteers in both trials except to say that all were 18 or over. Another wrinkle is that the volunteers were all healthy or had “stable underlying medical conditions”. That may mean that the results don’t reflect how the vaccine will perform among vulnerable groups such as people with serious health problems.
The results of the early trials of the Sputnik V vaccine were published in The Lancet Study on September 4, no serious adverse effects were reported. However, the results have been criticised by several scientists around the world, including a group of researchers who wrote an open letter against the published trial results of Sputnik V. In this letter, they have highlighted that the data appears to be duplicated, while also arguing that the paper presents its results only as box plots—a method for graphically depicting groups of numerical data through their quartiles—without providing a detailed breakdown of the data. “We believe that poor methodology, study design flaws, errors in data analysis, and a poor description of the study call into question the main conclusions about the safety and efficacy of the vaccine,” Vlassov and his colleagues, members of the Russian Society of Specialists in Evidence Based Medicine, wrote.
Further, Konstantin Andreev, who studies viral respiratory infections at Northwestern University at Evanston, Illinois, USA, stated: “To see such similar data patterns between unrelated measurements is really not likely. These discrepancies are not minor.” Other experts have urged the Russian authors to publish the underlying, supplementary data as well, just like the pharmaceutical company did when publishing the results of their vaccine trials.
Amid the controversy, The Lancet, in a statement, invited the authors of the Russian vaccine study to respond to the questions raised by Enrico Bucci open letter. However, Denis Logunov, the Russian paper’s lead author, told the Russian media that he has no intention of responding to the letter. He also denied the errors highlighted in the letter, and stated that the measured antibody levels were “exactly as they were presented”.
Recently questions have been raised on Bharat Biotech’s COVAXIN too when Haryana health minister, Anil Vij, who was given a trial dose of corona vaccine, Covaxin, has been tested positive for the Covid-19. On November 20, he was administered a dose of Covaxin at a hospital in Ambala, as part of its third phase trial, according to his twitter post.
In the long term as these COVID-19 vaccines are new, scientists do not know for certain the potential long term side effects which can pose long term side effects which can pose danger to entire humankind, may not just existing generation but to coming generations as well. Thus, long term studies in large different ethnic groups are required to make a final conclusion before giving EUA or authorization as given by FDA, WHO, European Union etc. We have seen loopholes in existing system of FDA and EU when they approved certain medications without any sufficient evidences and later these studies were challenged and retracted. All these incidences not only can decrease trust of general public in such authorities but can also make people’s life miserable if any serious side effect succumb the public at large.