Some people justify their hesitation about COVID-19 vaccines by saying they fear possible long-term effects or some as yet undetected consequences. But is that really true? An article recently published in the journal Science analyzes a set of data around the possibility of giving an answer.

Among the data he recounts, he recounts the experience of Brianne Dressen, former preschool teacher in Saratoga Springs, Utah, who in late 2020 began sharing time online for people experiencing prolonged COVID, a chronic and disabling syndrome that can follow an attack with the virus. He was interested in compiling all the information that scientists issued about it and in recording the experiences that people reported.

Dressen had not been infected until that moment. As a volunteer in a clinical trial, she received a dose of AstraZeneca. That night, his vision became blurred and the sound was distorted. Her symptoms included heart rate fluctuations, muscle weakness and what she describes as debilitating internal electrical discharges. He was diagnosed with anxiety. Meanwhile, her husband Brian, a chemist by profession, began reviewing the scientific literature trying to understand the events surrounding his wife. Along the way, the couple encountered other people who had experienced health problems after a COVID-19 vaccine, regardless of the manufacturer.

By January 2021, researchers at the National Institutes of Health (NIH) began hearing about such reports and sought further information, starting with Dressen herself. The study was small in scale and did not draw conclusions about whether the vaccines may have caused rare and long-lasting health problems. “The patients had what the scientists called ‘temporary associations’ between vaccination and their failing health,” told Science Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke (NINDS), who has been leading the NIH efforts. “But an etiological association? I dont know.” That is to say: they were unable to effectively demonstrate with data whether vaccination directly caused subsequent health problems.

Now, a small number of other researchers are beginning to study whether the biology of long-standing COVID, still in the dark in scientific terms, could somehow be linked to certain vaccine actions.

“You have to be very careful before linking COVID-19 vaccines with complications,” he explained to Science Nath. “You can reach the wrong conclusion. The implications would be huge.” And complex and persistent symptoms like Dressen’s are even more difficult to study because patients may lack a clear diagnosis.

However, measuring the difficulties in this regard can help guide the design of the next generation of vaccines and perhaps identify those who are at high risk of serious side effects. “We shouldn’t be averse to adverse events,” he explained. William Murphy, an immunologist at the University of California. In a November 2021 paper published by The New England Journal of Medicine, he proposed that an autoimmune mechanism triggered by the SARS-CoV-2 spike protein could explain both the symptoms of long COVID and some rare side effects of the vaccine, and called for an investigation into possible connections. “Assuring the public that everything is being done, in terms of research, to understand vaccines is more important than just saying everything is safe,” Murphy maintains.

What is certain today for science is that it remains unclear how often side effects like those of Dressen occur. Prolonged COVID has become a certain and recognized ailment that is known to affect between 5% and 30% of people infected with SARS-CoV-2. Researchers are making tentative headway with various insights into the underlying biology. Some studies suggest that, in certain cases, the virus can remain in the tissues and cause ongoing damage. Other evidence indicates that secondary effects from the original infection could play a role even after the body clears the virus. Evidence from animal studies supports the idea that antibodies targeting the SARS-CoV-2 spike protein, “the same protein many vaccines use to trigger a protective immune response, could cause collateral damage,” reported to Science Harald Prüss, a neurologist at the German Center for Neurodegenerative Diseases (DZNE) and the Charité University Hospital in Berlin.

In 2020, while searching for antibody therapies for COVID-19, he and his colleagues discovered that Of the 18 antibodies they identified as having potent effects against SARS-CoV-2, four also targeted healthy tissues in mice, a sign that they could trigger autoimmune problems. The compilation made for this article in the scientific journal confirms that the first clinical data point in a similar direction. Over the past year, research groups have detected unusually high levels of autoantibodies, which can attack the body’s own cells and tissues, in people after SARS-CoV-2 infection.

In Nature in May 2021, immunologists Aaron Ring and Akiko Iwasaki of the Yale School of Medicine and your team reported finding autoantibodies in patients with acute COVID-19 that targeted the immune system and the brain; they are now investigating how long autoantibodies persist and whether they can damage tissues. This month, the cardiologist Susan Cheng of Cedars-Sinai Medical Center and protein chemistry Justyna Fert-Bober in a material published in the Journal of Translational Medicine pointed out that autoantibodies could last up to 6 months after infection, although the researchers did not correlate the persistence of autoantibodies with continued symptoms.

On another front, other specialists are looking at tiny blood clots. In an acute SARS-CoV-2 infection, small clots can form that can damage the cells that line the blood vessels. Resia Pretorius, a physiologist at the University of Stellenbosch in South Africa, and colleagues published preliminary evidence in August in Cardiovascular Diabetology. There they noted that microscopic clots can persist after an infection clears up. They could interfere with oxygen supply, which could explain some symptoms of prolonged COVID, such as brain fog. Pretorius is now teaming up with colleagues to develop diagnostics for this microcoagulation and study ways to treat it in Long Covid.

Farinaz Safavi, a neurologist at the National Institute of Neurological Disorders and Stroke is part of the US National Institutes of Health (NINDS), has gathered dozens of patients with this symptomatology to try to arrive at some accurate conclusions. “34 people signed up for the protocol -reported the specialist-, 14 of whom spent time at the NIH; the other 20 sent their blood samples and, in some cases, cerebrospinal fluid.” But over time they stopped following up on the issue. According to the authorities informed Science, “they are not equipped to treat a large number of patients in the long term.”

The NIH data, which documented the patient cases, has yet to be published. Two major medical journals refused to publish a case series of about 30 people, first reported by that team in March 2021. Safavi says he understands the rejection: “The data were observational studies,” he says. This month, scientists submitted a case series of 23 people to a third publication, and an amendment to a Long COVID protocol to include patients with post-vaccine side effects.

Researchers exploring post-vaccine side effects emphasize that the risk of complications from SARS-CoV-2 infection far outweighs that of any vaccine side effect. But understanding the cause of symptoms after it, and whether early treatment can help prevent long-term problems, could be crucial to design even safer vaccines and effective, as well as providing clues about the biology of prolonged COVID and further encouraging the use of vaccines.

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