In small study, COVID-19 vaccine protects against aHUS complications

One person of 21 studied saw symptom worsening after first mRNA vaccine

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Getting vaccinated against COVID-19 may protect people with atypical hemolytic uremic syndrome (aHUS) from the infection’s severe complications, without raising major safety issues, a small study finds.

Receiving a double booster shot may be important to provide full protection, especially for transplant patients.

“Our findings support the use of COVID-19 vaccination as an effective strategy to protect individuals with aHUS from severe complications of COVID-19,” the researchers wrote in “Immune responses and safety of COVID-19 vaccination in atypical hemolytic uremic syndrome patients in Taiwan,” which was published as a short communication in Vaccine.

In aHUS, there is an excessive activation of the complement system, a part of the immune system responsible for eliminating harmful microorganisms, such as viruses, and damaged cells.

This causes red blood cells to break down, resulting in anemia, and reduces the number of platelets, which play a key role in blood clotting. It also causes kidney damage. When the kidneys become damaged to where they no longer work on their own, a transplant may be needed.

While the disease is often associated with mutations in genes that regulate complement activity, these mutations alone may not be enough to cause symptoms of aHUS. Usually, a trigger event, such as an infection, is needed.

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COVID-19 Booster Vaccine Suspected as Cause of aHUS in Woman, 38

Responses to COVID-19 vaccine

Isolated reports have suggested COVID-19 infection and vaccination can trigger aHUS, but it’s unclear if getting vaccinated may be safe and benefit people with aHUS, leading researchers to examine if the vaccine was safe and a benefit for aHUS patients who got vaccinated before the COVID-19 outbreak in Taiwan in May 2022. They studied 21 patients (11 women, 10 men; median age, 46). Eight had end-stage kidney disease, or kidney failure, and five had undergone a kidney transplant.

The available vaccines were the adenovirus-based Astrazeneca’s ChAdOx1 nCoV-19 vaccine, Moderna’s mRNA-1273 vaccine, Pfizer-BioNTech’s mRNA-based BNT162b2 vaccine, and Medigen’s protein subunit vaccine. All are given as a shot into a muscle at a schedule of two doses spaced by four or eight weeks, followed by a booster that’s usually half the dose of the primary series. For those with certain immune diseases, including aHUS, a full dose can be used, which is double that given to healthy people.

Two patients received a single dose, six received two doses, and 13 got all three doses, including the full-dose booster. Of those who received all three doses, six received a mix and match of different vaccines.

One patient saw a worsening of aHUS after the first dose of one of the mRNA-based vaccines, but no organs other than the kidneys were affected. The patient improved and chose a different mRNA-based vaccine for the second dose.

“COVID-19 vaccination can be a trigger for aHUS, with an incidence rate of 4.76% in our study, but [the disease] was self-limited,” the researchers said.

Stronger response with full vaccine regimen

A vaccine prompts the immune system to produce antibodies to protect the body from SARS-CoV-2, the virus that causes COVID-19.

As part of the immune response, T-cells, a type of white blood cell, release interferon gamma, a signaling molecule that boosts the body’s immune response against infection.

When researchers measured interferon gamma in the blood, they found its levels tended to be higher in those who received all three doses over those who received one or two doses.

Measuring the levels of antibodies against the spike protein, which is unique to the SARS-CoV-2 virus, revealed similar findings. Being on a complement inhibitor didn’t affect the levels of interferon gamma or of anti-spike antibodies.

In the 13 patients who received all three doses, the levels of interferon gamma tended to be higher among those who got a mix of different vaccines and in those who didn’t develop end-stage kidney disease or had a transplant.

All received a double booster dose, meaning that “all known vaccinations given to aHUS patients with a three-dose regimen were at double the dosage typically administered to healthy individuals,” the researchers wrote.

The levels of both interferon gamma and anti-spike antibodies were similar in these patients compared with healthy (control) people of the same age and sex who also were fully vaccinated, regardless of the type of vaccine they received.

“A double amount booster dose for the third dose of COVID-19 vaccine could be a choice for optimal efficacy in aHUS patients,” the researchers wrote.

“aHUS patients can receive COVID-19 vaccination without major safety concerns if aHUS disease activity is closely monitored before and after vaccination,” they wrote, singling out patients who’ve had a transplant or are in end-stage renal disease. “These results are important for healthcare providers who care for aHUS patients and may be hesitant to administer the vaccine due to concerns about potential side effects or disease [worsening].”