Value of Fourth COVID-19 Vaccine Shot in Patients With Solid-Organ Transplants Questionable

By Megan Brooks

December 01, 2021

NEW YORK (Reuters Health) - Giving solid-organ-transplant recipients a fourth dose of mRNA COVID-19 vaccine may lead to only a slight improvement in SARS-CoV-2 antibody concentrations for some patients, according to a study from France.

The researchers say their findings are similar to those of another recent study in which a fourth dose of SARS-CoV-2 vaccine was associated with "slightly improved humoral response among patients with a weak response after 3 doses and with no improvement among those with no response after 3 doses."

In JAMA Network Open, Dr. Nassim Kamar with Toulouse University Hospital and colleagues report on 37 solid-organ-transplant recipients (20 male; mean age, 60 years) given a fourth dose of the Pfizer mRNA COVID vaccine.

Five of these patients (13.5%) had a weak response to the previous three doses (antibody concentration <14 binding antibody units (BAU)/mL) and 31 (83.8%) had no response to the three previous doses.

Among the five patients with a weak response before the fourth dose, the median antibody concentration increased from 4 BAU/mL to 402 BAU/mL four weeks after the fourth dose (P<0.001) and neutralizing antibody titers (NAb) increased from a median of 8 IU/mL to 16 IU/mL (P=0.07).

Among the 31 patients with no vaccine response before the fourth dose, 13 (41.9%) became seropositive (median antibody concentration, 9.5 BAU/mL four weeks after fourth dose).

Six of these patients (19.4%) had antibody concentrations above 14 BAU/mL and two (6.5%) had antibody concentrations greater than 140 BAU/mL. Among these patients, the median NAb titer was 8 IU/mL.

Four weeks after the fourth dose, antibody concentrations were significantly higher among patients who had detectable antibodies before the fourth dose than among those who had no response. However, NAb titers at four weeks after the fourth dose did not differ between responders and non-responders to three doses, the authors report.

Overall, at four weeks after the fourth dose, 32 of 37 patients (86.5%) had antibody concentrations less than 140 BAU/mL, "a threshold providing 12.4% protection among health care workers," and all 37 patients had NAb titers less than 64 IU/mL, the researchers report.

In an email to Reuters Health, Dr. Kamar said all solid-organ-transplant "patients should be given 3 doses, one month apart."

"In non-responders or very weak (<30 BAU/mL) responders at one month post-3 doses, the fourth dose is useless," he added.

"In patients having a weak response (30 to 141 BAU/ML) at one month post-3 doses, a fourth dose can be offered although the data are scarce and not convincing. Few patients will have a protective neutralizing antibodies titer," he said.

In updated guidance issued in October, the U.S. Centers for Disease Control and Prevention said some moderately or severely immunocompromised adults may receive a fourth dose of mRNA COVID-19 vaccine six months after a third shot.

SOURCE: JAMA Network Open, online November 24, 2021.


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