Age, fibrosis, immune suppression link to less COVID vaccine response

A study from Israel, where vaccination for COVID reached most of the population older than 16 years, showed older patients, post-transplant patients and those with advanced liver disease produced less immune response to the Pfizer COVID-19 vaccine.

“We had the chance to vaccinate until now almost 96% of the adult population who were 16 and above and just a week ago, we started to vaccinate the young people between the ages of 12 years and 16 years,” Rifaat Safadi, MD, director of the liver institute at the Hadassah-Hebrew University Hospital in Israel, said during a press conference. “I wondered if this was affecting our liver patients.”

Liver transplant, less response

This research came out of Safadi’s analysis of post-liver transplant patients. He explained that 41 post-LT patients contracted COVID-19 at his institution over the course of the pandemic but only five had received the vaccination so he wanted to understand the vaccine response in LT patients.

“Unfortunately, we have in my center 41 liver transplantation patients who were infected with COVID, and we lost two patients. Luckily with the vaccination and the extremely significant results we had globally, the last 3 months we have not had any recorded transplant patients with COVID-19,” Safadi said. “Was that a result of their vaccination or the result of the population vaccination? That was the question.”

In looking at that cohort, Safadi showed 90 post-LT patients who received the vaccine. Of those, 58.9% showed an anti-serum IgG level of 19 AU/mL or greater while 35.6% had levels less than 19 AU/mL. Additionally 5.6% contracted COVID-19 after vaccination – one after the first shot and four after full vaccination. This put the failure rate at 41.1%.

There was a correlation between time to vaccine from transplant with responders averaging 57.3 months from transplant to vaccine and failures being just 38.4 months (P = .017).

“Therefore, the 40% of failure indeed looks like a result of immune suppression. However, that very nice result of decline in disease in our transplant patients is more related to the general population vaccination,” Safadi said. “Those infected after vaccine had an easier course of disease and no death” suggesting some protective factor of the vaccine.

“I looked further to see if the severity of liver disease in non-transplant patients – commonly fatty liver disease – is affecting response to the vaccine,” he said.

Fibrosis impacts response

Safadi and colleagues looked at serum IgG levels and fibrosis in a cohort of vaccinated HMO employees. Of the 719 tested more than 7 days after their second vaccine dose, 98.5% were considered responders. There were FIB-4 data available for 501 of those responders and 10 of the 11 failures.

Of the failures, two were prior kidney transplant patients on the traditional medications, two patients had rheumatoid arthritis taking steroids and another immunosuppressant, two had lymphoma and were immunosuppressed, one had multiple sclerosis and was on biologic therapy, three had metabolic syndrome, one was on hemodialysis.

“I am now starting to boost my transplant patients who failed to develop any serologic response with a third shot,” Safadi added.

Of those responders who had FIB-4 numbers, 70.5% had a FIB-4 score less than 1.3; 26.8% were between 1.3 and 2.67; and 2.7% had a FIB-4 higher than 2.67.

Safadi showed that lower immune response to the vaccine correlated with older age where those with IgG response between 19 and 100 AU/mL had a mean age of 61 years while those that had responses higher than 400 AU/mL had a mean age of 46.3 years (P < .0001).

A similar correlation occurred with FIB-4 score and titers. Of those with a FIB-4 score less than 1.3, 68% had IgG greater than 200 AU/mL while those with FIB-4 greater than 2, just 44.2%, had IgG in that range (P = .002).

Safadi and colleagues measured serum IgG levels in a small group of patients (n = 140) diagnosed with NAFLD, designating 200 AU/mL as the cutoff between “good” and “excellent” responses. Only two patients fell under the “failure” category of less than 12 AU/mL.

Safadi reported that 72.7% achieved excellent response while 26.1% achieved good response. Those in the good response group were older at 61.5 ± 10.4 years vs. the excellent response group who had a mean age of 53.7 ± 13.3 years (P < .0001).

Mean serum IgG levels in the excellent group were 358 ± 10.6 AU/mL while the good group showed a mean level of 117.4 ± 51.4 AU/mL.

While both groups had similar BMI and sex distribution, Safadi noted that the groups showed differences in their NAFLD activity score (NAS) and NASH Clinical Research Network (CRN) fibrosis scores. Excellent responders scored 3.6 ± 1.9 on the NAS compared with 2.9 ± 1.2 in the good responders (P = .045). Investigators attributed this mainly to significant steatosis changes of 1.6 ± 0.9 vs. 1.2 ± 0.7, respectively (P = .02).

Advanced fibrosis correlated with weaker vaccine responses, with fibrosis scoring at 1.7 ± 1.1 vs. 2.2 ± 1.5 and advanced fibrosis (F3-F4) seen in 21.8% of the excellent responders vs. 39.6% of the good responders (P = .05). Similarly, in those diagnosed with NAFLD by Fibroscan (Echosens; n = 60), the fibrosis kPa was lower at 8.8 in the excellent responders group vs. 13.7 in the good responder group (P = .02).

“The bottom line says the most fibrosis, the less efficacy,” Safadi said. “All of them are showing the more fibrosis, the lower the response.”