Immune responses to Omicron in Immunocompromised patients

A CITF-funded study published in Nature Communications by Drs. Deepali Kumar and Atul Humar (University Health Network, Toronto), reported that partially and fully vaccinated transplant recipients who were infected with Omicron (the BA.1 variant) have BA.1-specific immune responses comparable to triple vaccinated individuals with normal immune systems. Moreover, they did show evidence of potent cross-neutralization against the BA.2 sub-variant.

The study analyzed four separate cohorts, including a total of 246 patients:

• Cohort 179.1% were unvaccinated, 5.5% received a single dose, and 15.4% received two doses of vaccine prior to infection. – 91 solid organ transplant patients infected with SARS-CoV-2 between March 2020 and September 2021, prior to the Omicron wave. 79.1% of patients were unvaccinated, while the rest had received at least one dose of mRNA vaccine.
• Cohort 24.0% were unvaccinated, 2.7% received a single dose, 16.0% were double-vaccinated, 70.7%were triple vaccinated, and 6.7% received four doses of mRNA vaccines. – 75 transplant patients with confirmed Omicron infection, most of whom were vaccinated prior to infection.
• Cohort 3 – 60 transplant recipients with three doses of Moderna vaccine and no infection history of SARS-CoV-2.
• Cohort 4 – immunocompetent healthcare workers who had received three doses of the Pfizer–BioNTech vaccine and had no prior SARS-CoV-2 infection.

Key findings:

• Unvaccinated transplant patients with a prior, non-Omicron SARS-CoV-2 infection, or patients vaccinated with three doses of mRNA vaccine, may be at higher risk for symptomatic or severe Omicron infection, owing to comparatively lower antibody and CD4+ T-cell responses to the BA.1 variant.
• Partially or fully immunized transplant recipients who recovered from an Omicron BA.1 infection developed potent neutralizing antibodies and T-cell responses (including polyfunctional CD4+ T-cells), at magnitudes similar to triple-vaccinated immunocompetent controls, including cross-reactive protective responses against BA.2.
• In cohort 1, transplant recipients infected with ancestral Wuhan, Alpha and Delta strains of SARS-CoV-2 demonstrated lower neutralizing capabilities against Omicron (BA.1 and BA.2). However, several patients who were negative for BA.1 showed robust neutralizing capabilities against BA.2 (45.7%). Most patients demonstrated SARS-CoV-2 spike-specific CD4+ T-cellCD4 T-cells help keep you healthy by attacking infection-causing pathogens. These powerful cells activate your body’s immune functions when they stimulate other cells in the immune system. responses to the ancestral virus, but the CD4+ T-cell response to BA.1 peptides in these patients was comparatively lower. Spike-specific CD8+ T cellCD8+ T-cells are a critical component of the cellular immune response and they play an important role in the control of viral infection. responses were less frequent against the ancestral and Omicron BA.1 strains.
• In cohort 2, organ transplant recipients who recovered from a BA. 1 infection showed robust immune responses to BA.1 and BA.2, however their immune response was lower than what was seen for the ancestral strain. Most patients with a breakthrough Omicron infection developed strong neutralizing antibodies and CD4+ T cells against the ancestral and BA.1 strains. A CD8+ T cell response was less commonly detected in this cohort.
• Neutralizing antibody titersNeutralization renders the particle no longer infectious or pathogenic, and neutralizing antibodies defend a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. against BA.1 were highest among transplant patients with a breakthrough Omicron BA.1 infection (cohort 2) when compared to immunocompetent, triple-vaccinated healthcare worker controls (cohort 4). Triple vaccinated transplant recipients (cohort 3) displayed the lowest neutralizing antibody titers when compared either with transplant patients infected with non-Omicron variants (cohort 1) or those with Omicron BA.1 infection (cohort 2).
• When all four cohorts were analyzed together, there were no differences in the anti-Omicron neutralizing antibody titers between patients with two or fewer doses of vaccine and patients with three or more doses of vaccine. The same was true for BA.1-directed CD4+ and CD8+ T cells. The severity of disease did not impact the magnitude of the neutralizing antibody response to Omicron BA.1.
• High anti-RBD antibody levels – which correlate with effective Omicron neutralization – were observed in all cohorts. The highest responses were among transplant patients after recovery from BA.1 infection and triple-vaccinated health care workers.

79.1% were unvaccinated, 5.5% received a single dose, and 15.4% received two doses of vaccine prior to infection.