ABSTRACT
Background: Immune responses to SARS-CoV-2 vaccines in people living with HIV (PLWH) have been the focus of several recent studies. As the gut microbiome can influence vaccine immunogenicity, in this study we are the first to investigate whether the baseline gut microbiota can predict immune responses to the BNT162b2 SARS-CoV-2 vaccine in people living with HIV (PLWH) and healthy controls (HC). Method(s): Fecal samples were collected from PLWH (n=68) and HC (n=75) at baseline, prior to the first vaccine dose, to extract DNA for 16S rRNA sequencing. The individuals were part of the COVAXID Clinical trial, where humoral and cellular responses to SARS-CoV-2 vaccine were evaluated on day 35 after the first dose. Comprehensive bioinformatic tools were used for bacterial identification to further reveal the associations between gut microbiota and SARS-CoV-2 antibody, spike CD4+ T cell responses, and clinical parameters such as age, gender, CD4/CD8 ratio, and length of antiretroviral (ART) treatment. Result(s): At day 35 post vaccination, HC showed significantly higher spike IgG titers than PLWH (p=0.0001). Interestingly, both phylogenetic and alpha-diversity were negatively correlated with antibody titers, in the whole cohort and within groups. Similarly, individuals with low alpha-diversity had higher levels of spike specific CD4+T-cell responses. Agathobacter, Lactobacillus, Bacteroides, and Lachnospira were positively correlated with both antibody levels and spike-specific CD4+ T-cell responses while Methanobrevibacter, Marvinbryantia, Cloacibacillus, and Succinivibrio have a negative one. Within the PLWH group, the gut microbiota taxa associated with CD4+ counts, such as Lachnospira (p=0.002), Oscillibacter (p=0.019) and Flavonifractor (p=0.017), were found to be positively correlated with spike IgG levels. Additionally, the length of ART treatment and CD4/CD8 ratio displayed a positive association with bacterial diversity. Notably, different microbiome profiles and immune status in PLWH, affect their immune responses to vaccination. Conclusion(s): Our results show potential associations between gut microbiota diversity and spike IgG responses after COVID-19 vaccination. These findings were consistent in the whole cohort, albeit group differences between the microbiome compositions in PLWH and HC were observed. Based on our findings, we propose that microbiome modulation could optimize immunogenicity to SARS-Cov-2 vaccines.
ABSTRACT
We studied the clinical and immunological outcomes of covid-19 infection in strictly consecutive patients with CLL from a well-defined area during the first 13 months of the pandemic. Sixty patients with a median age of 71 years (range 43-97) were identified. Median CIRS was 8 (4-20), median BMI 25 (19-42) and 65% were men. Patients had indolent CLL (n=38), were previously treated (n=12) or had ongoing therapy (n=10, among which seven received BTKi). Forty-six patients (77%) were hospitalized due to severe covid-19 and among them, 11 (24%) were admitted to the intensive care unit (ICU). Severe covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except for comorbidities (CIRS >6, p<0.05). Fourteen patients (23%) died;age ≥75 years was the only significant risk factor (p<0.05, uni- and multivariate analyses). Comparing months 1-6 vs. 7-13 of the pandemic, death rates were reduced from 32 to 18%, ICU admission from 37 to 15% and hospitalizations remained frequent (86 vs. 71%). Seroconversion occurred in 34/41 tested patients (83%) and anti-SARS-CoV-2 antibodies remained detectable at 6 and 12 months of follow-up in 17/22 and 8/11 patients, respectively. In-depth immunological analysis revealed that 13/17 tested patients had neutralizing antibodies (including all 12 patients that were also seropositive in conventional serology in this cohort), and 19/28 (68%) had antibodies in saliva. SARS-CoV- 2-specific T-cells (IFN-gamma ELISpot) were detected in 14/17 patients (82%). We conclude that covid-19 in non-selected CLL patients continued to result in a high admission rate even among young early-stage patients. A robust and durable B and/or T cell immunity was observed in most convalescents.
ABSTRACT
Background and study design: Patients with immunodeficiencies including CLL have an increased risk of severe infections and may not respond well to conventional vaccines. Two early international surveys reported that hospital-admitted Covid-19 patients with CLL had a high fatality rate (Mato et al., 2020;Scarfo et al., 2020). We recently showed that a robust and durable B and/or T cell immunity occurred in most convalescent CLL patients (Blixt et al., 2021). In contrast, the first publication on vaccination against SARS-CoV-2 in CLL reported seroconversion in only 39.5% of patients (Herishanu et al., 2021). We conducted a prospective clinical trial (COVAXID, clinicaltrials.gov: NCT04780659) in patients with various types of immunodeficiency and matched controls (n=539). Five equally sized cohorts were included: primary immunodeficiency, HIV, allogeneic transplantation or CAR-T, solid organ transplantation as well as CLL. The primary endpoint was seroconversion measured 2 weeks after the 2nd dose of the Pfizer-BioNTech vaccine (Comirnaty). Antispike antibodies in saliva (which may better correlate with protection, Khoury et al., 2020) and T cells (IFN-gamma ELISpot) were also measured. We report here the results of the CLL cohort. Results: Ninety CLL patients were included in four predefined subgroups: indolent untreated disease (n=30);prior chemoimmunotherapy including a CD20 mAb 9-30 months ago (n=20);ongoing BTKi therapy (n=30);and stopped/paused ibrutinib (all >3 months ago) (n=10). The median age was 70 years (range 23-87) and 67% were men. Median IgG was 6.7 g/L (range 1.0-20.8) and 50% had a value below the lower normal range. Reactogenicity occurred in 82.9 and 77.1% of the CLL patients and 81.6 and 85.0% of the controls after doses 1 and 2, respectively. The severity of reactogenicity was similar in patients and controls. AEs≥grade 2 was seen in five patients within 2 weeks after dose 2 but none was considered related to the vaccine. No hematological toxicity was observed. Data analysis on seroconversion is ongoing. Preliminary analysis of saliva showed that on D35 (i.e. 14 days after 2nd dose) 62% of CLL patients (95% of healthy controls) had developed IgG to S1S2 spike antigen compared to only 23% on D21 (i.e. 21 days after dose 1). Subgroup analysis (D35) indicates that ibrutinib-treated patients showed the lowest response in saliva whilst indolent and prior chemoimmunotherapy-treated groups were the best responders. A different pattern was observed for IFNgamma positive T cells with the highest responses in the (few) patients who had paused/stopped ibrutinib with other subgroups having lower T cell responses. Conclusions: This prospective clinical trial verified that the BNT162b2 mRNA vaccine was well-tolerated in patients with CLL. Our preliminary results indicate that anti-spike antibodies in saliva and T cell responses were frequently observed after full vaccination but with different response patterns in CLL subgroups. Details of the study including seroconversion and the overall response rate will be presented at the meeting.