Altered immune response to vaccination in patients with plasma cell premalignancy

Introduction Patients with hematological malignancies, including multiple myeloma (MM), experience suboptimal responses to SARS-CoV-2 vaccination. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) are precursors to MM and exhibit altered immune cell composition and function. The SARS-CoV-2 pandemic and the subsequent population-wide vaccination represent an opportunity to study the real-life immune response to a common antigen. Here, we present updated results from the IMPACT study, a study we launched in November 2020 to characterize the effect of plasma cell premalignancy on response to SARS-CoV2 vaccination (vx). Methods We performed: (i) ELISA for SARS-CoV-2-specific antibodies on 1,887 peripheral blood (PB) samples (237 healthy donors (HD), and 550 MGUS, 947 SMM, and 153 MM patients) drawn preand post-vx;(ii) single-cell RNA, T cell receptor (TCR), and B cell receptor (BCR) sequencing (10x Genomics) on 224 PB samples (26 HD, and 20 MGUS, 48 SMM, and 24 MM patients) drawn preand post-vx;(iii) plasma cytokine profiling (Olink) on 106 PB samples (32 HD, and 38 MGUS and 36 SMM patients) drawn pre- and post-vx;and (iv) bulk TCR sequencing (Adaptive Biotechnologies) on 8 PB samples from 4 patients (2 MGUS, 2 SMM) drawn pre- and post-vx. Results Patients with MGUS and SMM achieved comparable antibody titers to HD two months post-vx. However, patient titers waned significantly faster, and 4 months post-vx we observed significantly lower titers in both MGUS (Wilcoxon rank-sum, p=0.030) and SMM (p=0.010). These results indicate impaired humoral immune response in patients with MGUS and SMM.At baseline, the TCR repertoire was significantly less diverse in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.039), while no significant difference was observed in the BCR repertoire (p=0.095). Interestingly, a significant increase in TCR repertoire diversity was observed post-vx in patients with SMM (paired t-test, p=0.014), indicating rare T cell clone recruitment in response to vaccination. In both HD and patients, recruited clones showed upregulation of genes associated with CD4+ naive and memory T cells, suggesting preservation of the T cell response in SMM, which was confirmed by bulk TCR-sequencing in 4 patients.Lastly, by cytokine profiling, we observed a defect in IL-1beta and IL-18 induction post-vx in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.047 and p=0.015, respectively), two key monocyte-derived mediators of acute inflammation, suggesting an altered innate immune response as well. Conclusion Taken together, our findings highlight that despite the absence of clinical manifestations, plasma cell premalignancy is associated with defects in both innate and adaptive immune responses. Therefore, patients with plasma cell premalignancy may require adjusted vaccination strategies for optimal immunization.

ANXIETY DURING THE COVID-19 PANDEMIC: PRELIMINARY FINDINGS FROM THE UCSF ASPIRE STUDY

OBJECTIVE: To describe the prevalence of anxiety symptoms in early pregnancy and identify predictors of early pregnancy anxiety during the COVID-19 pandemic. MATERIALS AND METHODS: We assessed baseline moderate-to-severe anxiety symptoms after enrollment into the UCSF ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) Prospective Cohort from May 2020 through February 2021. Pregnant persons <10 weeks' gestation completed questions regarding sociodemographic characteristics, obstetric/ medical history, and pandemic-related experiences. Chi-square and multivariate hierarchical logistic regression analyses determined predictors of moderate or severe anxiety symptoms (GAD-7 R10). All analyses performed with Statistical Analysis Software (SAS®) version 9.4. RESULTS: 4,303 persons completed the GAD-7 questionnaire. The mean age of this nationwide sample was 33 years and 25.7% of participants received care through a fertility clinic. 12.6% of pregnant persons reported moderate-to-severe anxiety symptoms. On univariate analysis, less than a college education (p<0.0001), pre-existing history of anxiety (p<0.0001), and history of prior miscarriage (p=0.0143) were predictors of moderate-to-severe anxiety symptoms;care at a fertility center was protective (26.6% vs 25.7%, p= 0.0009). COVID-19 related stressors were strongly predictive of anxiety in pregnancy (p<0.0001). Race/ ethnicity and a prior history of live birth were not predictors of moderate- to-severe anxiety. In the hierarchical logistic regression model, pre-existing history of anxiety remained associated with anxiety during pregnancy. While education was no longer significant, there was a trend towards this being predictive. Hierarchical Logistic regression predicting moderate to severe anxiety symptoms CONCLUSIONS: Pre-existing history of anxiety and low maternal educational attainment likely exacerbated the contribution of stressors due to the COVID-19 pandemic on early pregnancy anxiety. IMPACT STATEMENT: Socioeconomic disparities may exacerbate the contribution of pandemic-related stressors to early pregnancy anxiety risk. With limitations in prenatal care administration during the pandemic, continued emotional health support should remain an important focus for providers.

VIRTUAL AND IN-PERSON CARE DURING THE COVID-19 PANDEMIC LED TO EQUIVALENT PATIENT SATISFACTION FOR REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY (REI) PATIENTS

OBJECTIVE: To evaluate whether a shiftto virtual care during the COVID-19 pandemic negatively impacted patient satisfaction among REI patients. MATERIALS AND METHODS: A modified version of a validated multiple-choice survey assessing satisfaction with care was sent to current patients who agreed to participate in research at a tertiary medical center. The survey evaluated satisfaction with multiple aspects of care. Respondents were categorized by visit type: in-person only (n=23), virtual-only (n=12), and a mix of both settings (n=52). Responses were dichotomized into “Agree” or “Disagree”, with neutral grouped with “agree”. Chi-squared tests of independence to assess differences between groups were conducted in R (Version 3.4.4). P<0.05 was interpreted as statistically significant. The study was approved by the University of California San Francisco Institutional Review Board. RESULTS: Out of 1282 patients who received an invitation to participate, 526 patients (41.0%) completed our survey. Eighty-seven of these were seen by the Division of REI and included in this study. Median participant age was 36.5 (range: 21-76). There were no significant differences in respondents' satisfaction with the type of care received (in-person vs. virtual vs. mixed, p=0.43). There were no statistically significant differences in respondents' ability to develop a relationship with their provider (p=0.25), provider's friendliness (p=0.50), skills or knowledge (p=0.71), and concern (p=0.80) as rated by respondents. The frequency of visits starting on time (p=0.50), convenience of the visit date and time (p=0.78), and the amount of time spent with the provider (p=0.89) were also similar across all three groups. Although 56% of respondents who had mixed care reported that virtual visits may have compromised their health, this was not shown in either the virtual-only or in-person only groups, introducing the possibility of a confounder. Sixty-eight percent of respondents seen virtually were likely to recommend virtual visits to others. When asked about preferences for primary visit type after the COVID-19 pandemic, at least 50% of participants in all groups preferred in-person visits, with a minority choosing virtual visits (22%), alternating between virtual and in-person (16%), or expressing no preference (5%). CONCLUSIONS: A shift to virtual care during the COVID-19 pandemic did not appear to impact patient satisfaction with the care received as patients were highly satisfied regardless of the setting in which they received care. A majority of patients seen virtually were likely to recommend virtual visits to others. Nonetheless, a plurality of patients in all three groups preferred their primary visit type to be in-person. IMPACT STATEMENT: This study shows no significant differences in patient satisfaction regardless of visit type. Further research is needed to understand how to optimize virtual care delivery after the COVID-19 pandemic.