Factors associated with increased financial toxicity after the completion of radiation treatment for gynecologic cancer.

PURPOSE: We evaluated financial toxicity (FT) in patients with gynecologic cancer treated with radiation and assessed the impact of the COVID-19 pandemic on patients' financial wellbeing. METHODS: Patients completed a survey 1 month after completing radiation from August 2019-March 2020 and November 2020-June 2021. The survey included the COmprehensive Score for Financial Toxicity (COST) tool, EQ-5D to measure quality of life (QOL) and pandemic-related questions for the second survey period. High FT was COST score ≤ 23. RESULTS: Of 97 respondents (92% response rate), 49% completed the survey pre-pandemic and 51% after; the majority were white (76%) and had uterine cancer (64%). Sixty percent received external beam radiation with or without brachytherapy; 40% had only brachytherapy. High FT was associated with worse QOL (r = -0.37, P < 0.001), younger age and type of insurance (both p ≤ 0.03). Respondents with high FT were 6.0 (95% CI 1.0-35.9) times more likely to delay/avoid medical care, 13.6 (95% CI 2.9-64.3) times more likely to borrow money, and 6.9 (95% CI 1.7-27.2) times as likely to reduce spending on basic goods. The pandemic cohort had a smaller proportion of respondents with high FT than the pre-pandemic cohort (20% vs. 35%, p = 0.10) and a higher median COST score (32 (IQR 25-35) vs. 27 (IQR 19-34), p = 0.07). CONCLUSION: Privately insured, younger respondents who received radiation for gynecologic cancer were at risk for FT. High FT was associated with worse QOL and economic cost-coping strategies. We observed less FT in the pandemic cohort, though not statistically different from the pre-pandemic cohort.

Acceptance of genetic editing and of whole genome sequencing of human embryos by patients with infertility before and after the onset of the COVID-19 pandemic.

RESEARCH QUESTION: Has acceptance of heritable genome editing (HGE) and whole genome sequencing for preimplantation genetic testing (PGT-WGS) of human embryos changed after the onset of COVID-19 among infertility patients? DESIGN: A written survey conducted between April and June 2018 and July and December 2021 among patients at a university-affiliated infertility practice. The questionnaire ascertained the acceptance of HGE for specific therapeutic or genetic 'enhancement' indications and of PGT-WGS to prevent adult disease. RESULTS: In 2021 and 2018, 172 patients and 469 patients (response rates: 90% and 91%, respectively) completed the questionnaire. In 2021, significantly more participants reported a positive attitude towards HGE, for therapeutic and enhancement indications. In 2021 compared with 2018, respondents were more likely to use HGE to have healthy children with their own gametes (85% versus 77%), to reduce disease risk for adult-onset polygenic disorders (78% versus 67%), to increase life expectancy (55% versus 40%), intelligence (34% versus 26%) and creativity (33% versus 24%). Fifteen per cent of the 2021 group reported a more positive attitude towards HGE because of COVID-19 and less than 1% a more negative attitude. In contrast, support for PGT-WGS was similar in 2021 and 2018. CONCLUSIONS: A significantly increased acceptance of HGE was observed, but not of PGT-WGS, after the onset of COVID-19. Although the pandemic may have contributed to this change, the exact reasons remain unknown and warrant further investigation. Whether increased acceptability of HGE may indicate an increase in acceptability of emerging biomedical technologies in general needs further investigation.

Characterization of immune responses in fully vaccinated individuals after breakthrough infection with the SARS-CoV-2 delta variant.

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported frequently in vaccinated individuals with waning immunity. In particular, a cluster of over 1000 infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. In this study, vaccinated individuals who tested positive for SARS-CoV-2 (n = 16) demonstrated substantially higher serum antibody responses than vaccinated individuals who tested negative for SARS-CoV-2 (n = 23), including 32-fold higher binding antibody titers and 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed higher mucosal antibody responses in nasal secretions and higher spike protein-specific CD8+ T cell responses in peripheral blood than did vaccinated individuals who tested negative. These data demonstrate that fully vaccinated individuals developed robust anamnestic antibody and T cell responses after infection with the SARS-CoV-2 delta variant. Moreover, these findings suggest that population immunity will likely increase over time by a combination of widespread vaccination and breakthrough infections.

Coronavirus Disease 2019 Messenger RNA Vaccine Immunogenicity in Immunosuppressed Individuals.

Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals.

The psychological impact of the coronavirus disease 2019 pandemic on women who become pregnant after receiving treatment for infertility: a longitudinal study.

OBJECTIVE: To compare the impact of the coronavirus disease 2019 (COVID-19) pandemic on the psychological health of patients with infertility who have become pregnant with that of women who have not. DESIGN: Prospective cohort study conducted from April 2020 to June 2020. The participants completed three questionnaires over this period. SETTING: A single large, university-affiliated infertility practice. PATIENTS: A total of 443 pregnant women and 1,476 women still experiencing infertility who completed all three questionnaires. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Patient-reported primary stressor over three months of the first major COVID-19 surge; further data on self-reported sadness, anxiety, loneliness, and the use of personal coping strategies. RESULTS: Pregnant participants were significantly less likely to report taking an antidepressant or anxiolytic medication, were less likely to have a prior diagnosis of depression, were more likely to cite COVID-19 as a top stressor, and overall were less likely to practice stress-relieving activities during the first surge. CONCLUSIONS: Women who became pregnant after receiving treatment for infertility cited the pandemic as their top stressor and were more distressed about the pandemic than their nonpregnant counterparts but were less likely to be engaging in stress-relieving activities. Given the ongoing impact of the pandemic, patients with infertility who become pregnant after receiving treatment should be counseled and encouraged to practice specific stress-reduction strategies.

Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.

Importance: Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited. Objective: To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern. Design, Setting, and Participants: An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection. Main Outcomes and Measures: SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants. Results: This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants. Conclusion and Relevance: In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.