ABSTRACT
Background: The ongoing COVID-19 pandemic has resulted in more than 419 million cases and more than 5.9 million deaths. Preious studies hae indicated inferior responses to SARS-CoV-2 accination across different hematological diseases. Through this prospectie cohort study, we examined the deelopment and durability of anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients with either multiple myeloma (MM) or Chronic Lymphatic B-cell Leukemia (B-CLL) six months after accination and compared to immunocompetent controls. Aims: We aimed to inestigate the durability of immune responses to COVID-19 accination in patients with MM or B-CLL compared to healthy controls, and to identify risk factors for humoral non-response, including type of diagnosis. Methods: We measured anti-receptor binding domain (RBD) IgG after two doses of BNT162b2 in 179 patients (MM: n=78, B-CLL: n=101) and 179 age and sex matched healthy controls up to six months after first accination. Anti- RBD IgG leels and neutralizing capacity of antibodies were measured at first and second dose of BNT162b2 and two and six months after first dose. Humoral response was defined as anti-RBD IgG > 225 AU/mL with a neutralizing index ≥ 25%. Humoral non-response was defined as the absence of a humoral response. T-cell responses were assessed six months after the first dose using an ELISA-based interferon-gamma release assay. A positie T-cell response was defined as IFN-γ release > 200 mIU/mL. Data on diagnoses were obtained through medical records, and data on accination status were obtained from the Danish Vaccination Register. Results: In patients with MM or B-CLL, the geometric mean concentration (GMC) of anti-RBD IgG increased from baseline 1.49 AU/mL (95% CI: 1.21-1.84) to three weeks after the first accine dose 15.10 AU/mL (95% CI: 9.39- 24.29) and after receiing the second dose 1179.60 AU/mL (95% CI: 727.78-1919.85). From two to six months after first accine there was a significant decline in the GMC of anti-RBD IgG to 252.75 AU/mL (95% CI: 159.17-403.43). The mean neutralizing capacity in patients with MM or B-CLL was lower than in controls at all time points after the first accine dose. Six months after first accine dose, 79 of 179 (44.1%) patients with MM or B-CLL had a positie humoral response, while this was the case for 170 of 179 controls (95.0%), p<0.001. Haing MM or B-CLL was significantly associated with risk of humoral non-response. This was most pronounced in B-CLL patients who had an age and sex adjusted risk ratio (RR) of 12.25 (95% CI: 6.42-23.38, p< 0.001) of humoral non-response compared to healthy controls. For MM patients the RR was 4.65 (95% CI: 2.21-9.80, p< 0.001). T-cell response was assessed in a subset of 48 patients with MM (n=28) or B-CLL (n=20) and 26 controls, six months after first accine dose. A total of 21 (43.8%) patients with MM (12/28) or B-CLL (9/20) and 14 (53.8%) controls had a positie T-cell response (p =0.56). Seen of 20 (35.0%) patients with MM or B-CLL who did not deelop a humoral response, deeloped a T-cell response (MM: 3/8, B-CLL: 4/12), while 14 of 28 (50.0%) patients with MM or B-CLL who deeloped a humoral response deeloped a T-cell response (p =0.46, MM: 9/11, B-CLL: 5/8). In healthy controls 14 of 25 (56.0%) people who deeloped a humoral response also deeloped a T-cell response. Summary/Conclusion: Humoral response to BNT162b2 was impaired in patients with MM or B-CLL compared to healthy controls. Both patients with MM and B-CLL were at higher risk of humoral non-response compared to healthy controls.
ABSTRACT
Aims: The COVID-19 pandemic has affected lives of Danish citizens in different ways, for example, through social distancing and other public health measures introduced to mitigate SARS-CoV-2 spread or through economic consequences. We assessed changes in self-reported measures of physical and mental health-related quality of life (MCS, PCS), stress levels, quality of sleep and loneliness during the COVID-19 pandemic in Denmark, and identified factors influencing such changes. Methods: This is a nation-wide prospective cohort study including 50,968 participants in the Danish Blood Donor Study, who answered health questionnaires before and during the COVID-19 pandemic. The questionnaires included the 12-Item Short Form Health Survey, Cohen's Perceived Stress Scale 10-item version, the 3-item UCLA loneliness scale, and three selected questions evaluating insomnia. During the pandemic, the questionnaire also contained items on the personality trait stamina, behaviours undertaken to avoid infection, and changes in experienced changes in job situation during the pandemic. Finally, information on socio-demographic factors and previous use of anti-depressive medication was collected for all study participants from national registers. Descriptive statistics, multivariable linear and multinomial logistic regression analyses were applied. Results: Comparing measurements from before March 2020 with those after May 2020, MCS and quality of sleep both worsened, while the overall stress levels decreased. PCS decreased in men and increased in women. The mean level of loneliness increased by 14%. The degree of health changes varied by age, type of job, changes in job situation during the pandemic, previous use of anti-depressive medication and by level of personal stamina. Conclusions: Living under the unusual circumstances that persisted during the COVID-19 pandemic negatively impacted the health of Danish blood donors.Our observations may herald an emerging public health problem.