Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults.

BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. RESULTS: Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19). CONCLUSIONS: We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

Frailty and Age Impact Immune Responses to Moderna COVID-19 mRNA Vaccine.

BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used antibody titers in linear mixed-effects linear regression with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used clinical predictors and cellular phenotype variables in linear regression models. RESULTS: Participants (n=15) had median age of 90 years and mild, moderate, or severe frailty scores (n=3, 7, or 5 respectively). After 2 vaccine doses, anti-spike antibody titers were higher in 5-fold higher in individuals with mild frailty compared to severe frailty and 9-fold higher in individuals with prior COVID-19 infection compared to uninfected (p=0.02 and p<0.001). Following the booster, titers improved regardless of COVID-19 infection or frailty. Antibody avidity significantly declined following 2 vaccine doses regardless of frailty status, but reached maximal avidity after the booster. Spike-specific CD4+ T cell responses were modulated by frailty and terminally differentiated effector memory TEMRA cells, and spike-specific TFH cell responses were inversely correlated with age. Additionally, an immune-senescent memory T cell phenotype was correlated with frailty and functional decline. CONCLUSIONS: We described the separate influences of frailty and age on adaptive immune responses to the Moderna COVID-19 mRNA vaccine. Though overall antibody responses were robust, higher frailty diminished initial antibody quantity, and all older adults had impaired antibody avidity. Following the booster, antibody responses improved, overcoming the effects of age and frailty. CD4+ T cell responses were independently impacted by age, frailty, and burden of immune-senescence. Frailty was correlated with increased burden of immune-senescence, suggesting an immune-mediated mechanism for physiological decline.

Detection of Environmental Spread of SARS-CoV-2 and Associated Patient Characteristics.

Understanding transmission of severe acute respiratory syndrome coronavirus 2 informs infection prevention practices. Air sampling devices were placed in patient hospital rooms for consecutive collections with and without masks. With patient mask use, no virus was detected in the room. High viral load and fewer days from symptom onset were associated with viral particulate dispersion.

Successful control of a methicillin-resistant Staphylococcus aureus outbreak in a burn intensive care unit by addition of universal decolonization with intranasal mupirocin to basic infection prevention measures.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is frequently implicated in health care-associated outbreaks in burn intensive care units, incurring substantial morbidity and mortality to these high-risk patients and excess costs to health care systems. METHODS: MRSA health care-associated infections (HAIs) were noted before and after the implementation of basic infection prevention measures and the subsequent implementation of universal decolonization with intranasal mupirocin. Pulsed-field gel electrophoresis was used to determine the relatedness of clinical isolates. A case-control study was conducted to characterize the risk factors for MRSA HAIs. RESULTS: Basic interventions failed to decrease the rate of MRSA HAIs, although compliance with these interventions was high throughout the study. MRSA HAIs decreased from 8.53 HAIs per 1,000 patient days before the implementation of intranasal mupirocin to 3.61 HAIs per 1,000 patient days after the implementation of intranasal mupirocin (P = .033). Pulsed-field gel electrophoresis disclosed 10 unique clones with no large clusters. The case-control study revealed a significant association between MRSA HAIs and lengths of stay, body surface area burned, intubation, pressor requirement, leukocytosis, lactic acidosis, development of pneumonia, MRSA colonization, and death. CONCLUSIONS: Basic environmental and behavioral interventions fell short of controlling a low-count, sporadic, and multiclonal MRSA outbreak in the burn intensive care unit of a tertiary medical center. However, the added implementation of universal decolonization with intranasal mupirocin was effective. Burn victims with greater disease severity were at higher risk for MRSA HAIs.

Detection of Measles Virus RNA in Air and Surface Specimens in a Hospital Setting.

Measles virus (MeV) is known to be highly contagious, with an infectious period lasting from 4 days before to 4 days after rash onset. An unvaccinated, young, female patient with measles confirmed by direct epidemiologic link was hospitalized on day 5 after rash onset. Environmental samples were collected over the 4-day period of hospitalization in a single room. MeV RNA was detectable in air specimens, on surface specimens, and on respirators on days 5-8 after rash onset. This is the first report of environmental surveillance for MeV, and the results suggest that MeV-infected fomites may be present in healthcare settings.

Aging promotes B-1b cell responses to native, but not protein-conjugated, pneumococcal polysaccharides: implications for vaccine protection in older adults.

The efficacy of different vaccines in protecting elderly individuals against Streptococcus pneumoniae infections is not clear. In the current study, aged mice (22-25 months old) exhibited significantly increased susceptibility to respiratory infection with serotype 3 S. pneumoniae relative to younger adult mice, regardless of whether mice were naive or immunized with native pneumococcal polysaccharide (PPS; Pneumovax23) or protein-PPS conjugate (Prevnar-13) vaccines. Nonetheless, Pneumovax-immunized aged mice developed limited bacteremia following respiratory challenge and exhibited significantly increased survival following systemic challenge relative to Prevnar-immune aged mice and young mice that had received either vaccine. This was explained by >10-fold increases in PPS-specific immunoglobulin G (IgG) levels in Pneumovax-immunized aged mice relative to other groups. Remarkably, PPS3-specific B-cell expansion, IgG switching, plasmablast differentiation, and spleen and bone marrow antibody-secreting cell frequencies were 10-fold higher in aged mice following Pneumovax immunization relative to young mice, due to significantly increased B-1b cell participation. In summary, this study highlights (1) the need to devise strategies to enhance respiratory immunity in aged populations, (2) the diverse responses young and aged populations generate to Pneumovax vs Prevnar vaccines, and (3) the potential value of exploiting B-1b cell responses in aged individuals for increased vaccine efficacy.

The influences of perinatal challenge persist into the adolescent period in socially housed bonnet macaques (Macaca radiata).

Social challenges during the perinatal period influence the mother-infant relationship in nonhuman primates and may affect the offspring's response to later social challenge(s). Relocation of a breeding colony of monkeys (Macaca radiata) created two groups of infants: one group experienced social group relocation to a new housing facility during the perinatal period (ATYPICAL) and the second group developed within a constant environment (TYPICAL). At a mean age of 25 months, all animals were removed from their natal group and placed in same sex adolescent social groups. Behavioral observations were collected after group formation or introduction to a new group. ATYPICAL subjects showed increased aggression and reduced affiliation compared to TYPICAL subjects. Hair cortisol in male subjects collected 6 months after introduction was elevated in the ATYPICAL subjects compared to TYPICAL subjects. These findings demonstrate that early life challenges affect behavior as well as stress hormone responses to social challenge in adolescence.

Hematological and serum biochemical indices in healthy bonnet macaques (Macaca radiata).

BACKGROUND: Blood reference values for bonnet macaques (Macaca radiata) are limited. The goal of this study was to determine reference ranges for hematological and serum biochemical indices in healthy, socially housed bonnet macaques for males and females over a range of ages. METHODS: Blood hematological and serum biochemical values were obtained from 50 healthy bonnet macaques of both sexes and aged 10-234 months. RESULTS: Age and sex differences were present in a number of measures. Globulins, total protein, and creatinine (CREAT) values were highest among older subjects, while alkaline phophatase, albumin, and phosphorus values were higher in juveniles. Sex differences were present in concentrations of red blood cells and CREAT, with higher values in males. CONCLUSION: The blood parameter data reported here as age-specific reference values for laboratory-housed, healthy bonnet macaques may be used to inform clinical care and laboratory primate research.