Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Ending Race-Conscious College Admissions and Its Potential Impact on the Infectious Disease Workforce.

On 29 June 2023, the Supreme Court of the United States ruled that race-conscious consideration for college admission is unconstitutional. We discuss the consequences of this ruling on the delivery of equitable care and health system readiness to combat current and emerging pandemics. We propose strategies to mitigate the negative impact of this ruling on diversifying the infectious disease (ID) workforce.

Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures.

Reported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group. IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide vaccines, conjugate vaccines have shown consistent efficacy against nasopharyngeal carriage and noninvasive pneumonia overall and for some prevalent individual serotypes. Given these different clinical profiles, it is crucial to understand the differential immunological responses induced by these two vaccines. Here, we used a high-throughput systems serology approach to profile the biophysical and functional features of serum antibodies induced by PCV13 and PPSV23 at 1 month and 1 year. In comparison with PPSV23, PCV13 induced higher titers across antibody isotypes; more durable antibody responses across immunoglobulin G (IgG), IgA, and IgM isotypes; and increased antigenic breadth. Although titers measured in opsonophagocytic activity (OPA) assays were similar between the two groups, confirming what was observed in clinical studies, serum samples from PCV13 vaccinees could induce additional non-OPA antibody-dependent functions, including monocyte phagocytosis and natural killer cell activation. In a multivariate modeling approach, distinct humoral profiles were demonstrated in each arm. Together, these results demonstrate that the glycoconjugate PCV13 vaccine induces an antigenically broader, more durable, polyfunctional antibody response. These findings may help explain the increased protection against S. pneumoniae colonization and noninvasive pneumonia and the longer duration of protection against invasive pneumococcal disease, mediated by PCV13.

Incidence, aetiology and serotype coverage for pneumococcal vaccines of community-acquired pneumonia in adults: a population-based prospective active surveillance study in Brazil.

OBJECTIVES: To determine the incidence, aetiology and pneumococcal serotype distribution of community-acquired pneumonia (CAP) in Brazilian adults during a 2-year period. DESIGN: Prospective population-based surveillance study. SETTING: Patients from two emergency hospitals in Brazil were consecutively included in this study. PARTICIPANTS: A total of 111 adults aged 50 years and older with radiographically-confirmed CAP requiring an emergency department visit were prospectively enrolled between January 2018 and January 2020. MAIN OUTCOME MEASURES: Incidence rates of CAP were calculated according to age and pathogen. Pathogens were identified by conventional microbiological methods. Additionally, a novel, Luminex-based serotype specific urinary antigen detection assay was used to detect serotypes included in pneumococcal vaccines. RESULTS: Mean age of participants was 64 years and 31% were aged ≥70 years. Aetiology was established in 61 (57%) patients; among identified cases, the most common pathogens were Streptococcus pneumoniae (42/61, 69%) and influenza (4/61, 7%). Among serotypes identified from the 42 cases of pneumococcal CAP, estimated coverage ranged by pneumococcal vaccine formulations from 47.6% (13-valent), 59.5% (20-valent, licenced in the USA only) and 71.4% (23-valent). In patients with CAP, 20-valent pneumococcal vaccine serotypes were identified 2.5 times more frequently than 10-valent pneumococcal vaccine serotypes (22.5% vs 9.0%). The incidence rate for CAP in adults aged ≥50 years was 20.1 per 10 000 person-years. In general, the incidence of CAP increased consistently with age, reaching 54.4 (95% CI 36.8 to -76.6) per 10 000 in adults 80 years or older. CONCLUSIONS: We observed a high burden of pneumococcal CAP among adults in Brazil. Despite the routine immunisation of children and high-risk adults against pneumococcal disease in the Brazilian national vaccination programme, a persistent burden of pneumococcal CAP caused by vaccine serotypes remains in this population.

Incidence and Estimated Vaccine Effectiveness Against Hospitalizations for All-Cause Pneumonia Among Older US Adults Who Were Vaccinated and Not Vaccinated With 13-Valent Pneumococcal Conjugate Vaccine.

Importance: Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended. Objective: To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants: This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018. Exposures: PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization. Main Outcomes and Measures: First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) × 100%. Results: Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI. Conclusions and Relevance: In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.

Detection of pneumococcus during hospitalization for SARS-CoV-2.

Background: Infections with respiratory viruses [e.g. influenza and respiratory syncytial virus (RSV)] can increase the risk of severe pneumococcal infections. Likewise, pneumococcal coinfection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 coinfection and the role of coinfection in influencing COVID-19 severity. We, therefore, investigated the detection of pneumococcus in COVID-19 inpatients during the early pandemic period. Methods: The study included patients aged 18 years and older, admitted to the Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease). Results: Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; and 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 [OR: 2.20; 95% CI: (0.72, 7.48)]; however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died. Conclusions: Pneumococcal lower respiratory tract infection (LRTI), as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.

Vaccination coverage among young homeless children compared to US national immunization survey data.

INTRODUCTION: Comprehensive vaccination coverage among homeless children in the United States (US) is largely unknown although a few studies suggest low coverage with single vaccinations. This study compared vaccination coverage with a combined 7-vaccines series among homeless children in the District of Columbia (DC) to coverage among other US children. MATERIALS AND METHODS: A cross-sectional survey of homeless children in DC was conducted from 2018 to 2019. Recruitment occurred at housing shelters, social services centers, and a diaper dispensary, and through limited chain referral. English-speaking parents of a child aged 19 to 35 months who spent the majority of the last 30 nights homeless were recruited. Participants consented for their child's healthcare providers to submit vaccination records. The vaccination coverage estimate of this sample was compared with estimates of three populations in the 2018 National Immunization Survey (NIS): children in DC (NIS DC), children in the US (NIS US), and children in the US below the federal poverty level (NIS poor). RESULTS: Most of the 135 children had experienced at least two lifetime episodes (63.7%) and 12 months (57%) of homelessness. The estimated percent up to date was 52.6% (95% CI: 43.8%, 61.3%). This estimate was 20.4 (95% CI: 11.9, 28.8, p < .0001), 20 (95% CI: 11.5, 28.4, p < .0001), and 11.5 (95% CI: 3.1, 20, p < .01) percentage points lower than estimates for the NIS DC, NIS US and NIS poor populations, respectively. After adjusting for child's age and race/ethnicity, vaccination coverage of the NIS DC sample was below that of NIS US (p < .01) and NIS poor samples (p < .05). CONCLUSION: Children experiencing homelessness may be at risk of under-vaccination, even when compared to a general population of children in poverty. Awareness of this heightened risk may allow for more precise targeting of vaccination delivery support specifically to children experiencing homelessness.

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-acquired Pneumonia in Hospitalized US Adults.

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

Parental Beliefs, Logistical Challenges, and Improvement Opportunities for Vaccination among Children Ages 19-35 Months Experiencing Homelessness.

OBJECTIVES: To examine parental beliefs and logistical challenges to early childhood vaccination completion as well as opportunities to support improved vaccine uptake among families experiencing homelessness. STUDY DESIGN: A cross-sectional survey was conducted between February 2018 and October 2019 with parents of children ages 19-35 months old experiencing homelessness. Participants were recruited from 10 locations that serve families experiencing homelessness in Washington, DC and by referral from other participants. Vaccination records were obtained from health care providers to determine the child's up-to-date (UTD) status with a combined 7-vaccine series. RESULTS: Of 135 children of participants, only 69 (51.1%) were UTD. Most participants had at least 1 concern about childhood vaccines and at least 1 logistical barrier to completing vaccination (57% and 85.9%, respectively). The most frequent barriers were getting a convenient appointment time (46.3%), remembering appointments (44.8%), and commuting to appointments (44.4%). Although only 53.3% of the participants' children attended a licensed daycare center and only 43.7% received benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), use of either of these programs that routinely assess vaccination status was associated with over 3 times higher adjusted odds of being UTD (aOR 3.4, 95% CI 1.6-7.3, and aOR 3.1, 95% CI 1.4-6.5, respectively). CONCLUSIONS: Logistical barriers to accessing primary care services are common among children experiencing homelessness, underscoring the importance of health care providers offering vaccines at every opportunity. Government-regulated programs are useful for promoting vaccination, and enrollment should be encouraged because many children experiencing homelessness may not access them.