INTRODUCTION: By the end of 2021, U.S. spike (S) antibody seroprevalence from COVID-19 vaccination, infection, or both (hybrid immunity) reached over 90%. With high seroprevalence, quantitative antibody concentrations are needed to characterize population immunity. We measured quantitative S antibody concentrations in a national blood donor cohort and evaluated their correlation with protection against infection. METHODS: One blood specimen per quarter in 2022 was tested for quantitative S IgG and infection-induced (nucleocapsid [N]) total Ig antibodies from a national blood donor sub-cohort of 106,969 people. Median S antibody concentrations were calculated by quarter and by history of vaccination and infection. Among vaccinated donors without N antibodies, protection (measured as 1 minus hazard ratios compared with unvaccinated donors) against N antibody seroconversion was estimated by S antibody concentration. Median S antibody levels were compared using the Kruskal-Wallis tests. RESULTS: Median S antibody concentrations increase from 1380 binding antibody units (BAU)/mL in quarter (Q) 1 2022 to 1720 BAU/mL in Q4 2022. In Q4, S antibody levels were lowest in the infection-only group (median: 75 BAU/mL) and higher in the vaccine-only (median: 1950 BAU/mL) and hybrid immunity group (median: 2550 BAU/mL). Protection against first-time infection increased with higher antibody concentrations; 5010 BAU/mL (95% CI 4120-6550) was associated with 50% protection. DISCUSSION: During 2022, this nationwide study showed mildly increased S IgG concentrations over time among blood donors. Vaccination and hybrid immunity resulted in higher antibody concentrations than infection alone. Higher antibody concentrations were associated with increased protection from infection.

Chromoblastomycosis, a fungal neglected tropical disease, is acquired through traumatic inoculation and is clinically characterized by a chronic granulomatous infection of the skin and subcutaneous tissue. Fonsecaea pedrosoi is the most commonly reported etiologic agent globally. Itraconazole is considered first-line therapy, but successful treatment with terbinafine, voriconazole, and posaconazole has been reported. F. pedrosoi minimum inhibitory concentration (MIC) data are limited, and epidemiological cutoffs (ECVs) are lacking; such data are important to help monitor antifungal resistance trends and guide initial antifungal selection. Thus, we performed antifungal susceptibility testing (AFST) on F. pedrosoi isolates and determined the MIC distributions and ECVs. AFST on Fonsecaea pedrosoi isolates was conducted at six laboratories from October 2023 to June 2024. Species identification was previously confirmed by DNA sequence analysis. AFST was performed by CLSI M38 standard broth microdilution method for itraconazole, voriconazole, posaconazole, isavuconazole, ketoconazole, terbinafine, flucytosine, and amphotericin B. The ECVs were established using the iterative statistical method with ECOFFinder (version 2.1) following CLSI M57 guidelines. We analyzed MIC results from 148 Fonsecaea pedrosoi isolates. The calculated ECVs were itraconazole, 0.5 µg/mL; voriconazole, 0.5 µg/mL; posaconazole, 0.5 µg/mL; isavuconazole, 1 µg/mL; ketoconazole, bimodal, no ECV determined; terbinafine, 0.25 µg/mL; flucytosine, rejected; and amphotericin, 8 µg/mL. These Fonsecaea pedrosoi ECVs, obtained through a multicenter international effort, provide a baseline to better understand the in vitro antifungal susceptibility profile of this species and monitor resistance. Clinicians and researchers can use these values to detect non-wild-type isolates with reduced susceptibility, reevaluate therapeutic options, and investigate potential clinical resistance if treatment failure occurs.IMPORTANCEChromoblastomycosis is a neglected tropical disease caused by an environmental, dematiaceous fungus. This fungal disease is acquired after a break in the skin that allows the fungus to enter, leading to a chronic infection in the skin and subcutaneous tissue. It is difficult to treat and often requires years of antifungal treatment. Fonsecaea pedrosoi is the most reported causative agent globally. Limited antifungal susceptibility data exist for F. pedrosoi making interpreting minimum inhibitory concentration (MIC) results difficult. We performed antifungal susceptibility testing on 148 F. pedrosoi isolates to establish MIC distributions and epidemiologic cutoff values (ECVs) for eight antifungals, including those commonly used to treat chromoblastomycosis. The calculated ECVs for the commonly used antifungals itraconazole and terbinafine were 0.5 and 0.25 µg/mL, respectively. ECVs can be helpful in choosing potential treatment options for F. pedrosoi and monitoring antifungal resistance epidemiology.

BACKGROUND: Amid changing variant and immunity landscapes since early in the coronavirus disease 2019 (COVID-19) pandemic, common COVID-19 symptoms need better understanding in relation to prior immunity or infecting variant. METHODS: American Red Cross blood donors were surveyed during February-April 2022 about prior COVID-19 vaccinations and symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Donations were tested for anti-nucleocapsid antibodies to inform infection history. Restricting analysis to donors with survey-reported infections during the Omicron BA.1-predominant period (19 December 2021 through 19 March 2022), we used multivariable logistic regression to compare symptoms by existing immunity from prior infection or vaccination. Restricting analysis to those with no existing immunity, we compared symptoms by variant-predominant period of their first reported infection (BA.1 vs before). RESULTS: Among 9505 donors with a BA.1-predominant period infection, donors with prior infection (n = 1115), vaccination (n = 5888), or both (n = 1738) were less likely than those without prior immunity (n = 764) to report loss of taste or smell, lower respiratory tract, constitutional, or gastrointestinal symptoms and more likely to report upper respiratory tract symptoms. Stronger associations followed recent prior infection, vaccination, or more vaccine doses. Among 8539 donors without prior immunity, those with survey-reported infections during the BA.1-predominant period (n = 764) were less likely to report loss of taste or smell, or lower respiratory tract symptoms than those with infections before this period (n = 7775). CONCLUSIONS: Our data suggest that both prior immunity and Omicron predominance redistributed COVID-19 symptoms toward upper respiratory tract presentations and likely both contributed to a decrease in COVID-19 severity over time. These findings may better inform COVID-19 identification in high-immunity settings and demonstrate additional benefits of vaccination.

Human metapneumovirus (hMPV) is an important cause of respiratory illness. However, information about hMPV incidence, patient characteristics, and symptoms outside hospital settings is limited. During June 2022-March 2024, participants aged 6 months-49 years who were enrolled in the CASCADIA community-based cohort study submitted weekly illness surveys and nasal swabs, and completed follow-up illness surveys. Swabs collected 0-3 days before reporting new or worsening symptoms were tested for hMPV and other respiratory viruses by multiplex polymerase chain reaction. Incidence was analyzed using an exponential survival model. Among 3,549 participants, 306 had symptomatic hMPV infection, representing an average of 7.5 cases per 100 persons per year (95% CI = 6.7-8.4). Incidence was highest during January-March (adjusted hazard ratio [aHR] = 4.3; 95% CI = 3.0-6.0) compared with October-December, and among those aged 2-4 years (aHR = 5.8; 95% CI = 3.8-9.0) compared with those aged ≥40 years. The most frequently reported symptoms were cough (80.4%) and nasal congestion (71.9%). Among 252 (82.4%) participants who completed a post-illness follow-up survey, 68 (27.0%) missed work, school, or child care facility attendance. Together, these findings indicate that hMPV is a common cause of respiratory illness during late winter to spring, particularly among young children, and frequently disrupts daily activities. Understanding hMPV epidemiology can guide surveillance definitions, clinical testing, and prioritization of prevention strategies.

Long-term effects of COVID-19 on multiple organ systems have been reported. Indigenous persons experienced disproportionate morbidity and mortality from COVID-19; however, Post-COVID-19 Conditions (PCC) have not been well described in this population. We conducted a longitudinal cohort study among Indigenous persons living in the Navajo Nation or White Mountain Apache Tribal lands in the Southwest United States who tested positive for SARS-CoV-2 between February 1, 2021 and August 31, 2022. Participants were enrolled during their acute illness and followed for three months. PCC was defined as the presence of any self-reported symptom and/or any sequelae or new condition recorded in the electronic health record at the 3-month visit. Risk factors for PCC were evaluated using Poisson regression with robust standard errors. The analysis included 258 adults and 84 children. Most participants (98.4% of adults, 90.5% of children) experienced a mild, symptomatic acute illness. Over half of adults (57.8%) and a third (39.3%) of children experienced six or more symptoms during the acute illness. Three months post-acute COVID-19, 39.8% of adults and 15.9% of children had symptoms consistent with PCC. Commonly reported symptoms were fatigue/tiredness, cough, headache, runny nose, and myalgia. Among adults enrolled during Omicron predominance, older age and hospitalization for COVID-19 were significantly associated with an increased risk of PCC, and COVID-19 vaccination was significantly associated with a decreased risk of PCC in univariable analysis. In a multivariable analysis, COVID-19 vaccination (risk ratio: 0.56; 95% confidence interval: 0.34, 0.90) remained significantly associated with a decreased risk of PCC. In this cohort of Indigenous persons in the Southwest US, PCC at three months post-acute COVID-19 illness were common, including among individuals with mild acute illness. While the absence of a control group is a limitation, these findings highlight the potential ongoing healthcare needs related to PCC in Indigenous populations.

Seroprevalence studies play an important role in estimating the number of children infected with SARS-CoV-2. We report SARS-CoV-2 seroprevalence in children seeking medical care for any reason at a free-standing pediatric hospital in Seattle, WA over a 2.5-year period and four distinct pandemic waves. We randomly selected residual serum samples from children and young adults seeking medical care as inpatients and outpatients at Seattle Children's Hospital between June 2020 and December 2022 to test for the presence of anti-nucleocapsid (N) antibodies. Samples were categorized into four distinct pandemic waves based on Washington State epidemiology: Wave 1 (June 2020-October 2020), Wave 2 (November 2020-June 2021), Wave 3 (July 2021-November 2021), and Wave 4 (December 2021-December 2022). Patient characteristics and COVID-19 vaccine status were obtained, and zip codes were used to ascertain the Social Vulnerability Index (SVI). Multivariable Poisson regression models with robust variance estimates were used to examine the relationship between patient characteristics and anti-N-positivity for each wave. Among 8,040 samples from 7,102 patients included in the analyses, seroprevalence rose from 2.4% (95% CI, 2.0%-3.1%) in Wave 1 to 25.5% (95% CI 23.3%-27.8%) in Wave 4 (following the Omicron surge). High SVI, Hispanic ethnicity, or use of government insurance was associated with increased anti-N positivity in most waves. We observed a steady increase in anti-N seroprevalence followed by a sharp increase after the Omicron surge in early 2022. Our data demonstrate the burden of COVID-19 on specific groups with health disparities within our region throughout the pandemic.IMPORTANCEOur results highlight the importance of seropositivity studies as essential tools to provide information on the incidence and prevalence of SARS-CoV-2 seropositivity. Our results also reinforce other reports demonstrating the inequitable burden of COVID-19 on groups with health disparities and that this inequitable burden continued to persist throughout the pandemic, even in a region with high adherence to COVID-19 mitigation efforts. It also highlights SVI's value in identifying communities that must be part of pandemic research, and public health and vaccination strategies.

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced -2.43 (95% CI: -3.76, -1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced -2.79 (95% CI: -4.99, -0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

BACKGROUND: Limited data are available regarding the development and durability of immune responses following COVID-19 infection or vaccination in pediatric solid-organ transplant (SOT) recipients. METHODS: Renal, liver, or intestinal transplant recipients < 21 years of age followed at Seattle Children's Hospital were enrolled from August 2020 to May 2021. Blood samples were collected at ~6-month intervals for up to 3 years and tested for antinucleocapsid (N) antibodies. COVID-19 vaccination data were collected from the Washington State Immunization Information System and/or the medical record. Semi-quantitative anti-S IgG testing was performed on all postvaccine samples using the Abbott Architect platform. We further evaluated a subset of postvaccine samples using variant-specific quantitative binding (Meso Scale Discovery, MSD) immunoassays and pseudovirus-neutralization assays. Antibody levels were compared over time and by vaccine category. RESULTS: We followed 83 SOT recipients for a median of 12.5 months (IQR 7.0, 28.3). Overall, 16 (19.3%) participants had evidence of SARS-CoV-2 infection based on anti-N antibody detection. Forty-six (55%) participants had a blood sample collected > 14 days after receipt of a vaccination. Serum IgG to spike antigens (anti-S antibody) increased following vaccination and increased with the number of vaccine doses received as assessed by both the Abbott and MSD assays. Neutralizing activity was significantly lower against the Omicron subvariants compared to the ancestral strain. CONCLUSION: Pediatric SOT recipients demonstrated strong antibody responses following SARS-CoV-2 vaccination, with higher anti-S antibody responses following > 2 doses of vaccine. Our study offers unique longitudinal immune response data in this vulnerable patient population.

Numerous studies have investigated vaccine-induced correlates of protection (CoP) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, but data on infection-induced CoP are limited. Given differences between vaccine- and infection-induced immune responses, in conjunction with low vaccination in many US populations, a better understanding of infection-induced CoP is needed. We used residual sera from a mid-2020 Rhode Island serosurvey of healthcare professionals (HCP) and corresponding state-collected SARS-CoV-2 testing data through February 2021 to generate an analytic cohort of HCP with a first SARS-CoV-2 infection prior to serosurvey blood collection and multiple viral tests after blood collection to assess for reinfection (defined as a positive viral test ≥90 days after their first positive). We tested sera for levels of IgG and IgA targeting ancestral spike (S), receptor-binding domain (RBD), or nucleocapsid (N). We used adjusted Cox proportional hazard ratios to assess the association between categorical antibody level and the risk of subsequent reinfection. Among 170 HCP included in this analysis (median age = 47 years; interquartile range: 35-55 years), 30 were reinfected during the analytic period. Adjusted Cox proportional hazard ratios indicated that higher levels of anti-S or anti-RBD IgG were significantly associated with a lower risk of reinfection. These findings support the use of anti-S or anti-RBD IgG levels as markers of immunologic protection, such as in population serosurveys, or immune-bridging studies in settings of high prevalence of prior infection.  IMPORTANCEThe measurement of antibodies in blood is a relatively simple process and commonly used to estimate overall levels of past infection in populations. But, if someone has antibodies, does this mean that they are protected from being infected again? And are people with higher levels of antibody better protected? There are good data in the literature exploring how antibodies from the coronavirus disease 2019 (COVID-19) vaccination are associated with protection. But, there is still a lot to learn about protection conferred by antibodies that develop after a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. In our study, we measure the levels of six different antibody types developed after infection and compare levels to the risk of subsequent infection to better understand which antibody types are best associated with protection. Our data are important for improving studies that use antibodies as proxies for protection, such as population immunity estimates, or those assessing new prevention products.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

To understand how coronavirus disease 2019 vaccines impact infection risk in children &lt;5 years, we assessed risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from September 2022 to April 2023 in 3 cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in naïve young children.

Purpose: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort. Design: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. MethodsThis analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity.

BACKGROUND: Understanding the risk of hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can guide effective public health interventions and severity assessments. This study calculated infection-hospitalization ratios (IHRs) and infection-case ratios (ICRs) to understand the relationship between SARS-CoV-2 infections, cases, and hospitalizations among different age groups during periods of Delta and Omicron variant predominance. METHODS: After calculating antinucleocapsid SARS-CoV-2 antibody seroprevalence using residual commercial laboratory serum specimens, 2 ratios were computed: (1) IHRs using coronavirus disease 2019 hospitalization data and (2) ICRs using Centers for Disease Control and Prevention surveillance data. Ratios were calculated across age groups (0-17, 18-49, 50-69, and ≥70 years) for 2 time periods (September-December 2021 [Delta] and December 2021-February 2022 [Omicron]). RESULTS: Pediatric IHRs increased from 76.7 during Delta to 258.4 during Omicron. Adult IHRs ranged from 3.0 (≥70 years) to 21.6 (18-49 years) during Delta and from 10.0 (≥70 years) to 119.1 (18-49 years) during Omicron. The pediatric ICR was lower during the Delta period (2.7) compared with the Omicron period (3.7). Adult ICRs (Delta: 1.1 [18-49 years] to 2.1 [70+ years]; Omicron: 2.2 [>70+ years] to 2.9 [50-69 years]) were lower than pediatric ICRs during both time periods. CONCLUSIONS: All age groups exhibited a lower proportion of infections associated with hospitalization in the Omicron period than the Delta period; the proportion of infections associated with hospitalization increased with each older age group. A lower proportion of SARS-CoV-2 infections were associated with reported cases in the Omicron period than in the Delta period among all age groups.

BACKGROUND: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. METHODS: We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. RESULTS: Among 3,344 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 12.3-55.7%) within 7-59 days of vaccination and 21.1% (95% CI: -0.5-37.1%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose ≥180 days prior. Overall, adjusted VE of bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI: 46.0-74.5%) within 7-179 days of vaccination and 39.4% (95% CI: 12.5-61.6%) ≥180 days compared to naïve participants who were unvaccinated/received a monovalent vaccine dose ≥180 days prior. CONCLUSIONS: Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

Understanding the dynamics of antibody responses following vaccination and SARS-CoV-2 infection is important for informing effective vaccination strategies and other public health interventions. This study investigates SARS-CoV-2 antibody dynamics in a Puerto Rican cohort, analyzing how IgG levels vary by vaccination status and previous infection. We assess waning immunity and the distribution of hybrid immunity with the aim to inform public health strategies and vaccination programs in Puerto Rico and similar settings. We conducted a prospective, longitudinal cohort study to identify SARS-CoV-2 infections and related outcomes in Ponce, Puerto Rico, from June 2020-August 2022. Participants provided self-collected nasal swabs every week and serum every six months for RT-PCR and IgG testing, respectively. IgG reactivity against nucleocapsid (N) antigens, which generally indicate previous infection, and spike (S1) and receptor-binding domain (RBD) antigens, which indicate history of either infection or vaccination, was assessed using the Luminex Corporation xMAP® SARS-CoV-2 Multi-Antigen IgG Assay. Prior infection was defined by positive RT-PCRs, categorized by the predominant circulating SARS-CoV-2 variant at the event time. Demographic information, medical history, and COVID-19 vaccination history were collected through standardized questionnaires. Of 882 participants included in our analysis, 34.0% experienced at least one SARS-CoV-2 infection, with most (78.7%) occurring during the Omicron wave (December 2021 onwards). SARS-CoV-2 antibody prevalence increased over time, reaching 98.4% by the final serum collection, 67.0% attributable to vaccination alone, 1.6% from infection alone, and 31.4% from both. Regardless of prior infection status, RBD and S1 IgG levels gradually declined following two vaccine doses. A third dose boosted these antibody levels and showed a slower decline over time. N-antibody levels peaked during the Omicron surge and waned over time. Vaccination in individuals with prior SARS-CoV-2 infection elicited the highest and most durable antibody responses. N or S1 seropositivity was associated with lower odds of a subsequent positive PCR test during the Omicron period, with N antibodies showing a stronger association. By elucidating the differential decay of RBD and S1 antibodies following vaccination and the complexities of N-antibody response following infection, this study in a Puerto Rican cohort strengthens the foundation for developing targeted interventions and public health strategies.

To understand how COVID-19 vaccines impact infection risk in children <5 years, we assessed risk of SARS-CoV-2 infection from Sept 2022-April 2023 in three cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in young children.

In most persons, human parvovirus B19 (B19) causes a mild respiratory illness, but infection can result in adverse health outcomes in persons who are pregnant, immunocompromised, or who have chronic hemolytic blood disorders. During the first quarter of 2024, several European countries reported increases in B19 activity. In the United States, there is no routine surveillance for B19. To assess increases in B19 activity in the United States, trends in testing and results from two independent populations were examined: 1) the presence of immunoglobulin (Ig) M antibodies, a marker of recent infection, in clinical specimens ordered by physicians and 2) B19 nucleic acid amplification testing (NAAT) in pooled donor source plasma from a large commercial laboratory during 2018-2024. The proportion of IgM-positive clinical specimens reached 9.9% in the second quarter (Q2) of 2024 after remaining <1.5% during 2020-2023 and was higher than Q2 peaks in 2018 (3.8%, p<0.001) and 2019 (5.1%, p<0.001). The prevalence of B19-NAAT-positive donor pools (512 donations per pool) reached 20% in June 2024 after remaining <2% during 2020-2023 and was higher than peaks in 2018 (6.7%, p<0.001) and 2019 (7.3%, p<0.001). Considering the B19 activity increase in the United States in 2024, promotion of measures to prevent respiratory viruses and monitor for adverse B19-related outcomes by health care providers and public health authorities might reduce adverse health outcomes in pregnant persons and others at increased risk.

SARS-CoV-2 antibody kinetics based on immunologic history is not fully understood. We analyzed anti-spike and anti-nucleocapsid antibody responses following acute infection in a cohort of Indigenous persons. The models of peak concentrations and decay rates estimated that one year after infection, participants would serorevert for anti-nucleocapsid antibodies and remain seropositive for anti-spike antibodies. The peak anti-spike concentrations were higher for individuals vaccinated prior to infection, but the decay rates were similar across immunologic status groups. Children had significantly lower peak anti-spike concentrations than adults. This study affirms the importance of continued vaccination to maintain high levels of immunity in the face of waning immunity.

BACKGROUND: The objective of this study was to test the hypothesis that subsequent doses of the coronavirus disease 2019 (COVID-19) vaccine are associated with lower incidence of COVID-19-like symptoms at 6 weeks after infection. METHODS: This study was a case-control analysis of health care personnel in an ongoing multicenter COVID-19 vaccine effectiveness study. We enrolled participants at the time of COVID-19-like symptoms between December 19, 2021, and April 27, 2022, which corresponded to the early Omicron-predominant period after original monovalent severe acute respiratory syndrome coronavirus 2 additional vaccination doses became available. Our outcome was self-reported symptoms completed 6 weeks after the onset of symptoms. RESULTS: We enrolled 2478 participants, of whom 1422 (57%) had COVID-19. The prevalence of symptoms at 6 weeks was 26% (n = 373) in those with COVID-19 and 18% (n = 195) in those without COVID-19. Fatigue (11%) and difficulty sleeping (7%) were most strongly associated with COVID-19. A total of 1643 (66%) participants received a subsequent vaccine dose (after the primary series). Participants with COVID-19 who had received a subsequent vaccination had lower odds of symptoms at 6 weeks (adjusted odds ratio [aOR], 0.55; 95% CI, 0.43-0.70), but this relationship was not observed in those without COVID-19 (aOR, 0.87; 95% CI, 0.59-1.29). CONCLUSIONS: Health care personnel who received subsequent doses of original monovalent COVID-19 vaccine had a lower prevalence of symptoms at 6 weeks than those that did not.

BACKGROUND: Health disparities, leading to worse health outcomes such as elevated COVID-19 mortality rates, are rooted in social and structural factors. These disparities notably impact individuals from lower socioeconomic backgrounds and more socially vulnerable areas. We analyzed the relationship between COVID-19 deaths and social vulnerability using the Minority Health Social Vulnerability Index (MHSVI). METHODS: COVID-19 death data in the U.S. was obtained from the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics, where COVID-19 deaths were defined using the ICD-10 code U07.1. MHSVI composite scores were calculated for 3089 U.S. counties and categorized into social vulnerability quartiles, where values ranged from 0 (lowest vulnerability) to 1 (highest vulnerability). Negative binomial regression was employed to determine death rate ratios for each quartile within each theme. Finally, a multivariate negative binomial regression including all MHSVI sub-themes, excluding the overall index ranking, was used to assess the association between each theme and COVID-19 death rates independently. RESULTS: There were 1,134,272 COVID-19 deaths from January 1, 2020 through June 24, 2023. Adjusted rate ratios for COVID-19 deaths in the overall index ranking were 1.06 (95% CI 0.99-1.13), 1.14 (95% CI 1.06-1.22), and 1.41 (95% CI 1.31-1.52) for the second, third and fourth quartiles, respectively. Sub-themes of socioeconomic status (SES), household characteristics (HC), racial and ethnic minority status (REMS), housing type and transportation (HTT), and medical vulnerability (MV) revealed increasing death rates in higher vulnerability quartiles. The healthcare infrastructure and access (HIA) theme had decreasing death rate ratios of 0.74 (95% CI 0.71-0.78), 0.59 (95% CI 0.56-0.62), and 0.42 (95% CI 0.39-0.44) for the second, third, and fourth quartiles, respectively. Finally, the multivariate analysis showed that the HC, HTT, HIA, and MV themes were associated with COVID-19 deaths (P < 0.05). CONCLUSION: Counties that were identified as more socially vulnerable experienced higher death rates from COVID-19. These areas may need additional public health and social support during future pandemics.

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed.

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

The taxonomy of the Cryptococcus gattii species complex continues to evolve, and has been divided into five pathogenic species. The objective of this systematic review was to summarise the geographical distribution of the C gattii species complex and the species within the C gattii species complex. We searched PubMed for articles related to human, animal, ecological, or laboratory-based studies of C gattii species complex isolates with traceable geographical origin published from January, 1970, until September, 2021. Having extracted their geographical origin, we used ArcMap to construct maps according to the highest degree of resolution allowed by their reported taxonomy, to reflect the most likely area of transmission on the basis of published reports of human isolates. 604 such articles were included in the study. This review indicated that although C gattii species complex isolates have been reported globally, understanding their heterogeneous geographical distribution by species can have implications for researchers and clinicians in formulating research questions and considering diagnostic quandaries.

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. METHODS: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021-August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14-59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. RESULTS: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). CONCLUSIONS: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.

PURPOSE: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort. DESIGN: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. METHODS: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity. RESULTS: Among the 83 SARS-CoV-2 infected participants, 10 (12%) had at least one RNA-positive tears specimen. Amongst these 10, 5 (50%) had concurrent presence of culturable virus, at a median of 7 days postsymptom onset (IQR: 4-7 days) (absolute range: 4-8 days). CONCLUSIONS: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of nonhospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines.

BACKGROUND: The kinetics and durability of T-cell responses to SARS-CoV-2 in children are not well-characterized. We studied a cohort of children aged 6 months to 20 years with COVID-19 in whom peripheral blood mononuclear cells (PBMC) and sera were archived at approximately 1, 6, and 12 months post-symptom onset. METHODS: We compared antibody (N = 85) and T-cell responses (N = 26) to nucleocapsid (N) and spike (S) glycoprotein over time across four age strata: 6 months to 5 years, 5-9, 10-14, and 15-20 years. RESULTS: N-specific antibody responses declined over time, becoming undetectable in 26/32 (81%) children by approximately one year post-infection. Functional breadth of anti-N CD4+ T-cell responses also declined over time and were positively correlated with N-antibody responses (Pearson's r = 0.31, p = 0.008). CD4+ T-cell responses to S displayed greater functional breadth than N in unvaccinated children, and, along with neutralization titers, were stable over time and similar across age strata. Functional profiles of CD4+ T-cell responses against S were not significantly modulated by vaccination. CONCLUSIONS: Our data reveal durable, age-independent T-cell immunity to SARS-CoV-2 structural proteins in children over time following COVID-19 infection as well as S-Ab responses overall, in comparison to declining antibody responses to N.

IMPORTANCE: Access to COVID-19 testing is critical to reducing transmission and supporting early treatment decisions; when made accessible, the timeliness of testing may also be an important metric in mitigating community spread of the infection. While disparities in transmission and outcomes of COVID-19 have been well documented, the extent of timeliness of testing and the association with demographic factors is unclear. OBJECTIVES: To evaluate demographic factors associated with delayed COVID-19 testing among health care personnel (HCP) during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Preventing Emerging Infections Through Vaccine Effectiveness Testing study, a multicenter, test-negative, case-control vaccine effectiveness study that enrolled HCP who had COVID-19 symptoms and testing between December 2020 and April 2022. Data analysis was conducted from March 2022 to Junne 2023. EXPOSURE: Displaying COVID-19-like symptoms and polymerase chain reaction testing occurring from the first day symptoms occurred up to 14 days after symptoms occurred. MAIN OUTCOMES AND MEASURES: Variables of interest included patient demographics (sex, age, and clinical comorbidities) and COVID-19 characteristics (vaccination status and COVID-19 wave). The primary outcome was time from symptom onset to COVID-19 testing, which was defined as early testing (≤2 days) or delayed testing (≥3 days). Associations of demographic characteristics with delayed testing were measured while adjusting for clinical comorbidities, COVID-19 characteristics, and test site using multivariable modeling to estimate relative risks and 95% CIs. RESULTS: A total of 5551 HCP (4859 female [82.9%]; 1954 aged 25-34 years [35.2%]; 4233 non-Hispanic White [76.3%], 370 non-Hispanic Black [6.7%], and 324 non-Hispanic Asian [5.8%]) were included in the final analysis. Overall, 2060 participants (37.1%) reported delayed testing and 3491 (62.9%) reported early testing. Compared with non-Hispanic White HCP, delayed testing was higher among non-Hispanic Black HCP (adjusted risk ratio, 1.18; 95%CI, 1.10-1.27) and for non-Hispanic HCP of other races (adjusted risk ratio, 1.17; 95% CI, 1.03-1.33). Sex and age were not associated with delayed testing. Compared with clinical HCP with graduate degrees, all other professional and educational groups had significantly delayed testing. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of HCP, compared with non-Hispanic White HCP and clinical HCP with graduate degrees, non-Hispanic Black HCP, non-Hispanic HCP of other races, and HCP all other professional and education backgrounds were more likely to have delayed COVID-19 testing. These findings suggest that time to testing may serve as a valuable metric in evaluating sociodemographic disparities in the response to COVID-19 and future health mitigation strategies.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m(2) (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m(2), and CD4 counts <200 cells/μL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/μL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Louisiana experienced high morbidity and mortality from COVID-19. To assess possible explanatory factors, we conducted a cohort study (ClinSeqSer) of patients hospitalized with COVID-19 in New Orleans during August 2020-September 2021. Following enrollment, we reviewed medical charts, and performed SARS-CoV-2 RT-PCR testing on nasal and saliva specimens. We used multivariable logistic regression to assess associations between patient characteristics and severe illness, defined as ≥ 6 L/min oxygen or intubation. Among 456 patients, median age was 56 years, 277 (60.5%) were Black non-Hispanic, 436 (95.2%) had underlying health conditions, and 358 were unvaccinated (92.0% of 389 verified). Overall, 187 patients (40.1%) had severe illness; 60 (13.1%) died during admission. In multivariable models, severe illness was associated with age ≥ 65 years (OR 2.08, 95% CI 1.22-3.56), hospitalization > 5 days after illness onset (OR 1.49, 95% CI 1.01-2.21), and SARS CoV-2 cycle threshold (Ct) result of < 32 in saliva (OR 4.79, 95% CI 1.22-18.77). Among patients who were predominantly Black non-Hispanic, unvaccinated and with underlying health conditions, approximately 1 in 3 patients had severe COVID-19. Older age and delayed time to admission might have contributed to high case-severity. An association between case-severity and low Ct value in saliva warrants further investigation.