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To the Editor: Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the [...]

After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work. [ABSTRACT FROM AUTHOR]

Background Pretransplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay because of high-risk RVs, we examined the impact of pretransplant RV detection on transplant outcomes in pediatric HCT recipients. Methods This retrospective cohort study included pediatric myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using reverse transcriptase polymerase chain reaction (PCR), regardless of symptoms. Posttransplant outcomes included days alive and out of hospital and progression to lower respiratory tract infection (LRTI). Results Among 310 patients, 134 had an RV detected in the 90 days before HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count <100/mm3, HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus as a virus type, and symptomatic pretransplant upper respiratory tract infection were associated with fewer days alive and out of hospital. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to posttransplant LRTI with the same pretransplant RV if the last positive PCR before HCT was ≤30 days compared with >30 days (P =.007). Conclusions In the setting of recommending HCT delay for high-risk RVs, symptomatic upper respiratory tract infection, including human rhinovirus infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test. [ABSTRACT FROM AUTHOR]

This study examines inequities in access to paid sick leave (PSL) by race/ethnicity, income, and sex and the role of PSL access on leave-taking and care-seeking behaviors among Seattle-area workers in the months leading up to and during the emergence of COVID-19 in the region. Survey responses were collected online and in-person from individuals experiencing acute respiratory illness symptoms between November 2019 and March 2020 as part of a community-based respiratory viral surveillance study. Chi-square tests and log-binomial models were used to assess the association between PSL access and various socioeconomic indicators. A total of 66.6% (n = 2,276) respondents reported access to PSL. Proportionally, access to PSL was highest in respondents identifying as Asian (70.5%), followed by White (68.7%), Latine (58.4%), Multiracial (57.1%), Black (47.1%), and Other (43.1%). Access to PSL increased with household income. Eighty three percent of high-income respondents reported access compared to 52.9% of low-income households. Only 23.3% of the lowest-income households reported access to PSL. Fewer females (65.2%) than males (70.7%) reported access to PSL. Access to PSL is inequitably distributed across income, race/ethnicity, and sex. This study reinforces the vast body of knowledge on how socioeconomic inequalities increase individual and community-level vulnerability to the impacts of infectious disease outbreaks. It also supports the role of labor and economic policy in mitigating (or exacerbating) these impacts. Exemplified by the COVID-19 pandemic, universal access to PSL, especially for marginalized populations, benefits all. [ABSTRACT FROM AUTHOR]

Background SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. Methods This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). Results From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%–56.4%) and 98.8% (95% CI, 98.5%–99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4–7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥ 2 (68.5%) and ≥ 4 (75.8%) days after an initial Ag-RDT-negative result. Conclusions Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV‐1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post‐transplant) who were not taking daily antiviral suppressive therapy. Methods: Participants self‐collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary. Results: Sample collection adherence was high (median 122 swabs/person, range: 85.7%–101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%–33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8–46.1 hrs). Conclusion: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice‐daily sampling may be sufficient to detect most episodes. These data show that self‐collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population. [ABSTRACT FROM AUTHOR]

Background Hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR) T-cell therapy recipients have high morbidity from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are limited data on outcomes from SARS-CoV-2 infection shortly before cellular therapy and uncertainty whether to delay therapy. Methods We conducted a retrospective cohort study of patients with SARS-CoV-2 infection within 90 days before HCT or CAR-T-cell therapy between January 2020 and November 2022. We characterized the kinetics of SARS-CoV-2 detection, clinical outcomes following cellular therapy, and impact on delays in cellular therapy. Results We identified 37 patients (n = 15 allogeneic HCT, n = 11 autologous HCT, n = 11 CAR-T-cell therapy) with SARS-CoV-2 infections within 90 days of cellular therapy. Most infections (73%) occurred between March and November 2022, when Omicron strains were prevalent. Most patients had asymptomatic (27%) or mild (68%) coronavirus disease 2019 (COVID-19). SARS-CoV-2 positivity lasted a median of 20.0 days (interquartile range, 12.5–26.25 days). The median time from first positive SARS-CoV-2 test to cellular therapy was 45 days (interquartile range, 37.75–70 days); 1 patient tested positive on the day of infusion. After cellular therapy, no patients had recrudescent SARS-CoV-2 infection or COVID-19–related complications. Cellular therapy delays related to SARS-CoV-2 infection occurred in 70% of patients for a median of 37 days. Delays were more common after allogeneic (73%) and autologous (91%) HCT compared to CAR-T-cell therapy (45%). Conclusions Patients with asymptomatic or mild COVID-19 may not require prolonged delays in cellular therapy in the context of contemporary circulating variants and availability of antiviral therapies. [ABSTRACT FROM AUTHOR]

A systematic review of randomized and observational studies from 2013 to 2023 demonstrated that antiviral preemptive therapy started at cytomegalovirus viral load thresholds between 2 and 3 log10 IU/mL was associated with similar cytomegalovirus disease rates. Thus, viral thresholds in this range appear to effectively protect patients not receiving prophylaxis. [ABSTRACT FROM AUTHOR]