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.

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.

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.

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.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

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.

IMPORTANCE: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited. OBJECTIVE: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents. DESIGN, SETTING, AND PARTICIPANTS: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms. EXPOSURE: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records. MAIN OUTCOME AND MEASURES: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence. RESULTS: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose. CONCLUSION AND RELEVANCE: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies.

BACKGROUND: The SARS-CoV-2 pandemic has underscored the need for field specimen collection and transport to diagnostic and public health laboratories. Self-collected nasal swabs transported without dependency on a cold chain have the potential to remove critical barriers to testing, expand testing capacity, and reduce opportunities for exposure of health professionals in the context of a pandemic. OBJECTIVE: We compared nasal swab collection by study participants from themselves and their children at home to collection by trained research staff. METHODS: Each adult participant collected 1 nasal swab, sampling both nares with the single swab, after which they collected 1 nasal swab from 1 child. After all the participant samples were collected for the household, the research staff member collected a separate single duplicate sample from each individual. Immediately after the sample collection, the adult participants completed a questionnaire about the acceptability of the sampling procedures. Swabs were placed in temperature-stable preservative and respiratory viruses were detected by shotgun RNA sequencing, enabling viral genome analysis. RESULTS: In total, 21 households participated in the study, each with 1 adult and 1 child, yielding 42 individuals with paired samples. Study participants reported that self-collection was acceptable. Agreement between identified respiratory viruses in both swabs by RNA sequencing demonstrated that adequate collection technique was achieved by brief instructions. CONCLUSIONS: Our results support the feasibility of a scalable and convenient means for the identification of respiratory viruses and implementation in pandemic preparedness for novel respiratory pathogens.

BACKGROUND: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses. METHODS: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022-May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2-4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose. RESULTS: Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%-43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%-65.6%) after 7-59 days to 21.6% (95% CI 5.6%-34.9%) after ≥60 days. CONCLUSIONS: Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines.

BACKGROUND: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals. METHODS: The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses. RESULTS: There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat. CONCLUSIONS: We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19.

Following a nuclear fission event, there likely would be a large number of contaminated persons who would seek assistance at community reception centers to be established outside the affected area. This paper provides a methodology for calculating inhalation doses to public health and other response personnel at such facilities who would be receiving and assisting potentially contaminated persons from whom particles can be resuspended. Three hypothetical facilities were considered: the Base Case is a rather small room with no forced air ventilation. The Preferred Case, which is more realistic, is a mid-sized room with an operating HVAC system with air being recirculated through a filter. The Gymnasium Case has only fresh air intake. Initial bounding calculations for the Base Case indicated the need for pre-screening of arrivals to avoid unacceptable doses to staff. The screening criterion selected was 1.67 × 106 Bq m-2. Calculations are presented for radionuclide concentrations in air, dose to staff from inhalation, and how exposures and the resulting doses can be altered by air-turnover rates and the use of filters with varying efficiency. Doses are presented for various arrival times and for both plutonium- and uranium-fueled detonations. The highest calculated dose via inhalation with no respiratory protection was 0.23 mSv for the Base Case. The more important radionuclides contributing to dose with exposure starting at day D + 1 were 239Np and 133I. At day D + 30, 131I and 140Ba were the more important dosimetrically. The variable creating the highest uncertainty was the slough-off factor for resuspension of contamination from people arriving at the reception center.

Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted &lt; 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value &lt; 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM.

We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79x106 gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1x105 gc/mg-dw and 1.86x103 gc/mgdw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10(4) and 1.4 × 10(4) gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE.

Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*(,)(†).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests. METHODS: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered. RESULTS: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making. CONCLUSIONS: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance.

COVID-19 can lead to severe outcomes in children (1). Vaccination decreases risk for COVID-19 illness, severe disease, and death (2). On December 13, 2020, CDC recommended COVID-19 vaccination for persons aged ≥16 years, with expansion on May 12, 2021, to children and adolescents (children) aged 12-15 years, and on November 2, 2021, to children aged 5-11 years (3). As of March 8, 2023, COVID-19 vaccination coverage among school-aged children remained low nationwide, with 61.7% of children aged 12-17 years and approximately one third (32.7%) of those aged 5-11 years having completed the primary series (3). Intention to receive COVID-19 vaccine and vaccination coverage vary by demographic characteristics, including race and ethnicity and socioeconomic status (4-6). Seattle Public Schools (SPS) implemented a program to increase COVID-19 vaccination coverage during the 2021-22 school year, focusing on children aged 5-11 years during November 2021-June 2022, with an added focus on populations with low vaccine coverage during January 2022-June 2022.(†) The program included strategic messaging, school-located vaccination clinics, and school-led community engagement. Vaccination data from the Washington State Immunization Information System (WAIIS) were analyzed to examine disparities in COVID-19 vaccination by demographic and school characteristics and trends over time. In December 2021, 56.5% of all SPS students, 33.7% of children aged 5-11 years, and 81.3% of children aged 12-18 years had completed a COVID-19 primary vaccination series. By June 2022, overall series completion had increased to 80.3% and was 74.0% and 86.6% among children aged 5-11 years and 12-18 years, respectively. School-led vaccination programs can leverage community partnerships and relationships with families to improve COVID-19 vaccine access and coverage.

BACKGROUND: Data assessing protection conferred from COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection during Delta and Omicron predominance periods in the U.S. are limited. METHODS: This cohort study included persons ≥18 years who had ≥1 healthcare encounter across four health systems and had been tested for SARS-CoV-2 before August 26, 2021. COVID-19 mRNA vaccination and prior SARS-CoV-2 infection defined the exposure. Cox regression estimated hazard ratios (HRs) for the Delta and Omicron periods; protection was calculated as (1-HR)x100%. RESULTS: Compared to unvaccinated and previously uninfected persons, during Delta predominance, protection against COVID-19-associated hospitalizations was high for those 2- or 3-dose vaccinated and previously infected, 3-dose vaccinated alone, and prior infection alone (range:91%-97%, with overlapping 95% confidence intervals (95%CIs)); during Omicron predominance, estimates were lower (range:77%-90%). Protection against COVID-19-associated emergency department/urgent care (ED/UC) encounters during Delta predominance was high for those exposure groups (range:86%-93%); during Omicron predominance, protection remained high for those 3-dose vaccinated with or without a prior infection (76% (95%CI=67%-83%) and 71% (95%CI=67%-73%), respectively). CONCLUSIONS: COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection provided protection against COVID-19-associated hospitalizations and ED/UC encounters regardless of variant. Staying up-to-date with COVID-19 vaccination still provides protection against severe COVID-19 disease, regardless of prior infection.

BACKGROUND: Prisoners generally have a higher prevalence of HIV infection compared to the general population from which they come. Whether this higher prevalence reflects a higher HIV prevalence in those entering prisons or intramural transmission of HIV within prisons or both is unclear. Any of these possibilities would increase the prevalence found in resident prisoners above that in the general population. Moreover, comparisons of HIV prevalence in entrants and residents and in men and women in African prisons are not well documented. The purpose of this study was to estimate and compare the prevalence and risk factors for HIV infection amongst both male as well as female and entrant and resident prisoners in a large Ethiopian Federal Prison. METHODS: We studied consenting prisoners cross-sectionally from August 2014 through November 2016. Prison entrants were screened continuously for HIV infection and its associated risk factors and residents were screened in two waves one year apart. HIV was diagnosed at the prison hospital laboratory based on the Ethiopian national HIV rapid antibody testing protocol. An external, internationally-accredited reference laboratory confirmed results. Agreement of results between the laboratories were assessed. RESULTS: A total of 10,778 participants were screened for HIV. Most participants were young (median age of 26 years, IQR: 21-33), male (84%), single (61%), literate (89%), and urban residents (91%) without prior incarceration (96%). Prevalence of HIV was 3.4% overall. Rates of HIV (p = 0.80) were similar in residents and entrants in wave 1 and in entrants in both waves, but were 1.9-fold higher (5.4% vs 2.8%) in residents than entrants in wave 2 (both p<0.001). At entrance to the prison women were more likely to be HIV+ than men (5.5% in women vs 2.5% in men, p< 0.001). In contrast resident women were less likely to be HIV+, but this difference was not statistically significant (3.2% in women vs 4.3% in men, p = 0.125). Other risk factors associated with HIV infection were increasing age (p<0.001), female gender (p<0.001), marital status (never vs other categories, p = 0.016), smaller number of rooms in their houses pre-imprisonment (p = 0.031), TB diagnosis ever (p<0.001), number of lifetime sex partners (especially having 2-10, p<0.001), and genital ulcer (p = 0.037). CONCLUSIONS: Prevalence of HIV in the residents at this large, central Ethiopian prison was higher than that estimated for the general population and lower than in many other studies from other smaller Ethiopian prisons. A higher prevalence in residents than in entrants were found only in our second wave of screening after one year of continuous screening and treatment, possibly representing increased willingness of residents at increased risk of HIV to participate in the second wave. Thus, this findings did not clearly support intramural transmission of HIV or the effectiveness of screening to reduce prevalence. Finally, the higher HIV prevalence in women than men requires that they be similarly screened and treated for HIV infection.

As COVID-19 cases increased during the first weeks of the pandemic in South Africa, the National Institute of Communicable Diseases requested assistance with epidemiologic and surveillance expertise from the US Centers for Disease Control and Prevention South Africa. By leveraging its existing relationship with the National Institute of Communicable Diseases for >2 months, the US Centers for Disease Control and Prevention South Africa supported data capture and file organization, data quality reviews, data analytics, laboratory strengthening, and the development and review of COVID-19 guidance This case study provides an account of the resources and the technical, logistical, and organizational capacity leveraged to support a rapid response to the COVID-19 pandemic in South Africa.

OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work.

From two SARS-CoV-2 household transmission studies (enrolling April 2020 - January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.