IMPORTANCE: Evidence is needed on the economic favorability of a 2023-2024 COVID-19 vaccination program to support policy decisions on recommendations for COVID-19 vaccination. OBJECTIVE: To measure the cost-effectiveness of vaccination with a 2023-2024 COVID-19 mRNA vaccine in adults aged 18 years or older compared with no updated vaccination (with a 2023-2024 vaccine). DESIGN, SETTING, AND PARTICIPANTS: This decision analytic modeling study used a simulation model to compare outcomes for hypothetical cohorts of vaccinated and unvaccinated, immunocompetent adults stratified by age (18-49 years, 50-64 years, and >/=65 years). Parameters were drawn from primary and published data to represent characteristics of the US adult population. The interventions included vaccination with a 2023-2024 mRNA vaccine against COVID-19-associated illness compared with no updated vaccination (with a 2023-2024 vaccine) using a 1-year analytic time frame. A phase 2 analysis also considered an intervention strategy of vaccination with an additional dose of 2023-2024 COVID-19 mRNA vaccine. MAIN OUTCOME AND MEASURE: The incremental cost-effectiveness ratio as reported in 2023 US dollars per quality-adjusted life-year. RESULTS: Vaccination averted substantial numbers of cases, hospitalizations, intensive care unit stays, and deaths across age groups. For adults aged 18 to 49 years and 50 to 64 years, vaccination yielded incremental cost-effectiveness ratios of $115 588 and $25 787 per quality-adjusted life-year gained, respectively. For individuals aged 65 years or older, vaccination was cost saving. Sensitivity analyses indicated that the results were most sensitive to the cost per vaccine dose, vaccine effectiveness, and probability of hospitalization. In phase 2 analyses, an additional dose strategy was only economically favorable in higher-risk scenarios for individuals aged 65 years or older. CONCLUSIONS AND RELEVANCE: In this modeling study, economic favorability of COVID-19 vaccination varied by age. Cost-effectiveness results for individuals in the 2 older age groups were favorable and generally robust to changes in parameter inputs, while results for the younger age group were sensitive to parameter input changes. As the evidence base for COVID-19 vaccination and burden of illness evolves, it may be important to continue to update and revise the economic evaluation of vaccination. The Advisory Committee on Immunization Practices considered these results in its decision to recommend vaccination with the 2023 to 2024 COVID-19 mRNA vaccines.

BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC. METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the 6 months following enrollment. Consistent with prior work, LC was defined as ≥3 post-infectious symptoms at 3 months, while those with <3 symptoms were categorized as not having LC. Our primary outcome was to compare the change in visit types between pre- and post-index testing (hospitalization, emergency department visit, office visit, procedure, telehealth, and other). As secondary outcomes, we assessed differences in visit complexity using the summative length of each encounter for each category as a measure of total healthcare usage. RESULTS: A total of 847 participants met inclusion criteria (179 LC, 668 non-LC). When compared with the pre-index period, there was an overall increase in visit numbers of all six visit categories during the post-index period for all groups, most pronounced in office and telehealth visits. When compared with the non-LC group, the LC group was less likely to have ED visits (OR: 0.1; 95% CI 0.0-0.5). However, among those with LC who had at least one hospitalization, they were more likely to have additional hospitalizations (OR: 2.6; 95% CI 1.5-4.6). Visit length for office visits and hospitalization in the LC group was increased when compared with the non-LC group, though this diminished after adjustment for patient baseline characteristics. CONCLUSIONS: All participants who were infected with SARS-CoV-2 had a marked increase in healthcare utilization during the subsequent 180 days. The LC group had significantly higher rates of additional hospitalization compared with those without LC, which may help to inform healthcare resource planning.

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S. METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data. RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to learn with researchers about COVID-19. They expressed divided opinions about the relevance of INSPIRE research questions. They reported difficulties navigating the virtual research platform and the need for making survey participation less cognitively demanding. They sought more regular feedback on study findings. CONCLUSIONS: Our findings offered insights into incorporating decentralized participatory methods in longitudinal research, strengthening reciprocal research communications, making virtual research platforms user-friendly, and employing strategies to reduce participants' cognitive burden in research. POLICY IMPLICATIONS: Longitudinal studies should focus on optimizing these aspects of participant engagement to produce rigorous findings that inform policy and practice on lasting effects of COVID-19 including Long COVID.

IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics. OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status. DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months. SETTING: Participants were recruited across eight US sites. PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey. EXPOSURE: SARS-CoV-2 index status and employment type (essential healthcare worker [HCW], essential non-HCW, and non-essential worker ["general worker"]). MAIN OUTCOMES AND MEASURES: PROMIS-29 (mental and physical health summary) and PROMIS Cognitive SF-CF 8a (cognitive function) scores were assessed at baseline, short-term (3-months), and long-term (12-18 months) timepoints using GEE modeling. RESULTS: Of the 1,463 participants: 53.5% were essential workers (51.4% HCWs, 48.6% non-HCWs) and 46.5% were general workers. Most associations between outcomes and employment type became non-significant after adjusting for sociodemographics, comorbidities, COVID-19 vaccination, and SARS-CoV-2 variant period. However, among COVID-negative participants, essential HCWs had higher cognitive scores at baseline (β: 3.91, 95% CI [1.32, 6.50]), short term: (β: 3.49, 95% CI: [0.80, 6.18]) and long-term: (β: 3.72, 95% CI: [0.98, 6.46]) compared to general workers. Among COVID-positive participants, essential non-HCWs had significantly worse long-term physical health summary scores (β:-1.22, 95% CI: [-2.35, -0.09]) compared to general workers. CONCLUSIONS AND RELEVANCE: Differences in outcomes by worker status were largely explained by baseline characteristics. However, compared to general workers, essential HCW status had higher cognitive function in the absence of SARS-CoV-2 infection at all timepoints, while essential non-HCWs were most vulnerable to poor recovery in long-term physical health following SARS-CoV-2 infection. Preparation efforts for future pandemics may consider enhanced protection and post-infection resources for frontline workers.

INTRODUCTION: Prior research has observed increased risks for numerous chronic conditions among individuals with Long COVID. Chronic conditions have been associated with employment limitations and increased economic hardships. Data from the Behavioral Risk Factor Surveillance System (BRFSS) present an opportunity to examine changes by employment status in the prevalence of a range of chronic conditions between 2019 (pre-pandemic) and, in 2022, by self-reported COVID-19 or Long COVID. METHODS: We assessed the prevalence of chronic conditions in 2022 by employment status and self-reported COVID-19 and Long COVID history using data from BRFSS for adults of prime working age (25-54 years) who were employed for wages, self-employed, unemployed less than 1 year, unemployed 1 year or more, or unable to work. For each chronic condition (coronary heart disease and myocardial infarction [combined], stroke, ever and current asthma, chronic obstructive pulmonary disease, kidney disease, diabetes, and arthritis), we generated adjusted prevalence ratios (aPRs) comparing 2022 prevalence by COVID-19/Long COVID category to prevalences among respondents in that employment status before the pandemic (2019). RESULTS: The prevalence of both asthma and diabetes increased significantly between 2019 and 2022 among respondents in all included employment categories and COVID-19/Long COVID histories combined. Among employed respondents with Long COVID in 2022, aPRs using 2019 prevalence figures for all employed respondents as a baseline for comparison had statistically significant elevations for every chronic condition assessed. CONCLUSIONS: The increased prevalence of a range of chronic conditions between 2019 and 2022 among adults with Long COVID may present a burden for individuals, the workplace, the healthcare system, and the economy. Additional research in a longitudinal context could better quantify these associations. Efforts to prevent, identify, and treat Long COVID can reduce this burden.

BACKGROUND: Post-COVID conditions (PCC) have proven difficult to diagnose. In this retrospective observational study, we aimed to characterize the level of variation in PCC diagnoses observed across clinicians from a number of methodological angles and to determine whether natural language classifiers trained on clinical notes can reconcile differences in diagnostic definitions. METHODS: We used data from 519 primary care clinics around the United States who were in the American Family Cohort registry between October 1, 2021 (when the ICD-10 code for PCC was activated) and November 1, 2023. There were 6,116 patients with a diagnostic code for PCC (U09.9), and 5,020 with diagnostic codes for both PCC and COVID-19. We explored these data using 4 different outcomes: 1) Time between COVID-19 and PCC diagnostic codes; 2) Count of patients with PCC diagnostic codes per clinician; 3) Patient-specific probability of PCC diagnostic code based on patient and clinician characteristics; and 4) Performance of a natural language classifier trained on notes from 5,000 patients annotated by two physicians to indicate probable PCC. RESULTS: Of patients with diagnostic codes for PCC and COVID-19, 61.3% were diagnosed with PCC less than 12 weeks after initial recorded COVID-19. Clinicians in the top 1% of diagnostic propensity accounted for more than a third of all PCC diagnoses (35.8%). Comparing LASSO logistic regressions predicting documentation of PCC diagnosis, a log-likelihood test showed significantly better fit when clinician and practice site indicators were included (p < 0.0001). Inter-rater agreement between physician annotators on PCC diagnosis was moderate (Cohen's kappa: 0.60), and performance of the natural language classifiers was marginal (best AUC: 0.724, 95% credible interval: 0.555-0.878). CONCLUSION: We found evidence of substantial disagreement between clinicians on diagnostic criteria for PCC. The variation in diagnostic rates across clinicians points to the possibilities of under- and over-diagnosis for patients.

BACKGROUND: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance. METHODS: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression. RESULTS: Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16-.85], 0.56 [.32-.97], and 0.48 [.25-.91], respectively). CONCLUSIONS: COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.

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.

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.

CONTEXT: Little is known about when and how the ICD-10-CM diagnosis code for Post-COVID Conditions (PCC; U09.9) is being used to document PCC. OBJECTIVES: To examine the use and characteristics of clinical coding for PCC. DESIGN: A retrospective cohort. SETTING: Transaction-level medical encounters, laboratory testing results, pharmacy claims, and medical claims for inpatient and outpatient care from the HealthVerity database. PARTICIPANTS: 382 400 US adults and children with private health insurance, Medicare, and Medicaid who had U09.9 code documented during October 1, 2021-June 30, 2023. OUTCOME MEASURES: Count of first use of the U09.9 code, (a) overall, over time, and proportion by provider type; (b) prevalence of PCC-associated incident conditions co-documented with U09.9; (c) number of documented SARS-CoV-2 infections preceding U09.9; (d) timing between infection and U09.9; (e) encounters during the 6 months following first use of U09.9. RESULTS: Overall, 0.6% of 65 556 068 patients had a PCC diagnosis code (64.6% female; 6 in 10 had ≥1 preexisting conditions). The highest count of new U09.9 codes occurred during Quarter 1 and Quarter 3 of 2022 and was documented by a variety of provider specialties. The most prevalent co-documented PCC-associated incident conditions were respiratory (13.4%) and malaise and fatigue (7.8%). Only 62% of patients had SARS-CoV-2 infection documented preceding U09.9; median time to PCC documentation was 17.0 days (interquartile range [IQR] = 5.0, 61.0). Patients with ≥1 encounters during which PCC was documented in the 6 months following their index encounter (n = 109 794) had, on average, 25.5 additional encounters (median = 14 [IQR = 7, 29]). CONCLUSIONS: Our study describes the sociodemographic characteristics, complex clinical manifestations, and high healthcare use of patients following a PCC diagnosis. These findings may inform efforts to identify and treat PCC, inform healthcare planning, and support efforts to educate clinicians about the definition of PCC and accurate application of the code.

OBJECTIVES: Direct electronic access to multiple electronic health record (EHR) systems through patient portals offers a novel avenue for decentralized research. Given the critical value of patient characterization, we sought to compare computable evaluation of health conditions from patient-portal EHR against the traditional self-report. MATERIALS AND METHODS: In the nationwide Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study, which linked self-reported questionnaires with multiplatform patient-portal EHR data, we compared self-reported health conditions across different clinical domains against computable definitions based on diagnosis codes, medications, vital signs, and laboratory testing. We assessed their concordance using Cohen's Kappa and the prognostic significance of differentially captured features as predictors of 1-year all-cause hospitalization risk. RESULTS: Among 1683 participants (mean age 41 ± 15 years, 67% female, 63% non-Hispanic Whites), the prevalence of conditions varied substantially between EHR and self-report (-13.2% to +11.6% across definitions). Compared with comprehensive EHR phenotypes, self-report under-captured all conditions, including hypertension (27.9% vs 16.2%), diabetes (10.1% vs 6.2%), and heart disease (8.5% vs 4.3%). However, diagnosis codes alone were insufficient. The risk for 1-year hospitalization was better defined by the same features from patient-portal EHR (area under the receiver operating curve [AUROC] 0.79) than from self-report (AUROC 0.68). DISCUSSION: EHR-derived computable phenotypes identified a higher prevalence of comorbidities than self-report, with prognostic value of additionally identified features. However, definitions based solely on diagnosis codes often undercaptured self-reported conditions, suggesting a role of broader EHR elements. CONCLUSION: In this nationwide study, patient-portal-derived EHR data enabled extensive capture of patient characteristics across multiple EHR platforms, allowing better disease phenotyping compared with self-report.

Background: Although short-term outcomes of Long COVID have been described, longer-term physical and mental health outcomes of Long COVID are less well-established. This study sought to assess differences in long-term physical and mental health outcomes extending up to three years among those with current, resolved, and no Long COVID, as well as duration of Long COVID and vaccination status. Methods: This was a prospective, multisite, study of participants with SARS-CoV-2 infection from 12/7/2020-8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by Long COVID status (never-had, resolved, current), Long COVID duration and vaccination status. Findings: Of 3663 participants, 2604 (71.1%) never had Long COVID, 994 (27.1%) reported current Long COVID, and 65 (1.8%) reported resolved Long COVID. Compared to never having Long COVID, current Long COVID had lower/worse scores for Patient-Reported Outcomes Measurement Information System (PROMIS) version 29 Physical (7.8; 95% confidence interval [CI] 7.3–8.3) and Mental Health (9.4; 95% CI 8.8–10.1) and higher likelihood of moderate-to-high stress (adjusted odds ratio [aOR]: 2.0; 95% CI 1.6–2.4), moderate-to-high loneliness (aOR: 1.6; 95% CI 1.4–2.0), moderate-to-severe fatigue (aOR: 3.0; 95% CI 2.5–3.7), insufficient activity (aOR for Speedy Nutrition and Physical Activity Assessment ≤4: 0.6; 95% CI 0.5–0.7; aOR for Exercise Vital Sign ≤150 min/week: 0.7, 95% CI 0.6–1.0), and worse dyspnea (aOR: 5.0; 95% CI 4.3–5.8). Resolved Long COVID had lower scores for PROMIS Physical by 2.0 (95% CI 0.2–3.8) and Mental Health by 2.3 (95% CI 0.2–4.4) than the never-had-Long COVID cohort. Number of COVID-19 vaccinations was associated with better outcomes across all measures. Interpretation: Among participants followed up to 3 years after initial infection, those with current Long COVID had worse physical and mental health outcomes. The majority of those with Long COVID did not resolve, with less than 2% having resolved Long COVID. The resolved Long COVID cohort had moderately worse physical and mental health compared with those never-having-Long COVID. COVID-19 vaccination was associated with better outcomes. Funding: Centers for Disease Control and Prevention. © 2025 The Author(s)

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.

IMPORTANCE: An estimated 1% to 3% of children with SARS-CoV-2 infection will develop post-COVID-19 condition (PCC). OBJECTIVE: To evaluate the odds of PCC among children with COVID-19 vaccination prior to SARS-CoV-2 infection compared with odds among unvaccinated children. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, children were enrolled in a multisite longitudinal pediatric cohort from July 27, 2021, to September 1, 2022, and followed up through May 2023. Analysis used a case (PCC reported)-control (no PCC reported) design and included children aged 5 to 17 years whose first real time-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection occurred during the study period, who were COVID-19 vaccine age-eligible at the time of infection, and who completed a PCC survey at least 60 days after infection. From December 1, 2022, to May 31, 2023, children had weekly SARS-CoV-2 testing and were surveyed regarding PCC (≥1 new or ongoing symptom lasting ≥1 month after infection). EXPOSURES: COVID-19 mRNA vaccination status at time of infection was the exposure of interest; participants were categorized as vaccinated (≥2-dose series completed ≥14 days before infection) or unvaccinated. Vaccination status was verified through vaccination cards or vaccine registry and/or medical records when available. MAIN OUTCOME AND MEASURES: Main outcomes were estimates of the odds of PCC symptoms. Multivariate logistic regression was performed to estimate the odds of PCC among vaccinated children compared with odds of PCC among unvaccinated children. RESULTS: A total of 622 participants were included, with 28 (5%) case participants and 594 (95%) control participants. Median (IQR) age was 10.0 (7.0-11.9) years for case participants and 10.3 (7.8-12.7) years for control participants (P = .37). Approximately half of both groups reported female sex (13 case participants [46%] and 287 control participants [48%]). Overall, 57% of case participants (16 children) and 77% of control participants (458 children) were vaccinated (P = .05). After adjusting for demographic characteristics, number of acute COVID-19 symptoms, and baseline health, COVID-19 vaccination was associated with decreased odds of 1 or more PCC symptom (adjusted odds ratio [aOR], 0.43; 95% CI, 0.19-0.98) and 2 or more PCC symptoms (aOR, 0.27; 95% CI, 0.10-0.69). CONCLUSIONS AND RELEVANCE: In this study, mRNA COVID-19 vaccination was associated with reduced odds of PCC in children. The aORs correspond to an estimated 57% and 73% reduced likelihood of 1 or more and 2 or more PCC symptoms, respectively, among vaccinated vs unvaccinated children. These findings suggest benefits of COVID-19 vaccination beyond those associated with protection against acute COVID-19 and may encourage increased pediatric uptake.

INTRODUCTION: While various demographic factors and underlying medical conditions are associated with the development of post-COVID conditions within a month after SARS-CoV-2 infection, less is known about factors associated with post-COVID symptoms that persist for 6 months or more. The aim of this review was to determine the association between underlying conditions, other risk factors, health behaviors, and the presence of symptoms ≥6 months after COVID-19. METHODS: Studies reporting on post-COVID symptoms were searched in databases, including Medline, EMBASE, Global Health, PsycInfo, Scopus, CINAHL, Proquest, and WHO COVID-19 literature, from the beginning of the pandemic until November 2022. Studies were included if they reported on symptoms ≥6 months after COVID-19 and a relevant measure of association (adjusted or unadjusted odds or risk ratio). RESULTS: A total of 17 studies with 109,293 participants met the inclusion criteria; they were conducted in China (3), Italy (3), Spain (3), Russia (2), France (1), Germany (1), Sweden (1), Scotland (1), United Kingdom (1), and the United States (1). When compared to males, female participants were at an increased risk of post-COVID-19 symptoms (risk ratio (RR): 1.24; adjusted odds ratio (aOR): 3.08). Underlying conditions, including COPD/lung disease, overweight status or obesity, hypertension, cardiovascular disease, and asthma, were identified as possibly being associated with an increased risk of post-COVID symptoms. CONCLUSION: Female gender and certain underlying medical conditions were associated with an increased risk of post-COVID symptoms ≥6 months after COVID-19. Further research is needed to better understand some of these associations and identify groups that are at increased risk for persistent post-COVID conditions.

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.

BACKGROUND: Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual's return to pre-COVID health. METHODS: We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual's return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March-December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters. FINDINGS: Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March-December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8-60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health. INTERPRETATION: Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.

This cross-sectional study examines the prevalence of ever and current post–COVID-19 condition (long COVID) and self-reported limitations of activity due to symptoms of post–COVID-19 condition among US adults. | eng

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.

Although most children are spared from developing complications from SARS-CoV-2 infection, some may suffer consequences including Long Covid and multisystem inflammatory syndrome in children (MIS-C). Although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention.

BACKGROUND: Long COVID can lead to functional disabilities and decreased well-being and limit the ability to work. No study has yet assessed associations of SARS-CoV-2-infection and Long COVID with specific measures of well-being and functional disabilities among workers by employment status. METHODS: Using data from the U.S. Behavioral Risk Factor Surveillance System, we assessed the prevalence of functional disabilities and well-being measures among adults of prime working age (25-54 years) by employment status and self-reported COVID-19 and Long COVID history. Within each employment status, we generated adjusted prevalence ratios (aPRs) comparing respondents from each 2022 COVID-19/Long COVID category to respondents in that employment status before the pandemic (2019). RESULTS: In 2022, prevalences of each functional disability except vision and all adverse well-being measures were highest among the 9.2% of respondents reporting a history of Long COVID. For each outcome, prevalences were lowest for workers and highest among those unable to work. 2022 prevalence of cognitive disability (16.4% of employees, 21.4% of the self-employed) and depression (31.2% and 36.4%, respectively) among workers reporting a history of Long COVID were more than double 2019 levels. Increases in cognitive disability and depression were lower but statistically significant among workers not reporting a history of Long COVID. CONCLUSIONS: The high prevalence of functional disabilities and adverse well-being among workers reporting a history of Long COVID have implications for workers and employers. Also concerning are smaller increases among workers not reporting a history of Long COVID, given the large number of affected workers. Mitigating the effects of Long COVID on workers will involve efforts in multiple domains: reducing incidence, increasing healthcare practitioner awareness, improving diagnosis and treatments, and increasing employer awareness of best practices for accommodating workers with Long COVID.

BACKGROUND: Workers in healthcare and other essential occupations had elevated risks for COVID-19 infection early in the pandemic. No survey of U.S. workers to date has comprehensively assessed the prevalence of both COVID-19 and Long COVID across industries and occupations (I&O) at a detailed level. METHODS: Behavioral Risk Factor Surveillance System data for 2022 from 39 states, Guam, and the U.S. Virgin Islands were used to estimate prevalence of self-reported history of COVID-19 and Long COVID, as well as the prevalence of Long COVID among those reporting prior COVID-19, by broad and detailed I&O. Adjusted prevalence ratios were used to compare outcome prevalence in each I&O to prevalence among all other workers combined. RESULTS: By broad I&O, workers in healthcare, protective services, and education had elevated prevalences of COVID-19. The prevalence of Long COVID was elevated in healthcare and protective service but not education workers. Detailed I&O with significantly elevated prevalences of COVID-19 but not Long COVID included Dairy Product Manufacturing industry workers and subsets of mining workers. Both COVID-19 and Long COVID were elevated among bartenders/drinking places and personal care and appearance workers. The prevalence of Long COVID was elevated among farmworkers who reported having had COVID-19. CONCLUSIONS: Industries and occupations with elevated levels of COVID-19 or Long COVID in this study may warrant increased measures to prevent transmission of airborne respiratory viruses. Accommodations are a key component for supporting workers in all workplaces. This new information about the distribution of Long COVID by I&O suggests where employer understanding and implementation of tailored workplace supports and accommodations are most needed to support continued employment of affected workers.

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.

PURPOSE: Limited information is known about the burden of Long COVID by occupation and industry. This study compares the occurrence of self-reported new long-term symptoms lasting 4 weeks or longer among blood donors with and without prior SARS-CoV-2 infection by occupation and industry. METHODS: The American Red Cross invited blood donors 18 years and older who donated during May 4-December 31, 2021 to participate in online surveys. New long-term symptoms lasting 4 weeks or longer were assessed by self-reported occurrence of any of 35 symptoms since March 2020. SARS-CoV-2 infection status was determined by serological testing and self-report. We describe the prevalence of new long-term symptoms by SARS-CoV-2 infection status. We calculate the difference in reported new long-term symptoms by SARS-CoV-2 infection status within occupation and industry categories. RESULTS: Data were collected from 27,907 employed adults - 9763 were previously infected and 18,234 were never infected with SARS-CoV-2. New long-term symptoms were more prevalent among those previously infected compared to the never-infected respondents (45% vs 24%, p < 0.05). Among all respondents, new long-term symptoms by occupation ranged from 26% (installation, maintenance, and repair) to 41% (healthcare support) and by industry ranged from 26% (mining) to 55% (accommodation and food services). New long-term neurological and other symptoms were commonly reported by those previously infected with SARS-CoV-2. DISCUSSION: New long-term symptoms are more prevalent among certain occupation and industry groups, which likely reflects differential exposure to SARS-CoV-2. These findings highlight potential need for workplace accommodations in a variety of occupational settings to address new long-term symptoms.

BACKGROUND: Track PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection). METHODS: The study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection. DISCUSSION: These data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients.

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.

BACKGROUND: Differences in acute COVID-19 associated morbidity based on race, ethnicity, and gender have been well described; however, less is known about differences in subsequent longer term health-related quality of life and well-being. METHODS: This prospective cohort study included symptomatic adults tested for SARS-CoV-2 who completed baseline and 3-month follow-up surveys. Using the PROMIS-29 tool, a validated measure of health and well-being, we compared outcomes at 3 months and change in outcomes from baseline to 3 months among groups with different races, ethnicities, and/or sexes. RESULTS: Among 6044 participants, 4113 (3202 COVID +) were included. Among COVID + participants, compared to non-Hispanic White participants, Black participants had better PROMIS T-scores for cognitive function (3.6 [1.1, 6.2]) and fatigue (- 4.3 [- 6.6, - 2.0]) at 3 months and experienced more improvement in fatigue over 3 months (- 2.7 [- 4.7, - 0.8]). At 3 months, compared with males, females had worse PROMIS T-scores for cognitive function (- 4.1 [- 5.6, - 2.6]), physical function (- 2.1 [- 3.1, - 1.0]), social participation (- 2.8 [- 4.2, - 1.5]), anxiety (2.8 [1.5, 4.1]), fatigue (5.1 [3.7, 6.4]), and pain interference (2.0 [0.9, 3.2]). Females experienced less improvement in fatigue over 3 months (3.1 [2.0, 4.3]). Transgender/non-binary/other gender participants had worse 3-month scores in all domains except for sleep disturbance and pain interference. CONCLUSIONS: Three months after the initial COVID-19 infection, Black participants reported better cognitive function and fatigue, while females and other gender minoritized groups experienced lower well-being. Future studies are necessary to better understand how and why social constructs, specifically race, ethnicity, and gender, influence differences in COVID-19-related health outcomes. Trials Registration ClinicalTrials.gov Identifier: NCT04610515.

IMPORTANCE: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023. EXPOSURE: COVID-19 status (positive vs negative) at enrollment. MAIN OUTCOME AND MEASURES: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms. RESULTS: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]). CONCLUSIONS AND RELEVANCE: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.