Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2.

Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used 'omic" assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8+ T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

Adjusting Incidence Estimates with Laboratory Test Performances: A Pragmatic Maximum Likelihood Estimation-Based Approach.

Understanding the incidence of disease is often crucial for public policy decision-making, as observed during the COVID-19 pandemic. Estimating incidence is challenging, however, when the definition of incidence relies on tests that imperfectly measure disease, as in the case when assays with variable performance are used to detect the SARS-CoV-2 virus. To our knowledge, there are no pragmatic methods to address the bias introduced by the performance of labs in testing for the virus. In the setting of a longitudinal study, we developed a maximum likelihood estimation-based approach to estimate laboratory performance-adjusted incidence using the expectation-maximization algorithm. We constructed confidence intervals (CIs) using both bootstrapped-based and large-sample interval estimator approaches. We evaluated our methods through extensive simulation and applied them to a real-world study (TrackCOVID), where the primary goal was to determine the incidence of and risk factors for SARS-CoV-2 infection in the San Francisco Bay Area from July 2020 to March 2021. Our simulations demonstrated that our method converged rapidly with accurate estimates under a variety of scenarios. Bootstrapped-based CIs were comparable to the large-sample estimator CIs with a reasonable number of incident cases, shown via a simulation scenario based on the real TrackCOVID study. In more extreme simulated scenarios, the coverage of large-sample interval estimation outperformed the bootstrapped-based approach. Results from the application to the TrackCOVID study suggested that assuming perfect laboratory test performance can lead to an inaccurate inference of the incidence. Our flexible, pragmatic method can be extended to a variety of disease and study settings.

Incidence and Prevalence of Coronavirus Disease 2019 Within a Healthcare Worker Cohort During the First Year of the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

BACKGROUND: Preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2_ infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of coronavirus disease 2019 (COVID-19) in a US HCW cohort and to identify risk factors associated with infection. METHODS: We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models. RESULTS: A total of 2435 HCWs contributed 768 person-years of follow-up time. We identified 21 of 2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% confidence interval [CI], .53%-1.32%). We identified 70 of 2414 incident infections (2.9%), yielding a cumulative incidence rate of 9.11 cases per 100 person-years (95% CI, 7.11-11.52). Community contact with a known COVID-19 case was most strongly correlated with increased hazard for infection (hazard ratio, 8.1 [95% CI, 3.8-17.5]). High-risk work-related exposures (ie, breach in protective measures) drove an association between work exposure and infection (hazard ratio, 2.5 [95% CI, 1.3-4.8). More cases were identified in HCWs when community case rates were high. CONCLUSIONS: We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections, but contact at work was not unless accompanied by high-risk exposure.

Lay Health Coaching to Increase Appropriate Inhaler Use in COPD: A Randomized Controlled Trial.

PURPOSE: Poor adherence to medications is more prevalent for chronic obstructive pulmonary disease (COPD) than for other chronic conditions and is associated with unfavorable health outcomes. Few interventions have successfully improved adherence for COPD medications; none of these use unlicensed health care personnel. We explored the efficacy of lay health coaches to improve inhaler adherence and technique. METHODS: Within a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from urban, public primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive 9 months of health coaching or usual care. Outcome measures included self-reported adherence to inhaled controller medications in the past 7 days and observed technique for all inhalers. We used generalized linear models, controlling for baseline values and clustering by site. RESULTS: Baseline adherence and inhaler technique were uniformly poor and did not differ by study arm. At 9 months, health-coached patients reported a greater number of days of adherence compared with usual care patients (6.4 vs 5.5 days; adjusted P = .02) and were more likely to have used their controller inhalers as prescribed for 5 of the last 7 days (90% vs 69%; adjusted P = .008). They were more than 3 times as likely to demonstrate perfect technique for all inhaler devices (24% vs 7%; adjusted P = .01) and mastery of essential steps (40% vs 11%; adjusted P <.001). CONCLUSIONS: Health coaching may provide a scalable model that can improve care for people living with COPD.

The impact of increasing general hospital admissions on Consultation-Liaison Psychiatry.

OBJECTIVE: The objective of this study was to identify changes in patients referred to CLP at a typical inner urban teaching hospital over two decades in the context of increased hospital admissions. METHOD: Multivariate analyses were conducted on data collected for all referrals to CLP at Royal Melbourne Hospital between 1998 and 2017. Analyses were conducted with reason for referral, current psychiatric contact, psychiatric diagnosis, discharge destination and follow up as dependent variables, and the year and annual hospital admissions as independent variables. RESULTS: Annual hospital admissions grew at a rate (4.6%), greater than the annual increase in beds (2.0%). Psychosis, suicide attempt, past psychiatric history and behaviour became more common reasons for referral, whilst depression and somatisation became less common. Transfers to and from mental health inpatient units increased. CONCLUSIONS: An increasing proportion of patients seen by CLP have 'acute' problems. Patients with somatisation and depression are seen less frequently. These findings indicate that CLP services need to provide timely assessment and work closely with other elements of the local mental health service in order to optimise patient flow and ensure continuity of care. Local strategies may be required to ensure an adequate breadth of experience for trainees.

Burnout and Health Care Workforce Turnover.

PURPOSE: Levels of burnout among primary care clinicians and staff are alarmingly high, and there is widespread belief that burnout and lack of employee engagement contribute to high turnover of the workforce. Scant research evidence exists to support this assertion, however. METHODS: We conducted a longitudinal cohort study using survey data on burnout and employee engagement collected in 2013 and 2014 from 740 primary care clinicians and staff in 2 San Francisco health systems, matched to employment roster data from 2016. RESULTS: Prevalence of burnout, low engagement, and turnover were high, with 53% of both clinicians and staff reporting burnout, only 32% of clinicians and 35% of staff reporting high engagement, and 30% of clinicians and 41% of staff no longer working in primary care in the same system 2 to 3 years later. Burnout predicted clinician turnover (adjusted odds ratio = 1.57; 95% CI, 1.02-2.40); there was also a strong trend whereby low engagement predicted clinician turnover (adjusted odds ratio with high engagement = 0.58; 95% CI, 0.33-1.04). Neither measure significantly predicted turnover for staff. CONCLUSIONS: High rates of burnout and turnover in primary care are compelling problems. Our findings provide evidence that burnout contributes to turnover among primary care clinicians, but not among staff. Although reducing clinician burnout may help to decrease rates of turnover, health care organizations and policymakers concerned about employee turnover in primary care need to understand the multifactorial causes of turnover to develop effective retention strategies for clinicians and staff.

A Longitudinal Study of Trends in Burnout During Primary Care Transformation.

PURPOSE: The quadruple aim of primary care transformation includes promoting well-being among the primary care workforce. We longitudinally assessed burnout among clinicians and staff in 2 health delivery organizations engaged in primary care redesign guided by a shared transformation model. METHODS: We conducted a descriptive longitudinal study, using repeated cross-sectional measures from 6 waves of surveys of employed primary care clinicians (physicians, nurse practitioners, physician assistants) and staff conducted between 2012 to 2018 in the San Francisco Health Network and in UCSF Health. The 2018 wave had 613 respondents (response rate 88%). Outcome measures were scores on the Maslach Burnout Inventory emotional exhaustion and cynicism subscales. We used regression models to test for time trends in mean scores. RESULTS: Trends in burnout differed by system and occupation. In one system, mean clinician scores steadily improved for emotional exhaustion (P = .04) and cynicism (P = .07). In the other system, clinician burnout scores initially worsened and then returned to baseline levels. In both systems, burnout trends among staff tended to move in the opposite direction from trends among clinicians. CONCLUSIONS: The divergent trends of steady reduction in clinician burnout in one system and clinician burnout getting worse before getting better in the other system suggest that the effects of primary care transformation are influenced by the organizational context. Moreover, practice changes that reduce clinician burnout may not decrease-and may potentially even worsen-burnout among staff. Primary care transformation requires continuing efforts to promote meaningful work and sustainable workloads among all members of the primary care team.

Strategies for recruitment and retention of underrepresented populations with chronic obstructive pulmonary disease for a clinical trial.

BACKGROUND: Recruitment and retention are two significant barriers in research, particularly for historically underrepresented groups, including racial and ethnic minorities, patients who are low-income, or people with substance use or mental health issues. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and disproportionately affects many underrepresented groups. The lack of representation of these groups in research limits the generalizability and applicability of clinical research and results. In this paper we describe our experience and rates of recruitment and retention of underrepresented groups for the Aides in Respiration (AIR) COPD Health Coaching Study. METHODS: A priori design strategies included minimizing exclusion criteria, including patients in the study process, establishing partnerships with the community clinics, and ensuring that the health coaching intervention was flexible enough to accommodate patient needs. RESULTS: Challenges to recruitment included lack of spirometric data in patient records, space constraints at the clinic sites, barriers to patient access to clinic sites, lack of current patient contact information and poor patient health. Of 282 patients identified as eligible, 192 (68%) were enrolled in the study and 158 (82%) completed the study. Race, gender, educational attainment, severity of disease, health literacy, and clinic site were not associated with recruitment or retention. However, older patients were less likely to enroll in the study and patients who used home oxygen or had more than one hospitalization during the study period were less likely to complete the study. Three key strategies to maximize recruitment and retention were identified during the study: incorporating the patient perspective, partnering with the community clinics, and building patient rapport. CONCLUSIONS: While the AIR study included design features to maximize the recruitment and retention of patients from underrepresented groups, additional challenges were encountered and responded to during the study. We also identified three key strategies recommended for future studies of COPD and similar conditions. Incorporating the approaches described into future studies may increase participation rates from underrepresented groups, providing results that can be more accurately applied to patients who carry a disparate burden of disease. TRIAL REGISTRATION: This trial was registered at ClinicalTrial.gov at identifier NCT02234284 on August 12, 2014. Descriptor number: 2.9 Racial, ethnic, or social disparities in lung disease and treatment.

Correction to: Health coaching to improve self-management and quality of life for low income patients with chronic obstructive pulmonary disease (COPD): protocol for a randomized controlled trial.

In the original article [1], the authors reference their intention to use the 'Morisky Medication Adherence Scale'.

Maslach Burnout Inventory and a Self-Defined, Single-Item Burnout Measure Produce Different Clinician and Staff Burnout Estimates.

BACKGROUND: Clinicians and healthcare staff report high levels of burnout. Two common burnout assessments are the Maslach Burnout Inventory (MBI) and a single-item, self-defined burnout measure. Relatively little is known about how the measures compare. OBJECTIVE: To identify the sensitivity, specificity, and concurrent validity of the self-defined burnout measure compared to the more established MBI measure. DESIGN: Cross-sectional survey (November 2016-January 2017). PARTICIPANTS: Four hundred forty-four primary care clinicians and 606 staff from three San Francisco Aarea healthcare systems. MAIN MEASURES: The MBI measure, calculated from a high score on either the emotional exhaustion or cynicism subscale, and a single-item measure of self-defined burnout. Concurrent validity was assessed using a validated, 7-item team culture scale as reported by Willard-Grace et al. (J Am Board Fam Med 27(2):229-38, 2014) and a standard question about workplace atmosphere as reported by Rassolian et al. (JAMA Intern Med 177(7):1036-8, 2017) and Linzer et al. (Ann Intern Med 151(1):28-36, 2009). KEY RESULTS: Similar to other nationally representative burnout estimates, 52% of clinicians (95% CI: 47-57%) and 46% of staff (95% CI: 42-50%) reported high MBI emotional exhaustion or high MBI cynicism. In contrast, 29% of clinicians (95% CI: 25-33%) and 31% of staff (95% CI: 28-35%) reported "definitely burning out" or more severe symptoms on the self-defined burnout measure. The self-defined measure's sensitivity to correctly identify MBI-assessed burnout was 50.4% for clinicians and 58.6% for staff; specificity was 94.7% for clinicians and 92.3% for staff. Area under the receiver operator curve was 0.82 for clinicians and 0.81 for staff. Team culture and atmosphere were significantly associated with both self-defined burnout and the MBI, confirming concurrent validity. CONCLUSIONS: Point estimates of burnout notably differ between the self-defined and MBI measures. Compared to the MBI, the self-defined burnout measure misses half of high-burnout clinicians and more than 40% of high-burnout staff. The self-defined burnout measure has a low response burden, is free to administer, and yields similar associations across two burnout predictors from prior studies. However, the self-defined burnout and MBI measures are not interchangeable.

Patient Engagement in Community Health Center Leadership: How Does it Happen?

Patient engagement in primary care leadership is an important means to involve community voices at community health centers. Federally qualified health centers (FQHCs) are mandated to have patient representation within their governing boards, while practices seeking patient-centered medical home certification receive credit for implementing patient advisory councils (PACs). Our objective was to compare and contrast how community health centers engage patients in clinic management, decision-making and planning within governing boards versus PACs. Qualitative study conducted from August 2016 to June 2017 at community health centers in California, Arizona and Hawaii. We interviewed practice leaders of patient engagement programs at their site. Eligible clinics had patient representatives within their governing board, PAC, or both. We assessed patient demographics, roles and responsibilities of patients participating, and extent of involvement in quality improvement among governing boards versus PACs. We interviewed 19 sites, of which 17 were FQHCs that had governing boards. Of the 17 FQHCs, 11 had also implemented PACs. Two non-FQHC safety-net sites had PACs but did not have governing boards. Governing board members had formal, structured membership responsibilities such as finances and hiring personnel. PAC roles were more flexible, focusing on day-to-day clinic operations. Clinics tended to recruit governing board patient members for their skill set and professional experience; PAC member recruitment focused more on demographic representation of the clinic's patient population. Both groups worked on quality improvement, but governing boards tended to review clinic performance metrics, while PAC members were involved in specific project planning and implementation to improve clinical outcomes and patient experience. Patient involvement in clinic improvement in CHCs includes higher-level decision-making and governance through mechanisms such as governing boards, as well as engagement in day-to-day practice improvement through PACs. These roles offer differing, but valuable insights to clinic programs and policies.

Management of a complex patient - intravenous olanzapine use.

OBJECTIVE:: This case report aims to highlight the challenges faced by mental health clinicians in managing complex medical and psychiatric presentation, with a particular interest in intravenous (IV) olanzapine use outside the emergency department (ED) and intensive care unit setting. CONCLUSION:: There is no current prescribing guideline regarding the use of IV olanzapine for acute agitation associated with schizophrenia and bipolar disorder. Most of the literature available regarding the use of IV olanzapine has originated from studies performed in the ED setting, with the majority of studies reporting a favourable efficacy and safety profile for IV olanzapine. Further research on the utilization of IV olanzapine in the general medical ward is required. Until more data is available, use of IV olanzapine in the acute arousal setting on a general medical ward remains off-label.

Health coaching to improve self-management and quality of life for low income patients with chronic obstructive pulmonary disease (COPD): protocol for a randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) severely hinders quality of life for those affected and is costly to the health care system. Care gaps in areas such as pharmacotherapy, inhaler technique, and knowledge of disease are prevalent, particularly for vulnerable populations served by community clinics. Non-professionally licensed health coaches have been shown to be an effective and cost-efficient solution in bridging care gaps and facilitating self-management for patients with other chronic diseases, but no research to date has explored their efficacy in improving care for people living with COPD. METHOD: This is multi-site, single blinded, randomized controlled trial evaluates the efficacy of health coaches to facilitate patient self-management of disease and improve quality of life for patients with moderate to severe COPD. Spirometry, survey, and an exercise capacity test are conducted at baseline and at 9 months. A short survey is administered by phone at 3 and 6 months post-enrollment. The nine month health coaching intervention focuses on enhancing disease understanding and symptom awareness, improving use of inhalers; making personalized plans to increase physical activity, smoking cessation, or otherwise improve disease management; and facilitating care coordination. DISCUSSION: The results of this study will provide evidence regarding the efficacy and feasibility of health coaching to improve self-management and quality of life for urban underserved patients with moderate to severe COPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02234284 . Registered 12 August 2014.

Rate of community treatment orders and readmission orders following reconfiguration of community mental health services.

OBJECTIVES: Community treatment orders (CTOs) are a controversial practice as they extend the practice of involuntary treatment into the community. This study aimed to determine whether there was a difference in the rate of CTOs and revocation (readmission) orders following the implementation of a recovery-orientated model across four adult mental health services. METHODS: A retrospective cohort study was conducted prior to and after the reconfiguration of services. Population data for those aged 15 to 65 were obtained from a census and rate rates were calculated. RESULTS: Prior to the reconfiguration, there were 893 individuals subject to a CTO and 136 of these individuals had a revocation of their CTO (i.e. were involuntarily readmitted). This represented a rate of 100.8 individuals on CTOs per 100,000 population and a rate of 15.4 revocations per 100,000 population. Following the reconfiguration, the rate of CTOs increased by 10% and there was a trend for the rate of revocation orders to have decreased by 17%. CONCLUSIONS: Rates of CTOs and readmissions varied across services and further research is warranted to identify factors associated with these increased rates. Additionally, the very high rate of CTOs in the catchment areas warrants further examination.

Innovation in public delivery systems: How one safety net hospital implemented new heart monitoring technology.

This case study examines how a public delivery system hospital implemented a heart monitoring patch in place of existing electrocardiogram (ECG) monitoring by pursuing a holistic value proposition. For example, leaders identified opportunity costs embedded in the existing ECG monitoring staffing. Stakeholders also rallied around values such as patient safety, patient experience, and quality of care. Implementation also benefited from external philanthropic and industry partnerships, which facilitated a pilot period to implement new workflows, demonstrate proof-of-concept, and evaluate process improvements. Despite implementation success, ongoing procurement and reimbursement challenges demonstrate the messiness of innovation, even after reaching a "maintenance" phase. Availability of patient-facing material in multiple languages is one example of an implementation gap in safety net settings. New policies by health systems, payers, and others are needed to establish pathways for future high-value innovations.

Pulmonary Specialist-Supported Health Coaching Delivered by Lay Personnel Improves Receipt of Quality Care for Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Purpose: Half of people living with chronic obstructive pulmonary disease (COPD) do not receive high-quality, evidenced-based care as described in international guidelines. We conducted secondary data analysis of a previously published study to assess the ability of a model of lay health coaching to improve provision of guideline-based care in a primary care setting. Methods: As part of a randomized controlled trial, we recruited English- and Spanish-speaking patients with moderate to severe COPD from primary care clinics serving a low-income, predominantly African American population. Participants were randomized to receive usual care or 9 months of health coaching from primary care personnel informed by a pulmonary specialist practitioner. Outcome measures included prescription of appropriate inhaler therapy, participation in COPD-related education, engagement with specialty care, prescription of smoking cessation medications, and patient ratings of the quality of care. Results: Baseline quality measures did not differ between study arms. At 9 months, coached patients were more likely (increase of 9.3% over usual care; P=0.014) to have received guideline-based inhalers compared to those in usual care. Coached patients were more likely to engage with pulmonary specialty care (increase of 8.3% over usual care with at least 1 visit; P=0.04) and educational classes (increase of 5.3% over usual care; P=0.03). Receipt of smoking cessation medications among patients smoking at baseline in the health coaching group increased 21.1 percentage points more than in usual care, a difference near statistical significance (P=0.06). Conclusions: Health coaching may improve the provision of quality chronic illness care for conditions such as COPD.

Association of protective behaviors with SARS-CoV-2 infection: results from a longitudinal cohort study of adults in the San Francisco Bay Area.

PURPOSE: In an effort to decrease transmission during the first years of the COVID-19 pandemic, public health officials encouraged masking, social distancing, and working from home, and restricted travel. However, many studies of the effectiveness of these measures had significant methodologic limitations. In this analysis, we used data from the TrackCOVID study, a longitudinal cohort study of a population-based sample of 3846 adults in the San Francisco Bay Area, to evaluate the association between self-reported protective behaviors and incidence of SARS-CoV-2 infection. METHODS: Participants without SARS-CoV2 infection were enrolled from August to December 2020 and followed monthly with testing and surveys (median of four visits). RESULTS: A total of 118 incident infections occurred (3.0% of participants). At baseline, 80.0% reported always wearing a mask; 56.0% avoided contact with nonhousehold members some/most of the time; 9.6% traveled outside the state; and 16.0% worked 20 or more hours per week outside the home. Factors associated with incident infection included being Black or Latinx, having less than a college education, and having more household residents. The only behavioral factor associated with incident infection was working outside the home (adjusted hazard ratio 1.62, 95% confidence interval 1.02-2.59). CONCLUSIONS: Focusing on protecting people who cannot work from home could help prevent infections during future waves of COVID-19, or future pandemics from respiratory viruses. This focus must be balanced with the known importance of directing resources toward those at risk of severe infections.

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and long COVID patients.

Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as long COVID. The underlying pathophysiology of long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of SARS-CoV-2 infection and certain other post-COVID sequelae, their potential role in long COVID is important to investigate. Here, we apply a well-established, unbiased, proteome-wide autoantibody detection technology (T7 phage-display assay with immunoprecipitation and next-generation sequencing, PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected that separated individuals with prior SARS-CoV-2 infection from those never exposed to SARS-CoV-2, we did not detect patterns of autoreactivity that separated individuals with long COVID from individuals fully recovered from COVID-19. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and long COVID was apparent by this assay.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.

BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity. METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens. RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection. CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.