Post-acute sequelae of COVID-19 in adults referred to COVID recovery clinic services in an integrated health system in Texas

The epidemiology and organ-specific sequelae following acute illness due to COVID-19 and prompting patients to seek COVID recovery care are not yet well characterized. This cross-sectional study reviewed data on 200 adult patients with prolonged symptoms of COVID-19 (>14 days after symptom onset) not resolved by usual primary care or specialist care who were referred for COVID-specific follow-up. Most patients sought COVID recovery clinic visits within the first 2 months of initial onset of symptoms (median 37 days), with some seeking care for sequelae persisting up to 10 months (median 82 days). At the time of telehealth evaluation, 13% of patients were using home oxygen, and 10% of patients had been unable to return to work due to persistent fatigue and/or subjective cognitive dysfunction ("brain fog"). The prominent specific symptom sequelae prompting patients to seek COVID-specific evaluation beyond usual primary care and specialist referrals were dyspnea, fatigue/weakness, and subjective cognitive dysfunction, irrespective of whether patients had required hospitalization or time since COVID-19 symptom onset

Symptom Clusters Seen in Adult COVID-19 Recovery Clinic Care Seekers

BackgroundCOVID-19 symptom reports describe varying levels of disease severity with differing periods of recovery and symptom trajectories. Thus, there are a multitude of disease and symptom characteristics clinicians must navigate and interpret to guide care.ObjectiveTo find natural groups of patients with similar constellations of post-acute sequelae of COVID-19 (PASC) symptoms.DesignCohort SETTING: Outpatient COVID-19 recovery clinic with patient referrals from 160 primary care clinics serving 36 counties in Texas.PatientsAdult patients seeking COVID-19 recovery clinic care between November 15, 2020, and July 31, 2021, with laboratory-confirmed mild (not hospitalized), moderate (hospitalized), or severe (hospitalized with critical care) COVID-19.Main measuresDemographics, COVID illness onset, and duration of persistent PASC symptoms via semi-structured medical assessments.Key resultsFour hundred forty-one patients (mean age 51.5 years; 295 [66.9%] women; 99 [22%] Hispanic, and 170 [38.5%] non-White, racial minority) met inclusion criteria. Using a k-medoids algorithm, we found that PASC symptoms cluster into two distinct groups: neuropsychiatric (N = 186) (e.g., subjective cognitive dysfunction) and pulmonary (N = 255) (e.g., dyspnea, cough). The neuropsychiatric cluster had significantly higher incidences of otolaryngologic (X2 = 14.3, p < 0.001), gastrointestinal (X2 = 6.90, p = 0.009), neurologic (X2 = 441, p < 0.001), and psychiatric sequelae (X2 = 40.6, p < 0.001) with more female (X2 = 5.44, p = 0.020) and younger age (t = 2.39, p = 0.017) patients experiencing longer durations of PASC symptoms before seeking care (t = 2.44, p = 0.015). Patients in the pulmonary cluster were more often hospitalized for COVID-19 (X2 = 3.98, p = 0.046) and had significantly higher comorbidity burden (U = 20800, p = 0.019) and pulmonary sequelae (X2 = 13.2, p < 0.001).ConclusionsHealth services clinic data from a large integrated health system offers insights into the post-COVID symptoms associated with care seeking for sequelae that are not adequately managed by usual care pathways (self-management and primary care clinic visits). These findings can inform machine learning algorithms, primary care management, and selection of patients for earlier COVID-19 recovery referral.Trial registrationN/A

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus versus Influenza in Adults Hospitalized with Acute Respiratory Illness from a Prospective Multicenter Study

BACKGROUND: Current understanding of severe RSV infections in adults is limited by clinical under-recognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across three respiratory seasons from hospitals participating across all sites of the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN, 2016-2019). All participants were tested for RSV and influenza by RT-PCR. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10,311 hospitalized adults, 6% tested positive for RSV (n=622), 18.8% positive for influenza (n=1,940), and 75.1% negative for RSV and influenza (n=7,749). Congestive Heart Failure (CHF) or Chronic Obstructive Pulmonary Disease (COPD) was more frequent among adults with RSV than influenza (CHF: 37.3% vs. 28.8%, pone week] and mechanical ventilation [OR=1.45 (95% CI: 1.09-1.93)] compared with influenza, but not compared to the influenza negative group [OR=1.03 (95% CI: 0.82-1.28); OR=1.17 (0.91-1.49), respectively.]. CONCLUSIONS: The prevalence of RSV across three recent respiratory illness seasons was considerable. Our findings suggest those with RSV might incur worse outcomes than influenza in hospitalized adults and frequently have pre-existing cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults experiencing severe ARI

Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021–April 2022

BackgroundCoronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines.MethodsBooster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE.ResultsA total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary.ConclusionsVaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric

Effectiveness of mRNA Vaccines Against COVID-19 Hospitalization by Age and Chronic Medical Conditions Burden Among Immunocompetent US Adults, March-August 2021

Vaccine effectiveness (VE) against COVID-19 hospitalization was evaluated among immunocompetent adults (≥18 years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was 96% (95% confidence interval [CI], 93%-98%) among patients with no chronic medical conditions and 83% (95% CI, 76%-88%) among patients with ≥ 3 categories of conditions. VE was similar between those aged 18-64 years versus ≥65 years (P > .05). VE against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing comorbidity burden

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years — IVY Network, 18 States, September 8–November 30, 2022

Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network§ assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5)

Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States

BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64 years, VE was 93 % (95 % CI: 90-94) using syndrome-negative controls and 91 % (95 % CI: 88-93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies

Effectiveness of the Ad26.COV2.S (Johnson & Johnson) COVID-19 Vaccine for Preventing COVID-19 Hospitalizations and Progression to High Disease Severity in the United States

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63-75%) overall, including 55% (29-72%) among immunocompromised patients, and 72% (64-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59-82%]), 91-180 days (71% [60-80%]), and 181-274 days (70% [54-81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18-65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients