Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Routine saliva testing for SARS-CoV-2 in children: Methods for partnering with community childcare centers.

While considerable attention was placed on SARS-CoV-2 testing and surveillance programs in the K-12 setting, younger age groups in childcare centers were largely overlooked. Childcare facilities are vital to communities, allowing parents/guardians to remain at work and providing safe environments for both children and staff. Therefore, early in the COVID-19 pandemic (October 2020), we established a PCR-based COVID-19 surveillance program in childcare facilities, testing children and staff with the goal of collecting actionable public health data and aiding communities in the progressive resumption of standard operations and ways of life. In this study we describe the development of a weekly saliva testing program and provide early results from our experience implementing this in childcare centers. We enrolled children (aged 6 months to 7 years) and staff at seven childcare facilities and trained participants in saliva collection using video chat technology. Weekly surveys were sent out to assess exposures, symptoms, and vaccination status changes. Participants submitted weekly saliva samples at school. Samples were transported to a partnering clinical laboratory or RT-PCR testing using SalivaDirect and results were uploaded to each participant's online patient portal within 24 h. SARS-CoV-2 screening and routine testing programs have focused less on the childcare population, resulting in knowledge gaps in this critical age group, especially as many are still ineligible for vaccination. SalivaDirect testing for SARS-CoV-2 provides a feasible method of asymptomatic screening and symptomatic testing for children and childcare center staff. Given the relative aversion to nasal swabs in younger age groups, an at-home saliva collection method provides an attractive alternative, especially as a routine surveillance tool. Results can be shared rapidly electronically through participants' private medical chart portals, and video chat technology allows for discussion and instruction between investigators and participants. This study fosters a cooperative partnership with participating childcare centers, parents/guardians, and staff with the goal of mitigating COVID-19 transmission in childcare centers. Age-related challenges in saliva collection can be overcome by working with parents/guardians to conceptualize new collection strategies and by offering parents/guardians continued virtual guidance and support.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Telehealth care before and during COVID-19: trends and quality in a large health system.

Objective: COVID-19 accelerated telehealth use to ensure care delivery, but there is limited data on the patient perspective. This study aimed to examine telehealth visit uptake before and during COVID-19 and correlates of patient satisfaction and interest in future telehealth visits. Materials and Methods: This was a cross-sectional observational study between October 2019 and April 2020. Participants included patients who completed satisfaction surveys following telehealth visits. Results: A total of 8930 patients completed the satisfaction survey using 4-point Likert Scales. Multivariable, hierarchical, cumulative logit models were constructed to examine correlates of satisfaction with quality of care and interest in future telehealth visits. Most patients were satisfied with the patient portal, video quality, and instructions (92.7%-96.8%). Almost half reported saving 1-2 h (46.9%). Correlates positively associated with quality of care and interest in future telehealth visits were ease of patient portal (odds ratio [OR], 1.43, 95% confidence interval [CI], 1.30-1.58; OR, 1.56, 95% CI, 1.41-1.73, respectively), video quality (OR, 1.62, 95% CI, 1.50-1.75; OR, 1.26, 95% CI, 1.16-1.37, respectively), instructions (OR, 5.62, 95% CI, 5.05-6.26; OR, 1.80, 95% CI, 1.62-2.01, respectively), and time saved (>4 h: OR, 1.69, 95%,CI, 1.22-2.34; OR, 3.49, 95% CI, 2.47-4.93, respectively). Being seen after the COVID-19 surge in telehealth (OR, 0.76, 95% CI, 0.63-0.93) or by providers with higher visit volume (OR, 0.71, 95% CI, 0.60-0.85) was associated with lower interest in future telehealth visits. Conclusions: Patients expressed relatively high satisfaction levels with telehealth. Better technical quality, quality of instructions, and greater time saved were associated with higher satisfaction ratings. To maintain interest in future telehealth use and improve the patient experience, we must enhance the quality of telehealth delivery platforms and instructions provided to patients.

Practical and Ethical Considerations in Telehealth: Pitfalls and Opportunities

Telehealth has been a long-awaited advancement with the potential to improve efficiency, convenience, and quality in healthcare. However, as telehealth becomes integrated into routine clinical care, it is imperative to consider the practical and ethical implications that could undermine or devalue care delivery. The medical profession must ensure that it is implemented judiciously and with robust quality standards, guided by fair and equitable policies that balance patient autonomy with rigorous standards of care and access. Such a system must recognize the opportunity for more patient input as stakeholders to tailor care to their needs and preferences, while also acknowledging the risk of suboptimal care if convenience is prioritized over quality. More studies of optimal care models are needed to integrate data in terms of both stakeholder input and outcomes.

Characteristics of patients referred to a cardiovascular disease clinic for post-acute sequelae of SARS-CoV-2 infection.

Introduction: There is limited literature on cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). Methods: This observational study aimed to describe the characteristics, diagnostic evaluations, and new cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC, and to identify factors associated with cardiovascular symptoms with no identifiable cardiac pathology. Results: Of 126 patients, average age was 46 years, and 34 % were male. Patients presented on average five months after COVID-19 diagnosis. The most common symptoms were dyspnea (52 %), chest pain/pressure (48 %), palpitations (44 %), and fatigue (42 %), commonly associated with exertion or exercise intolerance. New cardiovascular diseases were present in 23 % of cases. The remainder exhibited common symptoms which we termed "cardiovascular PASC syndrome." Discussion: We found that only one in four patients had a new cardiovascular diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.

Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

Chest pain and coronary endothelial dysfunction after recovery from COVID‐19: A case series

Endothelial cell damage related to coronavirus disease 2019 (COVID‐19) has been described in multiple vascular beds, and many survivors of COVID‐19 report chest pain. This case series describes two previously healthy middle‐aged individuals who survived COVID‐19 and were subsequently found to have symptomatic coronary endothelial dysfunction months after initial infection. COVID‐19 can lead to the development of vascular endothelial dysfunction, which may be present in coronary arteries, and can be uncovered by invasive coronary physiology testing.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With the Risk of Hospitalization and Death in Hypertensive Patients With COVID-19.

Background Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with severe acute respiratory syndrome coronavirus 2 infection who receive angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain. Methods and Results In a propensity score-matched outpatient cohort (January-May 2020) of 2263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS-CoV-2, we determined the association of ACE inhibitors and ARBs with COVID-19 hospitalization. In a concurrent inpatient cohort of 7933 hospitalized with COVID-19, we tested their association with in-hospital mortality. The robustness of the observations was assessed in a contemporary cohort (May-August). In the outpatient study, neither ACE inhibitors (hazard ratio [HR], 0.77; 0.53-1.13, P=0.18) nor ARBs (HR, 0.88; 0.61-1.26, P=0.48) were associated with hospitalization risk. ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61; 0.41-0.93, P=0.02), but not the younger commercially insured group (HR, 2.14; 0.82-5.60, P=0.12; P-interaction 0.09). Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort. In the primary inpatient study cohort, neither ACE inhibitors (HR, 0.97; 0.81-1.16; P=0.74) nor ARBs (HR, 1.15; 0.95-1.38, P=0.15) were associated with in-hospital mortality. These observations were consistent in the validation cohort. Conclusions ACE inhibitors and ARBs were not associated with COVID-19 hospitalization or mortality. Despite early evidence for a potential association between ACE inhibitors and severe COVID-19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.