The Epidemiology of Long Coronavirus Disease in US Adults.

BACKGROUND: We estimated the prevalence of long COVID and impact on daily living among a representative sample of adults in the United States. METHODS: We conducted a population-representative survey, 30 June-2 July 2022, of a random sample of 3042 US adults aged 18 years or older and weighted to the 2020 US population. Using questions developed by the UK's Office of National Statistics, we estimated the prevalence of long COVID, by sociodemographics, adjusting for gender and age. RESULTS: An estimated 7.3% (95% confidence interval: 6.1-8.5%) of all respondents reported long COVID, corresponding to approximately 18 828 696 adults. One-quarter (25.3% [18.2-32.4%]) of respondents with long COVID reported their day-to-day activities were impacted "a lot" and 28.9% had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection more than 12 months ago. The prevalence of long COVID was higher among respondents who were female (adjusted prevalence ratio [aPR]: 1.84 [1.40-2.42]), had comorbidities (aPR: 1.55 [1.19-2.00]), or were not (vs were) boosted (aPR: 1.67 [1.19-2.34]) or not vaccinated (vs boosted) (aPR: 1.41 [1.05-1.91]). CONCLUSIONS: We observed a high burden of long COVID, substantial variability in prevalence of SARS-CoV-2, and risk factors unique from SARS-CoV-2 risk, suggesting areas for future research. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.

Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

Long-haul COVID: healthcare utilization and medical expenditures 6 months post-diagnosis.

BACKGROUND: Despite extensive evidence that COVID-19 symptoms may persist for up to a year, their long-term implications for healthcare utilization and costs 6 months post-diagnosis remain relatively unexplored. We examine patient-level association of COVID-19 diagnosis association of COVID-19 diagnosis with average monthly healthcare utilization and medical expenditures for up to 6 months, explore heterogeneity across age groups and determine for how many months post-diagnosis healthcare utilization and costs of COVID-19 patients persist above pre-diagnosis levels. METHODS: This population-based retrospective cohort study followed COVID-19 patients' healthcare utilization and costs from January 2019 through March 2021 using claims data provided by the COVID-19 Research Database. The patient population includes 250,514 individuals infected with COVID-19 during March-September 2020 and whose last recorded claim was not hospitalization with severe symptoms. We measure the monthly number and costs of total visits and by telemedicine, preventive, urgent care, emergency, immunization, cardiology, inpatient or surgical services and established patient or new patient visits. RESULTS: The mean (SD) total number of monthly visits and costs pre-diagnosis were .4783 (4.0839) and 128.06 (1182.78) dollars compared with 1.2078 (8.4962) visits and 351.67 (2473.63) dollars post-diagnosis. COVID-19 diagnosis associated with .7269 (95% CI, 0.7088 to 0.7449 visits; P < .001) more total healthcare visits and an additional $223.60 (95% CI, 218.34 to 228.85; P < .001) in monthly costs. Excess monthly utilization and costs for individuals 17 years old and under subside after 5 months to .070 visits and $2.77, persist at substantial levels for all other groups and most pronounced among individuals age 45-64 (.207 visits and $73.43) and 65 years or older (.133 visits and $60.49). CONCLUSIONS: This study found that COVID-19 diagnosis was associated with increased healthcare utilization and costs over a six-month post-diagnosis period. These findings imply a prolonged burden to the US healthcare system from medical encounters of COVID-19 patients and increased spending.

Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

A randomised controlled trial testing the efficacy of Fit after COVID, a cognitive behavioural therapy targeting severe post-infectious fatigue following COVID-19 (ReCOVer): study protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) results in debilitating long-term symptoms, often referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), in a substantial subgroup of patients. One of the most prevalent symptoms following COVID-19 is severe fatigue. Prompt delivery of cognitive behavioural therapy (CBT), an evidence-based treatment that has shown benefit in reducing severe fatigue in other conditions, may reduce post-COVID-19 fatigue. Based on an existing CBT protocol, a blended intervention of 17 weeks, Fit after COVID, was developed to treat severe fatigue after the acute phase of infection with SARS-CoV-2. METHOD: The ReCOVer study is a multicentre 2-arm randomised controlled trial (RCT) to test the efficacy of Fit after COVID on severe post-infectious fatigue. Participants are eligible if they report severe fatigue 3 up to and including 12 months following COVID-19. One hundred and fourteen participants will be randomised to either Fit after COVID or care as usual (ratio 1:1). The primary outcome, the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue), is assessed in both groups before randomisation (T0), directly post CBT or following care as usual (T1), and at follow-up 6 months after the second assessment (T2). In addition, a long-term follow-up (T3), 12 months after the second assessment, is performed in the CBT group only. The primary objective is to investigate whether CBT will lead to a significantly lower mean fatigue severity score measured with the CIS-fatigue across the first two follow-up assessments (T1 and T2) as compared to care as usual. Secondary objectives are to determine the proportion of participants no longer being severely fatigued (operationalised in different ways) at T1 and T2 and to investigate changes in physical and social functioning, in the number and severity of somatic symptoms and in problems concentrating across T1 and T2. DISCUSSION: This is the first trial testing a cognitive behavioural intervention targeting severe fatigue after COVID-19. If Fit after COVID is effective in reducing fatigue severity following COVID-19, this intervention could contribute to alleviating the long-term health consequences of COVID-19 by relieving one of its most prevalent and distressing long-term symptoms. TRIAL REGISTRATION: Netherlands Trial Register NL8947 . Registered on 14 October 2020.

Small fiber neuropathy associated with SARS-CoV-2 infection.

INTRODUCTION/AIMS: The development and persistence of neurological symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is referred to as "long-haul" syndrome. We aimed to determine whether small fiber neuropathy (SFN) was associated with SARS-CoV-2 infection. METHODS: We retrospectively studied the clinical features and outcomes of patients who were referred to us between May 2020 and May 2021 for painful paresthesia and numbness that developed during or after SARS-CoV-2 infection and who had nerve conduction studies showing no evidence of a large fiber polyneuropathy. RESULTS: We identified 13 patients, Eight women and five men with age ranging from 38-67 y. Follow-up duration ranged from 8 to 12 mo. All patients developed new-onset paresthesias within 2 mo following SARS-CoV-2 infection, with an acute onset in seven and co-existing autonomic symptoms in seven. Three patients had pre-existing but controlled neuropathy risk factors. Skin biopsy confirmed SFN in six, all of whom showed both neuropathy symptoms and signs, and two also showed autonomic dysfunction by autonomic function testing (AFT). Of the remaining seven patients who had normal skin biopsies, six showed no clinical neuropathy signs and one exhibited signs and had abnormal AFT. Two patients with markedly reduced intraepidermal nerve fiber densities and one with normal skin biopsy had severe and moderate coronavirus disease 2019 (COVID-19); the remainder experienced mild COVID-19 symptoms. Nine patients received symptomatic neuropathy treatment with paresthesias controlled in seven (77.8%). DISCUSSION: Our findings suggest that symptoms of SFN may develop during or shortly after COVID-19. SFN may underlie the paresthesias associated with long-haul post-COVID-19 symptoms.

Day-by-day symptoms following positive and negative PCR tests for SARS-CoV-2 in non-hospitalized healthcare workers: A 90-day follow-up study.

OBJECTIVE: Our study aimed to compare symptoms day by day for non-hospitalized individuals testing positive and negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In total, 210 positive-test and 630 negative-test healthcare workers in the Central Denmark Region were followed for up to 90 days after testing, between April and June, 2020. Their daily reported COVID-19-related symptoms were compared graphically and by logistic regression. RESULTS: Thirty per cent of the positive-test and close to 0% of the negative-test participants reported a reduced sense of taste and smell during all 90 days (adjusted odds ratio [aOR] 86.07, 95% CI 22.86-323). Dyspnea was reported by an initial 20% of positive-test participants, declining to 5% after 30 days, without ever reaching the level of the negative-test participants (aOR 6.88, 95% CI 2.41-19.63). Cough, headache, sore throat, muscle pain, and fever were temporarily more prevalent among the positive-test participants; after 30 days, no increases were seen. Women and older participants were more susceptible to long-lasting COVID-19 symptoms. CONCLUSION: The prevalence of long-lasting reduced sense of taste and smell is highly increased in mild COVID-19 patients. This pattern is also seen for dyspnea at a low level, but not for cough, sore throat, headache, muscle pain, or fever.

Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments.

Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.

Persistent Antiphospholipid Antibodies, Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome and Post-COVID Syndrome: 1 Year On.

This is the first case report of a patient with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) with multiple persistent antiphospholipid antibody (aPL)-positivity more than a year after illness onset who also meets Global Consensus-2 criteria for mast cell activation syndrome (MCAS), suggesting pathological activation of the acquired and innate immune systems by SARS-CoV-2. While the patient continues to meet criteria for POTS 1 year on, her functional ability has improved significantly with therapy directed at MCAS, POTS and aPL-positivity. LEARNING POINTS: A subset of long-haul COVID-19 patients have postural orthostatic tachycardia syndrome (POTS), which can be diagnosed by a 10-minute in-office stand test.Antiphospholipid antibodies may be associated with POTS in patients with long-haul COVID-19 and have important clinical implications.Mast cell activation syndrome (MCAS) may be associated with long-haul COVID-19 (with or without POTS) and can often be easily treated, including with over-the-counter medications, supplements and dietary changes.