Ultrasonographic findings in long COVID: A cross-sectional study of 312 patients.

Background: Fatigue and muscle weakness are common complaints in COVID-19 survivors. However, little is still known about the skeletal muscle qualitative and quantitative characteristics after hospitalization due to moderate and severe COVID-19. Objectives: To assess rectus femoris and vastus intermedius muscle thickness (MT) and rectus femoris echo intensity (EI) and to establish its association with demographic, clinical, functional, and inflammatory parameters in long COVID patients after hospital discharge. Methods: Cross-sectional study with 312 COVID-19 patients (53.53% male; age: 54.59 ± 13.50 years), with a laboratory-confirmed diagnosis of COVID-19. Patients were assessed 3-11 months after hospital discharge. We evaluated MT of the right rectus femoris and vastus intermedius and EI of the right rectus femoris using a portable ultrasound system, 6-13 MHz, broadband linear transducer. We corrected EI using the subcutaneous fat thickness. Ultrasonographic parameters were tested in association with demographic (sex and age); functional (Handgrip strength measurement, Timed Up and Go, 1 min Sit-to-Stand test, EuroQoL-5 Dimensions-5 Levels, World Health Organization Disability Assessment Schedule (WHODAS 2.0), Post-COVID-19 Functional Status, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), Medical Research Council (MRC) sum score, Borg Dyspnea Scale, MRC Dyspnea score, Visual Analogue Scale (VAS), Epworth Sleepiness Scale, Insomnia Severity Index, Functional Independence Measurement (FIM), and Functional Oral Intake Scale); clinical (length of hospital stay, intubation, and presence of comorbidities such as systemic hypertension, diabetes, obesity, chronic obstructive pulmonary disease, asthma), and inflammatory data assessed by the C-reactive protein and D-dimer serum concentrations. Results: Rectus femoris MT was associated with age, handgrip strength, Epworth Sleepiness Scale, and subcutaneous fat thickness (r2 = 27.51%; p < 0.0001). Vastus intermedius MT was associated with age, pain intensity, handgrip strength, Epworth Sleepiness scale, FIM, and time since hospital discharge (r2 = 21.12%; p < 0.0001). Rectus femoris EI was significantly associated with the male sex, TUG, Epworth Sleepiness Scale, and C-Reactive Protein levels (r2 = 44.39%; p < 0.0001). Mean MT of rectus femoris and vastus intermedius are significantly different (p < 0.001). Conclusion: After hospital discharge, long COVID patients present qualitative and quantitative skeletal muscle characteristics associated with a combination of demographic, clinical, and functional parameters.

Ultrasonographic findings in long COVID: A cross-sectional study of 312 patients

Background Fatigue and muscle weakness are common complaints in COVID-19 survivors. However, little is still known about the skeletal muscle qualitative and quantitative characteristics after hospitalization due to moderate and severe COVID-19. Objectives To assess rectus femoris and vastus intermedius muscle thickness (MT) and rectus femoris echo intensity (EI) and to establish its association with demographic, clinical, functional, and inflammatory parameters in long COVID patients after hospital discharge. Methods Cross-sectional study with 312 COVID-19 patients (53.53% male;age: 54.59 ± 13.50 years), with a laboratory-confirmed diagnosis of COVID-19. Patients were assessed 3–11 months after hospital discharge. We evaluated MT of the right rectus femoris and vastus intermedius and EI of the right rectus femoris using a portable ultrasound system, 6–13 MHz, broadband linear transducer. We corrected EI using the subcutaneous fat thickness. Ultrasonographic parameters were tested in association with demographic (sex and age);functional (Handgrip strength measurement, Timed Up and Go, 1 min Sit-to-Stand test, EuroQoL-5 Dimensions-5 Levels, World Health Organization Disability Assessment Schedule (WHODAS 2.0), Post-COVID-19 Functional Status, Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT), Medical Research Council (MRC) sum score, Borg Dyspnea Scale, MRC Dyspnea score, Visual Analogue Scale (VAS), Epworth Sleepiness Scale, Insomnia Severity Index, Functional Independence Measurement (FIM), and Functional Oral Intake Scale);clinical (length of hospital stay, intubation, and presence of comorbidities such as systemic hypertension, diabetes, obesity, chronic obstructive pulmonary disease, asthma), and inflammatory data assessed by the C-reactive protein and D-dimer serum concentrations. Results Rectus femoris MT was associated with age, handgrip strength, Epworth Sleepiness Scale, and subcutaneous fat thickness (r2 = 27.51%;p < 0.0001). Vastus intermedius MT was associated with age, pain intensity, handgrip strength, Epworth Sleepiness scale, FIM, and time since hospital discharge (r2 = 21.12%;p < 0.0001). Rectus femoris EI was significantly associated with the male sex, TUG, Epworth Sleepiness Scale, and C-Reactive Protein levels (r2 = 44.39%;p < 0.0001). Mean MT of rectus femoris and vastus intermedius are significantly different (p < 0.001). Conclusion After hospital discharge, long COVID patients present qualitative and quantitative skeletal muscle characteristics associated with a combination of demographic, clinical, and functional parameters.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

Technical performance of a lateral flow immunoassay for detection of anti-SARS-CoV-2 IgG in the outpatient follow-up of non-severe cases and at different times after vaccination: comparison with enzyme and chemiluminescent immunoassays.

This study assessed the technical performance of a rapid lateral flow immunochromatographic assay (LFIA) for the detection of anti-SARS-CoV-2 IgG and compared LFIA results with chemiluminescent immunoassay (CLIA) results and an in-house enzyme immunoassay (EIA). To this end, a total of 216 whole blood or serum samples from three groups were analyzed: the first group was composed of 68 true negative cases corresponding to blood bank donors, healthy young volunteers, and eight pediatric patients diagnosed with other coronavirus infections. The serum samples from these participants were obtained and stored in a pre-COVID-19 period, thus they were not expected to have COVID-19. In the second group of true positive cases, we chose to replace natural cases of COVID-19 by 96 participants who were expected to have produced anti-SARS-CoV-2 IgG antibodies 30-60 days after the vaccine booster dose. The serum samples were collected on the same day that LFIA were tested either by EIA or CLIA. The third study group was composed of 52 participants (12 adults and 40 children) who did or did not have anti-SARS-CoV-2 IgG antibodies due to specific clinical scenarios. The 12 adults had been vaccinated more than seven months before LFIA testing, and the 40 children had non-severe COVID-19 diagnosed using RT-PCR during the acute phase of infection. They were referred for outpatient follow-up and during this period the serum samples were collected and tested by CLIA and LFIA. All tests were performed by the same healthcare operator and there was no variation of LFIA results when tests were performed on finger prick whole blood or serum samples, so that results were grouped for analysis. LFIA's sensitivity in detecting anti-SARS-CoV-2 IgG antibodies was 90%, specificity 97.6%, efficiency 93%, PPV 98.3%, NPV 86.6%, and likelihood ratio for a positive or a negative result were 37.5 and 0.01 respectively. There was a good agreement (Kappa index of 0.677) between LFIA results and serological (EIA or CLIA) results. In conclusion, LFIA analyzed in this study showed a good technical performance and agreement with reference serological assays (EIA or CLIA), therefore it can be recommended for use in the outpatient follow-up of non-severe cases of COVID-19 and to assess anti-SARS-CoV-2 IgG antibody production induced by vaccination and the antibodies decrease over time. However, LFIAs should be confirmed by using reference serological assays whenever possible.

Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome.

Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome. Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis. Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status. Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.

Long-term functioning status of COVID-19 survivors: a prospective observational evaluation of a cohort of patients surviving hospitalisation.

OBJECTIVES: The study investigated the long-term functional status of hospitalised COVID-19 survivors to explore and document their functional situation. DESIGN: This prospective observational study assessed 801 COVID-19 survivors at 3-11 months after hospital discharge. It analyses participants' sociodemographic background, COVID-19 clinical manifestations, and clinical and functional evaluations. SETTING: Tertiary-level university hospital in São Paulo, Brazil. PARTICIPANTS: Study participants are COVID-19 survivors admitted to hospital care for at least 24 hours to treat acute SARS-CoV-2 infection. OUTCOME MEASURES: Epworth Sleepiness Scale, EuroQoL-5 Dimensions-5 Levels, Functional Assessment of Chronic Illness Therapy-Fatigue, Functional Independence Measure, Functional Oral Intake Scale, Handgrip Strength, Insomnia Severity Index, Medical Research Council (MRC) Dyspnea Scale, MRC sum score, Modified Borg Dyspnea Scale, pain Visual Analogue Scale, Post-COVID-19 Functional Status, Timed Up and Go, WHO Disability Assessment Schedule 2.0, 1-Minute Sit to Stand Test. RESULTS: Many participants required invasive mechanical ventilation (41.57%, 333 of 801). Mean age was 55.35±14.58 years. With a mean of 6.56 (SD: 1.58; 95% CI: 6.45 to 6.67) months after hospital discharge, 70.86% (567 of 800) reported limited daily activities, which were severe in 5.62% (45 of 800). They also reported pain and discomfort (64.50%, 516 of 800), breathlessness (64.66%, 514 of 795), and anxiety and depression (57.27%, 457 of 798). Daytime sleepiness and insomnia evaluations showed subthreshold results. Most (92.85%, 727 of 783) participants reported unrestricted oral intake. Data indicated no generalised fatigue (mean score: 39.18, SD: 9.77; 95% CI: 38.50 to 39.86). Assessments showed poor handgrip strength (52.20%, 379 of 726) and abnormal Timed Up and Go results (mean 13.07 s, SD: 6.49). The invasive mechanical ventilation group seemed to have a better handgrip strength however. We found no clear trends of change in their functional status during months passed since hospital discharge. CONCLUSIONS: Muscle weakness, pain, anxiety, depression, breathlessness, reduced mobility, insomnia and daytime sleepiness were the most prevalent long-term conditions identified among previously hospitalised COVID-19 survivors.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Post-acute sequelae of SARS-CoV-2 infection (PASC): a protocol for a multidisciplinary prospective observational evaluation of a cohort of patients surviving hospitalisation in Sao Paulo, Brazil.

INTRODUCTION: COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity. METHODS AND ANALYSES: We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1-2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6-9 months and 12-15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics. ETHICS AND DISSEMINATION: All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples. TRIAL REGISTRATION NUMBER: RBR-8z7v5wc; Pre-results.

Rehabilitation of patients after COVID-19 recovery: An experience at the Physical and Rehabilitation Medicine Institute and Lucy Montoro Rehabilitation Institute.

OBJECTIVES: As patients recovering from the novel coronavirus disease 2019 (COVID-19) present with physical, respiratory, cognitive, nutritional, and swallowing-related impairments and mental health complications, their rehabilitation needs are complex. This study aimed to describe the demographic, clinical, and functional status after the discharge of COVID-19 survivors who underwent intensive multidisciplinary inpatient rehabilitation at the Physical and Rehabilitation Medicine Institute of the University of Sao Paulo Medical School General Hospital and Lucy Montoro Rehabilitation Institute. We determined the most important factors related to the length of inpatient rehabilitation treatment and present the functional outcomes. METHODS: This was a retrospective study based on electronic medical records. In addition to the severity of COVID-19 and length of hospital stay for the management of COVID-19 and comorbidities, we collected sociodemographic data including age, sex, height, and weight. Functional assessments were performed using the Functional Independence Measure (FIM); Short Physical Performance Battery; Montreal Cognitive Assessment; Depression, Anxiety and Stress Scale; Revised Impact of Events Scale; bioelectrical impedance; Functional Oral Intake Scale; oropharyngeal dysphagia classification; and nutritional assessment. RESULTS: There was a significant improvement in FIM before and after inpatient rehabilitation treatment (p<0.0001). Muscle strength and walking capacity were significantly improved (p<0.01). The most important factors related to the length of inpatient rehabilitation treatment were improvement in FIM scores (Spearman's r=0.71) and gain in lean mass (Spearman's r=0.79). CONCLUSIONS: Rehabilitation of patients after COVID-19 recovery improves their functional status and should be considered in the post-acute phase for selected patients with COVID-19.