Delayed recovery from severe acute respiratory syndrome coronavirus-2 related anosmia predicts incomplete olfactory restoration.

OBJECTIVE: This study aimed to assess the olfactory recovery rates and patterns in a cohort of coronavirus disease 2019 positive patients, and to investigate the clinical predictors of poor long-term olfactory restoration. METHODS: An observational retrospective study was conducted on 146 patients between September 2020 and January 2021 at a tertiary referral hospital. Coronavirus disease 2019 positive patients with olfactory dysfunction were sent a modified version of the COVID-19 Anosmia Reporting Tool for Clinicians via e-mail. RESULTS: The difference in median recovery time between complete recovery and incomplete or no recovery was statistically significant. On multivariate analysis, the only significant factor associated with incomplete or no recovery was anosmia duration. CONCLUSION: After a mean time of 5.6 months from severe acute respiratory syndrome coronavirus-2 infection, persistent olfactory disorders were self-reported in 36.7 per cent of patients. Complete recovery was more likely to occur within 15 days. Given the high prevalence of coronavirus disease 2019, a large number of patients are expected to suffer from long-term olfactory morbidity.

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study.

BACKGROUND: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. METHODS: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. RESULTS: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, - 0.19 [- 0.28 to - 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. CONCLUSIONS: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020.

Severity does not impact on exercise capacity in COVID-19 survivors.

BACKGROUND: current data on the impact of acute illness severity on exercise capacity and ventilatory efficiency of COVID-19 survivors, evaluated at cardiopulmonary exercise test (CPET), are limited. METHODS: in this post-hoc analysis of our previous observational, prospective, cohort study on mechanisms of exercise intolerance in COVID-19 survivors, we aimed at evaluating the impact of acute COVID-19 severity on exercise capacity, pulmonary function testing (PFT) and chest computed tomography (CT) outcomes. RESULTS: we enrolled 75 patients (18 with mild-to-moderate disease, 18 with severe disease, and 39 with critical disease). Mean (standard deviation - SD) follow-up time was 97 (26) days. Groups showed a similar PFT and CT residual involvement, featuring a mildly reduced exercise capacity with comparable mean (SD) values of peak oxygen consumption as percentage of predicted (83 (17) vs 82 (16) vs 84 (15), p = 0.895) among groups, as well as the median (interquartile range - IQR) alveolar-arterial gradient for O2 in mmHg at exercise peak (20 (15-28) vs 27 (18-31) vs 26 (21-21), p = 0.154), which was in the limit of normal. In addition, these patients featured a preserved mean ventilatory efficiency evaluated through the slope of the relation between ventilation and carbon dioxide output during exercise (27.1 (2.6) vs 29.8 (3.9) vs 28.3 (2.6), p = 0.028), without a clinically relevant difference. CONCLUSIONS: Disease severity does not impact on exercise capacity in COVID-19 survivors at 3 months after discharge, including a ventilatory response still in the limit of normal.

Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study.

OBJECTIVES: We performed a comprehensive health assessment in mechanically ventilated coronavirus disease 2019 survivors to assess the impact of respiratory and skeletal muscle injury sustained during ICU stay on physical performance at 3 months following hospital discharge. DESIGN: Preregistered prospective observational cohort study. SETTING: University hospital ICU. PATIENTS: All mechanically ventilated coronavirus disease 2019 patients admitted to our ICU during the first European pandemic wave. MEASUREMENTS AND MAIN RESULTS: At 3 months after hospital discharge, 46 survivors underwent a comprehensive physical assessment (6-min walking distance, Medical Research Council sum score and handgrip strength), a full pulmonary function test, and a chest CT scan which was used to analyze skeletal muscle architecture. In addition, patient-reported outcomes measures were collected. Physical performance assessed by 6-minute walking distance was below 80% of predicted in 48% of patients. Patients with impaired physical performance had more muscle weakness (Medical Research Council sum score 53 [51-56] vs 59 [56-60]; p < 0.001), lower lung diffusing capacity (54% [44-66%] vs 68% of predicted [61-72% of predicted]; p = 0.002), and higher intermuscular adipose tissue area (p = 0.037). Reduced lung diffusing capacity and increased intermuscular adipose tissue were independently associated with physical performance. CONCLUSIONS: Physical disability is common at 3 months in severe coronavirus disease 2019 survivors. Lung diffusing capacity and intermuscular adipose tissue assessed on CT were independently associated with walking distance, suggesting a key role for pulmonary function and muscle quality in functional disability.

Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study.

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

The outcome of olfactory impairment in patients with otherwise paucisymptomatic coronavirus disease 2019 during the pandemic.

OBJECTIVE: This study aimed to measure the duration and recovery rate of olfactory loss in patients complaining of recent smell loss as their prominent symptom during the coronavirus disease 2019 outbreak. METHOD: This was a prospective telephone follow-up observational study of 243 participants who completed an online survey that started on 12 March 2020. RESULTS: After a mean of 5.5 months from the loss of smell onset, 98.3 per cent of participants reported improvement with a 71.2 per cent complete recovery rate after a median of 21 days. The chance of complete recovery significantly decreased after 131 days from the onset of loss of smell (100 per cent sensitive and 97.7 per cent specific). Younger age and isolated smell loss were associated with a rapid recovery, whereas accompanying rhinological and gastrointestinal symptoms were associated with longer loss of smell duration. CONCLUSION: Smell loss, occurring as a prominent symptom during the coronavirus disease 2019 pandemic, showed a favourable outcome. However, after 5.5 months from the onset, around 10 per cent of participants still complained of moderate or severe hyposmia.

COVID-19: Recovery from Chemosensory Dysfunction. A Multicentre study on Smell and Taste.

OBJECTIVE/HYPOTHESIS: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease. STUDY DESIGN: Prospective cohort study. METHODS: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities. RESULTS: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction. CONCLUSIONS: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1095-1100, 2021.

Predictors of adverse in-hospital outcome and recovery in patients with diabetes mellitus and COVID-19 pneumonia in Iraq.

BACKGROUND AND AIMS: There is limited data about the prognosis and impact of COVID-19 pneumonia on patients with diabetes mellitus (DM). We aimed to assess blood indices, ECG markers of sudden death and malignant arrhythmias on admission, and diabetes lowering drugs as possible predictors of adverse in-hospital outcome and COVID-19 pneumonia recovery status. METHODS: A retrospective study included patients with newly diagnosed COVID-19 pneumonia from August 20, to October 5, 2020. RESULTS: A total of 192 patients with COVID-19 pneumonia were included in the present study, of whom 67 patients had DM. Low lymphocytes % [0.4(0.1-0.9), P = .011] and QTc interval prolongation [0.4(0.1-0.8), P = .022] were associated with increased length of ICU stay. On the other hand, metformin use [0.3(0.2-4), P = .032] and DPP-4 inhibitors use [0.3(0.2-3), P = .040] were associated with decreased length of ICU stay. QTc interval prolongation [0.4(0.1-0.9), P = .017] was associated with increased length of hospital stay, while using metformin [0.4(0.2-3), P = .022] was associated with decreased length of hospital stay. Low lymphocytes % [0.5(0.4-1.6), P = .001], insulin use [0.4(0.3-5), P = .003], and old age [0.5(0.1-2.3), P = .025] were associated with extensive lung injury. The risk for in-hospital death was associated with high neutrophil% [1(1-1.4), P = .045], while metformin use was associated with decreased risk for in-hospital death [0.1(0.1-0.6), P = .025]. Insulin use [0.3(0.2-4), P = .013] was associated with partial recovery following acute COVID pneumonia. CONCLUSIONS: Metformin and DPP-4 inhibitors use were associated with favorable in-hospital outcomes, while insulin use was associated with extensive lung injury and post-acute COVID-19 pneumonia partial recovery.

Clinical characteristics and short term outcomes after recovery from COVID-19 in patients with and without diabetes in Bangladesh.

BACKGROUND AND AIMS: This study investigated the clinical manifestations, outcomes and long-term complications of COVID-19 inpatients in southern part of Bangladesh while emphasizing on individuals having diabetes. METHODS: A cross-sectional study was conducted for a sample of COVID-19 inpatients across four different hospitals of Bangladesh between April 1and June 30, 2020. Variation in clinical characteristics, contact history, comorbidities, treatment patterns, and immediate post COVID complications were investigated. RESULTS: There were 734 COVID-19 presentations in this study of which 19.8% of patients had diabetes and 76% of the COVID-19 patients were male. Among biochemical parameters, plasma glucose, D-dimer, and Troponin-I levels were significantly elevated amidst the cohort with diabetes. The frequency of patients requiring insulin increased threefold during infection with SARS CoV-2. 1.4% patients developed new onset of diabetes mellitus. A number of COVID-19 patients with diabetes have been suffering from complications post-recovery including pain, discomfort, and sleep disturbance. CONCLUSION: Individuals with diabetes have experienced a severe manifestation of COVID-19 and post disease complications. Further in-depth studies focused on larger sample sizes are entailed to assess the relationships elaborately.

Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19.

BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.

European Society for Neurogastroenterology and Motility recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID-19 pandemic.

BACKGROUND: During the peak of the COronaVIrus Disease 2019 (COVID-19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non-urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH-monitoring probes carry a risk of SARS-CoV-2 spread through droplet formation. METHODS: A panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single-center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients. RESULTS: At a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the healthcare professional(s) involved, provision of the test planning and test units, education and training of staff, and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring, and breath tests. CONCLUSIONS AND INFERENCES: The ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID-19 pandemic and early recovery phase.

A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase.

BACKGROUND: The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals. METHODS: We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center. RESULTS: Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly. CONCLUSIONS AND INFERENCES: Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.