Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.

OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19. METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published. RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time. CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.

High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: A randomized, phase 2, crossover trial.

Background: Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms. Methods: In this placebo-controlled, double-blind, 2 × 2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for 6 weeks, with crossover treatment after a 4-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the 6-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment. Findings: From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods - 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43.06 (95% CI: 40.18; 45.94), and the mean EQ-5D health index was 0.66 (95% CI: 0.64; 0.68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0.01; 95% CI: -0.02; 0.04; p = 0.45) or the change in PCC-related symptom score (with a mean difference of -1.18; 95% CI: -3.54; 1.17; p = 0.32). Interpretation: Based on self-reported data, CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo. However, we observed a significant spontaneous improvement on both scores regardless of treatment during 20 weeks observation. Funding: Placebo and CoQ10 capsules were provided by Pharma Nord, and the trial was supported by grants from the Novo Nordisk Foundation (NNF21OC0066984). This trial is registered with EudraCT, 2020-005961-16 and ClinicalTrials.gov, NCT04960215. The trial is completed.

Outcomes following SARS-CoV-2 infection among individuals living with and without HIV; a Danish nationwide cohort study.

OBJECTIVE: To compare the risk of a positive SARS-CoV-2 test and COVID-19 outcomes in people living with HIV (PLWH) with the general population, and estimate the association with vaccination status. DESIGN: A nationwide, population based, matched cohort study. METHODS: We included all Danish PLWH ≥18 years (n = 5,276) and an age-and sex matched general population cohort (n = 42,308).We used Cox regression analyses to calculate (adjusted) incidence rate ratios [(a)IRR] and further stratified and restricted the analyses. RESULTS: We observed no major difference in risk of first positive SARS-CoV-2 test [aIRR: 0.8 (95%CI: 0.8-0.9)], but a higher risk of first hospital contact with COVID-19 and hospitalization with severe COVID-19 for PLWH vs. controls [IRR: 2.0; (1.6-2.5), 1.8 (1.4-2.3)]. Risk of first hospitalization decreased substantially in PLWH with calendar time [First half of year 2022 vs. 2020 IRR: 0.3; (0.2-0.6)], whereas the risk compared to population controls remained almost 2-fold increased. We did not observe increased risk of death after SARS-CoV-2 infection [aIRR: 0.7 (95%CI: 0.3-2.0)]. Compared to PLWH who had received two vaccines PLWH who receiving a third vaccine had reduced risk of first positive SARS-CoV-2 test, death (individuals ≥60years) and hospitalization [aIRR: 0.9 (0.7-1.0); 0.2 (0.1-0.7); 0.6 (0.2-1.2)]. CONCLUSION: PLWH have almost the same risk of a positive SARS-CoV-2 test as the general population. Although risk of hospital contacts and severe outcomes following SARS-CoV-2 infection is increased, the risk of death does not seem to be substantially increased. Importantly, a third vaccine is associated with reduced risk of infection, and death.

Mental Fatigue, Activities of Daily Living, Sick Leave and Functional Status among Patients with Long COVID: A Cross-Sectional Study.

Studies suggest that persistent symptoms after COVID-19 (long COVID) influence functioning and activities of daily living (ADL). However, it is still uncertain how and to what extent. This study aimed to describe patient-reported mental fatigue, ADL problems, ADL ability, sick leave and functional status among patients with long COVID. In this cross-sectional study, 448 patients, ≥18 years old and referred to occupational therapy at a Danish Post-COVID-19 Clinic, were included. Mental fatigue was measured by the Mental Fatigue Scale, ADL problems and ability were measured by the Canadian Occupational Performance Measure, sick leave was self-reported and functional status was evaluated by the Post-COVID-19 Functional Status Scale. Mean age was 46.8 years, 73% of the patients were female, and 75% suffered from moderate to severe mental fatigue. The majority reported difficulties performing productive and leisure activities. The median performance and satisfaction scores were 4.8 and 3, respectively. In total, 56% of the patients were on sick leave, and 94% were referred to rehabilitation. A decrease in functional status was found between pre-COVID-19 and assessment. Conclusively, the patients were highly affected in their everyday life and had distinct rehabilitation needs. Future research is needed to address causalities and rehabilitation for this patient group.

Cardiac Performance and Cardiopulmonary Fitness After Infection With SARS-CoV-2.

Aims: Persistent cardiac symptoms are an increasingly reported phenomenon following COVID-19. However, the underlying cause of cardiac symptoms is unknown. This study aimed to identify the underlying causes, if any, of these symptoms 1 year following acute COVID-19 infection. Methods and Results: 22 individuals with persistent cardiac symptoms were prospectively investigated using echocardiography, cardiovascular magnetic resonance (CMR), 6-min walking test, cardio-pulmonary exercise testing and electrocardiography. A median of 382 days (IQR 368, 442) passed between diagnosis of COVID-19 and investigation. As a cohort their echocardiography, CMR, 6-min walking test and exercise testing results were within the normal ranges. There were no differences in left ventricular ejection fraction (61.45 ± 6.59 %), global longitudinal strain (19.80 ± 3.12 %) or tricuspid annular plane systolic excursion (24.96 ± 5.55 mm) as measured by echocardiography compared to a healthy control group. VO2 max (2045.00 ± 658.40 ml/min), % expected VO2 max (114.80 ± 23.08 %) and 6-minute distance walked (608.90 ± 54.51 m) exceeded that expected for the patient cohort, whilst Troponin I (5.59 ± 6.59 ng/l) and Nt-proBNP (88.18 ± 54.27 ng/l) were normal. Conclusion: Among a cohort of 22 patients with self-reported persistent cardiac symptoms, we identified no underlying cardiac disease or reduced cardiopulmonary fitness 1 year following COVID-19.

Fatigue Is a Major Symptom at COVID-19 Hospitalization Follow-Up.

Persistent symptoms after hospitalization with COVID-19 are common, but the frequency and severity of these symptoms are insufficiently understood. We aimed to describe symptoms and pulmonary function after hospitalization with COVID-19. Patients hospitalized with COVID-19 in Central Denmark Region were invited for follow-up 3 months after discharge. Clinical characteristics, patient reported outcomes (Fatigue Assessment Scale (FAS), anxiety and depression (HADS)), symptoms, pulmonary function test and 6-min walk test were collected. We included 218 patients (mean age 59.9 (95% CI: 58.2, 61.7), 59% males). Fatigue, dyspnea and impaired concentration were the most prevalent symptoms at follow-up. Using FAS, 47% reported mild-to-moderate fatigue and 18% severe fatigue. Mean HADS was 7.9 (95% CI: 6.9, 8.9). FAS was correlated to HADS (ß = 0.52 (95% CI: 0.44, 0.59, p < 0.001)). Mean DLCO was 80.4% (95% CI: 77.8, 83.0) and 45% had DLCO ˂ 80%. Mean DLCO was significantly reduced in patients treated in the ICU (70.46% (95% CI 65.13, 75.79)). The highest FAS and HADS were seen in patients with the shortest period of hospitalization (2.1 days (95% CI: 1.4, 2.7)) with no need for oxygen. In conclusion, fatigue is a common symptom after hospitalization for COVID-19 and ICU treatment is associated to decreased diffusion capacity.

Long-Term Symptoms among Hospitalized COVID-19 Patients 48 Weeks after Discharge-A Prospective Cohort Study.

Follow-up studies of COVID-19 survivors have been performed to characterize persistence of long-term symptoms, but data are scarce on one year of follow-up. This study provides data from 48 weeks of follow-up after discharge. All patients discharged from the Department of Infectious Diseases at Aarhus University Hospital, Denmark between 1 March and 1 July 2020 were followed for 48 weeks. In total, 45 of 66 eligible patients were interviewed after 48 weeks. The median age was 57 (IQR 51-70) years, the majority were female (53%) and Caucasian (87%). Median BMI was 28.1 (IQR 24.8-32.6) kg/m2. One or more comorbidities were registered among 62% of the patients. In total, 39 out of 45 (87%) interviewed patients reported persistence of at least one symptom 48 weeks after hospitalization with COVID-19. Most frequently reported symptoms were fatigue, dyspnea, and concentration difficulties. This study provides new long-term data following COVID-19, contributing to the accumulating data of COVID-19 sequelae. Many patients suffer long-term sequelae and further research is urgently needed to gain further knowledge of the duration and therapeutic options.

Positive Predictive Value of ICD-10 Diagnosis Codes for COVID-19.

PURPOSE: To examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for Coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Medical record review of all patients assigned a diagnosis code of COVID-19 (DB342A or DB972A) at six Danish departments of infectious diseases from February 27 through May 4, 2020. Confirmed COVID-19 diagnosis was defined as either: 1) definite, a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) on a respiratory sample combined with symptoms suggestive of COVID-19: 2) probable, clinical presentation of COVID-19 without detection of SARS-CoV-2 and no alternative diagnoses considered more likely; or 3) possible, clinical presentation of COVID-19 without detection of SARS-CoV-2, and the patient was discharged or deceased before further investigations were carried out. We computed the PPV with 95% confidence intervals (CI) as the number of patients with confirmed (i.e., definite, probable, and possible) COVID-19 divided by the number of patients assigned a diagnosis code for COVID-19. RESULTS: The study included 710 patients with a median age of 61 years (interquartile range [IQR] 47-74) and 285/710 (40%) were female. COVID-19 was confirmed in 706/710 (99%) with 705/710 (99%) categorized as definite, 1/710 (0.1%) as probable, and 0 patients as possible COVID-19. The diagnosis was disproven in 4/710 (0.6%) patients who were hospitalized due to bacterial pneumonia (n = 2), influenza (n = 1), and urinary tract infection (n = 1). The overall PPV for COVID-19 was 99% (95% CI 99-100) and remained consistently high among all subgroups including sex, age groups, calendar period, and stratified by diagnosis code and department of infectious diseases (range 97-100%). CONCLUSION: The overall PPV of diagnosis codes for COVID-19 in Denmark was high and may be suitable for future registry-based prognosis studies of COVID-19.

Persistent Symptoms in Patients Recovering From COVID-19 in Denmark.

BACKGROUND: Although persistent symptoms after coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on the diversity and duration of symptoms are needed. METHODS: Patients aged ≥18 years with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 who were hospitalized at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, in the period from March 11 to May 15 were offered follow-up after hospitalization. On admission, a comprehensive symptom and medical history was collected, including demographic characteristics, duration of symptoms, comorbidities, and concomitant medications. At discharge, patients were offered follow-up consultations-either by telephone or at an in-person visit-at 6 and 12 weeks at our post-COVID-19 outpatient clinic to assess whether symptoms present at admission had resolved. RESULTS: During the inclusion period, 71 patients were admitted with COVID-19. Of these, 10 patients died, 3 were transferred to another region, 4 declined to participate, and 5 were lost to follow-up before the 12-week evaluation. Thus, 49 patients were included. Overall, 96% reported 1 or more persisting symptoms at 12-week follow-up. The main symptoms were fatigue, dyspnea, cough, chemosensory dysfunction, and headache. CONCLUSIONS: A wide range of persistent symptoms in patients recovering from COVID-19 were present 12 weeks after hospitalization, calling for larger descriptive studies and interdisciplinary research collaborations.

Recovery of Moderate Coronavirus Disease 2019 in a Liver Transplant Recipient on Continued Immunosuppression: A Case Report.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an enormous impact on the world. Owing to limited data available, it remains unclear to what extent liver transplant recipients should be considered at a higher risk of severe disease. We describe a moderate course of coronavirus disease 2019 (COVID-19) in a patient who underwent a liver transplant 2 years earlier because of Budd-Chiari syndrome. The patient presented with malaise, headache, dry cough, and fever for 4 days. Immunosuppressive therapy with tacrolimus and mycophenolate mofetil was continued throughout the course of infection. Oxygen therapy was given for a single night, and the patient gradually recovered with supportive care only. With this case report, we demonstrate that liver transplantation and immunosuppression is not necessarily associated with severe COVID-19 and emphasize that more information on this matter is urgently required. Withdrawal of immunosuppressive therapy could be associated with higher mortality.

Uneventful case of COVID-19 in a kidney transplant recipient.

Kidney transplant recipients have been reported at a particularly high risk of severe COVID-19 illness due to chronic immunosuppression and coexisting conditions. Yet, here we describe a remarkably mild case of COVID-19 in a 62-year-old female who had a kidney transplantation 10 years earlier due to autosomal dominant polycystic kidney disease. The patient was admitted for 1 day; immunosuppressive therapy with tacrolimus and low-dose prednisolone was continued; and the patient recovered successfully without the use of antiviral agents or oxygen therapy. The case demonstrates that kidney transplant recipients are not necessarily severely affected by COVID-19. Withdrawal of immunosuppressive therapy could be associated with poorer outcomes and should not be implemented thoughtlessly.