Diaphragm Muscle Weakness Might Explain Exertional Dyspnea 15 Months after Hospitalization for COVID-19.

Rationale: Dyspnea is often a persistent symptom after acute coronavirus disease (COVID-19), even if cardiac and pulmonary function are normal. Objectives: This study investigated diaphragm muscle strength in patients after COVID-19 and its relationship to unexplained dyspnea on exertion. Methods: Fifty patients previously hospitalized with COVID-19 (14 female, age 58 ± 12 yr, half of whom were treated with mechanical ventilation, and half of whom were treated outside the ICU) were evaluated using pulmonary function testing, 6-minute-walk test, echocardiography, twitch transdiaphragmatic pressure after cervical magnetic stimulation of the phrenic nerve roots, and diaphragm ultrasound. Diaphragm function data were compared with values from a healthy control group. Measurements and Main Results: Moderate or severe dyspnea on exertion was present at 15 months after hospital discharge in approximately two-thirds of patients. No significant pulmonary function or echocardiography abnormalities were detected. Twitch transdiaphragmatic pressure was significantly impaired in patients previously hospitalized with COVID-19 compared with control subjects, independent of initial disease severity (14 ± 8 vs. 21 ± 3 cm H2O in mechanically ventilated patients vs. control subjects [P = 0.02], and 15 ± 8 vs. 21 ± 3 cm H2O in nonventilated patients vs. control subjects [P = 0.04]). There was a significant association between twitch transdiaphragmatic pressure and the severity of dyspnea on exertion (P = 0.03). Conclusions: Diaphragm muscle weakness was present 15 months after hospitalization for COVID-19 even in patients who did not require mechanical ventilation, and this weakness was associated with dyspnea on exertion. The current study, therefore, identifies diaphragm muscle weakness as a correlate for persistent dyspnea in patients after COVID-19 in whom lung and cardiac function are normal. Clinical trial registered with www.clinicaltrials.gov (NCT04854863).

[Weaning from prolonged mechanical ventilation on a specialised weaning unit: a retrospective comparison of patients with and without SARS-CoV-2 infection]. / Entwöhnung von der Langzeitbeatmung nach ARDS auf einer spezialisierten Weaning-Einheit ­ ein retrospektiver Vergleich von Patienten mit und ohne SARS-CoV-2 Infektion.

BACKGROUND: Available data on patients requiring prolonged mechanical ventilation due to severe COVID-19 are sparse. Here we compare patients with ARDS related or not related to SARS-CoV-2 infection treated in a specialised weaning unit. METHODS: A retrospective analysis of all patients with prolonged mechanical ventilation associated with an ARDS admitted from the 21st November 2013 to the 23rd July 2021 to the weaning unit of the University Hospital RWTH Aachen was performed. ARDS patients with COVID-19 (cARDS) were compared to patients with ARDS not related to COVID-19 (ncARDS). RESULTS: In total, n=129 patients in prolonged need for mechanical ventilation after ARDS were treated in the weaning unit, of whom n=38 had been suffering from ARDS related to COVID-19. Both patients groups were similar in terms of demographic parameters, underlying chronic illnesses, severity of ARDS and the duration of mechanical ventilation before being admitted to the weaning unit. During ICU stay, prone positioning and therapy with systemic corticosteroids was used more frequently in cARDS patients. Furthermore, therapy with vasoconstrictors was needed more often (cARDS: 42.1% vs. ncARDS 12.1%; p=0.0003) and urinary output was lower (cARDS: 1980 ml vs. ncARDS: 2600 ml; p=0.0037) in this patient group. The clinical course of the weaning process was similar in patients with cARDS and ncARDS, there were no significant differences in the occurrence of complications and the duration of mechanical ventilation. There were n=5 deaths (13.2%) in the cARDS and n=15 deaths (16.5%) in the ncARDS group. After hospital discharge, n=4 patients required non-invasive ventilation whereas out-of-hospital invasive ventilation was only necessary in one patient (all in the ncARDS group). CONCLUSION: After having survived the acute phase, the disease prognosis of patients with severe COVID-19 is favourable and most patients can be successfully weaned from mechanical ventilation. In addition, there were only minor differences compared to patients with ARDS unrelated to COVID-19.

Cardiopulmonary work up of patients with and without fatigue 6 months after COVID-19.

The pathogenesis of long-Covid symptoms remains incompletely understood. Therefore, we aimed to determine cardiopulmonary limitations 6 months after surviving COVID-19 using pulmonary function tests, echocardiographic studies to the point of analysis of global-longitudinal-strain (GLS), which describes the cycling myocardium deformation and provides better data on left ventricular (LV) dysfunction than LV ejection fraction (LVEF), and validated questionnaires. Overall, 60 consecutive hospitalized patients were included (61 ± 2 years, 40% treated in the ICU). At follow-up (194 ± 3 days after discharge), fatigue was the most prevalent symptom (28%). Patients with fatigue were more symptomatic overall and characterized by worse quality of life (QoL) scores compared to patients without fatigue (all p < 0.05), mainly due to limited mobility and high symptom burden. While PFT variables and LVEF were normal in the vast majority of patients (LVEF = 52% (45-52%)), GLS was significantly reduced (- 15% (- 18 to - 14%)). However, GLS values were not different between patients with and without fatigue. In conclusion, fatigue was the most prevalent long-Covid symptom in our cohort, which was associated with worse QoL mainly due to limited mobility and the high burden of concomitant symptoms. Patients showed a subtle myocardial dysfunction 6 months after surviving COVID-19, but this did not relate to the presence of fatigue.

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.

Successful treatment of prolonged COVID-19 with Bamlanivimab in a patient with severe B-Cell aplasia due to treatment with an anti-CD20 monoclonal antibody: A case report.

A 71-year-old female patient with B-cell depletion due to treatment with an anti-CD20 monoclonal antibody was admitted for worsening COVID-19. Overall, she had persistent viral shedding, worsening respiratory failure, and progressive pneumonia that did not improve despite dexamethasone and antibiotic therapy. After administration of bamlanivimab, a monoclonal antibody with high affinity for the receptor-binding domain of the SARS-CoV-2 spike protein, inflammatory markers rapidly decreased, SARS-CoV2 RT-PCR became negative, and the patient improved clinically and radiologically. In conclusion, we demonstrated successful treatment of prolonged COVID-19 in a patient with severe B-cell aplasia with a virus-neutralizing monoclonal antibody.

Pulmonary rehabilitation in long COVID: more than just natural recovery!?

In the light of missing randomised controlled trials, some arguments suggest that pulmonary rehabilitation has beneficial effects beyond natural recovery https://bit.ly/3ze2xvw.

Broncho-alveolar lavage in patients with acute respiratory distress syndrome due to COVID-19.

As data about microbiological testing and the cellular composition of the broncho-alveolar lavage (BAL) fluid in patients ventilated due to coronavirus disease 2019 (COVID-19) are lacking, this was investigated in a retrospective analysis (n = 58). Co-infection with pathogens was detected in 31 patients, whereas the analysis of BAL cellularity showed an increased total cell count and an alveolitis dominated by neutrophils. None of the physicians performing bronchoscopies in COVID-19 patients had serological evidence of severe acute respiratory syndrome coronavirus 2 infection.

Six Months Follow-Up of Patients with Invasive Mechanical Ventilation due to COVID-19 Related ARDS.

Although patients who recovered from acute coronavirus disease 2019 (COVID-19) may have prolonged disabilities, follow-up data of those who have survived COVID-19 related acute respiratory distress syndrome (ARDS) is still very scarce. Therefore, COVID-19-ARDS survivors requiring invasive mechanical ventilation (IMV) were followed six months after discharge. Pulmonary function tests (PFTs), 6-min walk test (6MWT) and echocardiography were performed. Quality of life (QoL), depression and anxiety were assessed using validated questionnaires. Patients were compared based on respiratory mechanics and CT-phenotype during intensive care unit (ICU) stay. Eighteen patients were included (61 ± 7 years; ICU-stay: 34 ± 16 days; IMV: 30 ± 15 days). At follow-up (197 ± 15 days after discharge), PFTs did not reveal significant limitations (VC: 92 ± 16%; FEV1: 92 ± 20%; DLco/VA: 81 ± 16%). Cardiac systolic function was normal in all patients, but 50% of them had diastolic dysfunction. 6MWT was under the lower limit of normal in only two patients. Eight patients (44%) reported tiredness, six (33%) suffered from fatigue and one patient (6%) had depression and anxiety. Surprisingly, patients with worse respiratory mechanics during IMV reported fewer symptoms and less exertional dyspnea at follow-up. In conclusion, patients with COVID-19-ARDS have the possibility to fully recover regarding pulmonary function and exercise capacity, which seems to be independent of disease severity during ICU stay.

Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19.

BACKGROUND: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups. DESIGN: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups. KEY RESULTS: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05). CONCLUSIONS: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.

Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit.

Patients suffering from CVOID-19 mostly experience a benign course of the disease. Approximately 14% of SARS-CoV2 infected patients are admitted to a hospital. Cohorts exhibiting severe lung failure in the form of acute respiratory distress syndrome (ARDS) have been well characterized. Patients without ARDS but in need of supplementary oxygen have received much less attention. This study describes the diagnosis, symptoms, treatment and outcomes of hospitalized patients with COVID-19 needing oxygen support during their stay on regular ward. All 133 patients admitted to the RWTH Aachen university hospital with the diagnosis of COVID-19 were included in an observational registry. Clinical data sets were extracted from the hospital information system. This analysis includes all 57 patients requiring supplemental oxygen not admitted to the ICU. 57 patients needing supplemental oxygen and being treated outside the ICU were analyzed. Patients exhibited the typical set of symptoms for COVID-19. Of note, hypoxic patients mostly did not suffer from clinically relevant dyspnea despite oxygen saturations below 92%. Patients had fever for 7 [2-11] days and needed supplemental oxygen for 8 [5-13] days resulting in an overall hospitalization time of 12 [7-20] days. In addition, patients had persisting systemic inflammation with CRP levels remaining elevated until discharge or death. This description of COVID-19 patients requiring oxygen therapy should be taken into account when planning treatment capacity. Patients on oxygen need long-term inpatient care.

Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae.

BACKGROUND: Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, pulmonary and extrapulmonary sequelae of COVID-19 after recovery from the acute disease are unknown. MATERIAL AND METHODS: Hospitalized COVID-19 patients not requiring mechanical ventilation were included and followed 6 weeks after discharge. Body plethysmography, lung diffusion capacity (DLco), blood gas analysis (ABG), 6-min walk test (6MWT), echocardiography, and laboratory tests were performed. Quality of life (QoL), depression, and anxiety were assessed using validated questionnaires. RESULTS: 33 patients with severe disease were included. Patients were discharged without prophylactic anticoagulation. At follow-up there were no thromboembolic complications in any patient. 11 patients (33%) had dyspnea, 11 (33%) had cough, and 15 (45%) suffered from symptoms of fatigue. Pulmonary function tests including ABG did not reveal any limitations (TLC: median=94% of predicted {IQR:85-105}; VC: 93% {78-101}; FEV1: 95% {72-103}; FEV1/FVC 79% {76-85}; PaO2: 72 mmHg {67-79}; PaCO2: 38 mmHg {35-38}), except for slightly reduced DLco (77% {69-95}). There were no echocardiographic impairments. 6MWT distance was reduced in most patients without oxygen desaturation. According to standardized questionnaires, patients suffered from reduced QoL, mainly due to decreased mobility (SGRQ activity score: 54 {19-78}). There were no indicators for depression or anxiety (PHQ-9: 7 {4-11}, GAD-7: 4 {1-9}, respectively). CONCLUSIONS: Hospitalized patients with severe COVID-19, who did not require mechanical ventilation, are unlikely to develop pulmonary long-term impairments, thromboembolic complications or cardiac impairments after discharge but frequently suffer from symptoms of fatigue.

The Characteristics of 50 Hospitalized COVID-19 Patients With and Without ARDS.

BACKGROUND: The type of pneumonia (coronavirus disease 2019, COVID-19) that is caused by the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is now spreading across the world in a pandemic. Many patients with COVID-19 were admitted to the University Hospital Aachen during an outbreak that first struck the Heinsberg district in February 2020. METHODS: A comparative presentation of the clinical features of the first 50 COVID-19 patients with and without acute respiratory distress syndrome (ARDS) who were hospitalized in the University Hospital Aachen. RESULTS: 24 intubated patients were treated in the intensive care unit for ARDS of varying degrees of severity, while 26 patients who were breathing spontaneously without ARDS, but nevertheless needed supplemental oxygen, were treated in a separate isolation ward. The median age of the patients was 65 (IQR 58-76). The median latency from symptom onset to hospitalization was four days (IQR 1-8). Patients with ARDS had preexisting respiratory diseases more commonly than patients without ARDS (58% [95% confidence interval: 39; 76] versus 42% [26; 61]) and were more commonly overweight or obese (83% [64; 93] versus 42% [26; 61]). The two groups did not differ in viral burden but displayed significant differences in laboratory findings: ARDS patients had persistently elevated values for leukocytes, interleukin-6, lactate dehydrogenase, creatine kinase, and D-dimers over the period of observation. Patients without ARDS had persistently elevated inflammatory parameters and fever for at least one week, with an accompanying need for supplemental oxygen. Three of the patients with ARDS died of multiorgan failure, while four in the non-ARDS group died of respiratory insufficiency. CONCLUSION: This initial description of a cohort of COVID-19 patients with and without ARDS in Germany reveals that those with ARDS more commonly have preexisting respiratory diseases and obesity, as well as persistently elevated inflammatory markers. COVID-19 patients without ARDS may likewise require prolonged hospitalization because of persistently elevated inflammatory values with a simultaneous need for supplemental oxygen.