Persistence of Diffusion Capacity Impairment and Its Relationship with Dyspnea 12 Months after Hospitalization for COVID-19.

Background: Dyspnea is a common persistent symptom after acute coronavirus disease 2019 illness (COVID-19). One potential explanation for post-COVID-19 dyspnea is a reduction in diffusion capacity. This longitudinal study investigated diffusion capacity and its relationship with dyspnea on exertion in individuals previously hospitalized with COVID-19. Methods: Eligible participants had been hospitalized for the treatment of acute COVID-19 and were assessed at 6 weeks, 6 months, and 12 months after discharge. Pulmonary function testing, diffusion capacity of carbon monoxide (DLCO), blood gas analysis and the level of dyspnea (Borg scale; before and after a 6 min walk test [6 MWT]) were performed. Participants were divided into subgroups based on the presence or absence of dyspnea during the 6 MWT at 12 months after hospitalization. Results: Seventy-two participants (twenty-two female, mean age 59.8 ± 13.5 years) were included. At 12 months after discharge, 41/72 participants (57%) had DLCO below the lower limit of normal and 56/72 (78%) had DLCO < 80% of the predicted value. Individuals with exertional dyspnea had significantly lower DLCO than those without exertional dyspnea (p = 0.001). In participants with DLCO data being available at three timepoints over 12 months (baseline, 6 months, and 12 months) after discharge (n = 25), DLCO improved between 6 weeks and 6 months after hospital discharge, but not thereafter (p = 0.017). Conclusions: About 2/3 of the post-COVID individuals in this study had impaired diffusion capacity at 12 months after hospital discharge. There was an association between persisting dyspnea on exertion and significantly reduced DLCO. Impaired diffusion capacity improved over the first 6 months after hospitalization but not thereafter.

Supplemental oxygen therapy in chronic obstructive pulmonary disease: is less is more? How much is too much?

PURPOSE OF REVIEW: Currently available evidence supporting the use of supplemental oxygen therapy (SOT) in chronic obstructive pulmonary disease (COPD) is complex, and data on the mortality reduction associated with SOT usage in patients with severe daytime resting hypoxemia have not been updated since the development of other treatments. RECENT FINDINGS: No reduction in mortality was found when SOT was used in patients with moderate resting daytime, isolated nocturnal, or exercise-induced hypoxemia. However, some of these patients obtain other significant benefits during SOT, including increased exercise endurance, and a mortality reduction is possible in these 'responders'. The adverse effects of long-term oxygen therapy also need to be considered, such as reduced mobility and social stigma. Furthermore, conservative SOT could improve outcomes in the setting of COPD exacerbations compared with higher concentration oxygen regimens. Compared with usual fixed-dose SOT, automated oxygen administration devices might reduce dyspnea during exercise and COPD exacerbations. SUMMARY: Current recommendations for SOT need to be revised to focus on patients who respond best and benefit most from this therapy. A conservative approach to SOT can reduce side effects compared with higher concentration oxygen regimens, and automated oxygen administration devices may help to optimize SOT.

[Pathophysiology, diagnosis, prognosis and treatment of pulmonary hypertension associated with chronic lung disease]. / Pulmonale Hypertonie bei Lungenerkrankungen und/oder Hypoxie.

The pathophysiology of pulmonary hypertension associated with chronic lung disease (PH-CLD) is complex, multifactorial, and not consistent among pulmonary diseases. However, pulmonary vasculopathy triggered by various factors, such as chronic alveolar hypoxia or cigarette smoking, seems to play a central role in the pathogenesis of PH-CLD. While the initial workup of PH-CLD is usually complicated by an overlap of symptoms of PH and the underlying lung disease, PH-CLD should be considered when there is a discrepancy between symptoms (especially exertional dyspnea) and pulmonary function tests. Clinical suspicion of PH-CLD can be strengthened by noninvasive diagnostic tools such as transthoracic echocardiography (TTE) or N-terminal pro-B-type natriuretic peptide (NT-pro-BNP). However, a right heart catheterization should only be performed in specialized centers to establish the diagnosis if therapeutic consequences for the patient were expected.The basic treatment of PH-CLD is optimal management of the underlying lung disease. Among the existing interventional and registry-based studies, only a small number of data suggests favorable outcomes when treating PH-CLD patients with PAH-specific medications. Some publications even suggest negative effects. Nevertheless, recent data on inhaled vasoactive therapy in PH-CLD showed positive results for inhaled Treprostinil, although long-term data for this therapeutic approach are still lacking. Treatment of PH-CLD patients with PAH-specific drugs should only be performed in specialized centers and preferably in the context of clinical trials.

Significance of Hypocapnia in the Risk Assessment of Patients with Pulmonary Hypertension.

Blood gas analysis is part of the diagnostic work-up for pulmonary hypertension (PH). Although some studies have found that the partial pressure of carbon dioxide (PaCO2) is an independent marker of mortality in individuals with pulmonary arterial hypertension (PH Group 1), there is a lack of data regarding the significance of PaCO2 in individuals with different types of PH based on the new 2022 definitions. Therefore, this study analyzed data from 157 individuals who were undergoing PH work-up, including right heart catheterization, using PH definitions from the 2022 European Society of Cardiology/European Respiratory Society guidelines. At diagnosis, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels were significantly higher, but the time-course of NT-pro-BNP levels during treatment was significantly more favorable in individuals with pulmonary arterial hypertension (PH Group 1) who did versus did not have hypocapnia (p = 0.026 and p = 0.017, respectively). These differences based on the presence of hypocapnia were not seen in individuals with PH Groups 2, 3, or 4. In conclusion, using the new definition of PH, hypocapnia may correlate with worse risk stratification at diagnosis in individuals with pulmonary arterial hypertension. However, hypocapnic individuals with pulmonary arterial hypertension may benefit more from disease-specific therapy than those without hypocapnia.

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.

Eight Patients With Pilonidal Carcinoma in One Decade-Is the Incidence Rising?

INTRODUCTION: Carcinoma secondary to pilonidal disease is very rare with fewer than 130 reported cases so far. It is presumed that underreporting and underpublishing contribute to the low reported incidence. METHODS: A post was published on a closed Facebook group with about 30,000 Syrian doctors asking if anyone had ever seen a patient with pilonidal carcinoma before. The patients' data were collected retrospectively from the treating physicians. RESULTS: Between 2010 and 2019, we identified eight patients with pilonidal carcinoma. All patients were males with a mean age of 55.5 years. The mean interval between diagnosis of pilonidal disease and diagnosis of carcinoma was 6.9 years. A growing ulcer on the background of a pilonidal sinus disease was the presenting complaint in 50% of cases. Three patients were lost from follow-up after the diagnosis due to referral. All other five patients underwent surgical resection and three of them received postoperative chemoradiation. Four patients were followed for six months or longer: two died of metastases, one survived after recurrence and re-excision, and one survived with no recurrence. CONCLUSION: This paper presents the largest cohort of pilonidal carcinoma so far and the first that describes the disease in the Syrian population. Due to underreporting, the real incidence of pilonidal carcinoma exceeds what is reported so far in the literature.

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.

Mathematical Arterialization of Capillary Blood for Blood Gas Analysis in Critically Ill Patients.

BACKGROUND: In clinical practice, capillary blood taken from hyperemized earlobes (CBGE) or fingertips (CBGF) is frequently used as substitute for arterial blood (ABG) for blood gas analysis. While there is a close agreement between ABG and CBGE/CBGF regarding pH and pCO2, pO2 is often underestimated by CBG. Recently, a software tool (v-TAC®; Roche Diagnostics, Risch-Rotkreuz, Switzerland) has been developed to calculate ABG values based on a peripheral venous blood gas analysis supplemented with peripheral oxygen saturation. OBJECTIVE: Here we investigate whether v-TAC can also be used to calculate ABG values from capillary blood samples. METHODS: Patients (n = 85) with an indwelling arterial line were included in the study. A reference ABG sample (ABG1) was obtained, followed by CBGE, CBGF, and finally a second ABG (ABG2). Results of CBGE/CBGF before and after mathematical arterialization by v-TAC (aCBGE/aCBGF) were compared to ABG1. RESULTS: After mathematical arterialization by v-TAC, the mean bias in pO2 between ABG1 and CBGE went down from 5.24 mm Hg (95% limit of agreement [95% LoA]: -14.19 to 24.67) to 0.18 mm Hg (95% LoA: -11.84 to 12.20) and was in a similar range as the mean bias between ABG1 and ABG2 (0.39 mm Hg [95% LoA: -13.46 to 14.24]). Differences in pH and pCO2 between arterial and capillary samples were small before and after mathematical arterialization. Very similar results were obtained when using fingertip instead of earlobe capillary blood. CONCLUSION: In summary, v-TAC can be used for mathematical arterialization of capillary blood samples for blood gas analysis resulting in increased diagnostic accuracy for pO2.

Safety and efficacy of transcatheter mitral valve repair in patients with COPD; results from real-world cohort.

OBJECTIVE: To evaluate the safety and efficacy of transcatheter mitral valve repair (TMVR) in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: Heart failure and COPD share many clinical features and commonly coexist. Data about the safety and efficacy of TMVR in patients with COPD is not conclusive. METHODS: Three hundred and forty consecutive patients undergoing TMVR were retrospectively included. COPD diagnosis was based on pulmonary function tests (PFTs). Intra-hospital, 30-day- and 1-year outcomes were compared between both groups. RESULTS: Eighty-two patients had COPD (24%). There was no difference in intra-hospital mortality between patients with and without COPD (both 5%, p = 0.95). Among patients who had a successful procedure and survived to discharge there was a trend toward more rehospitalization due to decompensated heart failure at 30-day follow-up in patients with COPD (12.9% vs. 6.8%, p = 0.08) with no difference in mortality. At median follow-up of 1 year, New York heart association (NYHA) category was comparable among both groups and there was no significant difference in rehospitalization (COPD: 29.9% vs. non-COPD: 34%, p = 0.5). There was a trend toward increased 1-year mortality in COPD patients (31.2% vs. 20.6%, p = 0.06). However, a composite endpoint of rehospitalization or death at 1 year did not differ between both groups (48% vs. 42.5%, p = 0.4). Regression analysis showed no correlation between COPD severity and worse TMVR outcomes. CONCLUSIONS: COPD is highly prevalent among patients undergoing TMVR. However, TMVR seems to be safe and effective in COPD patients. COPD severity and PFT impairment alone should not be considered as a contraindication for TMVR.

Effects of COPD on Left Ventricular and Left Atrial Deformation in Patients with Acute Myocardial Infarction: Strain Analysis Using Speckle-Tracking Echocardiography.

Myocardial strain analysis, which describes myocardial deformation (shortening or lengthening), provides more detailed information about left ventricular (LV) and atrial (LA) functions than conventional echocardiography and delivers prognostic information. To analyze the effects of COPD on left heart function upon acute myocardial infarction (AMI), consecutive AMI patients were retrospectively screened, and patients were included if a post-AMI echocardiography and results of recent pulmonary function tests (PFTs) were available. Strain analysis was performed by a cardiologist who was blinded to clinical information. Overall, 109 AMI patients were included (STEMI: 38%, non-STEMI: 62%). COPD patients (41%) had significantly more impaired LV "global-longitudinal-strain" (LV-GLS) compared to non-COPD patients (−15 ± 4% vs. −18 ± 4%; p < 0.001, respectively), even after adjusting for LV-ejection-fraction (LVEF) and age (mean estimated difference: 1.7%, p = 0.009). Furthermore, COPD patients had more impaired LA strain (LAS) than non-COPD patients in all cardiac cycle phases (estimated mean differences after adjusting for LVEF and age: during reservoir phase: −7.5% (p < 0.001); conduit phase: 5.5% (p < 0.001); contraction phase: 1.9% (p = 0.034)). There were no correlations between PFT variables and strain values. In conclusion, the presence of COPD was associated with more impaired LV and LA functions after AMI, as detected by strain analysis, which was independent of age, LVEF, and PFT variables.

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.

Effects of Transcatheter Mitral Valve Repair Using MitraClip® Device on Sleep Disordered Breathing in Patients with Mitral Valve Regurgitation.

Sleep disordered breathing (SDB) is common among patients with valvular heart disease, and successful valve surgery could reduce SDB severity. However, data about the effects of transcatheter mitral valve repair on SDB are scarce. Therefore, mitral regurgitation (MR) patients undergoing MitraClip-placement were prospectively enrolled. Before MitraClip-placement, daytime sleepiness and sleep quality were assessed using the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), respectively; and all patients underwent SDB screening using five-channel respiratory polygraphy. After 3-6 months, patients had a similar reassessment including: ESS, PSQI, and respiratory polygraphy. 67 patients were included (77 ± 8years). Despite normal sleepiness scores, 41 patients (61%) had SDB with apnea-hypopnea-index (AHI) ≥ 15 h before MitraClip-placement, of whom only three patients had known SDB previously. Compared to patients without SDB, patients with SDB had similar sleepiness scores but higher NT-proBNP values at baseline (4325 vs. 1520 pg/mL, p < 0.001). At follow-up, there were significant AHI improvements among patients with SDB (p = 0.013). However, there were no significant sleepiness score changes. In conclusion, the prevalence of SDB among MitraClip candidates is very high even in those without daytime sleepiness. MR patients with SDB have higher NT-proBNP values, which may reflect a worse prognosis. MitraClip-placement may improve the underlying SDB, which could be an additional benefit of the procedure.

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.

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.

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.

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.

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.