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1.
Blood Purif ; : 1-10, 2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2020585

ABSTRACT

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

2.
J Clin Med ; 11(4)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1701768

ABSTRACT

The spread of SARS-CoV-2 caused a worldwide healthcare threat. High critical care admission rates related to Coronavirus Disease 2019 (COVID-19) respiratory failure were observed. Medical advances helped increase the number of patients surviving the acute critical illness. However, some patients require prolonged critical care. Data on the outcome of patients with a chronic critical illness (CCI) are scarce. Single-center retrospective study including all adult critically ill patients with confirmed COVID-19 treated at the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf, Germany, between 1 March 2020 and 8 August 2021. We identified 304 critically ill patients with COVID-19 during the study period. Of those, 55% (n = 167) had an ICU stay ≥21 days and were defined as chronic critical illness, and 45% (n = 137) had an ICU stay <21 days. Age, sex and BMI were distributed equally between both groups. Patients with CCI had a higher median SAPS II (CCI: 39.5 vs. no-CCI: 38 points, p = 0.140) and SOFA score (10 vs. 6, p < 0.001) on admission. Seventy-three per cent (n = 223) of patients required invasive mechanical ventilation (MV) (86% vs. 58%; p < 0.001). The median duration of MV was 30 (17-49) days and 7 (4-12) days in patients with and without CCI, respectively (p < 0.001). The regression analysis identified ARDS (OR 3.238, 95% CI 1.827-5.740, p < 0.001) and referral from another ICU (OR 2.097, 95% CI 1.203-3.654, p = 0.009) as factors significantly associated with new-onset of CCI. Overall, we observed an ICU mortality of 38% (n = 115) in the study cohort. In patients with CCI we observed an ICU mortality of 28% (n = 46) compared to 50% (n = 69) in patients without CCI (p < 0.001). The 90-day mortality was 28% (n = 46) compared to 50% (n = 70), respectively (p < 0.001). More than half of critically ill patients with COVID-19 suffer from CCI. Short and long-term survival rates in patients with CCI were high compared to patients without CCI, and prolonged therapy should not be withheld when resources permit prolonged therapy.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320952

ABSTRACT

BACKGROUND Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. We sought to characterize sex differences in hormone levels and cytokine responses in critically ill COVID-19 patients. METHODS We performed a retrospective cohort study of critically ill COVID-19 patients. Males and females were compared. Multivariate regression was performed to assess the association between sex hormones, cytokine responses and the requirement for extracorporeal membrane oxygenation (ECMO) treatment. RESULTS We analyzed sex hormone levels (estradiol and testosterone) of n =181 male and female individuals. These consisted of n =50 critically ill COVID-19 patients ( n =39 males, n =11 females), n =42 critically ill non-COVID-19 patients ( n =27 males, n =15 females), n =39 non-COVID-19 patients with coronary heart diseases (CHD) ( n =25 males, n =14 females) and n =50 healthy individuals ( n =30 males, n =20 females). We detected highest estradiol levels in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0123), patients with CHD ( p =0.0002) or healthy individuals ( p =0.0007). Lowest testosterone levels were detected in critically ill male COVID-19 patients compared to non-COVID-19 patients ( p =0.0094), patients with CHD ( p =0.0068) or healthy individuals ( p <0.0001). No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends in estradiol levels were observed. In critically ill male COVID-19 patients, cytokine and chemokine responses (IFN-γ, p =0.0301;IL-1RA, p =0.0160;IL-6, p =0.0145;MCP-1, p =0.0052;MIP-1α, p =0.0134) were significantly elevated in those with higher Sequential Organ Failure Assessment (SOFA) scores (8-11). Linear regression analysis revealed that herein IFN-γ levels correlate with estradiol levels in male and female COVID-19 patients (R 2 =0.216, =0.0009). Male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment in the course of their ICU stay ( p =0.0009). CONCLUSIONS We identified high estradiol and low testosterone levels as a hallmark of critically ill male COVID-19 patients. Elevated estradiol levels in critically ill male COVID-19 patients were positively associated with IFN-γ levels and increased risk for ECMO requirement.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313239

ABSTRACT

Purpose: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from removal of inflammatory mediators via hemadsorption. Methods: : Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 μg/kg/min to maintain a mean arterial pressure ≥ 65 mmHg), IL-6≥500 ng/l and an indication for renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18–24 hours. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min≥24h). Secondary endpoints included 28-day mortality, SOFA, and reduction of IL-6, PCT, and MR-proADM. Results: : Of 242 screened patients, 24 were randomized and assigned to either HT (N=12) or SMT (N=12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p=0.590) and SOFA (17 vs. 16, p=0.551). At randomization, 22 (92%) patients were on RRT and 11 (46%) had vv-ECMO. Median IL-6 levels were 2269 (IQR 948–3679) and 3747 (1301–5415) ng/l in the HT and SMT group at baseline, respectively (p=0.378). Serum IL-6 reduction in the first 24h of treatment compared between both groups was 83% vs. 46% (p=0.235). Shock resolution (primary endpoint) was reached in 33% (4/12) vs. 17% (2/12) in the HT and SMT group, respectively (p=0.640). 28-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p=1.0). Conclusion: HT was associated with a non-significant trend towards clinical improvement within the intervention period including reduction of IL-6 levels and shock resolution. In selected patients, HT might therefore be an option for stabilization and bridge to transfer and decision. ( Trial registration: ClinicalTrials.gov: NCT04344080, https://clinicaltrials.gov/ct2/show/NCT04344080, trial registration date 04/14/2020)]

5.
J Med Virol ; 94(5): 1920-1925, 2022 05.
Article in English | MEDLINE | ID: covidwho-1589024

ABSTRACT

The role of respiratory superinfections in patients with coronavirus disease 2019 (COVID-19) pneumonia remains unclear. We investigated the prevalence of early- and late-onset superinfections in invasively ventilated patients with COVID-19 pneumonia admitted to our department of intensive care medicine between March 2020 and November 2020. Of the 102 cases, 74 (72.5%) received invasive ventilation and were tested for viral, bacterial, and fungal pathogens on Days 0-7, 8-14, and 15-21 after the initiation of mechanical ventilation. Approximately 45% developed one or more respiratory superinfections. There was a clear correlation between the duration of invasive ventilation and the prevalence of coinfecting pathogens. Male patients with obesity and those suffering from chronic obstructive pulmonary disease and/or diabetes mellitus had a significantly higher probability to develop a respiratory superinfection. The prevalence of viral coinfections was high, with a predominance of the herpes simplex virus (HSV), followed by cytomegalovirus. No respiratory viruses or intracellular bacteria were detected in our cohort. We observed a high coincidence between Aspergillus fumigatus and HSV infection. Gram-negative bacteria were the most frequent pathogen group. Klebsiella aerogenes was detected early after intubation, while Klebsiella pneumoniae and Pseudomonas aeruginosa were related to a prolonged respiratory weaning.


Subject(s)
COVID-19 , Superinfection , COVID-19/epidemiology , COVID-19/therapy , Humans , Male , Prevalence , Respiration, Artificial/adverse effects , SARS-CoV-2 , Superinfection/epidemiology , Superinfection/microbiology
6.
J Clin Med ; 10(22)2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1524051

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53-64) and 52 (39-58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1-5) and 2 (0-5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24-36) vs. 32 (28-41) points (p = 0.009), and SOFA score was 13 (11-14) vs. 12 (8-15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46-78) and 73 (56-104) (p = 0.089); pH was 7.20 (7.16-7.29) and 7.26 (7.18-7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7-27) and 11 (7-20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13-44) and 28 (16-14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

7.
Emerg Microbes Infect ; 10(1): 1807-1818, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1360311

ABSTRACT

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.


Subject(s)
COVID-19/mortality , COVID-19/pathology , Estradiol/blood , Testosterone/blood , Aged , Aged, 80 and over , COVID-19/blood , Critical Care , Critical Illness , Extracorporeal Membrane Oxygenation , Female , Humans , Hypogonadism/pathology , Intensive Care Units , Interferon-gamma/blood , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Distribution
8.
J Clin Med ; 10(10)2021 May 19.
Article in English | MEDLINE | ID: covidwho-1234757

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) led to an ongoing pandemic with a surge of critically ill patients. Very little is known about the occurrence and characteristic of cardiac arrest in critically ill patients with COVID-19 treated at the intensive care unit (ICU). The aim was to investigate the incidence and outcome of intensive care unit cardiac arrest (ICU-CA) in critically ill patients with COVID-19. This was a retrospective analysis of prospectively recorded data of all consecutive adult patients with COVID-19 admitted (27 February 2020-14 January 2021) at the University Medical Centre Hamburg-Eppendorf (Germany). Of 183 critically ill patients with COVID-19, 18% (n = 33) had ICU-CA. The median age of the study population was 63 (55-73) years and 66% (n = 120) were male. Demographic characteristics and comorbidities did not differ significantly between patients with and without ICU-CA. Simplified Acute Physiological Score II (SAPS II) (ICU-CA: median 44 points vs. no ICU-CA: 39 points) and Sequential Organ Failure Assessment (SOFA) score (median 12 points vs. 7 points) on admission were significantly higher in patients with ICU-CA. Acute respiratory distress syndrome (ARDS) was present in 91% (n = 30) with and in 63% (n = 94) without ICU-CA (p = 0.002). Mechanical ventilation was more common in patients with ICU-CA (97% vs. 67%). The median stay in ICU before CA was 6 (1-17) days. A total of 33% (n = 11) of ICU-CAs occurred during the first 24 h of ICU stay. The initial rhythm was non-shockable (pulseless electrical activity (PEA)/asystole) in 91% (n = 30); 94% (n = 31) had sustained return of spontaneous circulation (ROSC). The median time to ROSC was 3 (1-5) minutes. Patients with ICU-CA had significantly higher ICU mortality (61% vs. 37%). Multivariable logistic regression showed that the presence of ARDS (odds ratio (OR) 4.268, 95% confidence interval (CI) 1.211-15.036; p = 0.024) and high SAPS II (OR 1.031, 95% CI 0.997-1.065; p = 0.077) were independently associated with the occurrence of ICU-CA. A total of 18% of critically ill patients with COVID-19 suffered from a cardiac arrest within the intensive care unit. The occurrence of ICU-CA was associated with presence of ARDS and severity of illness.

9.
Biomarkers ; 26(5): 417-424, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1146879

ABSTRACT

BACKGROUND: About 20% of ICU patients with COVID-19 require renal replacement therapy (RRT). Mid-regional pro-adrenomedullin (MR-proADM) might be used for risk assessment. This study investigates MR-proADM for RRT prediction in ICU patients with COVID-19. METHODS: We analysed data of consecutive patients with COVID-19, requiring ICU admission at a university hospital in Germany between March and September 2020. Clinical characteristics, details on AKI, and RRT were assessed. MR-proADM was measured on admission. RESULTS: 64 patients were included (49 (77%) males). Median age was 62.5y (54-73). 47 (73%) patients were ventilated and 50 (78%) needed vasopressors. 25 (39%) patients had severe ARDS, and 10 patients needed veno-venous extracorporeal membrane oxygenation. 29 (45%) patients required RRT; median time from admission to RRT start was 2 (1-9) days. MR-proADM on admission was higher in the RRT group (2.491 vs. 1.23 nmol/l; p = 0.002) and showed the highest correlation with renalSOFA. ROC curve analysis showed that MR-proADM predicts RRT with an AUC of 0.69 (95% CI: 0.543-0.828; p = 0.019). In multivariable logistic regression MR-proADM was an independent predictor (OR: 3.813, 95% CI 1.110-13.102, p<0.05) for RRT requirement. CONCLUSION: AKI requiring RRT is frequent in ICU patients with COVID-19. MR-proADM on admission was able to predict RRT requirement, which may be of interest for risk stratification and management.


Subject(s)
Acute Kidney Injury/therapy , Adrenomedullin/metabolism , COVID-19/prevention & control , Critical Illness/therapy , Protein Precursors/metabolism , Renal Replacement Therapy/methods , SARS-CoV-2/isolation & purification , Acute Kidney Injury/diagnosis , Aged , Biomarkers/metabolism , COVID-19/virology , Cohort Studies , Female , Germany , Hospitals, University , Humans , Intensive Care Units , Male , Middle Aged , Predictive Value of Tests , ROC Curve , SARS-CoV-2/physiology
10.
Ann Intensive Care ; 11(1): 44, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1133608

ABSTRACT

BACKGROUND: SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19. METHODS: Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (> 20-fold ULN). RESULTS: 72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO2/FiO2: 82 (58-114) vs. 117 (83-155); p < 0.05). Thus, required more frequently mechanical ventilation (95% vs. 64%; p < 0.01), rescue therapies (ECMO) (27% vs. 12%; p = 0.106), vasopressor (95% vs. 72%; p < 0.05) and renal replacement therapy (86% vs. 30%; p < 0.001). Severity of illness was significantly higher (SAPS II: 48 (39-52) vs. 40 (32-45); p < 0.01). Patients with SLD and without presented viremic during ICU stay in 68% and 34%, respectively (p = 0.002). Occurrence of SLD was independently associated with presence of viremia [OR 6.359; 95% CI 1.336-30.253; p < 0.05] and severity of illness (SAPS II) [OR 1.078; 95% CI 1.004-1.157; p < 0.05]. Mortality was high in patients with SLD compared to other patients (68% vs. 16%, p < 0.001). After adjustment for confounders, SLD was independently associated with mortality [HR3.347; 95% CI 1.401-7.999; p < 0.01]. CONCLUSION: One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause.

11.
Aust Crit Care ; 34(2): 167-175, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-950142

ABSTRACT

BACKGROUND: There are large uncertainties with regard to the outcome of patients with coronavirus disease 2019 (COVID-19) and mechanical ventilation (MV). High mortality (50-97%) was proposed by some groups, leading to considerable uncertainties with regard to outcomes of critically ill patients with COVID-19. OBJECTIVES: The aim was to investigate the characteristics and outcomes of critically ill patients with COVID-19 requiring intensive care unit (ICU) admission and MV. METHODS: A multicentre retrospective observational cohort study at 15 hospitals in Hamburg, Germany, was performed. Critically ill adult patients with COVID-19 who completed their ICU stay between February and June 2020 were included. Patient demographics, severity of illness, and ICU course were retrospectively evaluated. RESULTS: A total of 223 critically ill patients with COVID-19 were included. The majority, 73% (n = 163), were men; the median age was 69 (interquartile range = 58-77.5) years, with 68% (n = 151) patients having at least one chronic medical condition. Their Sequential Organ Failure Assessment score was a median of 5 (3-9) points on admission. Overall, 167 (75%) patients needed MV. Noninvasive ventilation and high-flow nasal cannula were used in 31 (14%) and 26 (12%) patients, respectively. Subsequent MV, due to noninvasive ventilation/high-flow nasal cannula therapy failure, was necessary in 46 (81%) patients. Renal replacement therapy was initiated in 33% (n = 72) of patients, and owing to severe respiratory failure, extracorporeal membrane oxygenation was necessary in 9% (n = 20) of patients. Experimental antiviral therapy was used in 9% (n = 21) of patients. Complications during the ICU stay were as follows: septic shock (40%, n = 90), heart failure (8%, n = 17), and pulmonary embolism (6%, n = 14). The length of ICU stay was a median of 13 days (5-24), and the duration of MV was 15 days (8-25). The ICU mortality was 35% (n = 78) and 44% (n = 74) among mechanically ventilated patients. CONCLUSION: In this multicentre observational study of 223 critically ill patients with COVID-19, the survival to ICU discharge was 65%, and it was 56% among patients requiring MV. Patients showed high rate of septic complications during their ICU stay.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Critical Illness , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Respiration, Artificial , Aged , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2
12.
Ann Intern Med ; 173(4): 268-277, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-782419

ABSTRACT

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.


Subject(s)
Autopsy/methods , Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Pulmonary Embolism/mortality , Venous Thromboembolism/mortality , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cause of Death , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
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