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1.
Front Immunol ; 13: 840126, 2022.
Article in English | MEDLINE | ID: covidwho-1775673

ABSTRACT

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4+ T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.


Subject(s)
COVID-19 , Interferon Type I , Primary Immunodeficiency Diseases , Antibodies, Viral , COVID-19/therapy , Humans , Immunity, Humoral , Immunization, Passive , RNA, Viral , SARS-CoV-2 , T-Lymphocytes
2.
Front Immunol ; 13: 821681, 2022.
Article in English | MEDLINE | ID: covidwho-1708117

ABSTRACT

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.


Subject(s)
Chemokine CXCL1/metabolism , Neovascularization, Pathologic/pathology , Peritoneal Dialysis/methods , Peritoneum/blood supply , Renal Replacement Therapy/methods , COVID-19/pathology , Cells, Cultured , Child , Child, Preschool , Epithelium/metabolism , Humans , Infant , Interleukin-17/metabolism , Kidney Failure, Chronic/therapy , Peritoneum/pathology , Vascular Endothelial Growth Factor A/metabolism , Vascular Remodeling/physiology
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314564

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Methods: : Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. Results: : We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11 5 (6 25-17 75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission;in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Conclusion: Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314013

ABSTRACT

Background: Enhanced coagulation in coronavirus disease 2019 (COVID-19) patients is considered a major obstacle for continuous renal replacement therapy (CRRT), but systematic analyses are sparse. We compared filter survival and citrate-induced complications during CRRT with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. Methods: : In this retrospective study we included all consecutive adult patients (n=97) with acute kidney injury (AKI) treated with RCA-CRRT at seven ICUs of a tertiary university hospital over the tree month period. Medical data were collected to compare the efficacy and complications of RCA-CRRT between COVID-19 (n=44) and Non-COVID-19 patients (n=53). Results: : There was no significant difference in the number of CRRT filters used per patient in COVID-19 vs. Non-COVID-19 patients (median 5 vs 3 filters, p=0.103). Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively;log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45 – 61) vs. 47 (IQR 41 - 58) seconds, respectively;p<0.001). A significantly higher incidence of combined metabolic disturbances (metabolic alkalosis, hypercalcemia and hypernatremia), consistent with reduced filter patency and citrate overload during RCA, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively;p=0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. Conclusions: : In contrast to initial concerns, adequate filter life-span can be achieved with RCA during CRRT in COVID-19 patients. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. Trial Registration (local authority): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin);date of registration 08.10.2020.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316133

ABSTRACT

Background: COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. Methods: We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. Results: We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed a normalization of the initial coagulation abnormality together without evidence of venous thrombosis in all thirteen patients. Conclusion: In our cohort the coagulation profile was completely normalized three months after COVID-19. It thus appears reasonable that anticoagulation can be discontinued beyond this timepoint in patients with complete venous reperfusion.

6.
J Crit Care ; 67: 126-131, 2022 02.
Article in English | MEDLINE | ID: covidwho-1509976

ABSTRACT

BACKGROUND: We compared filter survival and citrate-induced complications during continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in COVID-19 and Non-COVID-19 patients. METHODS: In this retrospective study we included all consecutive adult patients (n = 97) treated with RCA-CRRT. Efficacy and complications of RCA-CRRT were compared between COVID-19 and Non-COVID-19 patients. RESULTS: Mean filter run-time was significantly higher in COVID-19 patients compared to Non-COVID-19 patients (68.4 (95%CI 67.0-69.9) vs. 65.2 (95%CI 63.2-67.2) hours, respectively; log-rank 0.014). COVID-19 patients showed significantly higher activated partial thromboplastin time (aPTT) throughout the CRRT due to intensified systemic anticoagulation compared to Non-COVID-19 patients (54 (IQR 45-61) vs. 47 (IQR 41-58) seconds, respectively; p < 0.001). A significantly higher incidence of metabolic alkalosis, hypercalcemia and hypernatremia, consistent with reduced filter patency and citrate overload, was observed in COVID-19 patients compared to Non-COVID-19 patients (19.1% vs. 12.7%, respectively; p = 0.04). These metabolic disarrangements were resistant to per-protocol adjustments and disappeared after replacement of the CRRT-filter. CONCLUSIONS: RCA-CRRT in COVID-19 patients with intensified systemic anticoagulation provides an adequate filter lifespan. However, close monitoring of the acid-base balance appears warranted, as these patients tend to develop reduced filter patency leading to a higher incidence of citrate overload and metabolic disturbances. TRIAL REGISTRATION (LOCAL AUTHORITY): EA1/285/20 (Ethikkommission der Charité - Universitätsmedizin Berlin); date of registration 08.10.2020.


Subject(s)
COVID-19 , Continuous Renal Replacement Therapy , Anticoagulants/adverse effects , Citrates , Citric Acid/adverse effects , Critical Illness , Humans , Retrospective Studies , SARS-CoV-2
7.
Eur J Immunol ; 52(1): 138-148, 2022 01.
Article in English | MEDLINE | ID: covidwho-1479399

ABSTRACT

The interferon pathway, a key antiviral defense mechanism, is being considered as a therapeutic target in COVID-19. Both, substitution of interferon and JAK/STAT inhibition to limit cytokine storms have been proposed. However, little is known about possible abnormalities in STAT signaling in immune cells during SARS-CoV-2 infection. We investigated downstream targets of interferon signaling, including STAT1, STAT2, pSTAT1 and 2, and IRF1, 7 and 9 by flow cytometry in 30 patients with COVID-19, 17 with mild, and 13 with severe infection. We report upregulation of STAT1 and IRF9 in mild and severe COVID-19 cases, which correlated with the IFN-signature assessed by Siglec-1 (CD169) expression on peripheral monocytes. Interestingly, Siglec-1 and STAT1 in CD14+ monocytes and plasmablasts showed lower expression among severe cases compared to mild cases. Contrary to the baseline STAT1 expression, the phosphorylation of STAT1 was enhanced in severe COVID-19 cases, indicating a dysbalanced JAK/STAT signaling that fails to induce transcription of interferon stimulated response elements (ISRE). This abnormality persisted after IFN-α and IFN-γ stimulation of PBMCs from patients with severe COVID-19. Data suggest impaired STAT1 transcriptional upregulation among severely infected patients may represent a potential predictive biomarker and would allow stratification of patients for certain interferon-pathway targeted treatments.


Subject(s)
COVID-19/immunology , Monocytes/immunology , SARS-CoV-2/immunology , STAT1 Transcription Factor/immunology , Signal Transduction/immunology , Up-Regulation/immunology , Adult , Aged , Female , Humans , Interferon Regulatory Factors/immunology , Male , Middle Aged , Patient Acuity , Phosphorylation/immunology
8.
J Clin Invest ; 131(20)2021 10 15.
Article in English | MEDLINE | ID: covidwho-1470551

ABSTRACT

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.


Subject(s)
COVID-19/therapy , SARS-CoV-2 , Aged , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/administration & dosage , Antibodies, Viral/therapeutic use , COVID-19/immunology , COVID-19/physiopathology , Combined Modality Therapy , Cross-Over Studies , Female , Humans , Immunization, Passive/adverse effects , Immunization, Passive/methods , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Treatment Outcome
9.
Sci Rep ; 11(1): 16039, 2021 08 06.
Article in English | MEDLINE | ID: covidwho-1345587

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) induces lung injury of varying severity, potentially causing severe acute respiratory distress syndrome (ARDS). Pulmonary injury patterns in COVID-19 patients differ from those in patients with other causes of ARDS. We aimed to explore the frequency and pathogenesis of cavitary lung lesions in critically ill patients with COVID-19. Retrospective study in 39 critically ill adult patients hospitalized with severe acute respiratory syndrome coronavirus 2 including lung injury of varying severity in a tertiary care referral center during March and May 2020, Berlin/Germany. We observed lung cavitations in an unusually large proportion of 22/39 (56%) COVID-19 patients treated on intensive care units (ICU), including 3/5 patients without mechanical ventilation. Median interquartile range (IQR) time between onset of symptoms and ICU admission was 11.5 (6.25-17.75) days. In 15 patients, lung cavitations were already present on the first CT scan, performed after ICU admission; in seven patients they developed during a subsequent median (IQR) observation period of 48 (35-58) days. In seven patients we found at least one cavitation with a diameter > 2 cm (maximum 10 cm). Patients who developed cavitations were older and had a higher body mass index. Autopsy findings in three patients revealed that the cavitations reflected lung infarcts undergoing liquefaction, secondary to thrombotic pulmonary artery branch occlusions. Lung cavitations appear to be a frequent complication of severely ill COVID-19 patients, probably related to the prothrombotic state associated with COVID-19.


Subject(s)
COVID-19/pathology , Lung/pathology , Pulmonary Embolism/pathology , Aged , COVID-19/complications , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Pulmonary Embolism/etiology , Retrospective Studies , SARS-CoV-2/isolation & purification
10.
Sci Rep ; 11(1): 13325, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281739

ABSTRACT

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders , COVID-19 , Thrombelastography , Thromboembolism , Venous Thrombosis , Aged , Blood Coagulation , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/pathology , COVID-19/blood , COVID-19/drug therapy , COVID-19/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index , Thromboembolism/drug therapy , Thromboembolism/pathology , Venous Thrombosis/drug therapy , Venous Thrombosis/pathology
11.
Cell Syst ; 12(8): 780-794.e7, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1267622

ABSTRACT

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.


Subject(s)
Biomarkers/analysis , COVID-19/pathology , Disease Progression , Proteome/physiology , Age Factors , Blood Cell Count , Blood Gas Analysis , Enzyme Activation , Humans , Inflammation/pathology , Machine Learning , Prognosis , Proteomics , SARS-CoV-2/immunology
12.
Sci Rep ; 11(1): 10678, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1238016

ABSTRACT

With an urgent need for bedside imaging of coronavirus disease 2019 (COVID-19), this study's main goal was to assess inter- and intraobserver agreement in lung ultrasound (LUS) of COVID-19 patients. In this single-center study we prospectively acquired and evaluated 100 recorded ten-second cine-loops in confirmed COVID-19 intensive care unit (ICU) patients. All loops were rated by ten observers with different subspeciality backgrounds for four times by each observer (400 loops overall) in a random sequence using a web-based rating tool. We analyzed inter- and intraobserver variability for specific pathologies and a semiquantitative LUS score. Interobserver agreement for both, identification of specific pathologies and assignment of LUS scores was fair to moderate (e.g., LUS score 1 Fleiss' κ = 0.27; subpleural consolidations Fleiss' κ = 0.59). Intraobserver agreement was mostly moderate to substantial with generally higher agreement for more distinct findings (e.g., lowest LUS score 0 vs. highest LUS score 3 (median Fleiss' κ = 0.71 vs. 0.79) or air bronchograms (median Fleiss' κ = 0.72)). Intraobserver consistency was relatively low for intermediate LUS scores (e.g. LUS Score 1 median Fleiss' κ = 0.52). We therefore conclude that more distinct LUS findings (e.g., air bronchograms, subpleural consolidations) may be more suitable for disease monitoring, especially with more than one investigator and that training material used for LUS in point-of-care ultrasound (POCUS) should pay refined attention to areas such as B-line quantification and differentiation of intermediate LUS scores.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Point-of-Care Systems , SARS-CoV-2 , COVID-19/therapy , Female , Humans , Male , Middle Aged , Monitoring, Physiologic , Observer Variation , Prospective Studies , Ultrasonography
13.
Cells ; 10(4)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1232577

ABSTRACT

Thrombin, the ligand of the protease-activated receptor 1 (PAR1), is a well-known stimulator of proangiogenic responses in vascular endothelial cells (ECs), which are mediated through the induction of vascular endothelial growth factor (VEGF). However, the transcriptional events underlying this thrombin-induced VEGF induction and angiogenic response are less well understood at present. As reported here, we conducted detailed promotor activation and signal transduction pathway studies in human microvascular ECs, to decipher the transcription factors and the intracellular signaling events underlying the thrombin and PAR-1-induced endothelial VEGF induction. We found that c-FOS is a key transcription factor controlling thrombin-induced EC VEGF synthesis and angiogenesis. Upon the binding and internalization of its G-protein-coupled PAR-1 receptor, thrombin triggers ERK1/2 signaling and activation of the nuclear AP-1/c-FOS transcription factor complex, which then leads to VEGF transcription, extracellular secretion, and concomitant proangiogenic responses of ECs. In conclusion, exposure of human microvascular ECs to thrombin triggers signaling through the PAR-1-ERK1/2-AP-1/c-FOS axis to control VEGF gene transcription and VEGF-induced angiogenesis. These observations offer a greater understanding of endothelial responses to thromboinflammation, which may help to interpret the results of clinical trials tackling the conditions associated with endothelial injury and thrombosis.


Subject(s)
Gene Expression Regulation , Neovascularization, Physiologic/genetics , Thrombin/pharmacology , Transcription, Genetic/drug effects , Vascular Endothelial Growth Factor A/metabolism , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation/drug effects , Humans , Microvessels/pathology , Neovascularization, Physiologic/drug effects , Promoter Regions, Genetic/genetics , Proto-Oncogene Proteins c-jun/metabolism , Receptor, PAR-1/metabolism , Transcription Factor AP-1/metabolism , Vascular Endothelial Growth Factor A/genetics
14.
J Clin Med ; 10(10)2021 May 13.
Article in English | MEDLINE | ID: covidwho-1227038

ABSTRACT

Background Antigen-detecting rapid diagnostic tests (Ag-RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) offer new opportunities for the quick and laboratory-independent identification of infected individuals for control of the SARS-CoV-2 pandemic. Despite the potential benefits, nasopharyngeal sample collection is frequently perceived as uncomfortable by patients and requires trained healthcare personnel with protective equipment. Therefore, anterior nasal self-sampling is increasingly recognized as a valuable alternative. Methods We performed a prospective, single-center, point of care validation of an Ag-RDT using a polypropylene absorbent collector for standardized self-collected anterior nasal swabs. Real-time polymerase chain reaction (RT-PCR) from combined oropharyngeal/nasopharyngeal swabs served as a comparator. Primary endpoint was sensitivity of the standardized Ag-RDT in symptomatic patients with medium or high viral concentration (≥1 million RNA copies on RT-PCR for SARS-CoV-2). Results Between 12 February and 22 March 2021, 388 participants were enrolled. After exclusion of 9 patients for which no PCR result could be obtained, the novel Ag-RDT was evaluated based on 379 participants, of whom 273 were symptomatic and 106 asymptomatic. In 61 samples from symptomatic patients with medium or high viral load (≥1 million RNA copies), the sensitivity of the standardized Ag-RDT was 96.7% (59/61; 95% confidence interval (CI): 88.7-99.6%) for the primary endpoint. In total, 62 positive Ag-RDT results were detected out of 70 RT-PCR positive individuals, yielding an overall sensitivity of 88.6% (95% CI: 78.7-94.9%). Specificity was 99.7% (95% CI: 98.2-100%) in 309 RT-PCR negative individuals. Conclusions Here, we present a validation of a novel Ag-RDT with a standardized sampling process for anterior nasal self-collection, which meets World Health Organisation (WHO) criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, this assay could be beneficial due to its rapid results, ease of use, and suitability for standardized self-testing.

15.
Z Geburtshilfe Neonatol ; 225(2): 183-187, 2021 04.
Article in English | MEDLINE | ID: covidwho-1192802

ABSTRACT

INTRODUCTION: SARS-CoV-2 is a novel coronavirus that was first isolated in Wuhan, China, and resulted in a rapidly spreading pandemic worldwide. Currently there is only limited evidence on the effect of COVID-19 on pregnant women. CASE: Here we present one of the first serious COVID-19 cases in pregnancy at term with subsequent delivery. Postpartum the mother required antibiotic and symptomatic treatment. She experienced acute worsening of symptoms and developed acute respiratory failure requiring endotracheal intubation and subsequently extracorporeal membrane oxygenation. CONCLUSION: COVID-19 affects all medical disciplines, requiring interdisciplinary approaches and development of patient care regimes. Obstetricians should be aware and be prepared for the special needs of pregnant women with potential prenatal and postnatal issues. Ideally pregnant COVID-19 patients should be cared for at a tertiary perinatal center with experienced perinatologists and neonatologists.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Respiratory Distress Syndrome , China , Female , Humans , Peripartum Period , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , SARS-CoV-2
16.
Kidney Int Rep ; 6(4): 905-915, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1169160

ABSTRACT

INTRODUCTION: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development. METHODS: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI. RESULTS: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings. CONCLUSION: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.

17.
Brain Behav Immun ; 93: 415-419, 2021 03.
Article in English | MEDLINE | ID: covidwho-987109

ABSTRACT

BACKGROUND: COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity. DESIGN: Blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies. RESULTS: Using cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. CONCLUSION: The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.


Subject(s)
Autoantibodies/cerebrospinal fluid , COVID-19/cerebrospinal fluid , Central Nervous System Diseases/virology , Aged , Autoantigens , Autoimmunity , Female , Humans , Male , Middle Aged
18.
Crit Care ; 24(1): 676, 2020 12 07.
Article in English | MEDLINE | ID: covidwho-962957

ABSTRACT

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.


Subject(s)
COVID-19/complications , Fibrinolysis/physiology , Thrombelastography/methods , Thromboembolism/diagnosis , Blood Coagulation/physiology , Blood Coagulation Tests/methods , Blood Coagulation Tests/standards , COVID-19/diagnostic imaging , COVID-19/physiopathology , Cohort Studies , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Male , Middle Aged , Point-of-Care Systems/standards , Point-of-Care Systems/statistics & numerical data , Thromboembolism/diagnostic imaging , Viscoelastic Substances/analysis , Viscoelastic Substances/therapeutic use
19.
Radiol Case Rep ; 15(10): 1764-1768, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-654505

ABSTRACT

A 64-year-old female patient presented with severe dyspnea shortly after apparent recovery from COVID-19 disease. Chest computed tomography revealed central pulmonary embolism and ultrasonography showed a deep vein thrombosis of her right leg. The patient was tachycardiac with evidence of right ventricular strain on echocardiography. An interdisciplinary decision for interventional therapy was made. Angiographic aspiration thrombectomy resulted in a significant reduction of thrombus material and improved flow in the pulmonary arteries and immediate marked clinical improvement and subsequent normalization of functional echocardiographic parameters. This case adds to the emerging evidence for severe thromboembolic complications following COVID-19 and suggests aspiration thrombectomy can be considered in pulmonary embolism of intermediate risk.

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