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1.
BMC Infect Dis ; 21(1): 901, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1455938

ABSTRACT

BACKGROUND: The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. CASE PRESENTATION: Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). CONCLUSION: Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.


Subject(s)
COVID-19 , Liver Failure, Acute , Aged, 80 and over , Female , Humans , Liver Cirrhosis/complications , Liver Failure, Acute/etiology , Peptidyl-Dipeptidase A , SARS-CoV-2
2.
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
3.
Blood ; 136(Supplement 1):46-46, 2020.
Article in English | PMC | ID: covidwho-1338956

ABSTRACT

Introduction: By now, the pandemic spread of COVID-19 (coronavirus disease 2019) has claimed more than 600,000 lives. The adaptive immune response seems to play a major role in the progression of the disease, since entry of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is determined by a spike protein recognized by T helper cells. This has been linked to the clinical finding of severe lymphocytopenia in these patients. However, detailed cellular immune responses in the bone marrow (BM) and in the spleen (SPL) of COVID-19 patients have not been addressed yet. Here, we provide novel immunologic insight with potential for therapeutic management and risk stratification in COVID-19.Material and Methods: We performed complete autopsies on 11 confirmed COVID-19 and 4 non-COVID-19 deceased, who were matched for risk profile and age. SARS-CoV-2 load was measured by rt-PCR (quantitative real-time polymerase chain reaction) targeting the SARS-CoV-2 E-gene in purified RNA extracts from 50mg of pulmonary tissue (MagNAPure 96 system, Viral NA Large Volume Kit, Roche). For histopathology, representative tissue samples of decalcified BM and SPL were fixed in 4 % buffered formalin, dehydrated and paraffin embedded. Sections were stained with HE, PAS, Giemsa-, Gomori- and Prussian blue stain. Furthermore, BM and SPL were stained with immunohistochemical reagents, namely MPO (Myeloperoxidase), CD235, CD34, CD117, CD68, CD61, CD20, CD3, CD4, CD8, CD138, HLA-DR (Human Leucocyte antigen - DR isotype), PD-1, PD-L1 (Programmed cell death protein and ligand 1), Ki67 and Caspase3 (Ventana Ultra and LEICA Bond III). Additionally, we performed in-situ hybridization of EBV (Epstein-Barr-Virus;LEICA Bond MAX), followed by PCR of the EBV nuclear antigen 1 (Thermo Fisher and Roche). Histopathology was evaluated by at least two hematopathologists. Clinical data were obtained from patients' files. Statistical analysis was done using GraphPad Prism8 Software. Inc, 2018.Results: Of all COVID-19 deceased, 73% (n = 8/11) showed BM hypercellularity, increased granulocyte / erythrocyte ratios, and left shift of erythro- and granulopoiesis with anemia and an increase of immature granulocytes in the peripheral blood. Thromboembolic events were present in 82% (n = 9/11) of COVID-19 patients and related to an increase and left shift of megakaryopoiesis in the BM. In the BM of patients with severe bacterial superinfection of COVID-19 pneumonia, we observed an early increase of PD-L1 expression on myeloid cells, lymphocytic apoptosis, and time-dependent macrophage anergy with a continuous loss of antigen-presenting capacity. Furthermore, we found CD20+ B-cell depletion in either BM or SPL in 64% (n = 7/11) of COVID-19 patients with B-cell counts of less than 1% in the BM and 1-5% in the SPL, followed by complete plasma cell depletion. This was reflected by severe lymphocytopenia in the peripheral blood. In contrast, BM T-cell counts were nearly as high in COVID-19 decedents (median 10%) as in cases not related to COVID-19 (median 12.5%). Interestingly, there was a tendency towards higher pulmonary SARS-CoV-2 RNA load in COVID-19 patients with B-cell depletion, as we observed maximum viral copy numbers of up to 1,150,000 / 10,000 cells in patients with B-cell depletion as compared to 6,500 / 10,000 cells in patients with B-cell preservation. EBV was absent in all cases. Clinical characteristics and time-intervals between initial symptoms and death of COVID-19 patients were heterogenous, therefore preventing the detection of a clinical risk profile in patients with B-cell depletion.Conclusion: Our results show that severe lymphocyte depletion in COVID-19 deceased is caused by a substantial loss of B-cells which is in turn associated with viral SARS-CoV-2 burden and presumably results from excessive activation of the adaptive immune system. It is yet to be determined how B-cell specific pathways are affected by SARS-CoV-2 and whether this might serve as a therapeutic target of interest. Moreover, we provide morphologic evidence, that COVID-19 pneu onia with bacterial superinfection is aggravated by sepsis acquired immunodeficiency. Since the latter is associated with an epigenetically determined switch to endotoxin tolerance, our findings may additionally aid in risk stratification of COVID-19 patients who undergo severe bacterial superinfection during the disease.

4.
Int J Infect Dis ; 108: 274-281, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1253010

ABSTRACT

OBJECTIVES: Studies on coronavirus disease 2019 (COVID-19) usually focus on middle-aged and older adults. However, younger patients may present with severe COVID-19 with potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of the underlying pathomechanisms is of utmost importance. METHODS: Our study investigated relevant, pre-existing medical conditions, clinical histories, and autopsy findings, together with SARS-CoV-2-RNA, determined by qPCR, and laboratory data in six COVID-19 decedents aged 50 years or younger, who were autopsied at the Charité University Hospital. RESULTS: From a total of 76 COVID-19 patients who underwent an autopsy at our institution, six (7.9%) were 50 years old or younger. Most of these younger COVID-19 decedents presented with pre-existing medical conditions prior to SARS-CoV-2 infection. These included overweight and obesity, arterial hypertension, asthma, and obstructive sleep apnea, as well as graft-versus-host disease following cancer and bone marrow transplantation. Furthermore, clinical histories and autopsy results revealed a disproportionally high prevalence of thromboembolism and ischemic organ damage in this patient cohort. Histopathology and laboratory results indicated coagulopathies, signs of immune dysregulation, and liver damage. CONCLUSIONS: In conclusion, pre-existing health conditions may increase the risk of severe and fatal COVID-19 in younger patients, who may be especially prone to developing thromboembolic complications, immune dysregulation, and liver damage.


Subject(s)
COVID-19 , Hypertension , Aged , Autopsy , Humans , Middle Aged , Overweight , SARS-CoV-2
5.
Sci Rep ; 11(1): 4263, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1091460

ABSTRACT

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.


Subject(s)
COVID-19/mortality , Cause of Death , Hospital Mortality , Adult , Aged , Aged, 80 and over , Autopsy , Berlin/epidemiology , COVID-19/complications , COVID-19/therapy , COVID-19/virology , Comorbidity , Female , Hospitals, Teaching/statistics & numerical data , Humans , Hypertension/epidemiology , Male , Middle Aged , Multiple Organ Failure/mortality , Multiple Organ Failure/virology , Myocardial Ischemia/epidemiology , Obesity/epidemiology , Prospective Studies , SARS-CoV-2/isolation & purification , Shock, Septic/mortality , Shock, Septic/virology
6.
Int J Infect Dis ; 103: 628-635, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1002639

ABSTRACT

OBJECTIVES: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified. METHODS: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. RESULTS: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts. CONCLUSIONS: The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.


Subject(s)
B-Lymphocytes/immunology , Bone Marrow/immunology , COVID-19/immunology , Lymphopenia/etiology , SARS-CoV-2 , Sepsis/immunology , Spleen/immunology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
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