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2.
Intern Med ; 60(3): 457-461, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-1110169

ABSTRACT

We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.


Subject(s)
/therapy , Immunoglobulins, Intravenous/administration & dosage , Respiratory Insufficiency/therapy , /isolation & purification , /complications , Cytokine Release Syndrome/prevention & control , Cytokines/drug effects , Humans , Ivermectin/therapeutic use , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Radiography, Thoracic , Viral Load
3.
Cells ; 10(2)2021 02 10.
Article in English | MEDLINE | ID: covidwho-1094233

ABSTRACT

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.


Subject(s)
/complications , Placenta/blood supply , Placenta/pathology , Pregnancy Complications, Cardiovascular/etiology , Pregnancy Complications, Infectious/etiology , Thrombosis/etiology , Adult , Antigens, CD/analysis , /virology , Cadherins/analysis , Claudin-5/analysis , Endothelium/blood supply , Endothelium/pathology , Endothelium/virology , Female , Humans , Infant, Newborn , Microvessels/pathology , Microvessels/virology , Pregnancy , Pregnancy Complications, Cardiovascular/pathology , Pregnancy Complications, Cardiovascular/virology , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , Thrombosis/pathology , Thrombosis/virology , Young Adult , von Willebrand Factor/analysis
4.
BMC Surg ; 21(1): 97, 2021 Feb 22.
Article in English | MEDLINE | ID: covidwho-1094031

ABSTRACT

BACKGROUND: In patients who are critically ill with COVID-19, multiple extrapulmonary manifestations of the disease have been observed, including gastrointestinal manifestations. CASE PRESENTATION: We present a case of a 65 year old man with severe COVID-19 pneumonia that developed hypercoagulation and peritonitis. Emergent laparotomy was performed and we found bowel necrosis in two sites. CONCLUSIONS: Although rare, the presentation of COVID-19 with bowel necrosis requires emergency treatments, and it has high mortality rate.


Subject(s)
Intestinal Diseases , Aged , /therapy , Humans , Intestinal Diseases/pathology , Intestinal Diseases/virology , Male , Necrosis , Severity of Illness Index
5.
BMC Infect Dis ; 21(1): 192, 2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1090689

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic that has raised worldwide concern. This study aims to investigate the correlation between the extent of lung infection and relevant clinical laboratory testing indicators in COVID-19 and to analyse its underlying mechanism. METHODS: Chest high-resolution computer tomography (CT) images and laboratory examination data of 31 patients with COVID-19 were extracted, and the lesion areas in CT images were quantitatively segmented and calculated using a deep learning (DL) system. A cross-sectional study method was carried out to explore the differences among the proportions of lung lobe infection and to correlate the percentage of infection (POI) of the whole lung in all patients with clinical laboratory examination values. RESULTS: No significant difference in the proportion of infection was noted among various lung lobes (P > 0.05). The POI of total lung was negatively correlated with the peripheral blood lymphocyte percentage (L%) (r = - 0.633, P < 0.001) and lymphocyte (LY) count (r = - 0.555, P = 0.001) but positively correlated with the neutrophil percentage (N%) (r = 0.565, P = 0.001). Otherwise, the POI was not significantly correlated with the peripheral blood white blood cell (WBC) count, monocyte percentage (M%) or haemoglobin (HGB) content. In some patients, as the infection progressed, the L% and LY count decreased progressively accompanied by a continuous increase in the N%. CONCLUSIONS: Lung lesions in COVID-19 patients are significantly correlated with the peripheral blood lymphocyte and neutrophil levels, both of which could serve as prognostic indicators that provide warning implications, and contribute to clinical interventions in patients.


Subject(s)
/diagnostic imaging , Lung/pathology , Machine Learning , Adult , Clinical Laboratory Techniques , Cross-Sectional Studies , Female , Humans , Lung/diagnostic imaging , Lung/virology , Lymphocyte Count , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Pandemics , Prognosis , Severity of Illness Index , Tomography, X-Ray Computed
6.
J Transl Med ; 19(1): 79, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1088601

ABSTRACT

BACKGROUND: The Sars-CoV-2 can cause severe pneumonia with multiorgan disease; thus, the identification of clinical and laboratory predictors of the progression towards severe and fatal forms of this illness is needed. Here, we retrospectively evaluated and integrated laboratory parameters of 45 elderly subjects from a long-term care facility with Sars-CoV-2 outbreak and spread, to identify potential common patterns of systemic response able to better stratify patients' clinical course and outcome. METHODS: Baseline white blood cells, granulocytes', lymphocytes', and platelets' counts, hemoglobin, total iron, ferritin, D-dimer, and interleukin-6 concentration were used to generate a principal component analysis. Statistical analysis was performed by using R statistical package version 4.0. RESULTS: We identified 3 laboratory patterns of response, renamed as low-risk, intermediate-risk, and high-risk, strongly associated with patients' survival (p < 0.01). D-dimer, iron status, lymphocyte/monocyte count represented the main markers discriminating high- and low-risk groups. Patients belonging to the high-risk group presented a significantly longer time to ferritin decrease (p: 0.047). Iron-to-ferritin-ratio (IFR) significantly segregated recovered and dead patients in the intermediate-risk group (p: 0.012). CONCLUSIONS: Our data suggest that a combination of few laboratory parameters, i.e. iron status, D-dimer and lymphocyte/monocyte count at admission and during the hospital stay, can predict clinical progression in COVID-19.


Subject(s)
/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Iron/blood , Lymphocytes/pathology , Monocytes/pathology , Aged , Aged, 80 and over , Biomarkers/blood , /mortality , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Leukocyte Count , Long-Term Care , Male , Middle Aged , Platelet Count , Prognosis , Retrospective Studies , Treatment Outcome
7.
J Clin Neuromuscul Dis ; 22(3): 147-154, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1087831

ABSTRACT

ABSTRACT: This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression.


Subject(s)
/complications , Myasthenia Gravis/complications , Neuromuscular Junction/pathology , /pathology , Humans , Myasthenia Gravis/drug therapy , Myasthenia Gravis/pathology , Myasthenia Gravis/therapy , Thymectomy
8.
Discov Med ; 30(161): 155-161, 2020.
Article in English | MEDLINE | ID: covidwho-1085799

ABSTRACT

SARS-CoV-2 is a novel coronavirus responsible for the global coronavirus 2019 pandemic (COVID-19), which started in early 2020 and is still ongoing today. COVID-19 has caused more than 1 million deaths worldwide and about 50 million infected. COVID-19 not only causes lung injury, but there may also be an involvement of other organs, including the cardiovascular system. SARS-CoV-2 penetrates host cells through the angiotensin 2 conversion enzyme (ACE-2). ACE-2 is expressed in the lungs, heart, testicles, liver, gastrointestinal tract, etc. Several studies have found that a sizeable percentage of patients with severe COVID-19 also have cardiac lesions, including myocardial fibrosis, edema, and pericarditis. Pathological remodeling of the extracellular matrix caused by SARS-CoV-2 leads to fibrotic lesions of myocardial tissue. These fibrotic lesions can cause cardiac dysfunction, reducing the ejection fraction caused by the presence of stiffened myocardial matrix and leading to heart failure, or cause an alteration in electrical conductance by creating cardiac arrhythmias. These cardiac dysfunctions can be fatal if left untreated and managed. It is therefore essential to identify cardiac involvement early in order to act with appropriate treatments to preserve the integrity of the heart. In this review, we describe what is known about cardiac damage from COVID-19, including the scientific rationale for effective therapeutic solutions to combat cardiac injury, and reduce or avoid cardiac damage from COVID-19.


Subject(s)
/complications , Heart Diseases/drug therapy , Heart Diseases/etiology , Myocardium/pathology , /physiology , /virology , Humans , Models, Biological , Risk Factors
9.
BMC Infect Dis ; 21(1): 175, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1085168

ABSTRACT

BACKGROUND: While hypertension is the most common comorbid condition in patients with coronavirus disease 2019 (COVID-19) in Korea, there is a lack of studies investigating risk factors in COVID-19 patients with hypertension in Korea. In this study, we aimed to examine the effects risk factors in hypertensive Korean COVID-19 patients. METHODS: We selected patients from the database of the project #OpenData4Covid19. This information was linked to their 3-year historical healthcare data. The severity of the disease was classified into five levels. We also clustered the levels into two grades. RESULTS: The risk factors associated with COVID-19 severity were old age, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), malignancy, and renal replacement therapy. The use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) both before and after a diagnosis of COVID-19 were not associated with COVID-19 severity. A multivariate analysis revealed that old age, male sex, diabetes mellitus, and renal replacement therapy were risk factors for severe COVID-19. CONCLUSION: The results suggest that in hypertensive patients with COVID-19, older age, male sex, a diagnosis of diabetes mellitus, and renal replacement therapy were risk factors for a severe clinical course. In addition, the use of ARBs and ACEIs before or after COVID-19 infection did not affect a patient's risk of contracting COVID-19 nor did it contribute to a worse prognosis for the disease. These results highlighted that precautions should be considered for hypertensive patients with those risk factors and do not support discontinuation of ARBs and ACEIs during COVID-19 pandemic.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , /pathology , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , /epidemiology , Diabetes Mellitus/pathology , Female , Humans , Hypertension/complications , Hypertension/pathology , Male , Medical History Taking , Middle Aged , Pandemics , Renin-Angiotensin System/drug effects , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , /physiology
10.
BMC Infect Dis ; 21(1): 176, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1085167

ABSTRACT

BACKGROUND: Epidemiological and clinical features of patients with corona virus disease 2019 (COVID-19) were well delineated. However, no researches described the patients complicated with pleural effusion (PE). In the present study, we aimed to clinically characterize the COVID-19 patients complicated with PE and to create a predictive model on the basis of PE and other clinical features to identify COVID-19 patients who may progress to critical condition. METHODS: This retrospective study examined 476 COVID-19 inpatients, involving 153 patients with PE and 323 without PE. The data on patients' past history, clinical features, physical checkup findings, laboratory results and chest computed tomography (CT) findings were collected and analyzed. LASSO regression analysis was employed to identify risk factors associated with the severity of COVID-19. RESULTS: Laboratory findings showed that patients with PE had higher levels of white blood cells, neutrophils, lactic dehydrogenase, C-reactive protein and D-dimer, and lower levels of lymphocytes, platelets, hemoglobin, partial pressure of oxygen and oxygen saturation. Meanwhile, patients with PE had higher incidence of severe or critical illness and mortality rate, and longer hospital stay time compared to their counterparts without pleural effusion. Moreover, LASSO regression analysis exhibited that pleural effusion, lactic dehydrogenase (LDH), D-dimer and total bilirubin (TBIL) might be risk factors for critical COVID-19. CONCLUSIONS: Pleural effusion could serve as an indicator for severe inflammation and poor clinical outcomes, and might be a complementary risk factor for critical type of COVID-19.


Subject(s)
/pathology , Pleural Effusion/pathology , Adult , C-Reactive Protein/analysis , /physiopathology , China , Exudates and Transudates , Female , Humans , Male , Middle Aged , Pleural Effusion/physiopathology , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed
11.
Med Sci Monit ; 27: e928837, 2021 Feb 13.
Article in English | MEDLINE | ID: covidwho-1084734

ABSTRACT

BACKGROUND Coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health Organization (WHO) in March 2020. To further reveal the pathologic associations between coronavirus and hypoxemia, we report the findings of 4 complete systematic autopsies of severe acute respiratory syndrome coronavirus 2-positive individuals who died of multiple organ failure caused by severe hypoxemia. MATERIAL AND METHODS We examined the donated corpses of 4 deceased patients who had been diagnosed with severe acute respiratory syndrome coronavirus 2. A complete post-mortem examination was carried out on each corpse, and multiple organs were macroscopically examined. RESULTS The 4 corpses were 2 males and 2 females, with an average age of 69 years. Bilateral lungs showed various degrees of atrophy and consolidation, with diffusely tough and solid texture in the sections. A thromboembolism was found in the main pulmonary artery extending into the atrium in 1 corpse, and significant atherosclerotic plaques tagged in the inner wall of the aortic arch were found in 2 corpses. Two corpses were found to have slightly atrophied bilateral renal parenchyma. Atrophic changes in the spleen were found in 2 corpses. Notably, there were significantly expanded alveolar septa and prominent fibroblastic proliferation. CONCLUSIONS The laboratory data of these corpses showed a progressive decrease in blood oxygen saturation, followed by refractory and irreversible hypoxemia. Clinical and laboratory information and autopsy and histologic presentations of multiple organs showed insufficient air exchange due to abnormalities in the respiratory system, and reduced erythropoiesis in bone marrow may play a role.


Subject(s)
Autopsy , /virology , Hypoxia/complications , Hypoxia/pathology , Pneumonia/pathology , Pneumonia/virology , /physiology , Aged , Aged, 80 and over , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Cell Aggregation , Female , Humans , Lung/pathology , Macrophages/pathology , Male , Middle Aged , Mucus/metabolism , Myocardium/pathology , Necrosis , Pneumonia/complications , Thoracic Cavity/pathology
12.
Front Immunol ; 11: 599736, 2020.
Article in English | MEDLINE | ID: covidwho-1081614

ABSTRACT

In the last few months, the coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and has provoked an exceptional effort from the scientific community to understand the disease. Clinical evidence suggests that severe COVID-19 is associated with both dysregulation of damage tolerance caused by pulmonary immunopathology and high viral load. In this review article, we describe and discuss clinical studies that show advances in the understanding of mild and severe illness and we highlight major points that are critical for improving the comprehension of different clinical outcomes. The understanding of pulmonary immunopathology will contribute to the identification of biomarkers in an attempt to classify mild, moderate, severe and critical COVID-19 illness. The interface of pulmonary immunopathology and the identification of biomarkers are critical for the development of new therapeutic strategies aimed to reduce the systemic and pulmonary hyperinflammation in severe COVID-19.


Subject(s)
Biomarkers/analysis , /pathology , Lung/immunology , Lung/pathology , Humans , Lung/virology
13.
J Immunother Cancer ; 9(2)2021 02.
Article in English | MEDLINE | ID: covidwho-1081352

ABSTRACT

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.


Subject(s)
/diagnosis , Lung Neoplasms/diagnosis , Pneumonia/diagnosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Aged , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , /immunology , Diagnosis, Differential , Humans , /adverse effects , Immunotherapy/adverse effects , Lung Injury/diagnosis , Lung Injury/diagnostic imaging , Lung Injury/pathology , Lung Injury/virology , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/virology , Male , Nasopharynx/metabolism , Nasopharynx/pathology , Neoplasm Metastasis , Pandemics , Pneumonia/drug therapy , Pneumonia/immunology , Pneumonia/virology , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology
14.
World J Gastroenterol ; 27(5): 377-390, 2021 Feb 07.
Article in English | MEDLINE | ID: covidwho-1081093

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.


Subject(s)
/complications , Liver Failure/virology , Antiviral Agents/adverse effects , /pathology , Gastrointestinal Tract/physiopathology , Host-Pathogen Interactions , Humans , Inflammation/complications , Liver/pathology , Liver Failure/chemically induced , Metabolic Syndrome/complications , Prognosis , /physiology
15.
PLoS One ; 16(1): e0245019, 2021.
Article in English | MEDLINE | ID: covidwho-1079325

ABSTRACT

The knowledge on the deposition and retention of the viral particle of SARS-CoV-2 in the respiratory tract during the very initial intake from the ambient air is of prime importance to understand the infectious process and COVID-19 initial symptoms. We propose to use a modified version of a widely tested lung deposition model developed by the ICRP, in the context of the ICRP Publication 66, that provides deposition patterns of microparticles in different lung compartments. In the model, we mimicked the "environmental decay" of the virus, determined by controlled experiments related to normal speeches, by the radionuclide 11C that presents comparable decay rates. Our results confirm clinical observations on the high virus retentions observed in the extrathoracic region and the lesser fraction on the alveolar section (in the order of 5), which may shed light on physiopathology of clinical events as well on the minimal inoculum required to establish infection.


Subject(s)
/virology , /physiology , Aerosols/analysis , Carbon Radioisotopes , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Models, Biological , Respiratory System/metabolism , Respiratory System/virology
16.
mSphere ; 6(1)2021 02 10.
Article in English | MEDLINE | ID: covidwho-1079035

ABSTRACT

Compared to other human coronaviruses, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) are relatively understudied. We report a fatal case of COVID-19 pneumonia coinfected with HCoV-229E in Hong Kong. Genome sequencing of SARS-CoV-2 and HCoV-229E from a nasopharyngeal sample of the patient showed that the SARS-CoV-2 strain HK13 was most closely related to SARS-CoV-2 type strain Wuhan-Hu-1 (99.99% nucleotide identity), compatible with his recent history of travel to Wuhan. The HCoV-229E strain HK20-42 was most closely related to HCoV-229E strain SC0865 from the United States (99.86% nucleotide identity). To investigate if it may represent a newly emerged HCoV-229E genotype in Hong Kong, we retrieved 41 archived respiratory samples that tested positive for HCoV-229E from 2004 to 2019. Pneumonia and exacerbations of chronic airway diseases were common among infected patients. Complete RdRp, S, and N gene sequencing of the 41 HCoV-229E strains revealed that our contemporary HCoV-229E strains have undergone significant genetic drift with clustering of strains in chronological order. Two novel genogroups were identified, in addition to previously described genogroups 1 to 4, with recent circulating strains including strain HK20-42 belonging to novel genogroup 6. Positive selection was detected in the spike protein and receptor-binding domain, which may be important for viral evolution at the receptor-binding interphase. Molecular dating analysis showed that HCoV-229E shared the most recent common ancestor with bat and camel/alpaca 229E-related viruses at ∼1884, while camel/alpaca viruses had a relatively recent common ancestor at ∼1999. Further studies are required to ascertain the evolutionary origin and path of HCoV-229E.IMPORTANCE Since its first appearance in the 1960s, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) have been relatively understudied. In this study, we report a fatal case of COVID-19 coinfected with HCoV-229E in Hong Kong. Genome sequencing revealed that our SARS-CoV-2 strain is highly identical to the SARS-CoV-2 strain from Wuhan, compatible with the patient's recent travel history, whereas our HCoV-229E strain in this study is highly identical to a recent strain in the United States. We also retrieved 41 archived HCoV-229E strains from 2004 to 2019 in Hong Kong for sequence analysis. Pneumonia and exacerbations of chronic airway diseases were common diagnoses among the 41 patients. The results showed that HCoV-229E was evolving in chronological order. Two novel genogroups were identified in addition to the four preexisting HCoV-229E genogroups, with recent circulating strains belonging to novel genogroup 6. Molecular clock analysis dated bat-to-human and bat-to-camelid transmission to as early as 1884.


Subject(s)
/pathology , Common Cold/pathology , Coronavirus 229E, Human/genetics , Genetic Variation/genetics , /genetics , Adolescent , Adult , Aged , Aged, 80 and over , Base Sequence , Child , Child, Preschool , Coinfection/virology , Evolution, Molecular , Female , Genome, Viral/genetics , Hong Kong , Humans , Infant , Male , Middle Aged , Protein Domains/genetics , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/genetics , Young Adult
17.
Ren Fail ; 43(1): 335-339, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1078673

ABSTRACT

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.


Subject(s)
Acute Kidney Injury/chemically induced , Adenine/analogs & derivatives , Nephritis, Interstitial/chemically induced , Piperidines/adverse effects , Proteinuria/chemically induced , Acute Kidney Injury/drug therapy , Adenine/adverse effects , Aged , Cytokines/drug effects , Glucocorticoids/therapeutic use , Humans , Kidney/pathology , Leukemia, Prolymphocytic/drug therapy , Male , Nephritis, Interstitial/drug therapy , Protein Kinase Inhibitors , Proteinuria/drug therapy
18.
Nat Commun ; 12(1): 944, 2021 02 11.
Article in English | MEDLINE | ID: covidwho-1078588

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits high levels of mortality and morbidity and has dramatic consequences on human life, sociality and global economy. Neutralizing antibodies constitute a highly promising approach for treating and preventing infection by this novel pathogen. In the present study, we characterize and further evaluate the recently identified human monoclonal MD65 antibody for its ability to provide protection against a lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice. Eighty percent of the untreated mice succumbed 6-9 days post-infection, while administration of the MD65 antibody as late as 3 days after exposure rescued all infected animals. In addition, the efficiency of the treatment is supported by prevention of morbidity and ablation of the load of infective virions in the lungs of treated animals. The data demonstrate the therapeutic value of human monoclonal antibodies as a life-saving treatment for severe COVID-19 infection.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , /immunology , Animals , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Chlorocebus aethiops , Female , Immunoglobulin G/administration & dosage , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Lung/pathology , Lung/virology , Male , Mice, Inbred C57BL , Mice, Transgenic , /physiology , Seroconversion , Vero Cells , Viral Load
19.
Viruses ; 13(1)2020 12 30.
Article in English | MEDLINE | ID: covidwho-1073492

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-α2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-α levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.


Subject(s)
Antiviral Agents/therapeutic use , Interferon-alpha/therapeutic use , Lung/abnormalities , Administration, Inhalation , Antiviral Agents/administration & dosage , Biomarkers/blood , C-Reactive Protein , CD8-Positive T-Lymphocytes , China , Cohort Studies , Cytokines/immunology , Drug Therapy, Combination , Humans , Indoles/administration & dosage , Indoles/therapeutic use , Interferon-alpha/administration & dosage , Interleukin-10 , Interleukin-6 , Lung/diagnostic imaging , Lung/pathology , /drug effects
20.
Blood Adv ; 5(3): 913-925, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1072925

ABSTRACT

Tyrosine kinase inhibitors (TKIs) are used to target dysregulated signaling pathways in virtually all hematologic malignancies. Many of the targeted signaling pathways are also essential in nonmalignant immune cells. The current coronavirus severe acute respiratory syndrome coronavirus 2 pandemic catalyzed clinical exploration of TKIs in the treatment of the various stages of COVID-19, which are characterized by distinct immune-related complications. Most of the reported effects of TKIs on immune regulation have been explored in vitro, with different class-specific drugs having nonoverlapping target affinities. Moreover, many of the reported in vivo effects are based on artificial animal models or on observations made in symptomatic patients with a hematologic malignancy who often already suffer from disturbed immune regulation. Based on in vitro and clinical observations, we attempt to decipher the impact of the main TKIs approved or in late-stage development for the treatment of hematological malignancies, including inhibitors of Bruton's tyrosine kinase, spleen tyrosine kinase, BCR-Abl, phosphatidylinositol 3-kinase/ mammalian target of rapamycin, JAK/STAT, and FMS-like tyrosine kinase 3, to provide a rationale for how such inhibitors could modify clinical courses of diseases, such as COVID-19.


Subject(s)
Adaptive Immunity , Hematologic Neoplasms/drug therapy , Immunity, Innate , Protein Kinase Inhibitors/therapeutic use , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Agammaglobulinaemia Tyrosine Kinase/metabolism , /immunology , Cytokines/metabolism , Fusion Proteins, bcr-abl/antagonists & inhibitors , Fusion Proteins, bcr-abl/metabolism , Hematologic Neoplasms/complications , Hematologic Neoplasms/pathology , Humans , /isolation & purification
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