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2.
J Pediatric Infect Dis Soc ; 9(6): 781-784, 2020 Dec 31.
Article in English | MEDLINE | ID: covidwho-1387931

ABSTRACT

We describe an 8-week-old infant with severe gastrointestinal symptoms, significant hypoalbuminemia, and mild carditis following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infant's symptoms, including their temporal appearance, were consistent with multisystem inflammatory syndrome in children (MIS-C). A unique finding on colonic histology which may shed light on the pathogenesis of MIS-C was identified. The patient improved significantly following several anti-inflammatory treatments. The lag between the presentation of MIS-C and initial SARS-CoV-2 exposure, which may often be asymptomatic, together with the young age of our patient, makes this a challenging diagnosis. Clinicians should be aware of this entity, even in the neonatal and infantile age groups, to facilitate timely identification and treatment.


Subject(s)
COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/pathology , COVID-19/therapy , Colon/pathology , Female , Gastrointestinal Tract/pathology , Humans , Infant , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/pathology , Systemic Inflammatory Response Syndrome/therapy
3.
Nephrologe ; : 1-6, 2020 Dec 11.
Article in German | MEDLINE | ID: covidwho-986660

ABSTRACT

The aim of this article is to explain the clinical benefits of the growing knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to the lungs, SARS-CoV­2 can invade multiple cell types in other organs, such as the kidneys and replicate there. Important damaging pathways of the virus, such as vascular endotheliitis, thrombotic events and systemic cytokine release are still incompletely understood. Coronavirus disease 2019 (COVID-19) is a systemic disease that necessitates intensive medical care and in particular, internal medicine involvement and represents a major challenge for all disciplines of internal medicine. Among these, nephrology in particular is involved in the fight against COVID-19 in a variety of ways: urine investigations can provide indications of multiple organ involvement, endotheliitis, microthrombi and microcirculation damage, etc. Experience with low serum albumin levels and antithrombin III activity in nephrotic patients helps to point out the decreasing effects of loop diuretics and heparin to other specialist disciplines. Nephrological knowledge of the complications of hypoalbuminemia and "resistance" to diuretics must lead to an early implementation of renal replacement procedures in order to be able to prevent mechanical ventilation in COVID-19 intensive care patients with increased extracellular lung fluid. The kidneys can be used as a seismograph for severe courses of COVID-19 and nephrological knowledge can be brought to use to optimize the intensive medical care for critically ill patients. Both together have the potential to considerably reduce morbidity and mortality further.

4.
Biomedicines ; 8(11)2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-949004

ABSTRACT

COVID-19 symptoms, including hypokalemia, hypoalbuminemia, ageusia, neurological dysfunctions, D-dimer production, and multi-organ microthrombosis reach beyond effects attributed to impaired angiotensin-converting enzyme 2 (ACE2) signaling and elevated concentrations of angiotensin II (Ang II). Although both SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) and SARS-CoV-2 utilize ACE2 for host entry, distinct COVID-19 pathogenesis coincides with the acquisition of a new sequence, which is homologous to the furin cleavage site of the human epithelial Na+ channel (ENaC). This review provides a comprehensive summary of the role of ACE2 in the assembly of Na+-dependent transporters of glucose, imino and neutral amino acids, as well as the functions of ENaC. Data support an osmotic adaptation mechanism in which osmotic and hemostatic instability induced by Ang II-activated ENaC is counterbalanced by an influx of organic osmolytes and Na+ through the ACE2 complex. We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients. This dual mechanism employed by SARS-CoV-2 calls for combinatorial treatment strategies to address and prevent severe complications of COVID-19.

5.
Chest ; 158(6): e267-e268, 2020 12.
Article in English | MEDLINE | ID: covidwho-860852

ABSTRACT

Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia, and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute coronavirus disease 2019 (COVID-19) infection who presented with hemoconcentration, shock, and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities, requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.


Subject(s)
COVID-19/physiopathology , Capillary Leak Syndrome/physiopathology , Compartment Syndromes/physiopathology , Hypoalbuminemia/physiopathology , Shock/physiopathology , Abdominal Pain/etiology , Acidosis, Lactic/etiology , Acidosis, Lactic/physiopathology , Acidosis, Lactic/therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , COVID-19/complications , COVID-19/therapy , Capillary Leak Syndrome/etiology , Compartment Syndromes/etiology , Compartment Syndromes/surgery , Continuous Renal Replacement Therapy , Crystalloid Solutions/therapeutic use , Edema/etiology , Edema/physiopathology , Fasciotomy , Fatal Outcome , Fluid Therapy , Hematocrit , Humans , Hypoalbuminemia/etiology , Hypoalbuminemia/therapy , Male , Middle Aged , Respiration, Artificial , Rhabdomyolysis/etiology , Rhabdomyolysis/physiopathology , Shock/etiology , Shock/therapy , Tomography, X-Ray Computed , Vasoconstrictor Agents/therapeutic use
6.
Front Cardiovasc Med ; 7: 153, 2020.
Article in English | MEDLINE | ID: covidwho-838591

ABSTRACT

The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. It is physiologically significant in capillary microcirculation and in fluid distribution to the tissues. Human serum albumin (HSA), the most abundant protein in plasma, is created in the liver which also maintains its concentration, but this reduces by 10-15% after 50 years of age. HSA transports hormones, free fatty acids and maintains oncotic pressure, but SARS-CoV-2 virions bind competitively to HSA diminishing its normal transport function. Furthermore, hypoalbuminemia is frequently observed in patients with such conditions as diabetes, hypertension, and chronic heart failure, i.e., those most vulnerable to SARS-CoV-2 infection. Hypoalbuminemia, coagulopathy, and vascular disease have been linked in COVID-19 and have been shown to predict outcome independent of age and morbidity. Hypoalbuminemia is also known factor in sepsis and Acute respiratory distress syndrome (ARDS) occurs when fluids build-up in the alveoli and it is associated with sepsis, whose mechanism is systemic, being associated with the fluid and logistic mechanisms of the circulation. Glycocalyx damage is associated with changes plasma protein concentration, particularly HSA and blockage of albumin transport can produce the systemic symptoms seen in SARS-CoV-2 infection and sepsis. We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites. We postulate that albumin therapy to replace bound albumin might alleviate some of the symptoms leading to sepsis and that clinical trials to test this postulation should be initiated as a matter of urgency.

7.
Eur J Cancer ; 139: 70-80, 2020 11.
Article in English | MEDLINE | ID: covidwho-746055

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has caused a major pandemic. Patients with cancer are at higher risk of severe COVID-19. We aimed to describe and compare the immunological features of cancer patients hospitalised for COVID-19 or other concomitant, cancer-related illness. METHODS: In this prospective study, the clinical and immunological characteristics of 11 cancer patients with COVID-19 and 11 non-COVID-19 cancer patients hospitalised in the same unit at the same period for other medical issues were analysed. We also used 10 healthy volunteers as controls. Peripheral immune parameters were analysed using multiparametric flow cytometry. RESULTS: The median age of COVID-19-positive cancer patients was 71.1 years, and 66.4 years for controls. Compared with non-COVID-19 cancer patients, COVID-19-positive cancer patients had more extensive lymphopenia and hypoalbuminemia, with higher levels of C-reactive protein. In COVID-19 patients, elevated procalcitonin was associated with a higher risk of death. By phenotypic analysis, COVID-19-positive patients presented CD3 lymphopenia, with inversion of the CD4/CD8 ratio and modification of monocyte activation, with accumulation of mMDSC (monocytic Myeloid-Derived Suppressor Cells) -like cells and a decrease in activated monocytes. Analysis of the T-cell compartment revealed a T-dependent inflammatory response with accumulation of Th17 cells and cytotoxic CD8 T cells producing TNFα, a decrease in HLA-DR (Human Leukocyte Antigen - DR isotype)-positive CD8 T cells and Treg/CD8 ratio. CONCLUSION: SARS-CoV-2 infection in cancer patients is associated with CD4 T-cell lymphopenia with induction of an inflammatory T-cell response, accumulation of IFNγ+ TNFα+ CD8 T and Th17 cells, and a concomitant modification of monocyte activation status.


Subject(s)
Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Neoplasms/immunology , Pneumonia, Viral/immunology , T-Lymphocytes, Cytotoxic/immunology , Aged , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , France/epidemiology , Humans , Male , Neoplasms/epidemiology , Neoplasms/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Time Factors
8.
Microorganisms ; 8(8)2020 Jul 24.
Article in English | MEDLINE | ID: covidwho-670174

ABSTRACT

There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for coronavirus disease 2019 (COVID-19). In this observational study, we aimed to describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior to hospitalization. Forty-eight patients (27 non-ICU and 21 ICU) with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were analyzed (mean age, 66 years, [range, 33-88 years]; 67% males). There were no differences in age or sex among groups. Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs. 61%, p = 0.022). ICU-patients had lymphopenia as well as hypoalbuminemia. Lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < 0.001). Lower albumin levels were associated with poor prognosis measured as longer hospital length (r = -0.472, p < 0.001) and mortality (r = -0.424, p = 0.003). As of 28 April 2020, 10 patients (8 ICU and 2 non-ICU) have died (21% mortality), and while 100% of the non-ICU patients have been discharged, 33% of the ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward). Critically ill patients with COVID-19 present lymphopenia, hypoalbuminemia and high levels of inflammation.

9.
Hepatol Int ; 14(5): 711-722, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-629718

ABSTRACT

BACKGROUND: Liver function derangements have been reported in coronavirus disease (COVID-19), but reported rates are variable. METHODS: We searched PubMed and Embase with terms COVID and SARS-COV-2 from December 1, 2019 till April 5, 2020. We estimated overall prevalence, stratified prevalence based on severity, estimated risk ratio (RR), and estimated standardized mean difference (SMD) of liver function parameters in severe as compared to non-severe COVID. Random effect method utilizing inverse variance approach was used for pooling the data. RESULTS: In all, 128 studies were included. The most frequent abnormalities were hypoalbuminemia [61.27% (48.24-72.87)], elevations of gamma-glutamyl transferase (GGT) [27.94% (18.22-40.27)], alanine aminotransferase (ALT) [23.28% (19.92-27.01)], and aspartate aminotransferase (AST) [23.41% (18.84-28.70)]. Furthermore, the relative risk of these abnormalities was higher in the patients with severe COVID-19 when compared to non-severe disease [Hypoalbuminemia-2.65 (1.38-5.07); GGT-2.31 (1.6-3.33); ALT-1.76 (1.44-2.15); AST-2.30 (1.82-2.90)]. The SMD of hypoalbuminemia, GGT, ALT, and AST elevation in severe as compared to non-severe were - 1.05 (- 1.27 to - 0.83), 0.76 (0.40-1.12), 0.42 (0.27-0.56), and 0.69 (0.52-0.86), respectively. The pooled prevalence and RR of chronic liver disease as a comorbidity was 2.64% (1.73-4) and 1.69 (1.05-2.73) respectively. CONCLUSION: The most frequent abnormality in liver functions was hypoalbuminemia followed by derangements in gamma-glutamyl transferase and aminotransferases, and these abnormalities were more frequent in severe disease. The systematic review was, however, limited by heterogeneity in definitions of severity and liver function derangements. Graphical depiction of the summary of meta-analytic findings a) pooled prevalence of abnormalities b) Risk ratio of abnormality in severe versus non-severe COVID-19 c) standardized mean difference (SMD) between severe and non-severe group and d) pooled prevalence for parameters based on severity stratification for bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), albumin, globulin and acute hepatic injury (AHI) . Also estimates for overall/total liver disease (TLD) and chronic liver disease (CLD) amongst COVID-19 patients are depicted in a, b, d. For d) In addition to severity stratification, Overall (all studies for a particular estimate) and combined (only those studies which reported severity) estimates are provided.


Subject(s)
Coronavirus Infections , Liver Cirrhosis , Liver Function Tests , Liver , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Humans , Liver/metabolism , Liver/pathology , Liver/physiopathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Liver Function Tests/methods , Liver Function Tests/statistics & numerical data , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Risk Assessment , SARS-CoV-2 , Severity of Illness Index
10.
J Assoc Physicians India ; 68(7): 19-26, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-622461

ABSTRACT

Importance: Rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in India. Since the first laboratory confirmed case of SARS-CoV-2 was reported from Kerala on January 30, 2020 novel coronavirus infected pneumonia (NCIP) has been presenting to the hospital emergencies as severe acute respiratory illness (SARI). We aim to find out the rate of SARS-CoV-2 positivity in SARI cases and further clarify the epidemiological and clinical characteristics of NCIP in New Delhi, India. Aims and Objectives: To find out the rate of SARS-CoV-2 positivity in SARI cases presenting to the hospital emergency and describe the epidemiological and clinical characteristics of NCIP. Design, Setting and Participants: Retrospective, single-center case series of the 82 consecutive hospitalized patients with SARI and subsequent confirmed NCIP cases at Dr Ram Manohar Lohia Hospital, New Delhi between 10th April 2020 and 30th April 2020. Main Outcomes and Measures: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. The primary composite end-point was admission to an intensive care unit (ICU), the use of mechanical ventilation or death. Patients were categorized as severe pneumonia and non-severe pneumonia at time of admission and outcome data was compared. Results: Of the 82 SARI cases, 32(39%) patients were confirmed to be SARS-CoV-2 positive. The median age of NCIP cases was 54.5 years (IQR, 46.25 - 60) and 19(59.3%) of them were males. 24(75%) cases were categorized as severe pneumonia on admission. 22(68.8%) patients had 1 or more co-morbidities. Diabetes mellitus 16(50%), hypertension 11(34.4%) and chronic obstructive airway disease 5(15.6%) were the most common co-existing illnesses. Compared with the patients who did not meet the primary outcome, patients who met the primary outcome were more likely to be having at least 1 underlying comorbidity (p-0.03), diabetes (p-0.003) and hypertension (p-0.03). Common symptoms included dyspnea 29(90.6%) followed by cough 27(84.4%), fever 22(68%), bodyache and myalgias 14(43.75%). Median time from symptom onset to hospital admission was 3 days. The most common pattern on chest X-ray was bilateral patchy nodular or interstitial infiltration seen in 30(93.8%) patients. Leucopenia was present in 10(31.2%) of the patients, with majority of patients presenting with lymphocytopenia, 24(75%) [lymphocyte count (1106 cells/ dL), interquartile range {IQR}, (970-1487)]. Thrombocytopenia was seen in 14(43.8%) patients, pancytopenia in 10(31.2%) patients and anemia was seen in 14(43.8%) patients. Hypoalbuminemia was present in 22(68.8%) cases. Raised CK-MB was seen in 7(21.9%) patients. The primary composite end-point occurred in 12(37.5%) patients, including 9(28.13%) patients who required mechanical ventilation and subsequently expired. 3(9.3%) of these patients who recovered, were subsequently shifted to COVID-19 ward from the ICU. The patients who met the primary outcome were older in age (56.5 years vs 50 years), had significantly higher SOFA scores (6 vs 3.5), were in shock (41.7% vs 5%), in higher respiratory distress (66.7% vs 10%), had lower mean arterial oxygen saturation (85% vs 89.5%), had higher CK-MB values (66 vs 26)U/L [6(54.5%) vs 2(9.5%)], had hypoalbuminemia (100% vs 50%) and acute kidney injury 8(72.7%) vs 5(23.8%) on admission. Of the 50 non-COVID-19 SARI patients in our study cohort, 13 (26%) patients met the primary composite outcome. Of them 9 (18%) patients expired and remaining 4 patients have subsequently recovered. As on 17th May 2020, 23 patients were still hospitalized, recovering in COVID-19 ward. Conclusion and Relevance: In this single-center case series from New Delhi, out of 82 patients of SARI, 32 patients were confirmed NCIP, with a COVID-19 positivity of 39%. 75% of NCIP presented in severe pneumonia and 37.5% required ICU care. The case fatality rate was 28%.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/epidemiology , Female , Humans , India , Male , Middle Aged , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2 , Tertiary Care Centers
11.
Sci China Life Sci ; 63(11): 1678-1687, 2020 11.
Article in English | MEDLINE | ID: covidwho-610883

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups-non-critically ill, critically ill, and death groups-in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52-71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients.


Subject(s)
COVID-19/blood , COVID-19/complications , Coronavirus Infections/blood , Coronavirus Infections/complications , Liver Diseases/etiology , Serum Albumin, Human/metabolism , Aged , COVID-19/mortality , China , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronavirus Infections/mortality , Critical Illness , Cytokines/blood , Female , Humans , Liver Diseases/blood , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Thromboplastin/metabolism , Time Factors
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