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1.
Int J Mol Sci ; 23(4)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1700470

ABSTRACT

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , COVID-19/complications , Kidney/virology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/mortality , Animals , Humans , Kidney/physiopathology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/virology
2.
BMC Nephrol ; 22(1): 278, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1352651

ABSTRACT

BACKGROUND: The recent COVID-19 pandemic has raised concerns about patient diagnosis and follow-up of chronically ill patients. Patients suffering from chronic illnesses, concomitantly infected by SARS-CoV-2, globally tend to have a worse prognosis and poor outcomes. Renal tropism and acute kidney injury following SARS-CoV-2 infection has recently been described in the literature, with elevated mortality rates. Furthermore, patients with pre-existing chronic kidney disease, infected by SARS-CoV-2, should be monitored carefully. Here, we report the case of a 69-year-old patient with splenic marginal zone lymphoma, suffering from longstanding chronic kidney disease following SARS-CoV-2 infection. CASE PRESENTATION: A 69-year-old male patient previously diagnosed with pulmonary embolism and splenic marginal zone lymphoma (Splenomegaly, Matutes 2/5, CD5 negative and CD23 positive), was admitted to the hospital with shortness of breath, fever and asthenia. A nasopharyngeal swab test was performed in addition to a CT-scan, which confirmed SARS-CoV-2 infection. Blood creatinine increased following SARS-CoV-2 infection at 130 µmol/l, with usual values at 95 µmol/l. The patient was discharged at home with rest and symptomatic medical treatment (paracetamol and hydration), then readmitted to the hospital in August 2020. A kidney biopsy was therefore conducted as blood creatinine levels were abnormally elevated. Immunodetection performed in a renal biopsy specimen confirmed co-localization of SARS-CoV2 nucleocapsid and protease 3C proteins with ACE2, Lewis x and sialyl-Lewis x antigens in proximal convoluted tubules and podocytes. Co-localization of structural and non-structural viral proteins clearly demonstrated viral replication in proximal convoluted tubules in this chronically ill patient. Additionally, we observed the co-localization of sialyl-Lewis x and ACE2 receptors in the same proximal convoluted tubules. Reverse Transcriptase-Polymerase Chain Reaction test performed on the kidney biopsy was negative, with very low Ct levels (above 40). The patient was finally readmitted to the haematology department for initiation of chemotherapy, including CHOP protocol and Rituximab. CONCLUSIONS: Our case emphasizes on the importance of monitoring kidney function in immunosuppressed patients and patients suffering from cancer following SARS-CoV-2 infection, through histological screening. Further studies will be required to decipher the mechanisms underlying chronic kidney disease and the putative role of sialyl-Lewis x and HBGA during SARS-CoV-2 infection.


Subject(s)
COVID-19/complications , Kidney Tubules/virology , Renal Insufficiency, Chronic/virology , SARS-CoV-2/physiology , Virus Replication , Aged , Angiotensin-Converting Enzyme 2/analysis , Biopsy , COVID-19/blood , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/analysis , Creatinine/blood , Humans , Kidney/chemistry , Kidney/pathology , Kidney/virology , Kidney Tubules/chemistry , Kidney Tubules/pathology , Lewis X Antigen/analysis , Lymphoma, B-Cell, Marginal Zone/complications , Male , Renal Insufficiency, Chronic/pathology , Sialyl Lewis X Antigen/analysis , Splenic Neoplasms/complications
3.
Am J Infect Control ; 49(2): 238-246, 2021 02.
Article in English | MEDLINE | ID: covidwho-1336188

ABSTRACT

INTRODUCTION: On February 11, 2020 WHO designated the name "COVID-19" for the disease caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a novel virus that quickly turned into a global pandemic. Risks associated with acquiring the virus have been found to most significantly vary by age and presence of underlying comorbidity. In this rapid literature review we explore the prevalence of comorbidities and associated adverse outcomes among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. METHODS: A comprehensive systematic search was performed on PubMed, Medline, Scopus, Embase, and Google Scholar to find articles published until May 15, 2020. All relevant articles providing information on PCR tested COVID-19 positive patient population with clinical characteristics and epidemiological information were selected for review and analysis. RESULTS: A total of 27 articles consisting of 22,753 patient cases from major epicenters worldwide were included in the study. Major comorbidities seen in overall population were CVD (8.9%), HTN (27.4%), Diabetes (17.4%), COPD (7.5%), Cancer (3.5%), CKD (2.6%), and other (15.5%). Major comorbidity specific to countries included in the study were China (HTN 39.5%), South Korea (CVD 25.6%), Italy (HTN 35.9%), USA (HTN 38.9%), Mexico, (Other 42.3%), UK (HTN 27.8%), Iran (Diabetes 35.0%). Within fatal cases, an estimated 84.1% had presence of one or more comorbidity. Subgroup analysis of fatality association with having comorbidity had an estimated OR 0.83, CI [0.60-0.99], p<0.05. CONCLUSIONS: Based on our findings, hypertension followed by diabetes and cardiovascular diseases were the most common comorbidity seen in COVID-19 positive patients across major epicenters world-wide. Although having one or more comorbidity is linked to increased disease severity, no clear association was found between having these risk factors and increased risk of fatality.


Subject(s)
COVID-19/epidemiology , Comorbidity , Global Health/statistics & numerical data , Hypertension/epidemiology , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/virology , Diabetes Mellitus/epidemiology , Diabetes Mellitus/virology , Female , Humans , Hypertension/virology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/virology , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/virology , Young Adult
4.
Front Immunol ; 12: 714511, 2021.
Article in English | MEDLINE | ID: covidwho-1320579

ABSTRACT

Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19.


Subject(s)
COVID-19/blood , Complement Activation/immunology , Complement System Proteins/metabolism , Lectins/blood , Renal Insufficiency, Chronic/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , COVID-19/pathology , COVID-19/physiopathology , Cohort Studies , Complement System Proteins/immunology , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/virology , Severity of Illness Index
6.
Nephrology (Carlton) ; 26(4): 328-332, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-991640

ABSTRACT

Recent World Health Organization guidance has aimed to provide pragmatic guidance acknowledging the role of sequential nasopharyngeal swabs taken >24 hours apart for SARS-CoV-2 in high-risk populations. Patients with chronic kidney disease (CKD) are known to have an altered immune milieu which may be associated with a delay in viral clearance. Here, a cross-sectional observational study of 138 patients admitted with SARS-CoV-2 infection at two large regional hospitals in Scotland, UK examined the median time to two consecutive negative nasopharyngeal swabs for SARS-CoV-2 in an inpatient population. The median time from admission to the first of two consecutive negative nasopharyngeal swabs was 18 days (range = 1-44) in patients with CKD, compared with 11 days (range: 1-71) in patients without CKD (P = .0007). Multivariable linear regression analysis using explanatory variables of age, sex, SARS-CoV-2 disease severity, key comorbidities and renal function showed that declining estimated glomerular filtration rate was independently associated with prolonged time to viral clearance. Our data suggest that patients with CKD who are admitted to hospital with SARS-CoV-2 take longer to achieve sequential negative nasopharyngeal swab reverse transcription-polymerase chain reaction results than those without CKD. This has implications for renal service provision, discharge planning and hospital capacity as well as a direct impact on patients due to extended hospital stay, anxiety and stigmatisation.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Renal Insufficiency, Chronic/complications , SARS-CoV-2/physiology , Virus Shedding , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/therapy , Cross-Sectional Studies , Female , Glomerular Filtration Rate , Hospitalization , Humans , Linear Models , Male , Middle Aged , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/virology , Reverse Transcriptase Polymerase Chain Reaction , Scotland , Time Factors
8.
J Nephrol ; 34(1): 173-183, 2021 02.
Article in English | MEDLINE | ID: covidwho-834119

ABSTRACT

BACKGROUND: The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. METHODS: We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. RESULTS: Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21-2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). CONCLUSION: Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.


Subject(s)
Acute Kidney Injury/mortality , COVID-19/complications , COVID-19/mortality , Renal Insufficiency, Chronic/mortality , Acute Kidney Injury/therapy , Acute Kidney Injury/virology , Aged , COVID-19/therapy , Female , Hospital Mortality , Hospitalization , Humans , Italy , Male , Middle Aged , Prevalence , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/virology , Renal Replacement Therapy , Retrospective Studies , Risk Factors , Survival Rate
9.
Am J Trop Med Hyg ; 103(6): 2419-2428, 2020 12.
Article in English | MEDLINE | ID: covidwho-809794

ABSTRACT

Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34-58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9-15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85-23.64), 40-59 years (aHR = 4.45, 95% CI: 1.83-10.79), and ≥ 60 years (aHR = 13.63, 95% CI: 5.70-32.60) compared with those aged 20-39 years, with obesity (aHR = 2.30, 95% CI: 1.24-4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85-15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88-2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35-1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Hospital Mortality/trends , Pandemics , SARS-CoV-2/pathogenicity , Adolescent , Adult , Asymptomatic Diseases , Azithromycin/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , Chloroquine/therapeutic use , Democratic Republic of the Congo/epidemiology , Drug Combinations , Enoxaparin/therapeutic use , Female , Hospitalization/statistics & numerical data , Hospitals , Humans , Intensive Care Units , Lopinavir/therapeutic use , Male , Middle Aged , Obesity/diagnosis , Obesity/physiopathology , Obesity/virology , Patient Discharge/statistics & numerical data , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/virology , Retrospective Studies , Risk Factors , Ritonavir/therapeutic use , Severity of Illness Index , Treatment Outcome
10.
Diabetes Res Clin Pract ; 169: 108454, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-778739

ABSTRACT

AIMS: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. METHODS: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. RESULTS: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases. CONCLUSIONS: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Renal Insufficiency, Chronic/pathology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , COVID-19/transmission , COVID-19/virology , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/virology , Female , Hospitalization , Humans , Incidence , Italy/epidemiology , Male , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/virology
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