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1.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
2.
Pediatr Nephrol ; 36(9): 2627-2638, 2021 09.
Article in English | MEDLINE | ID: covidwho-1520348

ABSTRACT

BACKGROUND AND OBJECTIVES: COVID-19 is responsible for the 2019 novel coronavirus disease pandemic. Despite the vast research about the adult population, there has been little data collected on acute kidney injury (AKI) epidemiology, associated risk factors, treatments, and mortality in pediatric COVID-19 patients admitted to the ICU. AKI is a severe complication of COVID-19 among children and adolescents. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE and Cochrane Center Trials to find all published literature related to AKI in COVID-19 patients, including incidence and outcomes. RESULTS: Twenty-four studies reporting the outcomes of interest were included. Across all studies, the overall sample size of COVID positive children was 1,247 and the median age of this population was 9.1 years old. Among COVID positive pediatric patients, there was an AKI incidence of 30.51%, with only 0.56% of these patients receiving KRT. The mortality was 2.55% among all COVID positive pediatric patients. The incidence of multisystem inflammatory syndrome in children (MIS-C) among COVID positive patients was 74.29%. CONCLUSION: AKI has shown to be a negative prognostic factor in adult patients with COVID-19 and now also in the pediatric cohort with high incidence and mortality rates. Additionally, our findings show a strong comparison in epidemiology between adult and pediatric COVID-19 patients; however, they need to be confirmed with additional data and studies.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Intensive Care Units/statistics & numerical data , Renal Replacement Therapy/statistics & numerical data , Systemic Inflammatory Response Syndrome/complications , Acute Kidney Injury/immunology , Acute Kidney Injury/therapy , Acute Kidney Injury/virology , Adult , Age Factors , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , Child , Hospital Mortality , Humans , Incidence , Pandemics/statistics & numerical data , Risk Factors , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality
4.
Cell Commun Signal ; 19(1): 76, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1318284

ABSTRACT

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. Video Abstract.


Subject(s)
Adaptive Immunity/genetics , B7-H1 Antigen/immunology , Inflammation/immunology , Tumor Hypoxia/genetics , Acute Kidney Injury/genetics , Acute Kidney Injury/immunology , Adaptive Immunity/immunology , B7-H1 Antigen/genetics , Humans , Immunity, Innate/genetics , Inflammation/genetics , Ischemic Stroke/genetics , Ischemic Stroke/immunology , Monitoring, Immunologic , Neoplasms/genetics , Neoplasms/immunology , Sleep Apnea, Obstructive/genetics , Sleep Apnea, Obstructive/immunology , Tumor Hypoxia/immunology
6.
Transplantation ; 105(6): 1365-1371, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1249352

ABSTRACT

BACKGROUND: Organ transplant recipients comprise an immunocompromised and vulnerable cohort. Outcomes of coronavirus disease 2019 (COVID-19) in solid organ transplant (SOT) recipients remain understudied. METHODS: We used a multicenter federated research network to compare clinical outcomes of COVID-19 in patients with SOT to a propensity--matched cohort of patients without SOT. RESULTS: We identified 2307 SOT recipients and 231 047 nontransplant patients with COVID-19. Transplant patients were more likely to be male individuals, older, have a body mass index >30 kg/m2, and have comorbid hypertension, diabetes, nicotine dependence, heart failure, and ischemic heart disease compared with the nontransplant group (P < 0.05). One-to-one matching was performed for diabetes, hypertension, chronic lung diseases, race, nicotine dependence, heart failure, ischemic heart disease, and gender. There was no difference in the composite outcome of intubation or mechanical ventilation at 30 days (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.86-1.26) or 60 days (RR, 1.03; 95% CI, 0.86-1.24) between the 2 groups. Hospitalization rate was higher in the transplant cohort (30.97% versus 25.47%; RR, 1.22; 95% CI, 1.11-1.34). There was no difference in mortality at 30 days (6.45% versus 5.29%; RR, 1.22; 95% CI, 0.88-1.68) or 60 days postdiagnosis (RR, 1.05; 95% CI, 0.83-1.32). More patients in the SOT group developed acute renal injury compared with non-SOT cohort (24.73% versus 14.29%; RR, 1.73; 95% CI, 1.53-1.96). CONCLUSIONS: Patients with SOT have high COVID-19-related mortality; however, propensity-matched analyses reveal that this increased risk is secondary to higher burden of comorbidities. SOT status independently increases risk of hospital admission and acute kidney injury.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/mortality , Immunocompromised Host , Organ Transplantation/adverse effects , Transplant Recipients/statistics & numerical data , Acute Kidney Injury/immunology , Adult , Aged , COVID-19/diagnosis , COVID-19/immunology , COVID-19/therapy , Comorbidity , Female , Hospital Mortality , Humans , Male , Middle Aged , Propensity Score , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , United States/epidemiology
7.
Pediatr Nephrol ; 36(11): 3771-3776, 2021 11.
Article in English | MEDLINE | ID: covidwho-1237500

ABSTRACT

BACKGROUND: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment. METHODS: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission. RESULTS: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9-17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5-10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days. CONCLUSIONS: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment.


Subject(s)
Acute Kidney Injury/physiopathology , Amides/administration & dosage , COVID-19/complications , COVID-19/drug therapy , Pyrazines/administration & dosage , Renal Elimination , Systemic Inflammatory Response Syndrome/drug therapy , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Adolescent , Alanine/administration & dosage , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Amides/pharmacokinetics , COVID-19/immunology , COVID-19/virology , Child , Creatinine/blood , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Glomerular Filtration Rate , Humans , Male , Pyrazines/pharmacokinetics , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/virology , Treatment Outcome
8.
Transplantation ; 105(6): 1365-1371, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1228579

ABSTRACT

BACKGROUND: Organ transplant recipients comprise an immunocompromised and vulnerable cohort. Outcomes of coronavirus disease 2019 (COVID-19) in solid organ transplant (SOT) recipients remain understudied. METHODS: We used a multicenter federated research network to compare clinical outcomes of COVID-19 in patients with SOT to a propensity--matched cohort of patients without SOT. RESULTS: We identified 2307 SOT recipients and 231 047 nontransplant patients with COVID-19. Transplant patients were more likely to be male individuals, older, have a body mass index >30 kg/m2, and have comorbid hypertension, diabetes, nicotine dependence, heart failure, and ischemic heart disease compared with the nontransplant group (P < 0.05). One-to-one matching was performed for diabetes, hypertension, chronic lung diseases, race, nicotine dependence, heart failure, ischemic heart disease, and gender. There was no difference in the composite outcome of intubation or mechanical ventilation at 30 days (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.86-1.26) or 60 days (RR, 1.03; 95% CI, 0.86-1.24) between the 2 groups. Hospitalization rate was higher in the transplant cohort (30.97% versus 25.47%; RR, 1.22; 95% CI, 1.11-1.34). There was no difference in mortality at 30 days (6.45% versus 5.29%; RR, 1.22; 95% CI, 0.88-1.68) or 60 days postdiagnosis (RR, 1.05; 95% CI, 0.83-1.32). More patients in the SOT group developed acute renal injury compared with non-SOT cohort (24.73% versus 14.29%; RR, 1.73; 95% CI, 1.53-1.96). CONCLUSIONS: Patients with SOT have high COVID-19-related mortality; however, propensity-matched analyses reveal that this increased risk is secondary to higher burden of comorbidities. SOT status independently increases risk of hospital admission and acute kidney injury.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/mortality , Immunocompromised Host , Organ Transplantation/adverse effects , Transplant Recipients/statistics & numerical data , Acute Kidney Injury/immunology , Adult , Aged , COVID-19/diagnosis , COVID-19/immunology , COVID-19/therapy , Comorbidity , Female , Hospital Mortality , Humans , Male , Middle Aged , Propensity Score , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , United States/epidemiology
9.
Medicina (Kaunas) ; 57(3)2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1167651

ABSTRACT

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.


Subject(s)
Acute Kidney Injury/pathology , COVID-19/pathology , Glomerulonephritis/pathology , Kidney/pathology , Thrombotic Microangiopathies/pathology , Acute Kidney Injury/blood , Acute Kidney Injury/immunology , Adaptive Immunity/immunology , Arteriosclerosis/immunology , Arteriosclerosis/pathology , COVID-19/blood , COVID-19/immunology , Cytokines/immunology , Glomerulonephritis/immunology , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Glomerulosclerosis, Focal Segmental/immunology , Glomerulosclerosis, Focal Segmental/pathology , Humans , Immunity, Innate/immunology , Infarction/immunology , Infarction/pathology , Kidney/blood supply , Kidney/immunology , Kidney Cortex Necrosis/immunology , Kidney Cortex Necrosis/pathology , Nephritis, Interstitial/immunology , Nephritis, Interstitial/pathology , Nephrosis, Lipoid/immunology , Nephrosis, Lipoid/pathology , Rhabdomyolysis , SARS-CoV-2 , Thrombophilia/blood , Thrombotic Microangiopathies/immunology
10.
Am J Nephrol ; 52(2): 161-172, 2021.
Article in English | MEDLINE | ID: covidwho-1150270

ABSTRACT

INTRODUCTION: Renal involvement in COVID-19 is less well characterized in settings with vigilant public health surveillance, including mass screening and early hospitalization. We assessed kidney complications among COVID-19 patients in Hong Kong, including the association with risk factors, length of hospitalization, critical presentation, and mortality. METHODS: Linked electronic records of all patients with confirmed COVID-19 from 5 major designated hospitals were extracted. Duplicated records due to interhospital transferal were removed. Primary outcome was the incidence of in-hospital acute kidney injury (AKI). Secondary outcomes were AKI-associated mortality, incident renal replacement therapy (RRT), intensive care admission, prolonged hospitalization and disease course (defined as >90th percentile of hospitalization duration [35 days] and duration from symptom onset to discharge [43 days], respectively), and change of estimated glomerular filtration rate (GFR). Patients were further stratified into being symptomatic or asymptomatic. RESULTS: Patients were characterized by young age (median: 38.4, IQR: 28.4-55.8 years) and short time (median: 5, IQR: 2-9 days) from symptom onset to admission. Among the 591 patients, 22 (3.72%) developed AKI and 4 (0.68%) required RRT. The median time from symptom onset to in-hospital AKI was 15 days. AKI increased the odds of prolonged hospitalization and disease course by 2.0- and 3.5-folds, respectively. Estimated GFR 24 weeks post-discharge reduced by 7.51 and 1.06 mL/min/1.73 m2 versus baseline (upon admission) in the AKI and non-AKI groups, respectively. The incidence of AKI was comparable between asymptomatic (4.8%, n = 3/62) and symptomatic (3.7%, n = 19/519) patients. CONCLUSION: The overall rate of AKI among COVID-19 patients in Hong Kong is low, which could be attributable to a vigilant screening program and early hospitalization. Among patients who developed in-hospital AKI, the duration of hospitalization is prolonged and kidney function impairment can persist for up to 6 months post-discharge. Mass surveillance for COVID-19 is warranted in identifying asymptomatic subjects for earlier AKI management.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19 Testing , COVID-19/diagnosis , Mass Screening/organization & administration , Renal Replacement Therapy/statistics & numerical data , Acute Kidney Injury/diagnosis , Acute Kidney Injury/immunology , Acute Kidney Injury/therapy , Adult , Age Factors , Aged , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Critical Care/statistics & numerical data , Early Diagnosis , Female , Glomerular Filtration Rate/immunology , Hong Kong/epidemiology , Hospital Mortality , Humans , Incidence , Length of Stay , Male , Mass Screening/statistics & numerical data , Middle Aged , Patient Discharge , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index
11.
Front Immunol ; 11: 594849, 2020.
Article in English | MEDLINE | ID: covidwho-1083385

ABSTRACT

Most patients who became critically ill following infection with COVID-19 develop severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of critically ill patients with COVID-19. Apart from the lung, the kidney is the second most common organ affected by COVID-19. Using immunohistochemistry for complement factors C1q, MASP-2, C3c, C3d, C4d, and C5b-9 we investigated the involvement of the complement system in six kidney biopsies with acute kidney failure in different clinical settings and three kidneys from autopsy material of patients with COVID-19. Renal tissue was analyzed for signs of renal injury by detection of thrombus formation using CD61, endothelial cell rarefaction using the marker E-26 transformation specific-related gene (ERG-) and proliferation using proliferating cell nuclear antigen (PCNA)-staining. SARS-CoV-2 was detected by in situ hybridization and immunohistochemistry. Biopsies from patients with hemolytic uremic syndrome (HUS, n = 5), severe acute tubular injury (ATI, n = 7), zero biopsies with disseminated intravascular coagulation (DIC, n = 7) and 1 year protocol biopsies from renal transplants (Ctrl, n = 7) served as controls. In the material clogging plasma adsorbers used for extracorporeal therapy of patients with COVID-19 C3 was the dominant protein but collectin 11 and MASP-2 were also identified. SARS-CoV-2 was sporadically present in varying numbers in some biopsies from patients with COVID-19. The highest frequency of CD61-positive platelets was found in peritubular capillaries and arteries of COVID-19 infected renal specimens as compared to all controls. Apart from COVID-19 specimens, MASP-2 was detected in glomeruli with DIC and ATI. In contrast, the classical pathway (i.e. C1q) was hardly seen in COVID-19 biopsies. Both C3 cleavage products C3c and C3d were strongly detected in renal arteries but also occurs in glomerular capillaries of COVID-19 biopsies, while tubular C3d was stronger than C3c in biopsies from COVID-19 patients. The membrane attack complex C5b-9, demonstrating terminal pathway activation, was predominantly deposited in COVID-19 biopsies in peritubular capillaries, renal arterioles, and tubular basement membrane with similar or even higher frequency compared to controls. In conclusion, various complement pathways were activated in COVID-19 kidneys, the lectin pathway mainly in peritubular capillaries and in part the classical pathway in renal arteries whereas the alternative pathway seem to be crucial for tubular complement activation. Therefore, activation of the complement system might be involved in the worsening of renal injury. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury.


Subject(s)
Acute Kidney Injury/immunology , Acute Kidney Injury/virology , COVID-19/complications , COVID-19/immunology , Complement Activation/physiology , Adult , Aged , Female , Humans , Male , Middle Aged , SARS-CoV-2
13.
Nephrology (Carlton) ; 26(3): 239-247, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1010961

ABSTRACT

Acute kidney injury (AKI) is a common complication, affecting up to 37% of hospitalized patients with SARS-CoV-2 infection and is proportional to its severity and portends poor prognosis. Diverse mechanisms have been proposed and studies reported conflicting results. Moreover, renal tropism of SARS-CoV-2 does not equate to its renal pathogenicity. For a virus to be pathogenic, in addition to its affinity (tropism) for specific tissue(s), host cells must allow viral entry, and discuss the important role played by transmembrane protease, serine 2 (TMPRSS2) and coexpression of both ACE2 and TMPRSS2 in the same cells is important to cause damage. Lack of coexpression of ACE2 and TMPRSS2 in the same cells of the kidneys is the limiting factor of SARS-CoV-2 direct effects in the kidney. We present the rationale and cumulative evidence supporting that AKI is secondary to hemodynamic and immunologic effects of SARS-CoV-2 infection than the direct injury or infection.


Subject(s)
Acute Kidney Injury , Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Kidney , SARS-CoV-2 , Serine Endopeptidases/metabolism , Acute Kidney Injury/etiology , Acute Kidney Injury/immunology , Acute Kidney Injury/physiopathology , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , Hemodynamics , Humans , Immunity , Kidney/metabolism , Kidney/pathology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Viral Tropism
14.
J Am Soc Nephrol ; 31(2): 257-278, 2020 02.
Article in English | MEDLINE | ID: covidwho-992926

ABSTRACT

BACKGROUND: Mononuclear phagocytes (MPs), including macrophages, monocytes, and dendritic cells (DCs), are phagocytic cells with important roles in immunity. The developmental origin of kidney DCs has been highly debated because of the large phenotypic overlap between macrophages and DCs in this tissue. METHODS: We used fate mapping, RNA sequencing, flow cytometry, confocal microscopy, and histo-cytometry to assess the origin and phenotypic and functional properties of renal DCs in healthy kidney and of DCs after cisplatin and ischemia reperfusion-induced kidney injury. RESULTS: Adult kidney contains at least four subsets of MPs with prominent Clec9a-expression history indicating a DC origin. We demonstrate that these populations are phenotypically, functionally, and transcriptionally distinct from each other. We also show these kidney MPs exhibit unique age-dependent developmental heterogeneity. Kidneys from newborn mice contain a prominent population of embryonic-derived MHCIInegF4/80hiCD11blow macrophages that express T cell Ig and mucin domain containing 4 (TIM-4) and MER receptor tyrosine kinase (MERTK). These macrophages are replaced within a few weeks after birth by phenotypically similar cells that express MHCII but lack TIM-4 and MERTK. MHCII+F4/80hi cells exhibit prominent Clec9a-expression history in adulthood but not early life, indicating additional age-dependent developmental heterogeneity. In AKI, MHCIInegF4/80hi cells reappear in adult kidneys as a result of MHCII downregulation by resident MHCII+F4/80hi cells, possibly in response to prostaglandin E2 (PGE2). RNA sequencing further suggests MHCII+F4/80hi cells help coordinate the recruitment of inflammatory cells during renal injury. CONCLUSIONS: Distinct developmental programs contribute to renal DC and macrophage populations throughout life, which could have important implications for therapies targeting these cells.


Subject(s)
Dendritic Cells/immunology , Kidney/immunology , Macrophages/immunology , Nephritis/immunology , Acute Kidney Injury/immunology , Age Factors , Animals , CD11b Antigen/analysis , CX3C Chemokine Receptor 1/analysis , Calcium-Binding Proteins/analysis , Cisplatin/pharmacology , Histocompatibility Antigens Class II/analysis , Kidney/drug effects , Kidney/metabolism , Lectins, C-Type/analysis , Mice , Mice, Inbred C57BL , Receptors, G-Protein-Coupled/analysis , Receptors, Immunologic/analysis
16.
BMJ Case Rep ; 13(11)2020 Nov 09.
Article in English | MEDLINE | ID: covidwho-917776

ABSTRACT

Renal transplant (RT) recipients are at increased risk for infectious complications. The clinical course of COVID-19 has been described in several RT recipients with varying clinical outcomes. Most present with pulmonary manifestations, however extrapulmonary presentations are not uncommon. Also, the timing and efficacy of seroconversion in transplant recipients is not well known. This report describes the duration of viral shedding and timing of seroconversion in a young adult RT recipient with COVID-19 who presented with severe diarrhoea and acute kidney injury requiring dialysis. She developed anti-SARS-CoV-2 IgG antibody after 5 weeks despite persistently shedding the virus in the nasopharynx until 6 weeks after symptom onset. Further studies are needed to determine if immunosuppressed patients have prolonged viral shedding and are still contagious despite seroconversion.


Subject(s)
Acute Kidney Injury/complications , Coronavirus Infections/complications , Coronavirus Infections/immunology , Kidney Transplantation , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Seroconversion , Virus Shedding/immunology , Acute Kidney Injury/immunology , Acute Kidney Injury/therapy , Adult , Betacoronavirus/immunology , COVID-19 , Female , Humans , Kidney/immunology , Kidney/surgery , Pandemics , Renal Dialysis/methods , SARS-CoV-2 , Transplant Recipients , Young Adult
17.
Rev Med Virol ; 31(3): e2176, 2021 05.
Article in English | MEDLINE | ID: covidwho-815924

ABSTRACT

The novel coronavirus (SARS-CoV-2) has turned into a life-threatening pandemic disease (Covid-19). About 5% of patients with Covid-19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS-CoV-2-driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid-19 is necessary to develop management strategies and design effective therapies.


Subject(s)
Acute Kidney Injury/pathology , COVID-19/physiopathology , Cytokine Release Syndrome/pathology , Disseminated Intravascular Coagulation/pathology , Lymphopenia/pathology , Necrosis/pathology , Proteinuria/pathology , Sepsis/pathology , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , COVID-19/immunology , COVID-19/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/genetics , Cytokines/immunology , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Kidney Tubules, Proximal/immunology , Kidney Tubules, Proximal/physiopathology , Lymphopenia/immunology , Lymphopenia/virology , Necrosis/immunology , Necrosis/virology , Podocytes/immunology , Podocytes/pathology , Proteinuria/immunology , Proteinuria/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Sepsis/immunology , Sepsis/virology , Serine Endopeptidases/genetics , Serine Endopeptidases/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
18.
Respir Physiol Neurobiol ; 283: 103548, 2021 01.
Article in English | MEDLINE | ID: covidwho-779595

ABSTRACT

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.


Subject(s)
Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Multiple Organ Failure/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Spike Glycoprotein, Coronavirus/metabolism , Acute Kidney Injury/immunology , Acute Kidney Injury/physiopathology , Angiotensin-Converting Enzyme 2 , Arrhythmias, Cardiac/immunology , Arrhythmias, Cardiac/physiopathology , Betacoronavirus/metabolism , COVID-19 , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/immunology , Endothelium, Vascular/metabolism , Erythrocytes/metabolism , Gastrointestinal Diseases/immunology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Tract/metabolism , Heart Failure/immunology , Heart Failure/physiopathology , Humans , Inflammation/immunology , Kidney/metabolism , Liver/metabolism , Liver Diseases/immunology , Liver Diseases/physiopathology , Lung/metabolism , Multiple Organ Failure/physiopathology , Myocardium/metabolism , Pandemics , Pneumonia, Viral/physiopathology , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Thromboembolism/immunology , Thromboembolism/physiopathology , Viral Load
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