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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335279

ABSTRACT

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir. From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community;47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis;2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy. Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016. In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes;it’s clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335248

ABSTRACT

Background Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. In this study, we report on immune responses to 3 rd - (V3) and 4 th - (V4) doses of heterologous and homologous vaccines in a kidney transplant population. Methods 724 kidney transplant recipients were prospectively screened for serological responses following 3 primary doses of a SARS-CoV2 vaccine. 322 patients were sampled post-V4 for anti-spike (anti-S), with 69 undergoing assessment of SARS-CoV-2 T-cell responses. All vaccine doses were received post-transplant, only mRNA vaccines were used for V3 and V4 dosing. All participants had serological testing performed post-V2 and at least once prior to their 1 st dose of vaccine. Results 586/724 (80.9%) patients were infection-naïve post-V3;141/2586 (24.1%) remained seronegative at 31 (21-51) days post-V3. Timing of vaccination in relation to transplantation, OR: 0.28 (0.15-0.54), p=0.0001;immunosuppression burden, OR: 0.22 (0.13-0.37), p<0.0001, and a diagnosis of diabetes, OR: 0.49 (0.32-0.75), p=0.001, remained independent risk factors for non-seroconversion. Seropositive patients post-V3 had greater anti-S if primed with BNT162b2 compared with ChAdOx1, p=0.001. Post-V4, 45/239 (18.8%) infection-naïve patients remained seronegative. De novo seroconversion post-V4 occurred in 15/60 (25.0%) patients who were seronegative post-V3. There was no difference in anti-S post-V4 by vaccine combination, p=0.50. Anti-S post-V4 were sequentially greater in those seroconverting post V2- compared with V3-, and V3- compared with V4-, at 1561 (567-5211), 379 (101-851) and 19 (9.7-48) BAU/ml respectively. T-cell responses were poor, with only 11/54 (20.4%) infection-naive patients having detectable T-cell responses post-V4, with no difference seen by vaccine type. Conclusion A significant proportion of transplant recipients remain seronegative following 3- and 4- doses of SARS-CoV-2 vaccines, with poor T-cell responses, and are likely to have inadequate protection against infection.

5.
Kidney360 ; 3(2): 293-306, 2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1776886

ABSTRACT

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.


Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/complications , COVID-19/epidemiology , Follow-Up Studies , Humans , Registries , SARS-CoV-2
6.
Curr Opin Nephrol Hypertens ; 31(2): 191-198, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1722704

ABSTRACT

PURPOSE OF REVIEW: Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease. RECENT FINDINGS: Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population. Glucocorticoid use prior to SARS-CoV-2 infection is associated with adverse outcomes from COVID-19. Rituximab significantly attenuates serological responses to both natural infection and vaccination against SARS-CoV-2, although it is not clear whether this leads to adverse outcomes. Case reports of disease flares occurring after vaccination have been reported, but causality in any of these cases has yet to be proven and the absolute risk remains very small. SUMMARY: Patients with glomerular disease represent an at-risk group for severe COVID-19 disease and vaccination is key to reducing this risk. As immunosuppressed patients demonstrate an attenuated response to vaccination, the efficacy of a third primary dose followed by a subsequent booster is being investigated.


Subject(s)
COVID-19 , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2
7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327145

ABSTRACT

Background: Emerging data suggest a reduction in SARS-CoV-2 vaccine effectiveness against Omicron SARS-CoV-2 infection. There is also evidence to show that Omicron is less pathogenic than previous variants. For clinically vulnerable populations, a less pathogenic variant may still have significant impact on morbidity and mortality. Herein we assess the clinical impact of Omicron infection, and vaccine effectiveness, in an in-centre haemodialysis (IC-HD) population. Methods One thousand, one hundred and twenty-one IC-HD patients were included in the analysis, all patients underwent weekly screening for SARS-CoV-2 infection via RT-PCR testing between 1st December 2021 and 16th January 2022. Screening for infection via weekly RT-PCR testing and 3-monthly serological assessment started prior to the vaccine roll out in 2020. Results Omicron infection was diagnosed in 145/1121 (12.9%) patients over the study period, equating to an infection rate of 3.1 per 1000 patient days. Vaccine effectiveness (VE) against Omicron infection in patients who had received a booster vaccine was 58 (23-75)%, p=0.002;VE was seen in patients who received either ChAdOx1, VE of 47(2-70)%, p=0.034, or BNT162b2, VE of 66 (36-81)%, p=0.0005, as their first two doses. No protection against infection was seen in patients who were partially vaccinated (2-doses), p=0.83. Prior infection was associated with reduced likelihood of Omicron infection, HR 0.69 (0.50-0.96), p=0.0289. Four (2.8%) patients died within 28 days of infection diagnosis, with no excess mortality was seen in patients with infection. Conclusion 3-doses of SARS-CoV-2 vaccines are required in ICHD to provide protection against Omicron infection.

8.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327143

ABSTRACT

Background: Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2. Methods 700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3rd doses were BNT162b2. All participants had serological testing performed post-2nd vaccination at a median time of 34 (IQR 26-46) days following the 2nd inoculation, and at least once prior to their 1st dose of vaccine. Results 366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection-naive participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3rd vaccine (V3);54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, p<0.0001. Cellular responses were investigated in 30 infection-naive participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77. Conclusion A significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

10.
Kidney Int ; 99(6): 1470-1477, 2021 06.
Article in English | MEDLINE | ID: covidwho-1386157

ABSTRACT

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.


Subject(s)
Antibodies, Viral/analysis , COVID-19/immunology , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , SARS-CoV-2/immunology , COVID-19 Testing , Female , Humans , Immunity , Male , Pandemics , Polymerase Chain Reaction , Reinfection , SARS-CoV-2/isolation & purification , Serologic Tests/methods
12.
Ann Rheum Dis ; 80(10): 1322-1329, 2021 10.
Article in English | MEDLINE | ID: covidwho-1346035

ABSTRACT

OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.


Subject(s)
Autoimmune Diseases/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoimmune Diseases/drug therapy , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunosuppressive Agents/immunology , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology
13.
Front Immunol ; 12: 671052, 2021.
Article in English | MEDLINE | ID: covidwho-1231338

ABSTRACT

We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity. We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.


Subject(s)
COVID-19/blood , Complement Pathway, Mannose-Binding Lectin , Lectins/blood , Renal Insufficiency, Chronic/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/ethnology , COVID-19/immunology , COVID-19/pathology , Female , Humans , Lectins/immunology , Male , Middle Aged , Renal Insufficiency, Chronic/ethnology , Renal Insufficiency, Chronic/immunology , Renal Insufficiency, Chronic/pathology , SARS-CoV-2/immunology
15.
Clin Med (Lond) ; 21(3): e287-e289, 2021 05.
Article in English | MEDLINE | ID: covidwho-1158450

ABSTRACT

Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China. The first analyses of cases described high numbers of critically ill patients requiring intensive care admission with significant late inflammatory features. By the time the first cases of SARS-CoV-2 infection were diagnosed in the UK, a wide range of drugs were under consideration and it became clear that the input of clinicians covering all organ systems (in particular, infectious diseases, haematology, rheumatology, renal medicine and intensive care) and of expert specialist pharmacists was necessary at the local level. Thus, an expert multidisciplinary (MDT) group within our organisation was convened to offer a standardised approach and robust clinical governance for the treatment of COVID-19 patients admitted to our hospitals and rapidly develop standards of care as evidence evolved. This commentary explores the methods and mechanisms for creating an MDT COVID-19 treatment working group which are applicable to any hospital likely to admit and care for high numbers of COVID-19 patients and demonstrates how the structure and governance of the group allowed for rapid adoption of both dexamethasone and tocilizumab into standard of care as data became available.


Subject(s)
COVID-19 , Pandemics , COVID-19/drug therapy , Humans , SARS-CoV-2 , Standard of Care
16.
Lupus Science & Medicine ; 8(Suppl 1):A10-A11, 2021.
Article in English | ProQuest Central | ID: covidwho-1155949

ABSTRACT

Case 1: 35-year-old patient with lupus nephritis presents with anasarca, hypertension and renal insufficiency at her 18th week of pregnancyLiz Lightstone, and Sandra NavarraA 35-year-old female was diagnosed lupus nephritis (LN) 7 years earlier with kidney biopsy showing LN Class IV-G activity 7, chronicity 3. She received methylprednisolone pulse and was thereafter maintained on prednisone, hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and calcium plus vitamin D. Her condition was ‘stable’ despite erratic follow-up and poor adherence. Two months ago, while on prednisone 10 mg/day, she consulted at clinic because of anasarca and hypertension at Week 18 of her 4th pregnancy. Obstetric history included two spontaneous abortions at 2 months gestation in 2013, 2015 and a successful term pregnancy in 2018 with a healthy baby girl delivered by C-section. Laboratory tests showed: Hemoglobin 83 g/L, hematocrit 0.24, WBC 6.97, platelets 270, creatinine 2.29 mg/dL, ↓ C3 0.20 g/L, ↑anti-dsDNA 1152.12 IU/mL, urine albumin 4+, RBC 90–95/hpf with dysmorphic RBCs, WBC 10–12/hpf, hyaline and granular casts. Anticardiolipin, lupus anticoagulant, anti-Ro and anti-La were negative.Clinical coursePrednisone was increased to 40 mg/day and she was started on methyldopa, azathioprine, HCQ, calcium plus vitamin D, iron plus folate, and aspirin 80 mg/d. A week later, she was admitted due to cough, dyspnea, orthopnea and low-grade fever. Chest radiograph showed hazy densities on both lung fields. Laboratory tests showed: Hemoglobin 74 g/L, hematocrit 0.22, WBC 17.20, platelets 433. Urine albumin 4+, RBC 18–22/hpf, WBC 10–15/hpf, hyaline, granular and waxy casts, urine total protein 822.40 mg/dL, urine creatinine 151.08 mg/dL, urine protein-creatinine ratio 5.44;BUN 62.6 mg/dL, creatinine 2.90 mg/dL, total protein 5.01 mg/dL, albumin 2.66 g/dL, Na 132 mmol/L, K 5.69 mmol/L, phosphorus 6.07 mmol/L, and iCa 1.19 mmol/L;SARS-CoV2 test was negative. She was started on antibiotics and received red cell transfusions;regular hemodialysis was initiated due to pulmonary congestion and metabolic acidosis.Discussion PointsDistinguish pre-eclampsia from LN flareManagement of severe LN flare with renal insufficiency during pregnancy including the role of plasma exchangeCase 2: 22–year-old female with refractory LN despite immunosuppressive regimens and rituximabLiz Lightstone, Sandra NavarraClinical dataA 22-year-old female presented with anti-phospholipid syndrome (APS) and LN at age 8. She had completed cyclophosphamide induction therapy, had been adherent to MMF (plus tacrolimus for 18 months), and received eight doses of rituximab. Renal histopathology (2008, 2016, 2019) shows persistent lupus nephritis ISN/RPS Class IV, varying activity and chronicity indices. She would attain partial renal remission for a few months, but never achieved complete remission. Blood pressure and renal function remain within normal range.Discussion PointUpdates in the management of LNCase 3: 35-year-old male with LN presents with persistent hypokalemiaLiz Lightstone, Sandra NavarraClinical dataA 35-year-old male with LN ISN/RPS Class IV – S, activity 11 and chronicity 4, presented with nephrotic-range proteinuria, hypertension, and impaired renal function. Renal ultrasound was normal without calcinosis. He received prednisone, MMF, HCQ, anti-hypertensives, and calcium plus vitamin D. He had persistently low levels of serum potassium (K) 2.4–3.8 meqs/L, and serum bicarbonate (HCO3) 11–20 mmol/L despite K and HCO3 supplementation. Urine pH was 6.0, urine sodium (Na) 80 mmol/L, urine K 20.63 mmol/L, urine chloride (Cl) 97.90 mmol/L. Serum anion gap was normal, and urine anion gap positive at 2.73 meq/L, confirming the diagnosis of an underlying distal renal tubular acidosis (RTA).Discussion PointsClinical significance and management of RTA in LNCase 4: 31-year-old patient with LN and APS presents with fever, deteriorating kidney function and an ovarian massLiz Lightstone, Sandra NavarraClinical dataA 31-year-old female was diagnosed with L and APS 8 years ago presenting with Raynaud’s, mononeuritis multiplex, proteinuria, pancytopenia, and pericarditis. She was given methylprednisolone pulse, cyclophosphamide, and belimumab then maintained on hydroxychloroquine, MMF, aspirin, nifedipine, iron plus folate, and calcium plus vitamin D. She developed hematologic flare a year ago which responded well to methylprednisolone pulse and two doses of rituximab. Two months ago, she presented with intermittent fever, dysuria, and cough. Laboratory results were: Hemoglobin 97 g/L, WBC 8.4 x109/L, platelet 109 x109/L, BUN 52.1 mmol/L, creatinine 2.73 mg/dL (eGFR 22.3 ml/min) →3.26 mg/dL (eGFR 18.1 ml/min), urine protein 2+, RBC 40–50, pus >100;urine PCR by Gene Xpert® was positive for Mycobacterium tuberculosis (TB), no rifampicin resistance. Chest radiograph showed infiltrates suggestive of miliary TB. Abdominal ultrasound showed renal cysts with calcifications, mild left ureteropelvocaliectasia from a left adnexal cystic mass measuring 8.57 cm. Exploratory laparotomy with left salpingo-oophorectomy was performed;histopathology showed caseating granuloma. She was started on an anti-TB regimen.Discussion PointsCauses of renal insufficiency in a patient with LNRenal involvement in APSLearning ObjectivesDescribe management approach to LNExplain special considerations in the management of LN flare during pregnancyDiscuss further management options in refractory LNDiscuss clinical situations which significantly contribute to morbidity in LN

18.
Kidney Med ; 3(1): 54-59.e1, 2021.
Article in English | MEDLINE | ID: covidwho-1065667

ABSTRACT

RATIONALE & OBJECTIVE: A number of serologic tests for immunoglobulin G (IgG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now commercially available, including multiple lateral flow immunoassays (LFIAs), which have the advantage of being inexpensive and easy to use, without the reliance on laboratory facilities. However, data on the development of humoral immunity to SARS-CoV-2 in patients with kidney disease is limited, and the utility of an LFIA to test for antibodies in these patients has not been assessed. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 60 patients (40 hemodialysis and 20 kidney transplant recipients) with SARS-CoV-2 infection confirmed by viral reverse transcriptase-polymerase chain reaction (RT-PCR) testing and 88 historic negative-control samples (collected before September 2019). TEST: A commercially available LFIA to test for SARS-CoV-2 IgG in patients with infection confirmed by viral RT-PCR testing. OUTCOMES: Sensitivity and specificity of the LFIA to detect SARS-CoV-2 IgG in dialysis patients and transplant recipients. RESULTS: 56/58 (96.6%) patients (38/39 hemodialysis and 18/19 transplant recipients) tested positive for SARS-CoV-2 IgG. 5/7 (71.4%) patients who were negative on preliminary testing had detectable IgG when retested more than 21 days postdiagnosis. Median times to first and second tests after diagnosis were 17 (interquartile range, 15-20) and 35 (interquartile range, 30-39) days, respectively. Calculation of test characteristics gave sensitivity of 96.6% (95% CI, 88.3%-99.4%) and specificity of 97.7% (95% CI, 92.0-99.6%). LIMITATIONS: Possible exposure to other beta-coronaviruses that may cross-react with the antigen used in the LFIA cannot be excluded. CONCLUSIONS: Symptomatic dialysis patients and transplant recipients commonly develop an immune response against SARS-CoV-2 infection that can be detected using an LFIA. Used diligently, an LFIA could be used to help screen the dialysis populations or confirm exposure on a patient level, especially in facilities in which laboratory resources are limited.

19.
Kidney Int Rep ; 6(1): 46-55, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-987632

ABSTRACT

INTRODUCTION: There are limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of coronavirus disease 2019 (COVID-19) remains. In this study we delineate the differential risks involved using serologic methods to help define exposure rates. METHODS: From a cohort of 1433 patients with end-stage kidney disease (ESKD), we analyzed COVID-19 infection rates and outcomes in 299 waitlist patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant program closed due to COVID-19. RESULTS: The overall mortality rates in waitlist and transplant populations were equivalent (P = 0.69). However, COVID-19 infection was more commonly diagnosed in the waitlist patients (P = 0.001), who were more likely to be tested by reverse transcriptase polymerase chain reaction (P = 0.0004). Once infection was confirmed, mortality risk was higher in the transplant patients (P = 0.015). The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6%, respectively (P = 0.0001). After adjusting for potential screening bias, the relative risk of death after a diagnosis of COVID-19 remained higher in transplant recipients (hazard ratio = 3.36 [95% confidence interval = 1.19-9.50], P = 0.022). CONCLUSIONS: Although COVID-19 infection was more common in the waitlist patients, a higher COVID-19‒associated mortality rate was seen in the transplant recipients, resulting in comparable overall mortality rates.

20.
Transplantation ; 105(1): 151-157, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-944555

ABSTRACT

BACKGROUND: From population studies, solid organ transplant recipients are at increased risk of mortality from RT-PCR confirmed COVID-19 infection. The risk factors associated with infection acquisition and mortality in transplant recipients using serological data have not been reported. METHODS: From 1725 maintenance transplant recipients, 855 consecutive patients were screened for SARS-CoV-2 antibodies. Serological screening utilized assays to detect both the N protein and receptor binding domain antibodies. Thirty-three of 855 (3.9%) of the screened patients had prior infection confirmed with RT-PCR. Twenty-one additional patients from our 1725 maintenance cohort with RT-PCR confirmed infection were included in our analysis. RESULTS: Eighty-nine of 855 (10.4%) patients tested positive for SARS-CoV-2 antibodies. Fifty-nine of 89 (66.3%) cases were patients newly identified as exposed, while 30/89 (33.7%) seropositive patients had previous infection confirmed by RT-PCR. A diagnosis of SARS-CoV-2 (RT-PCR or Ab+) was associated with being from a noncaucasoid background, P = 0.015; having a diagnosis of diabetes, P = 0.028 and a history of allograft rejection, P < 0.01. Compared with the RT-PCR+ cohort, patients with serological-proven infection alone were more likely to be receiving tacrolimus monotherapy, P < 0.01, and less likely to have a diagnosis of diabetes, P = 0.012. Seventeen of 113 (15.0%) of all patients with infection (RT-PCR and Ab+) died. Risk factors associated with survival were older age, odds ratio (OR): 1.07 (1.00-1.13), P = 0.041; receiving prednisolone, OR: 5.98 (1.65-21.60), P < 0.01 and the absence of diabetes, OR: 0.27 (0.07-0.99), P = 0.047. CONCLUSIONS: This study identifies risk factors and outcome for COVID-19 infection incorporating data on serologically defined infection and highlights the important contribution of immunosuppression regimen on outcomes.


Subject(s)
Antibodies, Viral/blood , COVID-19/etiology , Kidney Transplantation/mortality , SARS-CoV-2 , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/mortality , COVID-19 Serological Testing , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged
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