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1.
PLoS One ; 16(4): e0250853, 2021.
Article in English | MEDLINE | ID: covidwho-1833535

ABSTRACT

BACKGROUND: Infection by SARS-CoV-2 in domestic animals has been related to close contact with humans diagnosed with COVID-19. Objectives: To assess the exposure, infection, and persistence by SARS-CoV-2 of dogs and cats living in the same households of humans that tested positive for SARS-CoV-2, and to investigate clinical and laboratory alterations associated with animal infection. METHODS: Animals living with COVID-19 patients were longitudinally followed and had nasopharyngeal/oropharyngeal and rectal swabs collected and tested for SARS-CoV-2. Additionally, blood samples were collected for laboratory analysis, and plaque reduction neutralization test (PRNT90) to investigate specific SARS-CoV-2 antibodies. RESULTS: Between May and October 2020, 39 pets (29 dogs and 10 cats) of 21 patients were investigated. Nine dogs (31%) and four cats (40%) from 10 (47.6%) households were infected with or seropositive for SARS-CoV-2. Animals tested positive from 11 to 51 days after the human index COVID-19 case onset of symptoms. Three dogs tested positive twice within 14, 30, and 31 days apart. SARS-CoV-2 neutralizing antibodies were detected in one dog (3.4%) and two cats (20%). In this study, six out of thirteen animals either infected with or seropositive for SARS-CoV-2 have developed mild but reversible signs of the disease. Using logistic regression analysis, neutering, and sharing bed with the ill owner were associated with pet infection. CONCLUSIONS: The presence and persistence of SARS-CoV-2 infection have been identified in dogs and cats from households with human COVID-19 cases in Rio de Janeiro, Brazil. People with COVID-19 should avoid close contact with their pets during the time of their illness.


Subject(s)
COVID-19/epidemiology , COVID-19/veterinary , Pets/virology , Animals , Animals, Domestic/virology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Brazil/epidemiology , Cat Diseases , Cats , Dog Diseases , Dogs , Longitudinal Studies , Prevalence , SARS-CoV-2/pathogenicity
2.
J Am Soc Nephrol ; 32(9): 2147-2152, 2021 09.
Article in English | MEDLINE | ID: covidwho-1708655

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in patients with ESKD, and vaccination is hoped to prevent infection. METHODS: Between January 18 and February 24, 2021, 225 kidney transplant recipients (KTRs) and 45 patients on hemodialysis (HDPs) received two injections of mRNA BNT162b2 vaccine. The postvaccinal humoral and cellular response was explored in the first 45 KTRs and ten HDPs. RESULTS: After the second dose, eight HDPs (88.9%) and eight KTRs (17.8%) developed antispike SARS-CoV-2 antibodies (P<0.001). Median titers of antibodies in responders were 1052 AU/ml (IQR, 515-2689) in HDPs and 671 AU/ml (IQR, 172-1523) in KTRs (P=0.40). Nine HDPs (100%) and 26 KTRs (57.8%) showed a specific T cell response (P=0.06) after the second injection. In responders, median numbers of spike-reactive T cells were 305 SFCs per 106 CD3+ T cells (IQR, 95-947) in HDPs and 212 SFCs per 106 CD3+ T cells (IQR, 61-330) in KTRs (P=0.40). In KTRs, the immune response to BNT162b2 seemed influenced by the immunosuppressive regimen, particularly tacrolimus or belatacept. CONCLUSION: Immunization with BNT162b2 seems more efficient in HDPs, indicating that vaccination should be highly recommended in these patients awaiting a transplant. However, the current vaccinal strategy for KTRs may not provide effective protection against COVID-19 and will likely need to be improved.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/pharmacology , COVID-19/immunology , Kidney Transplantation , Renal Dialysis , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Aged , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cohort Studies , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Male , Middle Aged , Pandemics , RNA, Messenger/genetics , Retrospective Studies , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Transplant Recipients
3.
Vox Sang ; 117(2): 185-192, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1685455

ABSTRACT

BACKGROUND AND OBJECTIVES: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel. MATERIALS AND METHODS: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0. RESULTS: Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4-3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. CONCLUSIONS: An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.


Subject(s)
COVID-19 , Blood Donors , COVID-19/therapy , Humans , Immunization, Passive , Israel , SARS-CoV-2
4.
Lancet ; 397(10289): 2049-2059, 2021 May 29.
Article in English | MEDLINE | ID: covidwho-1671320

ABSTRACT

BACKGROUND: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79). INTERPRETATION: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
COVID-19/therapy , Hospital Mortality , Length of Stay/statistics & numerical data , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/mortality , Female , Humans , Immunization, Passive/methods , Immunization, Passive/mortality , Male , Middle Aged , Pandemics , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Treatment Outcome , United Kingdom/epidemiology
5.
Clin Infect Dis ; 74(2): 327-334, 2022 01 29.
Article in English | MEDLINE | ID: covidwho-1662105

ABSTRACT

Convalescent plasma (CP) have been used for treatment of coronavirus disease 2019 (COVID-19), but their effectiveness varies significantly. Moreover, the impact of CP treatment on the composition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 patients and antibody markers that differentiate between those who survive and those who succumb to the COVID-19 disease are not well understood. Herein, we performed longitudinal analysis of antibody profile on 115 sequential plasma samples from 16 hospitalized COVID-19 patients treated with either CP or standard of care, only half of them survived. Differential antibody kinetics was observed for antibody binding, immunoglobulin M/immunoglobulin G/immunoglobulin A (IgM/IgG/IgA) distribution, and affinity maturation in "survived" versus "fatal" COVID-19 patients. Surprisingly, CP treatment did not predict survival. Strikingly, marked decline in neutralization titers was observed in the fatal patients prior to death, and convalescent plasma treatment did not reverse this trend. Furthermore, irrespective of CP treatment, higher antibody affinity to the SARS-CoV-2 prefusion spike was associated with survival outcome. Additionally, sustained elevated IgA response was associated with fatal outcome in these COVID-19 patients. These findings propose that treatment of COVID-19 patients with convalescent plasma should be carefully targeted, and effectiveness of treatment may depend on the clinical and immunological status of COVID-19 patients, as well as the quality of the antibodies in the convalescent plasma.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive
6.
PLoS One ; 16(3): e0247797, 2021.
Article in English | MEDLINE | ID: covidwho-1605332

ABSTRACT

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31-60 days PSO. By 61-90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1-4 days PSO with 86% positivity observed at 5-7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Serological Testing/instrumentation , COVID-19 Serological Testing/methods , Equipment Design , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2/isolation & purification , Young Adult
7.
Int Immunol ; 33(10): 515-519, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1574756

ABSTRACT

Blockade of IL-6 function by an anti-IL-6 receptor (IL-6R) antibody (tocilizumab, trade name Actemra) has been shown to be effective for the treatment of chronic autoimmune inflammatory diseases including rheumatoid arthritis. Interestingly, treatment with tocilizumab has also been found to alleviate the cytokine storm induced by chimeric antigen receptor (CAR)-T-cell therapy. Patients with serious cases of coronavirus disease 2019 (COVID-19) exhibit cytokine release syndrome (CRS), which suggested that tocilizumab might be an effective therapeutic for serious cases of COVID-19. In the first part of this short review, the therapeutic effect of tocilizumab for the disease induced by IL-6 overproduction is described. CRS induced by CAR-T-cell therapy and COVID-19 is then discussed.


Subject(s)
Arthritis/immunology , COVID-19/immunology , Interleukin-6/immunology , Receptors, Chimeric Antigen/immunology , SARS-CoV-2/immunology , Cell- and Tissue-Based Therapy/methods , Cytokine Release Syndrome/immunology , Humans
8.
Clin Infect Dis ; 73(11): e4082-e4089, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559187

ABSTRACT

BACKGROUND: Leronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19). METHODS: Twenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records. RESULTS: Mean age was 69.5 ±â€…14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died. CONCLUSIONS: Leronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , COVID-19/therapy , HIV Antibodies , Humans , Immunization, Passive , Middle Aged , SARS-CoV-2 , Treatment Outcome
9.
J Nippon Med Sch ; 88(4): 380-383, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1551292

ABSTRACT

We assessed the association of severity of coronavirus disease 2019 (COVID-19) with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load, IgG antibody level, and prognostic indicators.Twenty-one patients hospitalized with COVID-19 were classified as having severe or mild disease on the basis of average respiratory rate during hospitalization (severe: ≥22 breaths/min; mild: <22 breaths/min). Viral load in nasopharyngeal samples, blood levels of C-reactive protein (CRP), lymphocytes, and D-dimer on admission and plasma immunoglobulin G (IgG) index on Day 7±2 after symptom onset were compared in relation to disease severity. Seven patients had severe disease and 14 had mild disease. Those with severe disease had a significantly higher IgG index (median: 3.75 vs 0.56, p=0.01) and CRP (median: 8.6 vs 1.0 mg/dL, p<0.001) and D-dimer levels (median: 1.65 vs 0.75 µg/mL; p=0.002) and a significantly lower lymphocyte count (median: 1,176 vs 666 cells/µL, p=0.005) and viral load (median: 8.7×106 vs 2.3×104 copies/mL, p=0.005). Furthermore, time from symptom onset to virus disappearance was significantly longer in severe patients (median: 24 vs 17 days, p=0.03). A high IgG index in the early phase of the disease was associated with severe disease and might serve as a prognostic indicator.


Subject(s)
Antibodies, Viral/blood , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , Immunoglobulin G/blood , SARS-CoV-2/pathogenicity , Viral Load , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/drug therapy , COVID-19/therapy , COVID-19/virology , Female , Hospitalization , Host-Pathogen Interactions , Humans , Japan , Male , Middle Aged , Oxygen Inhalation Therapy , Predictive Value of Tests , Prognosis , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors
10.
J Clin Med ; 10(8)2021 Apr 19.
Article in English | MEDLINE | ID: covidwho-1526843

ABSTRACT

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients' humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.

11.
J Clin Med ; 10(8)2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1526828

ABSTRACT

A novel coronavirus-Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)-outbreak correlated with the global coronavirus disease 2019 (COVID-19) pandemic was declared by the WHO in March 2020, resulting in numerous counted cases attributed to SARS-CoV-2 worldwide. Herein, we discuss current knowledge on the available therapy options for patients diagnosed with COVID-19. Based on available scientific data, we present an overview of solutions in COVID-19 management by use of drugs, vaccines and antibodies. Many questions with non-conclusive answers on the measures for the management of the COVID-19 pandemic and its impact on health still exist-i.e., the actual infection percentage of the population, updated precise mortality data, variability in response to infection by the population, the nature of immunity and its duration, vaccine development issues, a fear that science might end up with excessive promises in response to COVID-19-and were raised among scientists. Indeed, science may or may not deliver results in real time. In the presented paper we discuss some consequences of disease, its detection and serological tests, some solutions to disease prevention and management, pitfalls and obstacles, including vaccination. The presented ideas and data herein are meant to contribute to the ongoing debate on COVID-19 without pre-selection of available information.

12.
Childs Nerv Syst ; 37(12): 3919-3922, 2021 12.
Article in English | MEDLINE | ID: covidwho-1525534

ABSTRACT

Anti-N-methyl-D-aspartate receptor encephalitis is a clinical condition characterized by acute behavioral and mood changes, abnormal movements, autonomic instability, seizures, and encephalopathy. We describe a 7-year-old boy diagnosed with autoimmune encephalitis due to NMDAR antibody in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019) (COVID-19), without pulmonary involvement or fever. The patient presented with acute ataxia, rapidly developed encephalopathy, and autoimmune encephalitis was suspected. Steroid treatment was withheld because of lymphopenia and intravenous immunoglobulin was started. The absence of clinical response prompted plasmapheresis and, when lymphocyte counts improved, pulse steroid treatment was applied. The latter was followed by significant improvement and the patient was discharged in a conscious and ambulatory state. Autoimmune encephalitis should be considered in the presence of neurological symptoms accompanying SARS-CoV-2 infection and steroid treatment should be preferred unless limited by contraindications.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , COVID-19 , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/complications , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/drug therapy , Child , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , SARS-CoV-2 , Seizures
13.
J Am Soc Nephrol ; 32(3): 708-722, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496675

ABSTRACT

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/therapy , Interleukin-6/antagonists & inhibitors , Kidney Transplantation/adverse effects , Adult , Allografts , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Infections/etiology , Interleukin-6/immunology , Isoantibodies/blood , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young Adult
14.
J Am Soc Nephrol ; 32(2): 479-494, 2021 02.
Article in English | MEDLINE | ID: covidwho-1496663

ABSTRACT

BACKGROUND: Binding of donor-specific antibodies (DSAs) to kidney allograft endothelial cells that does not activate the classic complement cascade can trigger the recruitment of innate immune effectors, including NK cells. Activated NK cells contribute to microvascular inflammation leading to chronic antibody-mediated rejection (AMR). Recipient NK cells can also trigger antibody-independent microvascular inflammation by sensing the absence of self HLA class I molecules ("missing self") on allograft endothelial cells. This translational study investigated whether the condition of missing self amplifies DSA-dependent NK cell activation to worsen chronic AMR. METHODS AND RESULTS: Among 1682 kidney transplant recipients who underwent an allograft biopsy at Lyon University Hospital between 2004 and 2017, 135 fulfilled the diagnostic criteria for AMR and were enrolled in the study. Patients with complement-fixing DSAs identified by a positive C3d binding assay (n=73, 54%) had a higher risk of transplant failure (P=0.002). Among the remaining patients with complement-independent chronic AMR (n=62, 46%), those in whom missing self was identified through donor and recipient genotyping exhibited worse allograft survival (P=0.02). In multivariable analysis, only proteinuria (HR: 7.24; P=0.01) and the presence of missing self (HR: 3.57; P=0.04) were independent predictors for transplant failure following diagnosis of chronic AMR. Cocultures of human NK cells and endothelial cells confirmed that addition of missing self to DSA-induced NK cell activation increased endothelial damage. CONCLUSIONS: The assessment of missing self at the time of diagnosis of chronic AMR identifies patients at higher risk for kidney transplant failure.


Subject(s)
Allografts/pathology , Complement Activation/physiology , Graft Rejection/etiology , Histocompatibility Antigens Class I/blood , Kidney Transplantation/adverse effects , Killer Cells, Natural/physiology , Adult , Allografts/immunology , Cell Culture Techniques , Complement C3d/metabolism , Endothelial Cells/physiology , Female , Graft Rejection/blood , Graft Rejection/pathology , Graft Survival , Humans , Killer Cells, Natural/pathology , Male , Middle Aged , Young Adult
15.
Dokl Biochem Biophys ; 496(1): 44-47, 2021 May.
Article in English | MEDLINE | ID: covidwho-1495017

ABSTRACT

The high efficiency of using thermoheliox (inhalation with a high-temperature mixture of helium and oxygen) in the treatment of patients affected by COVID-19 was shown. The dynamics of accumulation of IgG, IgM, and C-reactive protein (CRP) in patients with coronavirus infection in the "working" and control groups was studied experimentally. It was shown that thermoheliox intensifies the synthesis of IgG, IgM, and CRP antibodies, while eliminating the induction period on the kinetic curves of the synthesis of specific antibodies in the IgG form and transfers the synthesis of CRP to a fast phase. The results of experiments confirm the previously obtained data based on the analysis of the kinetic model of the development of coronaviral infection in the human body.


Subject(s)
Antibodies, Viral/immunology , C-Reactive Protein/biosynthesis , COVID-19/metabolism , COVID-19/prevention & control , Immunity/immunology , Vaccination/methods , COVID-19/immunology , Humans , Kinetics , Spike Glycoprotein, Coronavirus/immunology
16.
J Clin Microbiol ; 59(7): e0051421, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1486483

ABSTRACT

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.


Subject(s)
COVID-19 , Malaria , Antibodies, Viral , Humans , Malaria/diagnosis , Nigeria , SARS-CoV-2 , Sensitivity and Specificity
17.
Engineering (Beijing) ; 7(7): 958-965, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1482579

ABSTRACT

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL-1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL-1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1ß, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

18.
Clin Infect Dis ; 73(7): 1805-1813, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1455252

ABSTRACT

BACKGROUND: The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. METHODS: We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020-25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%-36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4-106.9) and 7.1 (95% CI: 1.2-42.5), respectively. CONCLUSIONS: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Contact Tracing , Family Characteristics , Humans , United States/epidemiology , Wisconsin
19.
J Med Virol ; 93(10): 5816-5824, 2021 10.
Article in English | MEDLINE | ID: covidwho-1453607

ABSTRACT

Serological testing for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme-linked immunosorbent assays. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information on whether or not the individual has been infected with SARS-CoV-2. Enzyme-linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Enzyme-Linked Immunosorbent Assay , Female , Fluorescent Antibody Technique, Indirect , Humans , Immunoglobulin Isotypes/blood , Kinetics , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
20.
Clin J Am Soc Nephrol ; 16(7): 1073-1082, 2021 07.
Article in English | MEDLINE | ID: covidwho-1444004

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients receiving hemodialysis are at high risk for both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe coronavirus disease 2019. A lifesaving vaccine is available, but sensitivity to vaccines is generally lower in patients on dialysis. Little is yet known about antibody responses after coronavirus disease 2019 (COVID-19) vaccination in this vulnerable group. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In this prospective single-center study, we included 22 patients on dialysis and 46 healthy controls from Heidelberg University Hospital between December 2020 and February 2021. We measured anti-S1 IgG with a threshold index for detection greater than one, neutralizing antibodies with a threshold for viral neutralization of ≥30%, and antibodies against different SARS-CoV2 fragments 17-22 days after the first dose and 18-22 days after the second dose of the mRNA vaccine BNT162b2. RESULTS: After the first vaccine dose, four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls developed positive anti-S1 IgG, with a median anti-S1 IgG index of 0.2 (interquartile range, 0.1-0.7) compared with nine (interquartile range, 4-16), respectively. SARS-CoV2 neutralizing antibodies exceeded the threshold for neutralization in four of 22 (18%) patients on dialysis compared with 43 of 46 (93%) healthy controls, with a median percent inhibition of 11 (interquartile range, 3-24) compared with 65 (interquartile range, 49-75), respectively. After the second dose, 14 of 17 (82%) patients on dialysis developed neutralizing antibodies exceeding the threshold for viral neutralization and antibodies against the receptor binding S1 domain of the spike protein, compared with 46 of 46 (100%) healthy controls, respectively. The median percent inhibition was 51 (interquartile range, 32-86) compared with 98 (interquartile range, 97-98) in healthy controls. CONCLUSIONS: Patients receiving long-term hemodialysis show a reduced antibody response to the first and second doses of the mRNA vaccine BNT162b2. The majority (82%) develop neutralizing antibodies after the second dose but at lower levels than healthy controls.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Renal Dialysis , SARS-CoV-2/immunology , Vaccination , Adult , Age Factors , Aged , Aged, 80 and over , BNT162 Vaccine , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged
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