Uremia-Associated Immunological Aging and Severity of COVID-19 Infection
TL;DR: In this review the different aspects, in particular thymus function and memory T cell expansion, of uremia-associated immunological aging are reviewed with respect to COVID 19 infection and the decreased generation of naïve T cells may be instrumental in suboptimal anti-viral immune responses.
Abstract: One year after the start of the COVID-19 pandemic it has become clear that some groups of individuals are at particular high risk of a complicated course of infection resulting in high morbidity and mortality. Two specific risk factors are most prominent, old age and the presence of co-morbidity. Recent studies have shown that patients with compromised renal function, especially those treated with renal replacement therapy or having received a kidney transplant are at a much higher risk for severe COVID infection and increased mortality. This may be in part due to the increased prevalence of co-morbid conditions in these patients but specific alterations in their immune system, reflecting premature immunological aging, may be equally important. In this review the different aspects, in particular thymus function and memory T cell expansion, of uremia-associated immunological aging are reviewed with respect to COVID 19 infection. In essence, the decreased generation of naive T cells may be instrumental in suboptimal anti-viral immune responses while the relatively uncontrolled expansion of effector T cells may facilitate the feared phase of the COVID-19 infection with excessive and live-threatening inflammation of the lung parenchyma.
Citations
More filters
TL;DR: In this paper, mycophenolate mofetil (MMF) treatment was evaluated in 225 kidney transplant recipients (KTRs) and compared to 176 controls, and MMF-free regimen was highly associated with seroconversion.
83 citations
TL;DR: In this paper , mycophenolate mofetil (MMF) treatment was evaluated in 225 kidney transplant recipients with SARS-CoV-2 infection and showed an adverse effect on their immune response.
83 citations
TL;DR: In this paper, levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike protein using ELISPOT technology were evaluated.
Abstract: Background Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. Methods In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7-15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. Results Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. Conclusions Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.
16 citations
TL;DR: The incidence of COVID-19 among Palestinian maintenance dialysis patients was notably high, with haemodialysis patients being three times more likely to get infected compared to their peritoneal dialysis counterparts, and the risk of mortality was significantly increased with age, male sex, smoking, diabetes, and having central venous catheter as vascular access for haemmodialysis.
Abstract: Abstract Patients on maintenance dialysis therapy are especially vulnerable to COVID-19 and its complications. This study aimed to assess the incidence, epidemiological characteristics, and mortality rate of COVID-19 among maintenance dialysis patients. This retrospective observational chart review study included 548 patients from all dialysis units in the West Bank of Palestine who acquired COVID-19 between 5 March 2020, and 11 August 2021. We collected data on patients' demographics, clinical features, and outcomes. A multivariable logistic regression model was used to assess independent risk factors for COVID-19-related mortality. The incidence of COVID-19 among maintenance dialysis patients was 35.3%, as 548 out of 1554 patients have tested positive during the study period. Patients on haemodialysis were three times riskier to get infected than those on peritoneal dialysis (37% vs 11.3%). Half (50.2%) of infected patients required hospitalisation, and 24.5% were admitted to an intensive care unit, while the mortality rate stood at 26.8%. Old age, male sex, central venous catheter use, comorbid diabetes, smoking, and having an RH negative blood group type were determined to be significantly associated with increased risk of mortality. In conclusion, the incidence of COVID-19 among Palestinian maintenance dialysis patients was notably high, especially among haemodialysis patients. High rates of hospitalisation, ICU admission, intubation and death were observed, and predictive factors for COVID-19-related mortality were identified. Therefore, the implementation of strict infection control measures and promotion of home dialysis are warranted to reduce the infection rate. KEY MESSAGES The incidence of COVID-19 among Palestinian maintenance dialysis patients was notably high; more than one-third of the total dialysis population acquired COVID-19, with haemodialysis patients being three times more likely to get infected compared to their peritoneal dialysis counterparts. The mortality rate among maintenance dialysis patients was 26.8%, more than 25 times higher than that of the general population. The risk of mortality was significantly increased with age, male sex, smoking, diabetes, and having central venous catheter as vascular access for haemodialysis. Strict infection control measures, as well as the promotion of home dialysis, are necessary to reduce the risk of infection.
5 citations
TL;DR: Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs, and contributes to future considerations on alternative vaccination strategies.
Abstract: Background. Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response. Methods. Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome. Results. The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model‚ 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval [CI], 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations. Conclusions. In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies.
4 citations
References
More filters
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
TL;DR: The four articles in this special section onMeta-analysis illustrate some of the complexities entailed in meta-analysis methods and contributes both to advancing this methodology and to the increasing complexities that can befuddle researchers.
Abstract: During the past 30 years, meta-analysis has been an indispensable tool for revealing the hidden meaning of our research literatures. The four articles in this special section on meta-analysis illus...
20,272 citations
"Uremia-Associated Immunological Agi..." refers background in this paper
...In the case of severe COVID-19 infection, controlling the inflammatory response by high dose steroid is currently the best option (103)....
[...]
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico1, University of Milan2, Vita-Salute San Raffaele University3, Catholic University of the Sacred Heart4, Agostino Gemelli University Polyclinic5, Ospedale di Circolo e Fondazione Macchi6, University of Milano-Bicocca7, University of Pavia8, University of Brescia9, Kessler Foundation10, University of Bologna11, Humanitas University12
TL;DR: Patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy were characterized, including data on clinical management, respiratory failure, and patient mortality.
Abstract: Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2was greater than 50% in 89% of patients. The median Pao2/Fio2was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0];P = .94). Median Fio2was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, −10% [95% CI, −14% to 6%];P = .006), and median Pao2/Fio2was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, −8 to 22];P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68];P Conclusions and Relevance In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.
4,331 citations
"Uremia-Associated Immunological Agi..." refers background in this paper
...Increasing morbidity and mortality associated with COVID-19 infection is highly associated with elderly age and co-morbid conditions (76)....
[...]
TL;DR: Investigation of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19 and shows the novel coronavirus might mainly act on lymphocytes, especially T lymphocytes.
Abstract: BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
3,532 citations
TL;DR: The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production, which may be of importance due to their correlation with disease severity in COVID-19.
Abstract: BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).
3,488 citations