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1.
Curr Opin Pulm Med ; 27(3): 176-183, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-2270628

ABSTRACT

PURPOSE OF REVIEW: Patients on chronic immunosuppressive treatments at baseline are at increased risk of opportunistic infections. These patients are at especially increased risk of morbidity and mortality during the coronavirus-19 (COVID-19) pandemic. This review will focus on patients with diseases in which immunosuppression is a vital part of the treatment regimen, including those with solid organ transplants, rheumatologic disorders, sarcoidosis, and inflammatory bowel disease (IBD). We will summarize the current knowledge of immunosuppression in these diseases and the risk of contracting COVID-19. Furthermore, we will discuss if immunosuppression increases severity of COVID-19 presentation. RECENT FINDINGS: Since the start of the COVID-19 pandemic, a large number patients receiving chronic immunosuppression have been infected with SARS-CoV-2. Moreover, our understanding of the immunology of SARS-CoV-2 is advancing at a rapid pace. Currently, a number of clinical trials are underway to investigate the role of immunosuppressive treatments in the management of this disease. SUMMARY: Currently, there is no conclusive evidence to suggest that solid organ transplant recipients on chronic immunosuppression are at increased risk of contracting COVID-19. Solid organ transplant recipients may be at increased risk for worse COVID-19 outcomes but the data are not consistent. There is evidence to suggest that patients with rheumatologic disorders or IBDs are not at increased risk of contracting COVID-19 and do not necessarily experience worse clinical outcomes. Patients with sarcoidosis are not necessarily at increased risk of COVID-19, although there is limited data available to determine if immunosuppression worsens outcomes in this population.


Subject(s)
COVID-19 , Immunosuppressive Agents , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Humans , Immunocompromised Host , Immunosuppression Therapy/methods , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/immunology , Immunosuppressive Agents/therapeutic use , Risk Assessment , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Transplant Recipients
2.
Int Immunopharmacol ; 115: 109635, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2165422

ABSTRACT

The therapeutic benefits of curcuminoids in various diseases have been extensively reported. However, little is known regarding their preventive effects on extensive immunosuppression. We investigated the immunoregulatory effects of a curcuminoid complex (CS/M), solubilized with stevioside, using a microwave-assisted method in a cyclophosphamide (CTX)-induced immunosuppressive mouse model and identified its new pharmacological benefits. CTX-treated mice showed a decreased number of innate cells, such as dendritic cells (DCs), neutrophils, and natural killer (NK) cells, and adaptive immune cells (CD4 and CD8 T cells) in the spleen. In addition, CTX administration decreased T cell activation, especially that of Th1 and CD8 T cells, whereas it increased Th2 and regulatory T (Treg) cell activations. Pre-exposure of CS/M to CTX-induced immunosuppressed mice restored the number of innate cells (DCs, neutrophils, and NK cells) and increased their activity (including the activity of macrophages). Exposure to CS/M also led to the superior restoration of T cell numbers, including Th1, activated CD8 T cells, and multifunctional T cells, suppressed by CTX, along with a decrease in Th2 and Treg cells. Furthermore,CTX-injected mice pre-exposed to CS/M were accompanied by an increase in the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), which play an essential role against oxidative stress. Importantly, CS/M treatment significantly reduced viral loads in severe acute respiratory syndrome coronavirus2-infected hamsters and attenuated the gross pathology in the lungs. These results provide new insights into the immunological properties of CS/M in preventing extensive immunosuppression and offer new therapeutic opportunities against various cancers and infectious diseases caused by viruses and intracellular bacteria.


Subject(s)
COVID-19 , Immune Reconstitution , Animals , Mice , Antioxidants/therapeutic use , SARS-CoV-2 , Immunosuppression Therapy/methods
4.
J Hepatol ; 75(2): 435-438, 2021 08.
Article in English | MEDLINE | ID: covidwho-1454287

ABSTRACT

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Immunosuppressive Agents/therapeutic use , Liver Transplantation/methods , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Immunosuppression Therapy/methods , Israel/epidemiology , Kidney Function Tests , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Serologic Tests/methods , Serologic Tests/statistics & numerical data , Vaccination/adverse effects , Vaccination/methods
6.
Rheumatol Int ; 41(11): 1941-1947, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1370384

ABSTRACT

Management of ANCA-associated vasculitis (AAV) during the COVID-19 pandemic poses unique therapeutic challenges. An online survey was conducted to understand physician's choices for treating AAV during the COVID-19 pandemic. Web-based survey featuring nineteen questions was circulated amongst physicians across various specialties. The responses regarding immunosuppressive therapy for remission induction and maintenance, COVID-19 testing, and preventive measures were recorded. A total of 304 responses were recorded. Most of the respondents were from India (83.9%) and comprised rheumatologists (66%) in practice for ≥ 5 years (71%). Though a majority preferred Rituximab or intravenous cyclophosphamide (CYC) as a remission induction agent, a significant proportion opted for oral CYC and mycophenolate mofetil (MMF) also. Only one-third wanted to test for COVID-19 before initiating immunosuppressive therapy in patients with organ/life-threatening manifestations. Rituximab was the most favored maintenance therapy (47%), followed by azathioprine, MMF, and methotrexate. The results of this focused survey of managing AAV patients depict the real-world dilemmas and physicians' choices in this setting.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Immunosuppression Therapy/methods , Practice Patterns, Physicians' , Rheumatology/methods , Adult , COVID-19/epidemiology , COVID-19 Testing , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pandemics , Remission Induction/methods , SARS-CoV-2 , Surveys and Questionnaires
7.
Nephrology (Carlton) ; 27(2): 195-207, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1352490

ABSTRACT

BACKGROUND: There is a scarcity of data comparing the consequences of first and second COVID-19 waves on kidney transplant recipients (KTRs) in India. METHODS: We conducted a single-centre retrospective study of 259 KTRs with COVID-19 to compare first wave (March 15-December 31 2020, n = 157) and second wave (April 1-May 31 2021, n = 102). RESULTS: KTRs during second wave were younger (43 vs. 40 years; p-value .04) and also included paediatric patients (0 vs. 5.9%; p-value .003). Symptoms were milder during the second wave (45 vs. 62.7%; p-value .007); COVID-19 positive patients had less frequent cough (32 vs. 13.8%; p-value .001), fever was less frequent (58 vs. 37%; p-value .001), and we observed fewer co-morbidities (11 vs. 20.6%; p-value .04). The percentages of neutrophils (77 vs. 83%; p-value .001) and serum ferritin (439 vs. 688; p-value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%; p-value .0001). Hydroxychloroquine (11 vs. 0%; p-value .0001) and tocilizumab (7 vs. 0%; p-value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%; p-value .0001) and remdesivir (47 vs. 65%; p-value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%; p-value .01) and ICU admissions (20 vs. 37.2%; p-value .002) were more frequent during second wave. The 28-day mortality rate (9.6 vs. 10%; p-value 1) was not different. CONCLUSIONS: There has been a different clinical spectrum of COVID-19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Kidney Transplantation , Transplant Recipients/statistics & numerical data , Adult , Age Factors , Antiviral Agents/administration & dosage , Antiviral Agents/classification , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Comorbidity , Female , Humans , Immunosuppression Therapy/methods , Immunosuppression Therapy/statistics & numerical data , India/epidemiology , Intensive Care Units/statistics & numerical data , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Kidney Transplantation/statistics & numerical data , Male , Mortality , Postoperative Period , Retrospective Studies , SARS-CoV-2 , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data
8.
Ocul Immunol Inflamm ; 29(4): 734-740, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1334067

ABSTRACT

Purpose: Determine the risk of immunomodulatory therapy (IMT) for COVID-19 infection morbidity.Method: A telemedicine survey on patients of a referral uveitis clinic was performed. Signs of infection, habits, and hospitalizations during the 7 months of the COVID-19 pandemic prior to the study date were recorded. Suggestive findings in chest CT scan and/or positive RT-PCR were considered as confirmed COVID-19 infection while those with only suggestive symptoms were considered as suspected cases. Risk factors including sanitary measures and IMT were compared between patients with confirmed cases and patients without infection.Result: 694 patients were included. Eight patients were identified as confirmed cases and 22 patients as suspected cases of COVID-19 infection. Close contact with infected persons was the only significant risk factor for contracting COVID-19.Conclusion: Using IMT did not affect hospitalization and/or ICU admission and can thus be continued during the pandemic, provided that instructions for preventive measures are followed.


Subject(s)
COVID-19/epidemiology , Immunomodulation/physiology , Immunosuppression Therapy/methods , Pandemics , SARS-CoV-2 , Telemedicine/methods , Uveitis/therapy , Adult , Comorbidity , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Risk Factors , Surveys and Questionnaires , Uveitis/epidemiology
9.
J Cancer Res Ther ; 17(2): 295-302, 2021.
Article in English | MEDLINE | ID: covidwho-1268380

ABSTRACT

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19.


Subject(s)
COVID-19/radiotherapy , Cytokine Release Syndrome/radiotherapy , Immunosuppression Therapy/methods , SARS-CoV-2/immunology , COVID-19/complications , COVID-19/immunology , COVID-19/virology , Clinical Decision-Making , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Humans , Immunosuppression Therapy/adverse effects , Radiotherapy Dosage , Severity of Illness Index , Treatment Outcome
10.
Curr Opin Organ Transplant ; 26(3): 339-345, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1211441

ABSTRACT

PURPOSE OF REVIEW: To assess the impact of coronavirus disease 2019 (COVID-19) and the pandemic on liver transplant candidates, recipients, and donors, and review guidelines and recommendations for integrating COVID-19 therapies into current practice. RECENT FINDINGS: COVID-19 has high morbidity and mortality for transplant candidates; interestingly, posttransplant comorbidities play a larger role than immunosuppression status. COVID-19 therapies and vaccinations are well tolerated in pre and postliver transplant patients with few exceptions, although further research is needed regarding effectiveness in this patient population. Provider practice patterns should evolve to minimize contagion during the current pandemic and prepare for an increase in liver disease due to after-shocks of missed diagnosis and progression of liver disease. SUMMARY: COVID-19 has spurred new research and technologies to ensure the safety of liver transplant candidates, recipients, and donors, and most COVID-19 therapies are safe in this patient population. Further work needs to be done regarding the use of COVID-19 positive organs and the efficacy of vaccines in the transplant population.


Subject(s)
COVID-19/epidemiology , Liver Transplantation/methods , Humans , Immunosuppression Therapy/methods , Pandemics , SARS-CoV-2/isolation & purification
11.
J Immunol Res ; 2021: 6659410, 2021.
Article in English | MEDLINE | ID: covidwho-1140376

ABSTRACT

The main basis for hydroxychloroquine (HCQ) treatment in COVID-19 is the compound's ability to inhibit viral replication in vitro. HCQ also suppresses immunity, mainly by interference in TLR signalling, but reliable clinical data on the extent and nature of HCQ-induced immunosuppression are lacking. Here, we discuss the mechanistic basis for the use of HCQ against SARS-CoV-2 in a prophylactic setting and in a therapeutic setting, at different stages of the disease. We argue that the clinical effect of prophylactic or therapeutic HCQ treatment in COVID-19 depends on the balance between inhibition of viral replication, immunosuppression, and off-target side effects, and that the outcome is probably dependent on disease stage and disease severity. This is supported by the initial outcomes of the well-designed randomized controlled trials: so far, evidence for a beneficial effect of HCQ treatment for COVID-19 is weak and conflicting.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , Humans , Immunosuppression Therapy/methods , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severity of Illness Index , Signal Transduction/drug effects , Treatment Outcome , Virus Replication/drug effects
12.
Transplant Proc ; 53(4): 1146-1153, 2021 May.
Article in English | MEDLINE | ID: covidwho-1104308

ABSTRACT

INTRODUCTION: The coronavirus, which first appeared in 2019, developed into a pandemic during 2020. It remains unclear to what extent the pandemic endangers the safety of kidney transplantation programs. In this study, we evaluated the short-term outcomes of our patients receiving a kidney transplant during the first phase and compared them with patients who received a kidney transplant immediately before the coronavirus pandemic. MATERIALS AND METHODS: Our retrospective study includes 34 kidney transplant recipients between October 1, 2019, and April 30, 2020. Nineteen patients from the phase immediately prior to the first coronavirus wave (pre-corona group), and 15 patients from the phase of the first coronavirus wave (corona group) were studied. We retrospectively evaluated demographic data, postoperative short-term outcomes and complications, immunosuppression regime, coronavirus infection status, and behavior during the first phase of the pandemic. RESULTS: There were no differences between the 2 groups regarding short-term outcomes and postoperative complications or in immunosuppressive medication. After the introduction of intensified hygienic conditions and routine swabs prior to transplantation, no nosocomial SARS-CoV-2 infections occurred. In the outpatient setting, none of the patients developed a SARS-CoV-2 infection. The majority of patients performed voluntary quarantine. CONCLUSIONS: The short-term outcomes after kidney transplantation during the first phase of the coronavirus pandemic were comparable to pre-pandemic patients, and no SARS-CoV-2-associated death or transplant failure occurred in our small cohort. We considered patient compliance with hygiene and self-isolation measures very high. Nevertheless, in further phases of the pandemic, the continuation of the living kidney donation program must be critically evaluated.


Subject(s)
COVID-19/epidemiology , Hospitals/statistics & numerical data , Kidney Transplantation/statistics & numerical data , Postoperative Complications/epidemiology , SARS-CoV-2 , Adult , COVID-19/prevention & control , COVID-19/transmission , Disease Transmission, Infectious/prevention & control , Female , Humans , Immunosuppression Therapy/methods , Infection Control/methods , Kidney Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/prevention & control , Postoperative Complications/virology , Retrospective Studies , Treatment Outcome
13.
Transplant Proc ; 53(4): 1138-1142, 2021 May.
Article in English | MEDLINE | ID: covidwho-1085466

ABSTRACT

INTRODUCTION: In recent months, the number of kidney transplants from deceased donors has declined significantly. One of the reasons is the possibility of infection of the recipient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Determining the risk of transmission of coronavirus disease 2019 (COVID-19) with a donor organ is very important for developing a kidney transplantation policy during a pandemic. MATERIALS AND METHOD: We present cases of kidney transplantation from COVID-19-positive deceased donors to 2 dialysis patients 49 and 45 years old. One of them was on hemodialysis for 28 months; the other received continuous ambulatory peritoneal dialysis (CAPD). Both patients received only basic immunosuppression, including tacrolimus, methylprednisolone, and mycophenolic acid. No antilymphocyte agents were used for induction therapy. RESULTS: Cold ischemia time was 22 and 21 hours, respectively. One recipient had delayed graft function with increasing of urine output on day 8; another had immediate function. Both patients had no febrile and no other symptoms of acute respiratory disease during their hospital stay. No abnormalities on the chest x-ray were seen. No serum anti-SARS-CoV-2 IgM and IgG were detected before and during 6 weeks after surgery. Repeated nasopharyngeal swabs real-time reverse transcription polymerase chain reaction (rRT-PCR) were negative during the period. Both recipients were discharged 5 weeks after surgery with serum creatinine levels of 122 and 91 mcmol/L, respectively. CONCLUSION: Today we have no evidence of the possibility of transmission of COVID-19 from a SARS-CoV-2 positive donor to a kidney recipient. We also have no reason to suspect kidney damage by COVID-19 in a deceased donor at normal serum creatinine level.


Subject(s)
COVID-19/transmission , Disease Transmission, Infectious/prevention & control , Donor Selection , Kidney Transplantation/methods , SARS-CoV-2 , Humans , Immunosuppression Therapy/methods , Kidney/virology , Kidney Transplantation/adverse effects , Middle Aged , Postoperative Complications/prevention & control , Postoperative Complications/virology , Transplants/virology , Treatment Outcome
14.
Int J Infect Dis ; 104: 426-432, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1071445

ABSTRACT

OBJECTIVES: The lack of effective treatments for coronavirus disease 2019 (COVID-19) has mandated the repurposing of several drugs, including antiretrovirals and remdesivir (RDV). These compounds may induce acute kidney injury and are not recommended in patients with poor renal function, such as kidney transplant (KTx) recipients. METHODS: The records of 42 KTx recipients with COVID-19 were reviewed. Some of them were receiving antiretrovirals (n = 10) or RDV (n = 8) as part of COVID-19 management. Most patients were male (71%) and their median age was 52 years. The median glomerular filtration rate in these patients was 56 ml/min. Regarding disease severity, 36% had mild disease, 19% had moderate disease, 31% had severe disease, and 12% had critical disease. Subgroups, i.e., patients receiving antiretrovirals, RDV, or no antivirals, were comparable in terms of patient age, comorbidities, and immunosuppression. RESULTS: Seven patients (16.6%) died during hospitalization. Acute kidney injury was found in 24% of KTx recipients at admission. Upon discharge, estimated glomerular filtration rate (eGFR) increased in 32% and decreased in 39% of the KTx recipients compared with the admission rate. The decrease was more prevalent in the RDV group (80%) compared with KTx recipients without any antiviral treatment (29%) (p < 0.05). Most patients (62%) returned to baseline eGFR values within 1 month of discharge. The proportion was similar between the patients receiving antiviral treatment and those not receiving this treatment. CONCLUSIONS: KTx recipients run a high risk of COVID-19-related renal impairment. Antivirals appear to be safe for use without major risks for kidney injury.


Subject(s)
Acute Kidney Injury/complications , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , COVID-19/complications , Glomerular Filtration Rate , Kidney Transplantation , Acute Kidney Injury/chemically induced , Adult , Aged , Antiviral Agents/adverse effects , Female , Hospitalization , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
15.
Respir Med ; 175: 106204, 2020 12.
Article in English | MEDLINE | ID: covidwho-1023739

ABSTRACT

COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.


Subject(s)
COVID-19/therapy , Immunosuppression Therapy/methods , Interferon-gamma Release Tests/methods , Latent Tuberculosis/diagnosis , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Female , Humans , Immunity/physiology , Interferon-gamma Release Tests/statistics & numerical data , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Italy/epidemiology , Latent Tuberculosis/epidemiology , Latent Tuberculosis/immunology , Latent Tuberculosis/prevention & control , Lymphopenia/immunology , Male , Retrospective Studies , SARS-CoV-2/genetics , Severity of Illness Index
16.
Adv Chronic Kidney Dis ; 27(5): 383-389, 2020 09.
Article in English | MEDLINE | ID: covidwho-1019900

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2, has led to the death of hundreds of thousands of people worldwide. If infected, older individuals and those with diabetes, hypertension, cardiovascular disease, and compromised immune systems are at higher risk for unfavorable outcomes. These comorbidities are prevalent in patients with kidney disease, hence the significant burden of COVID-19 on kidney transplant programs. Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers however have adopted early antimetabolite withdrawal in addition to other interventions. This review summarizes the published COVID-19 literature as it relates to outcomes and immunosuppression management in kidney transplant recipients. It also discusses challenges pertaining to pretransplant evaluation and wait-listed patients.


Subject(s)
COVID-19/therapy , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Telemedicine , COVID-19/mortality , COVID-19/prevention & control , Cross Infection/prevention & control , Delivery of Health Care/methods , Deprescriptions , Humans , Immunosuppression Therapy/methods , Personal Protective Equipment , Physical Distancing , Preoperative Care , SARS-CoV-2 , Waiting Lists
17.
Am J Kidney Dis ; 77(5): 777-785, 2021 05.
Article in English | MEDLINE | ID: covidwho-1003349

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures and a striking pause in the conduct of living donation and living-donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences worldwide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic and consider lessons learned, including those related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased-donor transplantation, living donation, and living-donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.


Subject(s)
COVID-19 , Critical Pathways , Immunosuppression Therapy/methods , Kidney Failure, Chronic , Kidney Transplantation/methods , COVID-19/epidemiology , COVID-19/prevention & control , Clinical Decision-Making , Critical Pathways/organization & administration , Critical Pathways/trends , Humans , Infection Control/methods , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/surgery , SARS-CoV-2 , Telemedicine/methods , Time-to-Treatment , Tissue Donors/statistics & numerical data , Transplant Recipients
18.
Transplantation ; 105(4): 851-860, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-991012

ABSTRACT

BACKGROUND: There is a scarcity of data on the consequences of coronavirus disease-19 (COVID-19) infections in kidney transplant recipients (KTRs) from emerging countries. METHODS: Here, we present a cohort study of 13 transplant centers in India including 250 KTR (226 living and 24 deceased donors) with polymerase chain reaction-confirmed COVID-19 positivity from March 23, 2020, until September 15, 2020. We detailed demographics, immunosuppression regimen, clinical profile, treatment, and outcomes. RESULTS: Median age of transplant recipients was 43 years, and recipients presented at a median of 3.5 years after transplant. Most common comorbidities (94%) included arterial hypertension (84%) and diabetes (32%); presenting symptoms at the time of COVID-19 included fever (88%), cough (72%), and sputum production (52%). Clinical severity ranged from asymptomatic (6%), mild (60%), and moderate (20%) to severe (14%). Strategies to modify immunosuppressants included discontinuation of antimetabolites without changes in calcineurin inhibitors and steroids (60%). Risk factors for mortality included older age; dyspnea; severe disease; obesity; allograft dysfunction before COVID-19 infection; acute kidney injury; higher levels of inflammatory markers including C-reactive protein, interleukin-6 level, and procalcitonin; chest X-ray abnormality, and intensive care unit/ventilator requirements. Overall patient mortality was 11.6% (29 of 250), 14.5% (29 of 200) in hospitalized patients, 47% (25 of 53) in intensive care unit patients, and 96.7% (29 of 30) in patients requiring ventilation. KTRs with mild COVID-19 symptoms (n = 50) were managed as outpatients to optimize the utilization of scarce resources during the COVID-19 pandemic. CONCLUSIONS: Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients, and high mortality was noted among those requiring intensive care and those on ventilator.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Kidney Transplantation/adverse effects , SARS-CoV-2 , Adult , Aged , Antiviral Agents/therapeutic use , Cohort Studies , Female , Humans , Immunosuppression Therapy/adverse effects , Immunosuppression Therapy/methods , India/epidemiology , Kidney Transplantation/mortality , Male , Middle Aged , Multivariate Analysis , Pandemics , Proportional Hazards Models , Retrospective Studies , Transplant Recipients , Treatment Outcome , Young Adult , COVID-19 Drug Treatment
19.
Transplantation ; 105(1): 115-120, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-990985

ABSTRACT

BACKGROUND: Patients with chronic kidney disease stage 5 and those on immunosuppression are particularly vulnerable and are shielded as per public health strategy. We present our experience of coronavirus disease 2019 (COVID-19) transplant patients in one of the most affected parts of the UK with direct comparison to waitlisted patients. METHODS: A single-center prospective study of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive waitlisted and transplant patients was undertaken to compare these groups and assess clinical outcomes. RESULTS: A total of 60 consecutive symptomatic SARS-CoV-2 positive patients were identified with 32 active waitlisted patients and 28 functioning renal transplants. Demographics were similar. The incidence of symptomatic COVID-19 in the waitlisted group was 9.9% compared to 1.9% in renal transplant patients (P < 0.001). Immunosuppression did not influence initial symptomology. Fifteen percent of patients in the waitlisted and 32% in the transplant groups died (P = 0.726). Mortality as proportion of total waitlisted (321 patients) and transplant population (1434 patients) of our centre was 1.5% and 0.6% (P < 0.001), respectively. C-reactive protein (CRP) at 48 h and peak CRP were associated with mortality in both groups while quick sequential organ failure assessment score at 48 h (P = 0.036) was associated with mortality for transplant patients. CONCLUSIONS: Incidence of COVID-19 is higher in the waitlisted population but transplant patients have more severe disease, reflected by higher mortality. CRP at 48 h can be used as a predictive tool. In the absence of effective treatments, the current strategy of shielding is arguably the most important factor in protecting patients while resuming transplantation.


Subject(s)
COVID-19/epidemiology , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , SARS-CoV-2/genetics , Waiting Lists , Adult , Aged , Comorbidity , Female , Follow-Up Studies , Humans , Immunocompromised Host , Kidney Failure, Chronic/epidemiology , Male , Middle Aged , Pandemics , Prospective Studies , RNA, Viral/analysis , Transplant Recipients
20.
Transplant Proc ; 53(4): 1118-1125, 2021 May.
Article in English | MEDLINE | ID: covidwho-978450

ABSTRACT

INTRODUCTION: Living-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic. MATERIALS AND METHODS: The changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months). RESULTS: Nineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected. CONCLUSION: This study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.


Subject(s)
COVID-19/prevention & control , Infection Control/methods , Liver Transplantation/methods , Postoperative Complications/prevention & control , SARS-CoV-2 , ABO Blood-Group System , Adult , Blood Group Incompatibility , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunosuppression Therapy/methods , Infant , Liver Transplantation/adverse effects , Liver Transplantation/standards , Living Donors , Male , Middle Aged , Postoperative Complications/immunology , Postoperative Complications/virology , Postoperative Period , Treatment Outcome
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