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2.
Neurol Neuroimmunol Neuroinflamm ; 9(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1596607

ABSTRACT

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.


Subject(s)
COVID-19/complications , COVID-19/immunology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Nervous System Diseases/complications , Nervous System Diseases/immunology , SARS-CoV-2/immunology , Adolescent , COVID-19/prevention & control , COVID-19/virology , Child , Delivery of Health Care/organization & administration , Delivery of Health Care/statistics & numerical data , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Masks/statistics & numerical data , Masks/virology , Nervous System Diseases/virology , Pandemics , Recurrence , Retrospective Studies , Vitamin D/blood
8.
Transplantation ; 105(11): e234-e243, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1494154

ABSTRACT

BACKGROUND: Data about SARS-CoV-2 vaccines efficacy in renal transplant recipients (RTR) are lacking. METHODS: To reveal predictors for humoral response to BNT162b2 vaccine among RTR, patients were divided into positive (N = 42) and negative (N = 78) response groups based on receptor-binding domain (RBD) immunoglobulin G (IgG) ≥1.1 and neutralizing antibodies (NA) ≥16 dilution versus RBD IgG <1.1 or NA <16, respectively. NA were detected using a SARS-CoV-2 pseudo-virus. RESULTS: NA were detected in only 42 of 120 (35%) of RTR versus 197 of 202 (97.5%) immunocompetent controls (P < 0.001). NA geometric mean titers in RTR were significantly lower versus the control group {83.7 (95% confidence interval [CI], 50.5-138.8) versus 482 (95% CI, 411-566), P < 0.001}. In a multivariable analysis, mycophenolic acid (MPA) dose and hemoglobin level were found to be independent predictors for antibody response in RTR. A positive response rate of 27% versus 63% was observed in patients on and off MPA, respectively. An increase in MPA dose by 1 mg/kg weight reduced the odds for a positive response by 17% (odds ratio = 0.83; 95% CI, 0.75-0.92; P < 0.001). Geometric mean titers for RBD IgG were significantly reduced as MPA daily dose increased. Hemoglobin blood level <13 g/dL reduced the antibody response by 63% (P = 0.04). Pain at the injection site after the second vaccine dose was significantly higher in the responders versus nonresponders (20.5% versus 5.5%, P = 0.01). CONCLUSIONS: Only 35% of RTR develop NA to the BNT162b2 mRNA vaccine. MPA is a major suppressor of antibody response in RTR.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunity, Humoral/drug effects , Immunogenicity, Vaccine/drug effects , Kidney Transplantation/adverse effects , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Cohort Studies , Dose-Response Relationship, Drug , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , SARS-CoV-2/immunology
9.
Aging Clin Exp Res ; 33(8): 2355-2359, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1491492

ABSTRACT

BACKGROUND: Older age has been reported as a risk factor for severe SARS-CoV-2 disease (COVID-19). The impact of immunosuppressants (IMS) on COVID-19 is still under debate. AIM: To describe the incidence and severity of COVID-19 in elderly patients with inflammatory bowel disease (IBD) in relation to the use of IMS. METHODS: IBD patients over 65 years of age were selected and grouped in terms of IMS use. Confirmed COVID-19, adherence to IST, comorbidities and concomitant non-IBD-related treatments between 1st of March 2020 to 1st of March 2021 were recorded. RESULTS: Out of 418 patients included, 89 (21.3%) were on IMS. Thirty-two patients (7.7%) had COVID-19, 7 of whom were on IMS (7.6% not on IMS vs. 7.9% on IMS; P = 0.933) and 7 (22%) patients died. CONCLUSIONS: Incidence of COVID-19 among elderly IBD patients was similar to that reported in the background population, regardless of the use of IMS.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Aged , Humans , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Risk Factors , SARS-CoV-2
10.
Ann Transplant ; 26: e933001, 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1485494

ABSTRACT

BACKGROUND There are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment. MATERIAL AND METHODS We retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients' outcomes were analyzed and compared to KTRs who received basiliximab induction. RESULTS During pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175-325) mg in the induction subgroup and 263 (200-275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0-1.9] vs 1.1 [1.0-1.4] mg/dl, respectively). CONCLUSIONS 1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.


Subject(s)
Antilymphocyte Serum , COVID-19 , Immunosuppressive Agents , Kidney Transplantation , Antilymphocyte Serum/adverse effects , Antilymphocyte Serum/therapeutic use , Basiliximab/therapeutic use , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney , Pandemics , Retrospective Studies
11.
Front Immunol ; 12: 708848, 2021.
Article in English | MEDLINE | ID: covidwho-1468339

ABSTRACT

Impressive efforts have been made by researchers worldwide in the development of target vaccines against the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and in improving the management of immunomodulating agents. Currently, different vaccine formulations, such as viral vector, mRNA, and protein-based, almost all directed toward the spike protein that includes the domain for receptor binding, have been approved. Although data are not conclusive, patients affected by autoimmune rheumatic diseases (ARDs) seem to have a slightly higher disease prevalence, risk of hospitalization, and death from coronavirus disease-2019 (COVID-19) than the general population. Therefore, ARD patients, under immunosuppressive agents, have been included among the priority target groups for vaccine administration. However, specific cautions are needed to optimize vaccine safety and effectiveness in these patients, such as modification in some of the ongoing immunosuppressive therapies and the preferential use of mRNA other than vector-based vaccines. Immunomodulating agents can be a therapeutic opportunity for the management of COVID-19 patients; however, their clinical impact depends on how they are handled. To place in therapy immunomodulating agents in the correct window of opportunity throughout the identification of surrogate markers of disease progression and host immune response is mandatory to optimize patient's outcome.


Subject(s)
Autoimmunity/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Rheumatic Diseases/immunology , Spike Glycoprotein, Coronavirus/immunology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Rheumatic Diseases/drug therapy , SARS-CoV-2/immunology , Vaccination
13.
Transplant Proc ; 53(9): 2743-2746, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1447201

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. METHODS: From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. RESULTS: The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. CONCLUSIONS: A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.


Subject(s)
COVID-19 , Heart Transplantation , Kidney Transplantation , Heart Transplantation/adverse effects , Humans , Immunosuppressive Agents/adverse effects , SARS-CoV-2 , Tertiary Care Centers , Transplant Recipients
14.
EBioMedicine ; 72: 103581, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1433160

ABSTRACT

BACKGROUND: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. METHODS: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. FINDINGS: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days). INTERPRETATION: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. FUNDING: FISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.


Subject(s)
Antibody Formation/drug effects , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/drug therapy , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/immunology , Cladribine/adverse effects , Cladribine/therapeutic use , Female , Fingolimod Hydrochloride/adverse effects , Fingolimod Hydrochloride/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Italy , Male , Middle Aged , Prospective Studies , Rituximab/adverse effects , Rituximab/therapeutic use , Treatment Outcome
15.
Ann Hematol ; 100(11): 2805-2812, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1432514

ABSTRACT

Rituximab is associated with prolonged B-cell depletion and secondary hypogammaglobulinemia and is associated with a dampened humoral response and increased infectious complications. To describe the potential impact of prior rituximab therapy on clinical outcomes from SARS-CoV-2 infection and development of COVID-19 antibodies, we conducted a retrospective study of adults across the Mount Sinai Health System diagnosed with COVID-19 who received rituximab for any indication from February 2019 to October 2020. Patients' baseline characteristics, markers of disease severity, clinical outcomes, and antibody development were examined. Of the 49 patients included in the analysis, 63.2% required hospitalization for COVID-19, 24.5% required an ICU admission, and 32.7% died. Proximity of last rituximab infusion and COVID-19 diagnosis did not affect rates of hospitalization, admission to intensive care units or death. Over half (51.7%) of those whose antibodies were checked developed neutralizing anti-spike protein antibodies. The median time between rituximab administration and COVID-19 diagnosis was not significantly different between those who developed antibodies and those who did not (p = .323). Of the 14 patients with documented negative COVID-19 antibody titers, 11 of them survived SARS-CoV-2 infection, indicating that development of neutralizing antibodies may not be necessary for recovery from COVID-19.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/pharmacology , Rituximab/pharmacology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , COVID-19/therapy , Comorbidity , Female , Hospitalization , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Risk Factors , Rituximab/adverse effects , Rituximab/therapeutic use , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
16.
J Med Virol ; 93(10): 5768-5776, 2021 10.
Article in English | MEDLINE | ID: covidwho-1432407

ABSTRACT

Though it is widely believed that chronic immunosuppressive medications increase the severity of coronavirus disease 2019 (COVID-19) illness, there is little data to support this. We performed a retrospective study of COVID-19 positive patients diagnosed at a single academic medical center between March 10, 2020 and October 13, 2020. A total of 835 patients diagnosed with COVID-19 by polymerase chain reaction were included (median age 64 years; 52% female). Of these, 46 (5.5%) had a prescription for an immunosuppressive therapy before diagnosis, most commonly oral steroids (20, 43%), mycophenolate (12, 26%), or tacrolimus (11, 24%). Patients on immunosuppressive therapy with COVID-19 had increased mortality (30% vs. 17%, p = 0.036; odds ratio 2.1, 95% confidence interval 1.11-4.04), which remained significant (p = 0.040) after performing multivariate logistic regression controlling for gender, age, race, and comorbidity status. Laboratory markers of inflammation were uniformly elevated in both patients on or not on immunosuppressive therapies who died, but lymphocytes and neutrophils were decreased in both COVID-19 patients on immunosuppressive therapies who died and who remained alive. These findings demonstrate that COVID-19 disease is more severe in patients taking prior immunosuppressive medications. This finding emphasizes the need for aggressive monitoring and supportive care for immunosuppressed patients who are diagnosed with COVID-19.


Subject(s)
COVID-19/mortality , /adverse effects , Aged , COVID-19/diagnosis , Female , Humans , Immunosuppressive Agents/adverse effects , Length of Stay , Male , Middle Aged , Risk Factors , SARS-CoV-2 , Severity of Illness Index
17.
Dtsch Med Wochenschr ; 146(19): 1277-1282, 2021 Oct.
Article in German | MEDLINE | ID: covidwho-1434175

ABSTRACT

HOW EFFECTIVE ARE THE APPROVED VACCINES IN KIDNEY DISEASES AND THOSE RECEIVING IMMUNOSUPPRESSION?: Several observational studies indicated that immunosuppression is associated with a weakened or absent humoral response. Patients with chronic kidney diseases or undergoing maintenance dialysis without immunosuppression have a reduced humoral response to COVID-19 vaccines. I HAD COVID-19. SHOULD I GET VACCINATED?: It is recommended to receive a booster after SARS-CoV-2 infection with a mRNA vaccine. IS A COVID-19 VACCINATION DESPITE ONGOING IMMUNOSUPPRESSION POSSIBLE?: Patients receiving immunosuppression have a reduced humoral response, and this is especially observed when anti-CD20 therapy is used. IS THERE A POSSIBILITY THAT THE VACCINE PROVOKES REJECTION OF MY TRANSPLANTED KIDNEY OR RELAPSE OF MY GLOMERULAR DISEASE?: Several reports were published in the last months highlighting new-onset diseases, recurrences and relapses of different glomerular diseases, which occurred after the receipt of the first or second vaccine dose. As a clear association of vaccines and induction of autoimmunity still needs to be established, most of these diseases are treatable, and COVID-19 in patients under immunosuppression is often fatal, there is a clear net benefit of vaccination. DO I HAVE A PERMANENT PROTECTION AFTER VACCINATION?: The antibody titers and likely the cellular immune response is significantly reduced in patients with kidney diseases, and titers are reducing at a fast pace under ongoing immunosuppression. A booster dose should be considered, especially taking into consideration the evolvement of virus variants and their impact on vaccine efficacy. AFTER THE FIRST SERIES OF VACCINATION, NO OR ONLY A MARGINAL AMOUNT OF ANTIBODIES WERE DETECTABLE. ARE THERE STRATEGIES TO IMPROVE VACCINE RESPONSE?: Many countries recommend the application of a third dose for vulnerable patient cohorts, especially because of a weakened response and their risk to develop a severe disease course of COVID-19. Prospective clinical trials are ongoing to test the ideal strategy to improve vaccine response in these cohorts.


Subject(s)
COVID-19 Vaccines , Immunosuppressive Agents , Renal Insufficiency, Chronic/therapy , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use
18.
Biomolecules ; 11(9)2021 09 17.
Article in English | MEDLINE | ID: covidwho-1430768

ABSTRACT

A growing body of evidence initially suggested that patients with multiple sclerosis (MS) might be more susceptible to coronavirus disease 2019 (COVID-19). Moreover, it was speculated that patients with MS treated with immunosuppressive drugs might be at risk to develop a severe diseases course after infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2). However, the recently published data have shown that MS patients do not have a higher risk for severe COVID-19. Although there is no indication that patients with MS and immunomodulatory/immunosuppressive therapy are generally at a higher risk of severe COVID-19, it is currently being emphasized that the hazards of poorly treated MS may outweigh the putative COVID-19 dangers. In this review, we discuss the challenges and considerations for MS patients in the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/therapeutic use , Immunotherapy , Multiple Sclerosis , Pandemics , SARS-CoV-2 , Humans , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy
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