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1.
Transplantation ; 2022 Sep 19.
Article in English | MEDLINE | ID: covidwho-2037606

ABSTRACT

BACKGROUND: Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization. METHODS: A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration. RESULTS: Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%). CONCLUSIONS: SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.

2.
Transplantation ; 106(10): e452-e460, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1948635

ABSTRACT

BACKGROUND: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ . CONCLUSIONS: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.


Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Antibodies, Viral , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Machine Learning , Mycophenolic Acid , SARS-CoV-2 , Vaccines , Vaccines, Synthetic , mRNA Vaccines
5.
Transplant Direct ; 6(7): e572, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1794966

ABSTRACT

BACKGROUND: The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. METHODS: To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. RESULTS: We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. CONCLUSIONS: These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

6.
BMC Cancer ; 21(1): 1354, 2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1632816

ABSTRACT

BACKGROUND: Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021. RESULTS: Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted. CONCLUSIONS: Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.


Subject(s)
/administration & dosage , Antibodies, Viral/blood , COVID-19/prevention & control , Immunization Schedule , Multiple Myeloma/blood , /adverse effects , Aged , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Cohort Studies , Female , Humans , Male , Middle Aged , Multiple Myeloma/epidemiology , Prospective Studies , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , /adverse effects
8.
BMJ Open ; 12(1): e055367, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1637282

ABSTRACT

OBJECTIVES: The COVID-19 pandemic significantly affected the provisions of health services to necessary but deprioritised fields, such as transplantation. Many programmes had to ramp-down their activity, which may significantly affect transplant volumes. We aimed to pragmatically analyse measures of transplant activity and compare them by a country's income level and cumulative COVID-19 incidence (CCI). DESIGN, SETTING AND PARTICIPANTS: From June to September 2020, we surveyed transplant physicians identified as key informants in their programmes. Of the 1267 eligible physicians, 40.5% from 71 countries participated. OUTCOME: Four pragmatic measures of transplant activity. RESULTS: Overall, 46.5% of the programmes from high-income countries anticipate being able to maintain >75% of their transplant volume compared with 31.6% of the programmes from upper-middle-income countries, and with 21.7% from low/lower-middle-income countries (p<0.001). This could be because more programmes in high-income countries reported being able to perform transplantation/s (86.8%%-58.5%-67.9%, p<0.001), maintain prepandemic deceased donor offers (31.0%%-14.2%-26.4%, p<0.01) and avoid a ramp down phase (30.9%%-19.7%-8.3%, p<0.001), respectively. In a multivariable analysis that adjusted for CCI, programmes in upper-middle-income countries (adjusted OR, aOR=0.47, 95% CI 0.27 to 0.81) and low/lower-middle-income countries (aOR 0.33, 95% CI 0.16 to 0.67) had lower odds of being able to maintain >75% of their transplant volume, compared with programmes in high-income countries. Again, this could be attributed to lower-income being associated with 3.3-3.9 higher odds of performing no transplantation/s, 66%-68% lower odds of maintaining prepandemic donor offers and 37%-76% lower odds of avoiding ramp-down of transplantation. Overall, CCI was not associated with these measures. CONCLUSIONS: The impact of the pandemic on transplantation was more in lower-income countries, independent of the COVID-19 burden. Given the lag of 1-2 years in objective data being reported by global registries, our findings may inform practice and policy. Transplant programmes in lower-income countries may need more effort to rebuild disrupted services and recuperate from the pandemic even if their COVID-19 burden was low.


Subject(s)
COVID-19 , Humans , Income , Pandemics , SARS-CoV-2 , Tissue Donors
10.
Transplant Direct ; 8(1): e1268, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1583924

ABSTRACT

BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

11.
Am J Transplant ; 22(4): 1253-1260, 2022 04.
Article in English | MEDLINE | ID: covidwho-1583700

ABSTRACT

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.


Subject(s)
COVID-19 , Organ Transplantation , Ad26COVS1 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Vaccines, Synthetic , mRNA Vaccines
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