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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.

4.
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.
Open Forum Infect Dis ; 9(6): ofac064, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1948416

ABSTRACT

Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir.

13.
Am J Transplant ; 22(9): 2254-2260, 2022 09.
Article in English | MEDLINE | ID: covidwho-1831928

ABSTRACT

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR = 1.10 1.401.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR = 0.44 0.921.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR = 1.38 2.635.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19 , Influenza Vaccines , Organ Transplantation , 2019-nCoV Vaccine mRNA-1273/adverse effects , Antibodies, Viral , BNT162 Vaccine/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Organ Transplantation/adverse effects , RNA, Messenger/genetics , SARS-CoV-2 , Transplant Recipients , Vaccination
15.
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.

18.
Am J Transplant ; 22(8): 2077-2082, 2022 08.
Article in English | MEDLINE | ID: covidwho-1745981

ABSTRACT

Estimating the total coronavirus disease 2019 (COVID-19) mortality burden of solid organ transplant recipients (SOTRs), both directly through COVID-19 infection and indirectly through other impacts on the healthcare system and society, is critical for understanding the disease's impact on the SOTR population. Using SRTR data, we modeled expected mortality risk per month pre-COVID (January 2015-February 2020) for kidney/liver/heart/lung SOTRs, and compared monthly COVID-era deaths (March 2020-March 2021) to expected rates, overall and among subgroups. Deaths above expected rates were designated "excess deaths." Between March 2020 and March 2021, there were 3739/827/265/252 excess deaths among kidney/liver/heart/lung SOTRs, respectively, representing a 41.2%/27.4%/18.5%/15.0% increase above expected deaths. 93.0% of excess deaths occurred in patients age≥50. The observed:expected ratio was highest among Hispanic SOTRs (1.82) and lowest among White SOTRs (1.20); 56.0% of excess deaths occurred among Black or Hispanic SOTRs. 64.7% of excess deaths occurred among patients who had survived ≥5 years post-transplant. Excess deaths peaked in January 2021; geographic distribution of excess deaths broadly mirrored COVID-19 incidence. COVID-19 likely caused over 5000 excess deaths among SOTRs in the US in a 13-month period, representing 1 in 75 SOTRs and a substantial proportion of all deaths among SOTRs during this time. SOTRs will remain at elevated mortality risk until the COVID-19 pandemic can be controlled.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/epidemiology , Humans , Incidence , Middle Aged , Organ Transplantation/adverse effects , Pandemics , Transplant Recipients
19.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-330643

ABSTRACT

Background: Biologic therapies that target B-cell function are effective for a range of medical conditions. Patients treated with such therapies do not reliably generate robust humoral responses which may increase their risk for severe viral infections, including SARS-CoV2.This study sought to characterize outcomes for patients previously treated with B-cell depleting drugs who were hospitalized with COVID-19 compared to similar patients by demographic background, comorbidities, clinical status and COVID19-specific treatment received. Methods: Registry data was reviewed to identify patients treated with B-cell depletion therapy who were hospitalized with COVID-19 from March 1, 2020 to November 30, 2021. 30-day mortality was the primary outcome, secondary outcomes included time to severe illness or death and time to clinical improvement. Overlap weighting method was applied to adjust for treatment bias, and Cox proportional-hazards models were used to analyze outcomes of interest. Age, BMI and COVID-19 specific medications were included in regression models as covariates. A prespecified subgroup analysis was conducted to examine effects in patients with B-cell treatment ≤ 90 days prior to COVID-19 hospitalization. Results 9,233 patients were admitted to the Johns Hopkins Medicine health system between March 1, 2020 and November 2021. 50 patients were identified that had been treated with B-cell depletion therapy who were hospitalized with COVID-19. 212 were selected as the control group via matching across selected variables. B-cell treated patients experienced a 30-day mortality of 6.0% compared to 4.2% in controls which was not statistically significant in overlap weight adjusted regression analysis, adjusted hazard ratio 1.13 (95%CI 0.23 to 5.48). The time to severe illness or death was 2.4 days (IQR 0.5 to 4.0 days) in the B-cell treated patients and 2.1 days (IQR 0.9 to 4.3 days) among controls, adjusted hazard ratio 1.01 (95% CI 0.47 to 2.18). Patients treated with B-cell depletion experienced a statistically significant longer time to clinical improvement, adjusted HR 0.66 (95% CI 0.47-0.94). The median time to improve or discharge was 6.3 days in B-cell depleted group (IQR 3.3 to 11.2 days) and 4.1 days in the matched control (IQR 2.1 to 7.7 days). These results were similar in subgroup analysis for patients who received B-cell depletion in the 90 days prior to hospitalization. Interpretation Patients treated with B-cell depletion were found to have more prolonged hospital courses however they did not experience higher mortality or a time to severe illness compared to controls. With appropriate close follow-up and clinical care, individuals can still receive life-saving B-cell depleting therapies in the middle of a pandemic. Further work should be devoted to characterizing the course of these patients considering new therapies and variants.

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