BACKGROUND:The effect of COVID-19 on immunosuppressant drug levels in organ transplant recipients (OTRs) has not been adequately studied.OBJECTIVE:To study the effect of COVID-19 on tacrolimus trough levels (primary outcome) in OTRs and the association of the later with acute kidney injury, bacterial infection, and oxygen requirements.METHODS:We studied adult (>18-year-old) hospitalized OTRs with COVID-19, who were receiving tacrolimus between 3/1 and 12/16/2020.RESULTS:Among 30 OTRs, 67% were men, 90% had a kidney transplant. Median age was 60.5 (interquartile range [IQR]: 45-68) years, median time from transplant 36 (IQR: 20-84) months. Tacrolimus troughs were higher on admission for COVID-19 than baseline (average over 6 months prior) (P = .001). Eighteen patients (60%) had admission tacrolimus trough >10, 5 (17%) >20 ng/mL. Patients with diarrhea had borderline higher tacrolimus troughs, compared to those without diarrhea (P = .09). Organ transplant recipients with a tacrolimus trough >10 ng/mL were more likely to have elevated aspartate aminotransferase on admission (P = .01) and require supplemental oxygen. (P = .026).CONCLUSION AND RELEVANCE:Tacrolimus trough levels were elevated in most OTRs with COVID-19 at the time of hospital admission, compared to baseline. Potential mechanisms are diarrhea and hepatic involvement in COVID-19. In OTRs with COVID-19, including outpatients, immunosuppressant drug levels should be closely followed; management of immunosuppression should be individualized.

Background. Kidney transplant recipients (KTR) are considered high-risk for morbidity and mortality from coronavirus disease 2019 (COVID-19). However, some studies did not show worse outcomes compared to non-transplant patients and there is little data about immunosuppressant drug levels and secondary infections in KTR with COVID-19. Herein, we describe our single-center experience with COVID-19 in KTR. Methods. We captured KTR diagnosed with COVID-19 between March 1, 2020 and May 18, 2020. After exclusion of KTR on hemodialysis and off immunosuppression, we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by age and sex (controls). Results. Eleven KTR were hospitalized and matched with 44 controls. One KTR and 4 controls died (case fatality rate: 9.1%). There were no significant differences in length of stay or clinical outcomes between KTR and controls. Tacrolimus or sirolimus levels were >10 ng/mL in 6 out of 9 KTR (67%). Bacterial infections were more frequent in KTR (36.3%), compared with controls (6.8%, P = .02). Conclusions. In our small case series, unlike earlier reports from the pandemic epicenters, the clinical outcomes of KTR with COVID-19 were comparable to those of non-transplant patients. Calcineurin or mammalian target of rapamycin inhibitor (mTOR) levels were high. Bacterial infections were more common in KTR, compared with controls.

Background In order for healthcare systems to prepare for future waves of COVID-19, an in-depth understanding of clinical predictors is essential for efficient triage of hospitalized patients. Methods We performed a retrospective cohort study of 259 patients admitted to our hospitals in Rhode Island to examine differences in baseline characteristics (demographics and comorbidities) as well as presenting symptoms, signs, labs, and imaging findings that predicted disease progression and in-hospital mortality. Results Patients with severe COVID-19 were more likely to be older (p = 0.02), Black (47.2% vs. 32.0%, p = 0.04), admitted from a nursing facility (33.0% vs. 17.9%, p = 0.006), have diabetes (53.9% vs. 30.4%, p<0.001), or have COPD (15.4% vs. 6.6%, p = 0.02). In multivariate regression, Black race (adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI]: 1.1-3.9) and diabetes (aOR 2.2, 95%CI: 1.3-3.9) were independent predictors of severe disease, while older age (aOR 1.04, 95% CI: 1.01-1.07), admission from a nursing facility (aOR 2.7, 95% CI 1.1-6.7), and hematological co-morbidities predicted mortality (aOR 3.4, 95% CI 1.1-10.0). In the first 24 hours, respiratory symptoms (aOR 7.0, 95% CI: 1.4-34.1), hypoxia (aOR 19.9, 95% CI: 2.6-152.5), and hypotension (aOR 2.7, 95% CI) predicted progression to severe disease, while tachypnea (aOR 8.7, 95% CI: 1.1-71.7) and hypotension (aOR 9.0, 95% CI: 3.1-26.1) were associated with increased in-hospital mortality. Conclusions Certain patient characteristics and clinical features can help clinicians with early identification and triage of high-risk patients during subsequent waves of COVID-19.

The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com ) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. Open Science Framework (OSF) registration DOI: https://doi.org/10.17605/osf.io/4n9d7 .

Abstract Background Organ transplant recipients may not mount an adequate immune response to COVID-19 infection, and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAb), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. Methods We identified KTR with COVID-19 between 3/1/2020 and 4/30/2021. Patients were excluded if they had multiorgan transplant or hospital-acquired COVID-19. Data were analyzed by Cox regression with mAb administration as time-dependent variable, and the day of symptom onset as baseline. Results We studied 95 KTR; 20 received mAb. Comorbidities and immunosuppression were balanced between the two groups. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15 vs. 76%, P< 0.001). This association remained significant after adjustment for confounders and by analyzing mAb administration as a time-dependent variable (Table: adj. HR 0.2, P=0.04). No KTR who received mAb died or required mechanical ventilation. Black or Hispanic KTR were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER (Table). Table Factors significantly associated with hospitalization or ER visit. Conclusion In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, were exacerbated by the COVID-19 pandemic. Acknowledging the nonconcurrent control group as a limitation, we found a strong signal for benefit from mAb treatment. Antiviral mAb are a promising therapeutic modality for immunosuppressed patients. Disclosures Dimitrios Farmakiotis, M.D., Astellas (Grant/Research Support)Merck (Grant/Research Support)Viracor (Grant/Research Support)

Organ transplant recipients may not mount an adequate immune response to COVID-19 infection and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAbs), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. We identified KTR with COVID-19 between March 1, 2020 and April 30, 2021. Patients were excluded if they had multi-organ transplant or hospital-acquired COVID-19. We studied 95 KTR; 20 received mAb. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15% vs. 76%, p < 0.001). This association remained significant after adjustment for potential confounders, and analysis of mAb administration as a time-dependent variable, with day of symptom onset as day 1 (adjusted HR 0.216, p = 0.04). Black or Hispanic patients were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER. In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, have been exacerbated by the COVID-19 pandemic. Antiviral mAbs are a promising therapeutic modality, especially for immunocompromised patients.

Background: Organ transplant recipients (OTR) are considered high-risk for morbidity and mortality from COVID-19 Case-fatality rates (CFR) vary significantly in different case series, and some patients were still hospitalized at the time of analyses To our knowledge, no case-control study of COVID-19 in OTR has been published to-date Methods: We captured kidney transplant recipients (KTR) diagnosed with COVID-19 between 3/1 and 5/18/2020 After exclusion of KTR on hemodialysis and off immunosuppression (IS), we compared the clinical course of COVID-19 between hospitalized KTR and non-transplant patients, matched by sex and age (controls) All patients were discharged from the hospital or died Results: 16 KTR had COVID-19 All 3 KTR off IS, who were excluded from further analyses, survived Median age was 54 (range: 34-65) years;5/13 KTR (38 4%) were men Median time from transplant was 41 (range: 1-203) months Two KTR, both transplanted >10 years ago, were managed as outpatients IS was reduced in 12/13 (92 3%), most often by discontinuation of the antimetabolite IL6 levels were >1,000 (normal: 10 ng/mL in 6/9 KTR (67%) (Table 1) Eleven KTR were hospitalized (84 6%) and matched with 44 controls One KTR, the only one treated with hydroxychloroquine, died (CFR 5 8%;7 6% in KTR on IS;9% in hospitalized KTR on IS) Four controls died (CFR: 9%;state CFR: 5 2%;inpatient CFR: 16 6%) There were no significant differences in length of stay or worst oxygenation status between hospitalized KTR and controls Four KTR (30 7%), received remdesivir, 4 convalescent plasma, 3 (23%) tocilizumab KTR received more often broad-spectrum antibiotics, convalescent plasma or tocilizumab, compared to controls (Table 2) Conclusion: Unlike early reports from the pandemic epicenters, the clinical course and outcomes of KTR with COVID-19 in our small case series were comparable to those of non-transplant patients Calcineurin or mTOR inhibitor levels were high, likely due to diarrhea and COVID-19-related hepatic dysfunction Extremely high IL6 levels were common The role of IS and potential benefits from investigational treatments remain to be elucidated A larger multi-institutional study is underway (Table Presented)

We aimed to externally validate the predictive performance of two recently developed COVID‐19‐specific prognostic tools, the COVID‐GRAM and CALL scores, and prior prognostic scores for community‐acquired pneumonia (CURB‐65), viral pneumonia (MuBLSTA) and H1N1 influenza pneumonia (Influenza risk score) in a contemporary US cohort.

Abstract Background To better understand patient factors that impact clinical outcomes in COVID-19, we performed a retrospective cohort study of patients hospitalized with COVID-19 in Rhode Island to identify patient and clinical characteristics associated with severe disease. Methods We analyzed 259 patients admitted to our academic medical center during a three month period with confirmed COVID-19. Clinical data was extracted via chart review and lab results within the first 24 hours of admission were extracted directly from electronic medical records. Patients were divided in two groups based upon the highest level of supplemental oxygen (O2) required during hospitalization: severe COVID-19 (high flow O2, non-invasive, or invasive mechanical ventilation) and non-severe COVID-19 (low flow O2 or no supplemental O2). SAS 9.4 (Cary, NC) was used for statistical analyses. Chi-square or Fisher’s exact tests for categorical variables and the Student’s t-test for continuous variables were used to compare demographics, baseline comorbidities, and clinical data between the severe and non-severe groups. Table 1: Demographics Results Of 259 patients, 166 (64%) had non-severe disease, and 93 (36%) severe disease; median age [IQR] was 62 [51,73]. There were 138(53%) males and 75 (29%) Hispanics. Among non-Hispanics,124(48%) were White, 48(19%) African Americans, and 12(5%) other races. Sixty (23%) were admitted from a nursing facility and the in-hospital mortality rate was 15% (38/259). Severe COVID-19 was associated with older age (p=0.02), admission from nursing facility (p=0.009), increased BMI (p=0.03), diabetes mellitus (p=0.0002), and COPD (p=0.03). At the time of presentation, severe COVID-19 was associated with tachypnea, hypoxia, hypotension (all p< 0.0001), elevated BUN (p=0.002) and AST (p=0.001), and acute or chronic kidney injury (p=0.01). Median hospital stay [IQR] was 11 days [7,18] in the severe vs. 6 days [3,11] in the non-severe group. In the severe group, 72% required ICU admission and 39% died. Table 2: Medical comorbidities Table 3: Presenting symptoms and signs in the first 48 hours of admission Table 4: Basic labs in the first 24 hours Conclusion In this cohort of patients with COVID-19, specific comorbidities, and vital signs at presentation were associated with severe COVID-19. These findings help clinicians with early identification and triage of high risk patients. Disclosures All Authors: No reported disclosures