Clinical Characteristics and Outcomes of COVID-19 in Solid Organ Transplant Recipients

A Cohort Study

Zohra S. Chaudhry; Jonathan D. Williams; Amit Vahia; Raef Fadel; Tommy Parraga Acosta; Rohini Prashar; Pritika Shrivastava; Nadeen Khoury; Julio Pinto Corrales; Celeste Williams; Shunji Nagai; Marwan Abouljoud; Milagros Samaniego-Picota; Odaliz Abreu-Lanfranco; Ramon del Busto; Mayur S. Ramesh; Anita Patel; George J. Alangaden

Disclosures

American Journal of Transplantation. 2020;20(11):3051-3060. 

In This Article

Discussion

In our cohort study, mortality, need for ICU care, and mechanical ventilation support were comparable between COVID-19-positive hospitalized SOT recipients and nontransplant controls. Furthermore, our study demonstrates that transplant status by itself does not confer an increased risk for mortality. Additionally, we showed that our HFH COVID-19 severity score was strongly predictive of mortality.

In our transplant cohort, age >60 years and severity of COVID-19 on presentation strongly correlated with mortality, similar to what has been previously reported in the general population.[12,13] Observational studies to date, as summarized in Table S3, report variable mortality in COVID-19-positive transplant recipients between 0% and 30%.[5,6,14–21] Our observed overall mortality rate of 17% in our transplant cohort is comparable to rates reported from urban centers. Lower mortality rates in other studies may be explained by smaller sample size, lesser severity of illness, limited follow-up, and population demographics.[5,6,14–21] In our hospitalized transplant cohort, those requiring ICU care and mechanical ventilation had a significantly higher mortality rate of 23% and 58%, respectively. This is comparable to recent reports from New York City.[20]

Of note, in our predominantly kidney transplant population, rates of AKI were high, 47%, comparable to rates of 25%-57% in other studies.[14–17,19] Of those who had AKI, about a third needed RRT, similar to previous reports.[5,15] The high incidence of kidney injury in patients with COVID-19 may be multifactorial, including binding and direct renal injury caused by SARS-CoV-2 suggested by renal histopathological studies. Hua Su et al demonstrated virus nucleoprotein antigens in the renal tubules and clusters of coronavirus particles in the tubular epithelium and podocytes.[22] Furthermore, the receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) found on renal epithelial cells, was found to be upregulated in patients with COVID-19. Modulators of the renin-angiotensin-aldosterone system (RAAS) including ACE2 and angiotensin receptor blockers may have a potential role in mitigating the risk for AKI.[23] The high proportion of CKD, diarrhea, and CNIs use in our transplant cohort may also have contributed to AKI. It is notable, matched controls had similar rates of AKI as our SOT cohort.

Early reports have suggested poorer outcomes in SOT recipients with COVID-19 because of chronic immunosuppression and higher rates of comorbidities. In our study, a greater proportion of COVID-19-positive SOT recipients had coexisting conditions, particularly congestive heart failure, diabetes, CKD, and hypertension compared to nontransplant patients. Interestingly, despite this observation, mortality and other adverse outcomes did not occur more frequently among SOT recipients. The reasons for this are currently unknown but may be related to blunting of inflammatory cascades and cytokine release due to chronic immune suppression in transplant recipients. More research is needed to elucidate these theories further.

Similar to other studies, fever, cough, and fatigue were the most common presenting symptoms in our entire cohort. Interestingly, diarrhea was the presenting symptom in more than half of our transplant recipients. Previous studies estimate incidence of diarrhea to range from 14% to 50% in COVID-19-positive transplant patients (Table S3). Diarrhea may be a direct consequence of infection with SARS-CoV-2 that uses ACE2 for entry and serine protease TMPRSS2 for protein priming. Both ACE2 and TMPRSS2 are expressed in the epithelium of the small intestine.[24] Diarrhea in our kidney transplant recipients may also be due to agents such as mycophenolate.

Hospitalized transplant patients were more likely to present with severe disease and COVID-19 pneumonia characterized by shortness of breath, hypoxia, and abnormal chest X-ray on presentation. Lymphopenia and anemia were more common among our hospitalized SOT recipients in comparison to nontransplant patients and may be the consequence of chronic immune suppression, and chronic disease.[1,2,12,13,25–29]

All of our hospitalized patients who qualified for treatment received HCQ as the antiviral agent. HCQ has been hypothesized to possess direct antiviral activity against SAR-COV-2 by increasing intracellular pH resulting in decreased phagolysosome fusion, impairing viral receptor glycosylation. In addition, it also has immune-modulating effect by inhibiting toll-like receptor signaling, and decreasing production of cytokines especially interleukin (IL)-1 and IL-6.[30] Most of our transplant patients who had infectious complications during their hospitalization were managed in the usual fashion of reducing immune suppression in stepwise fashion and prompt antimicrobial therapy when needed. As per institutional COVID-19 treatment protocol, the majority of patients received corticosteroids early in their clinical course to mitigate the hyperinflammatory syndrome.[7] Other immunomodulatory agents or other antiviral agents such as remdesivir may have a role in the management of COVID-19.[31,32]

This study has limitations. It is a single-center retrospective study with convenience sampling. Almost all SOT recipients were hospitalized for moderate or severe COVID-19 and so the spectrum of COVID-19 including mild disease is undefined. Most SOT recipients were remote (> 1year) from transplantation and were receiving maintenance immunosuppression. This is similar to other reports and consequently the impact of COVID-19 in the early posttransplant period remains undefined. Our cohort of hospitalized transplant patients was composed of mostly kidney transplant recipients, and when compared to nonkidney transplant recipients there was no difference in presenting symptoms, comorbidities, laboratory markers, severity of disease, and mortality. However, the lack of a large cohort of nonkidney transplant limits extrapolation of these findings. Even though our median follow-up was more than 28 days, long-term outcomes such as graft function in our SOT cohort need further study.

In conclusion, hospitalized SOT recipients with COVID-19 have comparable mortality to nontransplant patients, despite a greater proportion of coexisting conditions and immune suppression. Mortality in COVID-19-positive SOT recipients is driven by the severity of illness at presentation, independent of transplant status.

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