Solid Organ Transplant

Last reviewed: June 3, 2021

On this page:

• Overview
• Guidelines
• Key Literature
  • Outcomes
    • Systematic Reviews
    • Matched Cohort Studies
    • Kidney Transplant Cohorts
    • Dialysis vs. Kidney Transplant
    • Liver Transplant
    • Lung Transplant
    • Heart Transplant
  • Special Transplant Populations
    • HIV
    • Active or Prior COVID-19
• Vaccination in Solid Organ Transplant Recipients
• Resources
• Multimedia

The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.

Overview

Solid organ transplant recipients, candidates and donors require special considerations in the context of the COVID-19 pandemic.

COVID-19 clinical presentation and outcomes may differ among solid organ transplant recipients compared to the general public. Case series report high hospitalization rates (70-80%) among solid organ transplant recipients with laboratory-confirmed COVID-19, as well as typically high rates of intensive care utilization (10-30%), and mortality (10-30%) (Molnar, November 2020; Webb, November 2020; Raja, January 2021). Fever may be absent in 30-50% of recipients, but gastrointestinal symptoms such as diarrhea have emerged as a prominent symptom (30%). Incidence of acute kidney injury and use of renal replacement therapy consistently appear more common in solid organ transplant populations, particularly among prior kidney recipients (Sharma, January 2021). Prolonged detection of viral RNA in the respiratory tract has been described (Gaston, October 2020), occasionally associated with cultivable virus (particularly in severely ill patients), which has implications for infection control (e.g., need for prolonged isolation) (Decker, June 2020). Cases of serious bacterial, viral and fungal coinfection have been reported in solid organ transplant recipients with COVID-19 (Raja, January 2021); these appear relatively uncommon for abdominal transplant recipients in the setting of frequent utilization of empirical antimicrobials.

Several matched analyses of solid organ transplant versus non-solid organ transplant COVID-19 patients show relatively similar mortality after adjusting for age and other comorbidities (Molnar, November 2020; Webb, November 2020). ICU utilization and therapeutic practices, however, appear to include more exhaustive interventions for solid organ transplant recipients versus controls. Data are lacking among some key subgroups of solid organ transplant recipients who may experience higher mortality, including lung transplant recipients and those with concomitant HIV infection.

The role of longitudinal immunosuppression as a principal contributor to severe COVID-19 outcomes in solid organ transplant recipients continues to be debated, given the common presence of multimorbidity (e.g., older age, diabetes, obesity, renal insufficiency) and the potential for immunosuppressives to blunt inflammatory response to SARS-CoV-2. Cohort and modeling studies indicating conflicting information regarding COVID-19 incidence and outcomes in transplant candidates (i.e., those not yet transplanted) versus recent recipients (Massie, June 2020; Ravanan, August 2020; Hilbrands, November 2020). Further research in this area is needed to clarify decision-making regarding timing of non-emergent organ transplantation.

Optimal therapeutic protocols for solid organ transplant recipient COVID-19 patients are not yet established, and there is no clear recommendation that therapies should differ from standard of care. While modification of immunosuppressive regimens in solid organ transplant recipients with confirmed COVID-19 has been heterogeneous, reduction in antimetabolite dosing and increase in corticosteroid dosing appear to be common interventions (Raja, January 2021; Bottio, January 2021; Boyarsky, April 2020). Acute rejection after COVID-19 appears uncommon; these patients are, however, at high risk for drug-drug interactions with COVID-19 therapeutics. Recent immunosuppressive intensification (Messika, January 2021), such as for transplant induction or rejection, may predispose worse outcomes. 

Solid organ transplant recipients’ immune responses to COVID-19 and vaccination are subjects of ongoing investigation. Although mRNA COVID-19 vaccination appears safe in this group (Ou, April 2021), the magnitude and durability of humoral response to vaccination might be suboptimal and requires further evaluation. It appears that many kidney recipients mount anti-spike and anti-nucleocapsid antibody responses after acute infection, though this may fade over time (Phadke, March 2021; Boyarsky, May 2021).

Guidelines on screening organ donors for SARS-CoV-2 infection generally recommend deferring donation from donors with recent confirmed or suspected COVID-19 and performing nucleic acid testing on all donors as close to donation as possible.

 

Guidelines

NIH treatment guidelines recommend molecular testing for all solid organ transplant candidates with signs/symptoms of COVID-19 (AIII - strong recommendation, expert opinion).

• If SARS-CoV-2 is detected, transplantation should be deferred if possible (BIII - moderate recommendation, expert opinion); the optimal disease-free interval is not known.
• All potential donors should be assessed for COVID-19 signs/symptoms and molecular testing performed if present (AIII).
• If SARS-CoV-2 is detected or strongly suspected, transplantation should be deferred (BIII).
• Consultation with transplant specialists is recommended before any immunosuppression adjustments (AIII).
• Guidance is provided regarding particular drug toxicities in solid organ transplant recipients.

American Society of Transplantation guidelines for organ donor testing recommend at least one respiratory sample by nucleic acid test (NAT) within 3 days of organ procurement, noting some experts recommend a second test within 24-48 hours of donation and that at least one lower respiratory sample is preferred in thoracic donors.

• Donors with prior COVID-19 should have resolved symptoms and >21 days elapsed since initial infection, noting that reinfection may be possible at >90 days.
• Living donors should be tested within 3 days of donation by NAT and similarly should have resolved symptoms >21 days from initial infection (and if NAT+ >90 days later may represent reinfection).
• Non-respiratory viral body site testing is not recommended, and the role for antibody testing was not defined.

HHS’s Organ Procurement & Transplantation Network maintains a summary of current evidence on donor screening for SARS-CoV-2 and considerations for organ acceptance from donors with a history of COVID-19.

• This document is very similar to American Society of Transplantation guidelines regarding donor NAT testing protocols (i.e., test within 72 hours of donation, as close to donation as possible, and include lower respiratory sample for lung donors).
• Chest imaging can serve as a diagnostic adjunct, but not a sole screening tool.
• For donors with prior COVID-19, assessment for end-organ dysfunction may be considered, though for those with resolved symptoms and negative NAT at time of donation, transmission appears unlikely.
  • Specifically, donors with resolved COVID-19 >21-90 days after initial infection appear low risk, though safety outside of this time window is not established and donation should be based on medical urgency of the candidate plus input from infectious diseases providers.
  • Living donation after mild or asymptomatic COVID-19 >21-28 days after disease onset is likely safe; need for repeat NAT within 90 days of diagnosis is not clear.

Transplantation Society guidance for recipients recommends that all solid organ transplant recipients continue physical distancing, limiting travel and avoiding all cruise ship travel.

• For diagnosis of candidates and recipients with possible COVID-19, PCR testing of respiratory secretions is recommended (nasopharyngeal or bronchoalveolar lavage).
• If SARS-CoV-2 is detected in an ill candidate, transplant should be deferred until clinical improvement and no virus detected (ideally with two negative PCR results 24 hours apart, unless transplantation is urgent).
• Although duration of viral shedding may be prolonged in solid organ transplant recipients, transmission risk is uncertain.
• Serology is not routinely recommended for diagnosis and degree and duration of serologic protection is not yet known.

Transplantation Society guidance for donors recommends universal screening by NAT, with better yield from lower respiratory tract particularly in the setting of abnormal chest imaging (routine chest imaging may help with diagnosis but may not be specific).

Overall, guidelines currently recommend not utilizing donors who have detectable SARS-CoV-2. Most groups recommend that donors with a history of COVID-19 be at least 14 days out from symptom onset and have two negative SARS-CoV-2 PCR tests before donation. Living donation should not be performed on either a donor or recipient who has been exposed to a person with suspected or confirmed COVID-19 within the prior 14 days.

A comprehensive overview of 18 international solid organ transplant guidance documents was maintained by the Canadian Donation and Transplantation Research Program through April 2021. Although there was broad agreement on key recommendations such as PCR-based screening of respiratory secretions for all potential donors, there were differing recommendations for recipients on topics including routine use of the antiviral remdesivir and deferral of lymphodepleting induction therapies.

 

Key Literature

 

Outcomes

Systematic Reviews

COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature (Raja, January 2021).

Overall, in this thorough systematic review documenting wide range in solid organ transplant COVID-19 management and outcomes reflecting primarily early pandemic experience, 30% of solid organ transplant recipients presented without fever (versus 30% with diarrhea), 80% were hospitalized and 20% died. Rejection was very uncommon, though details on secondary infections are sparse.

Study population:

• Systematic review encompassing 215 studies of 2,772 solid organ transplant recipients (54% kidney, 18% liver, 9% thoracic) from January-October 2020.

Primary endpoint:

• Clinical presentation (symptoms, lab values, radiology), management (immunosuppression modulation, therapeutics) and outcomes (rejection, mortality).

Key findings:

• Among solid organ transplant recipients, 70% had fever, 49% dyspnea, 64% cough and 30% diarrhea at presentation.
• Many had immunosuppression decreased, particularly antimetabolites during acute illness (76%).
• 60% were treated with hydroxychloroquine, whereas 39% were given steroids and 15% treated with IL-6 antagonists (little remdesivir or plasma use).
• 81% required hospital admission, 29% received ICU care and overall mortality was 19% (95% CI, 15-22%).
• Secondary bacterial infection data were only variably reported, with 14 cases of predominately lower-level CMV viremia and 16 total cases of aspergillosis.
• Rejection was very uncommon (1%).
• Nasopharyngeal swab negativity usually occurred by ~3-5 weeks from diagnosis (range 5-56 days).

Limitations:

• Included studies primarily ranged from January-June 2020. Significant study heterogeneity limits meta-analysis conclusions.

 

Matched Cohort Studies

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States (Molnar, November 2020).

Overall, in this robust propensity-matched analysis of solid organ transplant recipients versus non-solid organ transplant controls confirmed COVID-19, there was similar, high, mortality.

Study population:

• Multicenter cohort of solid organ transplant recipients across 68 U.S. hospital ICUs with laboratory-confirmed COVID-19 from March to June 2020 (STOP-COVID).
• Propensity matched 98 solid organ transplant to 288 non-solid organ transplant recipients (planned 1:4) based on age, sex, race, comorbidities and medication use.
• The cohort was 70% male, 40% Black, median age 60 years with good balance.

Primary endpoint:

• 28-day mortality. Other endpoints included use of mechanical ventilation, development of ARDS and receipt of vasopressors.

Key findings:

• No difference in 28-day mortality: 40% vs. 43% (RR, 0.92 [0.72-1.22]), though there was a trend toward higher renal replacement therapy needs in solid organ transplant recipients (RR, 1.34 [0.97-1.85]).
• There was more corticosteroid use in solid organ transplant recipients (65% vs. 38%), though other therapeutics were similar (7% received remdesivir, 80% received hydroxychloroquine and azithromycin, 18% received tocilizumab, 3% received plasma).

Limitations:

• All solid organ transplant recipients were considered together, with few lung recipients.
• There was no matching or controlling for receipt of corticosteroids, and most patients received earlier therapies such as hydroxychloroquine.
  
  

COVID-19 Outcomes Among Solid Organ Transplant Recipients: A Case-Control Study (Sharma, January 2021).

Overall, in this matched cohort of solid organ transplant recipients versus controls, mortality was similar, though renal replacement therapy use was much more common.

Study population:

• Case-control study at single U.S. center in Michigan, March-May 2020, of adults with PCR-confirmed COVID-19, with 1:3 matching of 41 solid organ transplant and 121 controls based on age, race and inpatient status.
• There was heavy overrepresentation of African American solid organ transplant patients (two-thirds of cases) versus their overall solid organ transplant patient panel.

Primary endpoint:

• Mortality, with secondary outcomes of severe disease, mechanical ventilation, and use of RRT.

Key findings:

• Solid organ transplant status was not significantly associated with death in both unadjusted (15% vs. 12%) and adjusted analyses (aHRs of 0.84 and 0.90 across models), though associations were seen for diabetes and cardiovascular disease.
• Adjusted odds of RRT use were five-fold higher in the solid organ transplant group, but incidence of severe disease and mechanical ventilation were similar.
• There was strong association between hydroxychloroquine use and mortality across multiple models (wide confidence intervals).

Limitations:

• Single center study, reflecting first-wave U.S. practice.
• Despite multiple adjusted analyses, there was potential for residual confounding (hydroxychloroquine association may reflect this).

 

Inpatient COVID‐19 outcomes in solid organ transplant recipients compared to non‐solid organ transplant patients: A retrospective cohort (Avery, December 2020).

Overall, in this single health system retrospective adjusted analysis, solid organ transplant versus non-solid organ transplant mortality did not differ, and solid organ transplant status was associated with a faster decline in WHO severity score.

Study population:

• Single health system, retrospective U.S. cohort of 45 solid organ transplant recipients versus 2,427 non-solid organ transplant patients admitted with COVID-19 between March-August 2020.

Primary endpoint:

• Trajectory of WHO COVID-19 severity scale over time, hospital length of stay and inpatient mortality.

Key findings:

• Baseline demographics were largely similar (e.g., median age of 59), though there was more diabetes (60% vs. 34%), HIV infection (7% vs. 2%) and history of malignancy (23% vs. 11%) in solid organ transplant recipients; 4% vs. 11% had do not resuscitate orders on admission.
• Admission and peak WHO severity scale were slightly lower on admission in solid organ transplant recipients, with faster decline in score over time after adjusting for admission score.
• 7% of solid organ transplant recipients vs. 16% non-solid organ transplant required mechanical ventilation.
• Solid organ transplant recipients were more frequently given tocilizumab (13% vs. 4%) and hydroxychloroquine (29% vs. 17%).
• Mortality was 4% in solid organ transplant recipients versus 11% in the control group, though when accounting for competing risk of discharge, this did not differ (sub-HR ₁0.4_1.6). This was stable in propensity-weighted analysis.

Limitations:

• More DNR orders in non-solid organ transplant recipients and more severe initial presentation may have skewed mortality interpretation.
• Dose of administered corticosteroids was not clear (maintenance versus higher dose in solid organ transplant recipients).

 

Kidney Transplant Cohorts

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study (Cucchiari, August 2020).

Overall, in this moderate-sized cohort of kidney transplant recipients in the Spanish first wave, mortality was high (27%), while older age, lung disease and obesity were associated with adverse outcomes.

Study population:

• Spanish multicenter cohort of kidney transplant recipients with PCR-confirmed COVID-19, March-April 2020.
• This included 104 hospitalized patients: 30% diabetes, 27% obese, 43% with preceding lymphopenia, at a median of 59 months from transplant.

Primary endpoint:

• Death and ARDS (defined as bilateral opacities with P/F ratio <315).

Key findings:

• Mortality was 27%, higher among those with pulmonary disease and older age, those with nosocomial infection (57% mortality), as well as those with higher LDH.
• Obesity was associated with 2.6-fold higher odds of ARDS. Notably, 50% received steroids (0.5-1 mg/kg/day methylprednisolone), though 97% received hydroxychloroquine and 48% received lopinavir/ritonavir.

Limitations:

• Shorter median follow-up (14 days), while also reflecting management of COVID-19 first wave (e.g., use of LPV/r). The multivariable models were limited (i.e., did not adjust for many patient factors).

 

 

Dialysis vs. Kidney Transplant

SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: A national cohort study (Ravanan, August 2020).

Overall, despite higher incidence of COVID-19 in transplant candidates versus solid organ transplant recipients in the U.K. first wave, unadjusted mortality was 2.5-fold higher among solid organ transplant recipients.

Study population:

• National cohort of three transplant registries in the U.K. comparing waitlist patients versus recipients with a functioning graft through late May 2020, predominately related to kidney transplant (>70% of both groups).

Primary endpoint:

• COVID-19 incidence and mortality.

Key findings:

• More waitlisted patients tested positive by PCR (3.8%, 197/5,184) than solid organ transplant recipients (1.3%, 597/46,789).
• Associations with testing positive in solid organ transplant recipients: older, non-White, living in the greater London area (urban), more recent transplant, deceased donation.
• In adjusted analysis, age was the only significant variable associated with death in solid organ transplant recipients (2.4-fold higher in those >70 versus those aged 50-59).
• Mortality was 10% in waitlisted patients versus 26% in solid organ transplant recipients; 30-day survival 90% versus 74%.
• Of 1,004 transplants performed in 2020, 4.1% recipients tested positive and 0.8% died (8 total).

Limitations:

• Reflects testing and management practices of the first COVID-19 wave.
• Did not evaluate if factors associated with mortality differed between candidates and recipients.
• Twice as many >70-year-old patients in solid organ transplant recipient group.
• Did not report hospital or ICU admission rates.

 

Incidence, Characteristics and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study (De Meester, February 2021).

Overall, COVID-19 incidence was higher in hemodialysis and kidney transplant patients than in the general population. Age-standardized mortality relatively similar in both groups, though both somewhat higher than in the general population.

Study population:

• Prospective multicenter cohort from March-May 2020 in Belgium of hemodialysis patients versus kidney transplant recipients with confirmed or suspected COVID-19 (total n=259).

Primary endpoint:

• COVID-19 incidence and mortality in HD versus KT recipients.

Key findings:

• Crude/adjusted incidence of COVID-19 was 5.3%/2.5% in HD versus 1.4%/1.6% in KT recipients.
• The incidence rate ratio versus the general population was 2.5 for HD versus 1.6 for KT recipients.
• Diabetes, obesity and nursing home residency were associated with testing positive in HD group.
• Crude/age-standardized mortality was 30%/20% (64/216) in HD patients versus 14%/23% (6/43) in KT recipients (15% in general population).
• 2% of the overall KT recipient population died during study period.
• There was no excess all-cause mortality seen in HD population versus 2015-2019 period, owing to lower mortality among uninfected patients.

Limitations:

• Reflects first-wave testing and management practices in Europe.
• There may have been more routine screening in HD patients; details on illness spectrum and management were not presented for either patient group (though 64% HD vs. 83% solid organ transplant recipients were hospitalized).

 

COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration (Hilbrands, November 2020).

Overall, in this large multicenter database, mortality was high and similar among KT recipients versus dialysis patients after adjusting for covariables. In subgroup analysis, mortality was much higher in a subgroup of recent KT recipients versus those on the active KT waitlist.

Study population:

• The ERACODA database from February-May 2020 representing 98 centers across 26 countries (predominately in Europe) enrolling 1,073 persons (28% with KT and 72% on dialysis) with PCR-confirmed or suspected COVID-19.

Primary endpoint:

• 28-day mortality.

Key findings:

• 28-day mortality in KT recipients was 21% versus 25% in dialysis patients; no difference in adjusted analysis (aHR, 0.81).
• In the subgroup of dialysis patients who were active transplant candidates at diagnosis, 8/148 died (4%) versus 7/23 (30%) who had received a transplant within the past year (aHR, 0.2 [0.07-0.56]).
• Notably, treatments included high dose steroids in 18% KT versus 11% HD patients, while 54% of KT recipients had mycophenolate withdrawn.
• Obesity, older age, frailty and worse pulmonary symptoms were associated with mortality.

Limitations:

• Higher ICU resource utilization in KT recipients.
• Small number of events in subgroup analysis.

 

Liver Transplant

Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study (Webb, November 2020).

Overall, in this multicenter, propensity-matched analysis of liver transplant recipients versus non-liver transplant recipients, COVID-19 mortality did not significantly differ after adjusting for comorbidities, though the two populations differed significantly at baseline. Age, renal injury and (non-liver) cancer were strong associations with mortality.

Study population:

• Multicenter dual registry study across 18 countries (COVID-HEP and SECURE-Cirrhosis) of 151 liver transplant recipients with comparison to 627 non-LT recipients from a U.K. hospital system between March and June 2020.

Primary endpoint:

• Propensity-matched mortality.

Key findings:

• In crude analysis, liver recipients were younger, with more men and persons with diabetes, while 30% versus 12% presented with gastrointestinal symptoms.
• Targeted therapeutics (32% vs. 3%) and ICU utilization (28% vs. 8%) were much more common in liver transplant recipients.
• Overall, 19% liver recipients versus 27% general patients died.
• After propensity matching on age, sex, ethnicity and comorbidities, there was no significant difference in mortality (maximum risk difference was +7.6% [-1.1 to 16.5], p=0.09 across several models).

Limitations:

• A large proportion of non-LT group had ICU care deferred (likely due to an imbalance in populations, with more non-LT recipients having advanced age or comorbidities), potentially biasing comparative mortality analysis.
  
  

 

Epidemiological pattern, incidence and outcomes of COVID-19 in liver transplant patients (Colmenero, January 2021).

Overall, in this large Spanish liver transplant cohort, mortality was high (18%, associated with age, male sex and use of mycophenolate), though overall lower than in the age/sex standardized general Spanish population.

Study population:

• Nationwide Spanish multicenter cohort of 111 liver transplant patients diagnosed with COVID-19, February-April 2020.

Primary endpoint:

• COVID-19 mortality versus matched general population.

Key findings:

• Of 111 patients, 87% of liver transplant patients were admitted to the hospital.
• Most were treated with hydroxychloroquine, lopinavir/ritonavir or azithromycin; 12% received steroids and 15% received tocilizumab.
• 20% required advanced respiratory support, including 10% ICU care.
• Associations with severe COVID-19 including advancing age, male sex and use of mycophenolate (RR, 3.9 [1.6-9.7]), particularly >1,000 mg/day.
• Mortality was 18% after median 23 days of follow-up, which was lower than in the matched general population by standardized incidence rate, adjusting for age and sex.

Limitations:

• Mortality comparisons to general population were not adjusted for major comorbidities. Management strategies reflect that of COVID-19 first wave in Spain.

 

Lung Transplant

COVID-19 in Lung Transplant Recipients (Messika, January 2021).

Overall, in this small series of lung transplant patients with COVID-19, mortality was 14%, predominately in those with recent immunosuppressive intensification.

Study population:

• Multicenter French case series of 35 lung transplant recipients with COVID-19 from March-May 2020.

Primary endpoint:

• Patient characteristics and outcomes (level of care, mortality).

Key findings:

• Median cohort age was 40 years, with 80% double lung recipients and 71% with community-acquired infection.
• Fever, cough and diarrhea were the most common symptoms.
• 17% had any chronic allograft dysfunction, though 40% had chronic kidney disease.
• 37% required ICU care, including 20% receiving mechanical ventilation.
• Pulmonary superinfection was diagnosed in 34% (one fungal infection).
• At 50 days of median follow-up, mortality was 14% (7/35), four of whom had recent preceding immunosuppressive intensification (for induction or treatment of rejection).

Limitations:

• Small sample size limited potential for analysis of associations with severe outcomes. Most patients did not have allograft dysfunction, so outcomes may not be generalizable to risks in general lung transplant population.

COVID-19 in lung transplant recipients: A single center case series from New York City (Aversa, November 2020).

Overall, in this small series of lung transplant recipients, severe disease and pulmonary bacterial coinfection were common, with 100% observed mortality in mechanically ventilated recipients.

Study population:

• Lung transplant recipients at an NYC academic center between March-May 2020 (n=32).

Primary endpoint:

• Clinical presentation and incidence of severe outcomes.

Key findings:

• Median age was 65, 50% with double lung transplantation median 5.6 years prior.
• 30% had allograft dysfunction and two-thirds had chronic kidney disease.
• Fever was seen in 37%; 44% had gastrointestinal symptoms.
• 11 patients had received immunosuppression intensification in prior 3 months, seven of whom developed severe disease.
• 41% had severe disease for whom high-dose steroids were frequently given (44% cohort) or tocilizumab (16% cohort).
• 47% had documented coinfections, predominately respiratory bacterial pathogens, three with detectable CMV in blood and two with bacteremia.
• Mortality was 34%, including 100% mortality in 10 mechanically ventilated patients.

Limitations:

• Single-center series during NYC first wave, not necessarily reflective of current management protocols.

 

Heart Transplant

COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak (Bottio, January 2021).

Overall, in this multicenter heart transplant cohort from the Italian epicenter, COVID-19 mortality was high (30%), particularly among those with other chronic comorbidities.

Study population:

• Multicenter Northern Italian heart transplant cohort including 47 cases of confirmed COVID-19 (2% of total heart transplant panel).

Primary endpoint:

• COVID-19 incidence and case fatality rate.

Key findings:

• 80% of recipients required hospitalization and these persons were significantly older (65 vs. 49 years) and had worse baseline renal function.
• Most (87%) had fever and pulmonary symptoms (70%), and 21% had gastrointestinal symptoms.
• Most were treated with hydroxychloroquine (81%), lopinavir/ritonavir (45%) and/or steroids (21%); reduction in antimetabolite therapy or calcineurin inhibitors was common.
• Bacterial coinfection was seen in 11%, with no fungal infections documented.
• 14/47 (30%) died, and these persons were older (72 vs. 62 years), more likely to have diabetes (36% vs. 9%), lower GFR, more coronary vasculopathy and worse New York Heart Association functional class.

Limitations:

• Frequent use of therapeutics not currently favored, with relatively uncommon steroid use.

 

Special Transplant Populations

People with HIV

Incidence and Outcomes of COVID-19 in Kidney and Liver Transplant Recipients With HIV: Report From the National HOPE in Action Consortium (Mehta, January 2021).

Overall, in a small sample of solid organ transplant recipients with HIV and good baseline HIV control, COVID-19 outcomes were poor, including high mortality.

Study population:

• Case series of PCR-confirmed COVID-19 in the multicenter U.S. HOPE in Action trial network of solid organ transplant recipients with HIV from March-September 2020.

Primary endpoint:

• COVID-19 incidence and mortality.

Key findings:

• Eleven cases of COVID-19 (4% of total cohort) were reported, predominately in male kidney recipients.
• Hispanic ethnicity was overrepresented. as were NYC transplant centers.
• All patients had suppressed HIV viral load, but 6/7 patients had CD4 <200 on admission (lower than baseline values).
• 10/11 recipients required hospitalization, 5/11 required ICU care and 4/11 (36%) died.

Limitations:

• Small series, predominately first-wave outcomes in NYC, which may not reflect current national management practices.

 

The Unpredictable Outcome of SARS-CoV-2 in Kidney Transplant Recipients with HIV Infection (de Sandes-Freitas, January 2021).

Overall, in this small cohort of KT recipients with COVID-19 and well-controlled HIV, most with other chronic medical conditions, outcomes were poor.

Study population:

• Eight Brazilian KT recipients with well-controlled HIV infection who had PCR-confirmed COVID-19, March-July 2020, from a national registry.

Primary endpoint:

• Clinical course and mortality.

Key findings:

• All patients had viral load <400 copies/mL and CD4 >200 cells/mL (most >400).
• All were on at least dual immunosuppression, including tacrolimus.
• 6 had diabetes, and five had significant graft dysfunction.
• Two received high-dose steroids, and five underwent complete immunosuppressive withdrawal.
• 4 patients had severe disease, two had graft loss and three died.

Limitations:

• Small series, no comparison to controls without HIV, routine immunosuppressive withdrawal which is not common practice.

 

Active or Prior COVID-19

Kidney Transplantation in Patients With SARS-CoV-2 Infection: A Case Series Report (Viana, January 2021).

Overall, in this very small series, KT recipients with + NP PCR pre-transplant did not develop severe COVID-19, though it is unclear if there was contribution to subsequent acute rejection (seen in 2/4).

Study population:

• Single Brazilian center experience from May-June 2020 of patients undergoing KT with PCR-confirmed COVID-19 during pre-KT screening (n=4).

Primary endpoint:

• Disease symptoms and severity.

Key findings:

• Four KT recipients, ages 27-65, of whom none were obese but three had hypertension.
• Symptoms were mild (50% asymptomatic), with no oxygen requirement and normal chest CT in all. Cycle thresholds were 17, 27, 27, 28.
• All received ATG induction, though antimetabolite dosing was decreased by 50% in three. Two had rejection on days 11 and 30 after KT, with ATN and thrombotic microangiopathy on biopsy.
• All had detectable SARS-CoV-2 IgG 28 days post KT. One recipient had +PCR out to 75 days, but negative viral culture.

Limitations:

• Very small sample, unclear timing of symptom onset with higher CTs in three recipients who may have had little live virus at KT.
  
  

Donor to recipient transmission of SARS‐CoV‐2 by lung transplantation despite negative donor upper respiratory tract testing (Kaul, February 2021).

Donor-derived COVID-19 is possible via lung transplantation and can be fatal. It is important to test lower respiratory tract specimens in these donors, even without clear evidence of infection.

Study population:

• Case report of donor-derived COVID-19 in a lung transplant recipient in Michigan.

Primary endpoint:

• Disease course.

Key findings:

• A female donor with trauma and brain death donated bilateral lungs to a recipient with COPD.
• The donor had posterior right lower lobe consolidation on chest CT consistent with pulmonary contusion.
• Nasopharyngeal PCR for SARS-CoV-2 was negative (bronchoscopic fluid was not sent).
• The recipient had negative rapid PCR 12 hours before transplant.
• Induction was with steroid bolus, maintenance with steroid, tacrolimus and mycophenolate.
• On post-operative day 3, the recipient developed fever, worsening lung function, with multifocal consolidations on chest CT.
• BAL PCR testing for SARS-CoV-2 was positive (cycle threshold 8.1) (NP negative) and banked donor BAL fluid was also positive (cycle threshold 8.5).
• One transplant surgeon also was infected during the operation, with sequence confirmation of donor virus.
• Despite remdesivir, convalescent plasma and holding of mycophenolate, the recipient had progressive deterioration and died on post-transplant day 61 (cycle threshold remained + at 29.3).

Limitations:

• Single-patient report.
   

Vaccination in Solid Organ Transplant Recipients

Solid organ transplant recipients were excluded from landmark COVID-19 vaccine clinical trials, representing <0.001% of Janssen COVID-19 vaccinees in published data (N=10). Several single and multicenter cohorts tracking vaccine response in this population predominately focus on anti-spike antibody level as a plausible correlate of neutralizing antibody and thus vaccine immunogenicity (Boyarsky, March 2021; Grupper, April 2021).

Safety and reactogenicity of mRNA vaccination appear reassuring, without a clear signal for unexpected organ rejection or allergy among solid organ transplant recipients (Ou, 2021). In contrast, despite ~100% sero-response among healthy non-solid organ transplant populations after a single mRNA vaccine dose, solid organ transplant anti-spike antibody responses to the full mRNA vaccination series have typically ranged from 30-60% (Boyarsky, March 2021; Grupper, April 2021; Marinaki, April 2021; Benotmane, April 2021). Additionally, among solid organ transplant recipients with detectable anti-spike antibody, levels have typically been lower than those observed in historical or contemporaneous control populations. Older age, more recent transplantation and use of antimetabolite maintenance therapies such as mycophenolate (1.5-2.5 fold lower odds of sero-response) have emerged as associations with low sero-response, particularly among kidney transplant recipients (Boyarsky, March 2021; Grupper, April 2021). Additionally, KT recipients on the selective T cell co-stimulation inhibitor belatacept appear to have very poor humoral responses (<5% anti-spike sero-response) (Chavarot, April 2021). It is not clear if corticosteroid use is associated with poor humoral vaccine responses, nor whether a particular mRNA vaccine platform appears more immunogenic, though early data suggested somewhat improved immunogenicity after the first dose of Moderna mRNA-1273 vaccine (vs. Pfizer-BioNTech 162b2) (Boyarsky, March 2021).

Persistent knowledge gaps include characterization of humoral vaccine responses in non-kidney transplant recipients (e.g., high risk lung recipients), those with recent solid organ transplant (<12 months) and those receiving lymphodepleting induction therapy, as well as clear understanding of real-world seroprotective thresholds. Additionally, immunogenicity of viral vectors such as the Oxford-AstraZeneca and Janssen COVID-19 vaccines is not yet characterized. T cell responses of solid organ transplant recipients after vaccination also remain poorly understood. Given that maintenance immunosuppression promotes exhausted cellular phenotypes to avoid graft rejection, these may further reduce cellular immune response to vaccine antigen. Limited published data include T cell responses measured by interferon-gamma ELISpot in subset of belatacept-treated KT recipients indicating 30% response one month after mRNA vaccination (Chavarot, April 2021). Additional non-peer-reviewed preprint data support that lack of T cell help may be a factor in poor humoral vaccine response in kidney transplant recipients (Rincon-Arevalo, April 2021 - preprint, not peer-reviewed).

Given there are mounting reports of breakthrough infection after vaccination in solid organ transplant recipients, including severe disease among those with evidence of low anti-spike antibody at time of diagnosis (Wadei, April 2021), closing the above knowledge gaps is of critical importance.

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