COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature

Raja, Mohammed; Mendoza, Maria A.; Villavicencio, Aasith; Anjan, Shweta; Reynolds, John M.; Kittipibul, Veraprapas; Fernandez, Anmary; Guerra, Giselle; Camargo, José F.; Simkins, Jacques; Morris, Michele; Abbo, Lilian; Natori, Yoichiro

doi:10.1016/j.trre.2020.100588

Cited by 169 publications

(193 citation statements)

References 127 publications

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“…As recent meta-analyses have focused exclusively on cancer 136 or SOT patients. 137 Herein, results show differences among the immunocompromised and general population cohorts after COVID-19. First, SOT patients with COVID-19 had more comorbidities (cardiovascular disease, diabetes, and hypertension), dyspnea and required intensive care more often, and had higher mortality despite having similar disease severity versus the general population with COVID-19.…”

Section: Discussionmentioning

confidence: 76%

COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients

Belsky¹,

Tullius²,

Lamb³

et al. 2021

Journal of Infection

162

141

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Background: The clinical impact of severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in immunocompromised patients has not been systematically evaluated. Methods: We reviewed current literature reporting on COVID-19 in cancer (CA), hematopoietic cell (HCT), and solid organ transplant (SOT) patients and compared their clinical data and outcomes to the general population. For adult CA, HCT and SOT patients, an extensive search strategy retrieved all articles published until July 20, 2020 by combining the terms coronavirus, coronavirus infection, COVID-19 , and SARS-CoV-2 in PubMed, Cochrane, and Web of Science, and following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. For the pediatric CA cohort, a global COVID-19 registry was used. For the general population cohort, a large meta-analysis was used to compare pooled prevalence estimates, and two large meta-analyses were utilized to serve as pooled comparators for hospitalized COVID-19 patients. Findings: Compared to the general population, adult CA and SOT patients with COVID-19 had higher comorbidities, greater levels of inflammatory markers at diagnosis, and higher rates of intensive care and hospital mortality. Pediatric CA patients and HCT patients with COVID-19 tended to have clinical presentations and outcomes similar to the general population. Interpretation: To our knowledge, this is the first systematic review evaluating COVID-19 phenotype and outcomes in immunocompromised patients and comparing them to the general population, which shows that hospital outcomes appear to be worse in adult CA and SOT patients, potentially due to their higher co-morbidity burden.

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Section: Discussionmentioning

confidence: 76%

COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients

Belsky¹,

Tullius²,

Lamb³

et al. 2021

Journal of Infection

162

141

View full text Add to dashboard Cite

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“…Upon SARS-CoV-2 infection, lung-transplanted pwCF were more frequently symptomatic, were admitted to hospital 1.7-fold more frequently and required intensive care 8-fold more frequently than pwCF without lung transplant. Previous studies also found that solid organ transplant recipients require more treatment and medical care upon SARS-CoV-2 infection, whether transplant was for CF [ 5 , 7 ] or other reasons [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

Naehrlich

Orenti

Dunlevy³

et al. 2021

Journal of Cystic Fibrosis

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Background Viral infections can cause significant morbidity in cystic fibrosis (CF). The current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic could therefore have a serious impact on the health of people with CF (pwCF). Methods We used the 38-country European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect case data about pwCF and SARS-CoV-2 infection. Results Up to 30 June 2020, 16 countries reported 130 SARS-CoV-2 cases in people with CF, yielding an incidence of 2.70/1000 pwCF. Incidence was higher in lung-transplanted patients (n=23) versus non-transplanted patients (n=107) (8.43 versus 2.36 cases/1000). Incidence was higher in pwCF versus the age-matched general population in the age groups <15, 15-24, and 25-49 years (p<0.001), with similar trends for pwCF with and without lung transplant. Compared to the general population, pwCF (regardless of transplantation status) had significantly higher rates of admission to hospital for all age groups with available data, and higher rates of intensive care, although not statistically significant. Most pwCF recovered (96.2%), however 5 died, of whom 3 were lung transplant recipients. The case fatality rate for pwCF (3.85%, 95% CI: 1.26-8.75) was non-significantly lower than that of the general population (7.46%; p=0.133). Conclusions SARS-CoV-2 infection can result in severe illness and death for pwCF, even for younger patients and especially for lung transplant recipients. PwCF should continue to shield from infection and should be prioritized for vaccination.

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“…Early on, acute phase reactants and systemic cytokines were implicated in patient outcomes 46 and hospital stay and mortality were decreased by dexamethasone 47 , suggesting that an excessive host immune response might contribute to COVID-19 mortality. However, there were also indications that inadequate host immunity might contribute to adverse COVID-19 outcomes, including the association of lymphopenia with mortality as well as the potentially inferior outcomes of patients on chronic immunosuppression, such as patients with autoimmune diseases or organ transplant recipients [48][49][50][51] . Recent studies defined immune signatures associated with severe COVID-19, including activated CD4, CD8 T cells, plasmablasts, and robust antibody responses 15,16,20,52 .…”

Section: Discussionmentioning

confidence: 99%

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer

Huang

Bange

Han

et al. 2021

Preprint

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Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

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COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature

Cited by 169 publications

References 127 publications

COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients

COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients

Incidence of SARS-CoV-2 in people with cystic fibrosis in Europe between February and June 2020

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer

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