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  • An W
  • Wang Q
  • Kim TE
  • Kang JS
J Infect Public Health. 2022 Mar;15(3):365-372 doi: 10.1016/j.jiph.2022.02.002.
BACKGROUND:

Although many studies have reported cases of COVID-19 infection in transplant recipients, most of them only involve a small number of patients and narrow geographic areas. This study aims to investigate the clinical characteristics, morbidity, severity, and mortality of COVID-19 infection among solid organ transplant (SOT) recipients by meta-analysis.

METHOD:

We performed a literature search using the databases PubMed, Web of Science, and Google Scholar as of November 26, 2020. We included randomized controlled trials and cohort studies, excluding case reports and small case series (n < 10). The pooled incidence proportion and 95% confidence intervals (CI) were used to estimate the combined results of forty-seven studies were included for the meta-analysis. Heterogeneity was assessed using I2. Freeman-Tukey double arcsine transformation was used to stabilize the specific rate variance. Publication bias was using Egger's test.

RESULTS:

The morbidity rate of COVID-19 in SOT recipients was 2.10% [95% CI 1.35-3.01], and the proportion of severe infection was 22.46% [95% CI 15.74-29.90]. The mortality rate was 17.38% [95% CI 13.72-21.34]. In the analysis by transplanted organ, the proportion of patients with severe infection was highest in recipients of two or more transplants 48.85% [95% CI 11.88-86.38]. The mortality rate was highest in lung transplant recipients 25.12% [95% CI 16.94-34.00]. The most common symptoms of COVID-19 in SOT recipients were fever (73.39%), cough (58.90%), and respiratory symptoms (45.77%).

CONCLUSION:

SOT was a risk factor for worse COVID-19 outcomes, although the morbidity of COVID-19 in SOT recipients was not markedly higher than the general population. These results may change when our understanding of the disease progress.

  • Marra AR
  • Kobayashi T
  • Suzuki H
  • Alsuhaibani M
  • Tofaneto BM
  • et al.
J Infect. 2022 Mar;84(3):297-310 doi: 10.1016/j.jinf.2021.12.035.
OBJECTIVES:

We aimed to assess the short-term effectiveness of COVID-19 vaccines among immunocompromised patients to prevent laboratory-confirmed symptomatic COVID-19 infection.

METHODS:

Systematic review and meta-analysis. We calculated the pooled diagnostic odds ratio [DOR] (95% CI) for COVID-19 infection between immunocompromised patients and healthy people or those with stable chronic medical conditions. VE was estimated as 100% x (1-DOR). We also investigated the rates of developing anti-SARS-CoV-2 spike protein IgG between the 2 groups.

RESULTS:

Twenty studies evaluating COVID-19 vaccine response, and four studies evaluating VE were included in the meta-analysis. The pooled DOR for symptomatic COVID-19 infection in immunocompromised patients was 0.296 (95% CI: 0.108-0.811) with an estimated VE of 70.4% (95% CI: 18.9%- 89.2%). When stratified by diagnosis, IgG antibody levels were much higher in the control group compared to immunocompromised patients with solid organ transplant (pOR 232.3; 95% Cl: 66.98-806.03), malignant diseases (pOR 42.0, 95% Cl: 11.68-151.03), and inflammatory rheumatic diseases (pOR 19.06; 95% Cl: 5.00-72.62).

CONCLUSIONS:

We found COVID-19 mRNA vaccines were effective against symptomatic COVID-19 among the immunocompromised patients but had lower VE compared to the controls. Further research is needed to understand the discordance between antibody production and protection against symptomatic COVID-19 infection.

  • Mehrabi Nejad MM
  • Moosaie F
  • Dehghanbanadaki H
  • Haji Ghadery A
  • Shabani M
  • et al.
Eur J Med Res. 2022 Feb 12;27(1):23 doi: 10.1186/s40001-022-00648-5.
BACKGROUND:

Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be prioritized for primary prevention through vaccination. This study aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach.

METHOD:

PubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity.

RESULTS:

A total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR = 0.52 [0.42, 0.65]). IC patients with autoimmune conditions were 54%, and patients with malignancy were 42% more likely to have positive seroconversion than transplant recipients (P < 0.01). Subgroup meta-analysis based on the type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR = 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P = 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others) showed no statistically significant between-group difference of seroconversion (P = 0.55).

CONCLUSIONS:

IC patients, especially transplant recipients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune conditions and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis could aid healthcare policymakers in making decisions regarding the importance of the booster dose or more strict personal protections in the IC patients.

  • Udomkarnjananun S
  • Kerr SJ
  • Townamchai N
  • Susantitaphong P
  • Tulvatana W
  • et al.
Sci Rep. 2021 Oct 8;11(1):20073 doi: 10.1038/s41598-021-99713-y.

Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in KTR are still not clearly identified. Our objective was to systematically analyze published evidence for risk factors associated with mortality in COVID-19 KTR. Electronic databases were searched for eligible studies on 1 August 2021. All prospective and retrospective studies of COVID-19 in KTR were considered eligible without language restriction. Since data in case reports and series could potentially be subsets of larger studies, only studies with ≥ 50 patients were included. Random-effects model meta-analysis was used to calculate weighted mean difference (WMD) and pooled odds ratio (OR) of factors associated with mortality. From a total 1,137 articles retrieved, 13 were included in the systematic review and meta-analysis comprising 4,440 KTR. Compared with survivors, non-survivors were significantly older (WMD 10.5 years, 95% CI 9.3-11.8). KTR of deceased donor were at higher risk of death (OR 1.73, 95% CI 1.10-2.74). Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11-15.33) and pneumonia (OR 10.64, 95% CI 3.37-33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47-0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36-7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6. A number of COVID-19 mortality risk factors were identified from KTR patient characteristics, presenting symptoms, and laboratory investigations. KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.

  • Becchetti C
  • Gschwend SG
  • Dufour JF
  • Banz V
J Clin Med. 2021 Sep 5;10(17) doi: 10.3390/jcm10174015.

Liver transplant (LT) recipients are considered a vulnerable population amidst the COVID-19 pandemic. To date, available data have been heterogeneous and scarce. Therefore, we conducted a systematic literature review identifying English-language articles published in PubMed between November 2019 and 30 May 2021. We aimed to explore three areas: (1) outcome and clinical course; (2) immunological response after COVID-19 in LT recipients; and (3) vaccination response. After systematic selection, 35, 4, and 5 articles, respectively, were considered suitable for each area of analysis. Despite the heterogeneity of the reports included in this study, we found that gastrointestinal symptoms were common in LT recipients. The outcome of the LT population was not per se worse compared to the general population, although careful management of immunosuppressive therapy is required. While a complete therapy discontinuation is not encouraged, caution needs to be taken with use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Although data conflicted about acquired immunity after SARS-CoV-2 infection, vaccine immunogenicity appeared to be low, suggesting that the level of surveillance should be kept high in this population.

  • Sarno G
  • Montalti R
Minerva Endocrinol (Torino). 2021 Sep;46(3):293-295 doi: 10.23736/S2724-6507.20.03209-5.
  • Kulkarni AV
  • Tevethia HV
  • Premkumar M
  • Arab JP
  • Candia R
  • et al.
BACKGROUND:

Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 (COVID-19) in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients.

METHODS:

The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality.

FINDINGS:

Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60·38 (5·24) years, and 68·5% were men. The mean time (SD) to COVID-19 infection was 5·72 (1·75) years. Based on 17 studies (I2 = 7·34) among 1,481 LT recipients, the cumulative incidence of mortality was 17·4% (95% confidence interval [CI], 15·4-19·6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0·8 [0·6-1·08]; P = 0·14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1·5 [0·63-3·56]; P = 0·35). The cumulative incidence of graft dysfunction was 2·3% (1·3-4·1). Nearly 23% (20·71-25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55·9% (38·1-72·2) patients after COVID-19 infection.

INTERPRETATION:

LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

  • Chu G
  • Jiao W
  • Xie F
  • Zhang M
  • Niu H
World J Mens Health. 2021 Jul;39(3):444-453 doi: 10.5534/wjmh.200168.

Severe Acute Respiratory Syndrome Coronavirus 2, which is quickly spreading around the world and causes coronavirus disease 2019, may attack the urogenital system. We thought that a summary of the current literature about urogenital disease associated with the virus would be useful for physicians treating patients with coronavirus disease 2019. PubMed was comprehensively screened for studies published from 2019 to 2020. Studies of coronavirus disease 2019 patients with kidney disease, reproductive system diseases, or urological cancer were included. Through reviewing current literature, we summarized that acute kidney injury is a risk factor for patients with coronavirus disease 2019 and is related to their survival. A diagnosis of chronic kidney disease increases the risk of infection. The therapy for kidney transplant patients should be cautious and implemented on a case-by-case basis. When the public health burden is too heavy to bear, a rational selection of treatment for patients with urological cancer is vital. The male reproductive system is at high risk of being attacked by the virus, which may cause damage to reproductive function, and the long-term effects require further study. So, the complications associated with the urogenital system should not be ignored during the course of infection treatment and more robust evidence of long-term effects on the urogenital system will be proposed as more studies are published.

  • Contributors to the C4 article
  • Kumar D
Am J Transplant. 2021 May;21(5):1801-1815 doi: 10.1111/ajt.16346.

A novel coronavirus has had global impact on individual health and health care delivery. In this C4 article, contributors discuss various aspects of transplantation including donor and recipient screening, management of infected patients, and prevention of coronavirus disease (COVID). Donor screening with SARS-CoV-2 nucleic acid testing (NAT) close to the time of procurement is recommended. Many programs are also screening all potential recipients at the time of admission. The management of COVID has evolved with remdesivir emerging as a new potential option for transplant recipients. Dexamethasone has also shown promise and convalescent plasma is under study. Prevention strategies for transplant candidates and recipients are paramount. Pediatric-specific issues are also discussed. Strategies for the psychological well-being of patients and providers are also imperative, in addition to future research priorities for transplantation.

  • Angelico R
  • Blasi F
  • Manzia TM
  • Toti L
  • Tisone G
  • et al.
Medicina (Kaunas). 2021 Apr 30;57(5) doi: 10.3390/medicina57050435.

Background and Objectives: In the era of the coronavirus disease 2019 (COVID-19) pandemic, the management of immunosuppressive (IS) therapy in kidney transplant (KT) recipients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires attention. It is not yet understood whether IS therapy may protect from the cytokine storm induced by SARS-CoV-2 infection or a temporary adjustment/withdrawal of IS therapy to restore the immune system may be necessary. We performed a systematic literature review to investigate the current management of IS therapy in KT recipients with COVID-1. Materials and Methods: Out of 71 articles published from 1 February 2020 until 30 October 2020, 554 KT recipients with SARS-CoV-2 infection were identified. Results: Modifications of IS therapy were based on the clinical conditions. For asymptomatic patients or those with mild COVID-19 symptoms, a "wait and see approach" was mostly used; a suspension of antimetabolites drugs (347/461, 75.27%) or mTOR inhibitors (38/48, 79.2%) was adopted in the majority of patients with symptomatic COVID-19 infections. For CNIs, the most frequent attitude was their maintenance (243/502, 48.4%) or dose-reduction (99/502, 19.72%) in patients asymptomatic or with mild COVID-19 symptoms, while drug withdrawal was the preferred choice in severely symptomatic patients (160/450, 31.87%). A discontinuation of all IS drugs was used only in severely symptomatic COVID-19 patients on invasive mechanical ventilation. Renal function remained stable in 422(76.17%) recipients, while 49(8.84%) patients experienced graft loss. Eight (1.44%) patients experienced a worsening of renal function. The overall mortality was 21.84%, and 53(9.56%) patients died with functioning grafts. Conclusion: A tailored approach to the patient has been the preferred strategy for the management of IS therapy in KT recipients, taking into account the clinical conditions of patients and the potential interactions between IS and antiviral drugs, in the attempt to balance the risks of COVID-19-related complications and those due to rejection or graft loss.