BACKGROUND:

Despite widespread implementation of vaccination against coronavirus disease 2019 (COVID-19), solid organ transplant recipients (SOTRs) can remain particularly vulnerable to this disease. The present study was conducted to investigate the efficacy and safety of sotrovimab in the treatment of SOTRs with COVID-19.

METHODS:

A search was performed of PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar to gather relevant evidence through July 25, 2023. The quality of the included studies was assessed using the risk of bias tool. Comprehensive Meta-Analysis software (ver. 3.0, Biostat) was employed for data analysis.

RESULTS:

Ten studies, involving a total of 1,569 patients, were included. The meta-analysis revealed significant differences between the patients administered sotrovimab and those treated with the standard of care. These differences were observed in mortality rate (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.03-0.67), hospitalization rate (OR, 0.35; 95% CI, 0.21-0.57), intensive care unit (ICU) admission rate (OR, 0.16; 95% CI, 0.04-0.62), the need for supplemental oxygen therapy (OR, 0.22; 95% CI, 0.09-0.51), and the need for mechanical ventilation (OR, 0.09; 95% CI, 0.01-0.70). However, no significant difference was observed between sotrovimab and other treatments regarding the rates of hospitalization or ICU admission (P>0.05). Regarding safety, sotrovimab was associated with a lower rate of adverse events compared to the absence of sotrovimab (OR, 0.15; 95% CI, 0.02-0.86).

CONCLUSIONS:

These results suggest that sotrovimab may improve efficacy outcomes among SOTRs with COVID-19. Nevertheless, additional high-quality trials are necessary to confirm these findings.

Purpose: Solid organ transplant recipients (SOTR) have a high risk for severe COVID-19 infection; hence it is necessary to find alternative treatment strategies to protect these patients from the complications caused by the severe progression of the disease. This study aimed to determine the effectiveness of sotrovimab among SOTR with COVID-19.Materials and methods: A systematic literature search was conducted with relevant keywords to find studies that reported clinical outcomes regarding sotrovimab administration in SOTR outpatients with confirmed COVID-19 infection, who had mild-to-moderate symptoms.Results: Of 796 records found by a systematic search, only 14 met the inclusion criteria for reporting in a systematic review and only 6 enrolled in a meta-analysis. This meta-analysis indicated that SOTR outpatients with mild to moderate COVID-19 who received sotrovimab had lower likelihood of all-cause hospitalization (OR: 0.29, CI: 0.16, 0.52, p < 0.001), ICU admission (OR: 0.17, CI: 0.05, 0.64, p = 0.009) and mortality (OR: 0.15, CI: 0.03, 0.64, p = 0.010) within 30 days of drug infusion compared to controls.Conclusions: Our findings confirm that monoclonal antibody therapy with sotrovimab in SOTR is associated with better outcomes and consequently a reduced risk of disease progression in this high-risk population.

INTRODUCTION:

The immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy.

AIM:

This purpose of this study is to assess seropositivity and seroconversion in solid-organ transplant recipients before and after third-dose COVID-19 vaccination.

METHODS:

This study is a systematic review and meta-analysis performed using PRISMA guidelines. To analyze clinical and cohort studies reporting immunologic response and seroconversion third-dose vaccination, a systematic search was performed using electronic databases (PubMed, Scopus, Cochrane, Directory of Open Access Journal (DOAJ), and Clinicaltrials.gov).

RESULT:

There were 18 full-text papers that could be analyzed qualitatively and quantitatively. After the third vaccination, the pooled rate seropositivity was 67.00% (95% CI 59.511; 74.047, I2 = 93.82%), and the pooled rate seroconversion was 52.51% (95% CI 44.03; 60.91, I2 = 92.15%). The pooled rate of seroconversion after the mRNA-based booster was 52.380% (95% CI 40.988; 63.649, I2 = 94.35%), and after the viral-vector-based booster was 42.478% (95% CI 35.222; 49.900, I2 = 0.00%).

CONCLUSION:

Based on the analysis of immunologic responses and seroconversion findings, the third-dose vaccination of solid organ transplant recipients is an effective method in establishing better immunity against COVID-19.

The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully elucidated. We conducted a systematic review and meta-analysis to assess the efficacy and safety associated with this additional dose of the COVID-19 vaccine in the SOT recipients. A comprehensive search was conducted to identify studies on SOT patients without prior natural SARS-CoV-2 infection who received the fourth dose of the COVID-19 vaccine. Serological antibody responses following vaccination were synthesized by a meta-analysis of proportions. The proportions for each outcome were integrated by using a random-effects model. Approximately 56-92% of the SOT patients developed a humoral immune response, and the pooled seroprevalence rate was 75% (95% confidence interval [CI], 62-82%) after administering the third vaccine dose. Following the fourth dose of vaccination, approximately 76-95% of the patients developed a humoral immune response. The pooled seroprevalence rate after the fourth dose was 85% (95% CI, 79-91%). Of the patients who initially tested seronegative after the second dose, approximately 22-76% of patients subsequently became seropositive after the third dose. The pooled seroconversion rate for the third dose was 47% (95% CI, 31-64%). Among the patients who were seronegative after the third dose, approximately 25-76% turned seropositive after the fourth dose. The pooled seroconversion rate after the fourth dose was 51% (95% CI, 40-63%). Safety data were reported in three studies, demonstrating that adverse effects following the fourth dose were generally mild, and patients with these adverse effects did not require hospitalization. No transplant rejection or serious adverse events were observed. A fourth dose of the COVID-19 vaccine in SOT recipients was associated with an improved humoral immune response, and the vaccine was considered relatively safe.

BACKGROUND:

The SARS-CoV-2 pandemic and corresponding acute respiratory syndrome have affected all populations and led to millions of deaths worldwide. The pandemic disproportionately affected immunocompromised and immunosuppressed adult patients who had received solid organ transplants (SOTs). With the onset of the pandemic, transplant societies across the world recommended reducing SOT activities to avoid exposing immunosuppressed recipients. Due to the risk of COVID-19-related outcomes, SOT providers adapted the way they deliver care to their patients, leading to a reliance on telehealth. Telehealth has helped organ transplant programs continue treatment regimens while protecting patients and physicians from COVID-19 transmission. This review highlights the adverse effects of COVID-19 on transplant activities and summarizes the increased role of telehealth in the management of solid organ transplant recipients (SOTRs) in both pediatric and adult populations.

METHODS:

A comprehensive systematic review and meta-analysis were conducted to accentuate the outcomes of COVID-19 and analyze the efficacy of telehealth on transplant activities. This in-depth examination summarizes extensive data on the clinical detriments of COVID-19 in transplant recipients, advantages, disadvantages, patient/physician perspectives, and effectiveness in transplant treatment plans via telehealth.

RESULTS:

COVID-19 has caused an increase in mortality, morbidity, hospitalization, and ICU admission in SOTRs. Telehealth efficacy and benefits to both patients and physicians have increasingly been reported.

CONCLUSIONS:

Developing effective systems of telehealth delivery has become a top priority for healthcare providers during the COVID-19 pandemic. Further research is necessary to validate the effectiveness of telehealth in other settings.

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees India to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision making. VITT is a rare entity, but a meticulous approach should be taken by the Organ Procurement Organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities like NOTTO, as a resource for data collection and ensuring compliance withprotocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and atreating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk-benefit equationbased on available experience, and an appropriate written informed consent of potential recipients and family members should be obtained before transplantation of organs from suspected or proven VITT donors.

BACKGROUND:

High rates of nonresponse to 2 doses of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine have been reported in transplant recipients. Several studies have investigated the efficacy of a third dose in this population. However, efficacy remains unclear, as response rates vary across studies. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in transplant recipients.

METHODS:

Preferred Reporting Items for Systematic Review and Meta-Analysis reporting guidelines (PROSPERO:CRD42021281498) were followed. Medline, Embase, and CENTRAL were searched from inception to December 2, 2021, without restrictions. All full-text studies reporting on the efficacy of a third dose of any mRNA SARS-CoV-2 vaccine in pediatric and adult transplant recipients were included. The National Institutes of Health quality assessment tool for case series and the Cochrane risk of bias tool determined study quality. Meta-analysis was performed via the DerSimonian-Laird random-effect model.

RESULTS:

Of 84 records, 12 studies totaling 1257 patients met inclusion criteria. One study was a randomized controlled trial, whereas all other studies were observational. Across 7 studies (801 patients), humoral response after 3 doses was observed in 66.1% (95% confidence interval, 62.8%-69.4%; I2 = 0%) of transplant recipients. Triple immunosuppression, mycophenolate, antiproliferatives, and belatacept use were associated with reduced odds of humoral response in studies reporting multivariate analyses. Transplant recipients receiving a third dose displayed higher levels of neutralizing antibodies to SARS-CoV-2 variants (Alpha, Beta, and Delta) compared with placebo.

CONCLUSIONS:

A third dose SARS-CoV-2 mRNA vaccine should be strongly considered in transplant recipients. Limitations included lack of controlled studies and clinically relevant thresholds to determine response to vaccination.

BACKGROUND:

We aimed to analyze the humoral and cellular response to standard and booster (additional doses) COVID-19 vaccination in solid organ transplantation (SOT) and the risk factors involved for an impaired response.

METHODS:

We did a systematic review and meta-analysis of studies published up until January 11, 2022, that reported immunogenicity of COVID-19 vaccine among SOT. The study is registered with PROSPERO, number CRD42022300547.

RESULTS:

Of the 1527 studies, 112 studies, which involved 15391 SOT and 2844 healthy controls, were included. SOT showed a low humoral response (effect size [ES]: 0.44 [0.40-0.48]) in overall and in control studies (log-Odds-ratio [OR]: -4.46 [-8.10 to -2.35]). The humoral response was highest in liver (ES: 0.67 [0.61-0.74]) followed by heart (ES: 0.45 [0.32-0.59]), kidney (ES: 0.40 [0.36-0.45]), kidney-pancreas (ES: 0.33 [0.13-0.53]), and lung (0.27 [0.17-0.37]). The meta-analysis for standard and booster dose (ES: 0.43 [0.39-0.47] vs. 0.51 [0.43-0.54]) showed a marginal increase of 18% efficacy. SOT with prior infection had higher response (ES: 0.94 [0.92-0.96] vs. ES: 0.40 [0.39-0.41]; p-value < .01). The seroresponse with mRNA-12723 mRNA was highest 0.52 (0.40-0.64). Mycophenolic acid (OR: 1.42 [1.21-1.63]) and Belatacept (OR: 1.89 [1.3-2.49]) had highest risk for nonresponse. SOT had a parallelly decreased cellular response (ES: 0.42 [0.32-0.52]) in overall and control studies (OR: -3.12 [-0.4.12 to -2.13]).

INTERPRETATION:

Overall, SOT develops a suboptimal response compared to the general population. Immunosuppression including mycophenolic acid, belatacept, and tacrolimus is associated with decreased response. Booster doses increase the immune response, but further upgradation in vaccination strategy for SOT is required.

BACKGROUND:

As mortality from coronavirus disease 2019 (COVID-19) is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age-/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.

METHODS:

We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including death, hospitalisation, intensive care unit (ICU) admission and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11 June 2021 in Ovid Medline and Embase. Results are presented as odds ratios with 95% confidence intervals and absolute risk differences in deaths per 1000 COVID-19 patients.

FINDINGS:

We included 88 cohort studies with age-/gender-adjusted data from 6 653 207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke and liver disease.

INTERPRETATION:

The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of nonpharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.