SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study.

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

Acute Liver Injury Among Pediatric Liver Transplantation Recipients With Coronavirus Disease 2019: An International Collaborative Study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic. The occurrence of acute liver injury (ALI) has been reported in liver transplant (LT) recipients; however, the findings on children remain controversial. This is the first extensive, worldwide report on the impact of COVID-19 on pediatric LT recipients. Our online survey reported 110 pediatric LT recipients with severe acute respiratory syndrome coronavirus 2 infection. Of these, 37 were symptomatic and 20 out of them (54%) had complicated COVID-19, which included ALI and acute liver graft rejection. No mortality was reported. Pediatric LT recipients who had undergone transplantation less than 6 months before contracting COVID-19 had a greater number of hospital admissions and a higher ALI frequency (P = 0.013 and P = 0.033, respectively) than those who had undergone transplantation more than 6 months prior. Our study found that COVID-19 cases among pediatric LT recipients demonstrated a high complication rate. We propose that these patients must be followed up strictly.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

Recomendaciones en enfermedad hepática crónica y trasplante hepático durante COVID-19 en pediatría

Abstract: The SARS-CoV-2 virus outbreak, which began in late 2019 in China, has spread very quickly to Chile and worldwide. In Chile, we currently have around 18,435 people infected with 1.4% of adult mor tality. Pediatric patients with chronic liver diseases (CLD) are susceptible as well to COVID-19 and could have a worse prognosis. The objective is to give recommendations about medical treatment to pediatric patients with chronic liver disease (CLD), autoimmune hepatitis (AIH), Non- Alcoholic fatty liver disease (NAFLD), and liver transplant in the context of COVID-19. The most important issue in the management of these patients is to avoid exposure to the virus, hand washing, the use of face masks in public and closed places, as well as social distancing, and avoiding contact with positive COVID-19 patients. In Children with CLD, AIH, NAFLD, and liver transplant, outpatient follow-up should be avoided when possible and replaced with videoconference consultation. No evidence re commends modifications to their baseline treatment. Positive COVID-19 patients should be isolated, the use of paracetamol as an antipyretic and analgesic and modifications to immunosuppressant drugs should be seen by the specialist in a case to case basis according to its severity. In addition, we reviewed current specific therapies for COVID-19 and their precautions in patients with liver disease. Protective measures, social distancing, and early diagnosis are very important in patients with liver disease to decrease the risk of SARS-CoV-2 infection.