Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

Emergence of Delta and Omicron variants carrying resistance-associated mutations in immunocompromised patients undergoing sotrovimab treatment with long-term viral excretion.

OBJECTIVES: To monitor the early emergence of genetic mutations related to reduced susceptibility to monoclonal anti-body (mAb)-based treatment in immunocompromised patients with long-term viral excretion using whole-genome sequencing at a tertiary university hospital in Barcelona, Spain. METHODS: Serial severe acute respiratory syndrome coronavirus 2-positive samples (mid-December 2021-mid-March 2022) from eight immunosuppressed, fully vaccinated patients (for solid-organ transplantation or haematologic malignancies) with long-term viral excretion despite undergoing mAb therapy (sotrovimab) for coronavirus disease 2019 were selected. Whole-genome sequencing was performed following the ARTIC, version 4.1, protocol on the MiSeq platform. Mutations in the coding sequence of the spike protein with a frequency of ≥5% were studied. RESULTS: A total of 37 samples from the studied cases were analysed. All the cases, except one, were confirmed to have the Omicron variant BA.1; one had Delta (AY.100). Thirty-four different mutations were detected within the receptor-binding domain of the spike protein in 62.5% of patients, eight of which were not lineage related and located in the sotrovimab target epitope (P337L, E340D, E340R, E340K, E340V, E340Q, R346T and K356T). Except for P337L, all changes showed a significant increase in frequency or fixation after the administration of sotrovimab. Some of them have been associated with either reduced susceptibility to mAb therapy, such as those at position 340, or the acquisition of a new glycosylation site (346 and 356 positions). CONCLUSIONS: This study highlights the importance of monitoring for early in vivo selection of mutations associated with reduced susceptibility to mAb therapy, especially in immunocompromised patients receiving anti-viral drugs, whose immune response is not able to control viral replication, resulting in long-term viral shedding, and those receiving selective evolution pressure. Virologic surveillance of genetically resistant viruses to available anti-viral therapies is considered a priority for both patients and the community.

Preliminary Clinical Experience of Molnupiravir to Prevent Progression of COVID-19 in Kidney Transplant Recipients.

BACKGROUND: Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs). METHODS: ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included. RESULTS: Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity. CONCLUSIONS: Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.

Positive Polymerase Chain Reaction for SARS-CoV-2 in a Candidate Does Not Always Preclude Liver Transplantation: Case Report and Literature Review.

We report a case of a liver transplant performed in a patient with a history of SARS-CoV-2 infection who presented with a positive polymerase chain reaction test for SARS-CoV-2 on the day of transplant. The transplant procedure was performed without complications, and the patient did not develop symptoms after the initiation of immunosuppression. We also reviewed the literature for similar cases. The emergence of SARS-CoV-2 has forced the medical community to continuously adapt protocols to the current situation. Prudence is needed in immuno- compromised patients, and clinical experience is being built day by day. Thus, a positive polymerase chain reaction test for SARS-CoV-2 in a recipient should not always prevent a liver transplant.

COVID-19 Follow-App. Mobile App-Based Monitoring of COVID-19 Patients after Hospital Discharge: A Single-Center, Open-Label, Randomized Clinical Trial.

INTRODUCTION: In the midst of a pandemic, apps can be used to provide close follow-up, ensure that patients are monitored at home, avoid excessive pressure on medical facilities, prevent the movement of people (both patients and health professionals), and reduce the risk of infection. OBJECTIVE: To adapt and validate the use of a smartphone application for outpatient follow-up of COVID-19 patients after hospital discharge. METHODS: We conducted an open-label clinical trial at Hospital Universitari Vall d'Hebron in Barcelona, Spain. Patients were randomly assigned in a 1:1 ratio to be followed by the Farmalarm app or by their primary care center. The primary endpoint was the reduction in the need for in-person return visits. RESULTS: From 31 March to 4 May 2020, 150 patients were enrolled in the study at hospital discharge: 74 patients were randomized to the experimental group, and 76 to the control group. All patients in the control group and all except for six in the experimental group completed the study. During hospitalization, before study inclusion, all but 4 (97.3%) had viral pneumonia, 91 (60.7%) required supplemental oxygen, and 16 (10.7%) required intensive care unit (ICU) admission. COVID-19-related return visits to the emergency department were significantly higher in the control group (7.9% vs. 0%; p = 0.028) in the per-protocol analysis. Telephone consultations with the emergency department were performed by 12 (15.8%) patients in the control group and 0 (0%) in the experimental group (p < 0.001). Satisfaction with outpatient monitoring was rated higher by the experimental group (5 vs. 4 points; p < 0.001). CONCLUSIONS: Following COVID-19 hospital discharge, home follow-up via a mobile app was effective in reducing in-person return visits without undermining patient satisfaction or perception of health, compared with standard follow-up.

Low seroprevalence of SARS-CoV-2 antibodies in a liver transplant cohort.

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d'Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.