Outcomes of SARS-CoV-2 infection among lung transplant recipients: A single center retrospective study.

BACKGROUND: Lung transplant recipients (LTRs) are at increased risk for coronavirus disease 2019 (COVID-19)-associated complications. METHODS: We aimed to describe the outcomes of polymerase chain reaction-documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LTRs followed at our institution from March 2020 to July 2022. The primary outcome investigated was hospitalization or death from COVID-19-related symptoms within 28 days from diagnosis. RESULTS: Overall, 60 cases were included, of which 18 (30%) reached the primary outcome. Only one patient (2%) died. Anti-spike monoclonal antibodies (mAbs) were administered as early treatment in 36 patients (casirivimab/imdevimab = 2, sotrovimab = 31, and tixagevimab/cilgavimab = 3). Multivariate analysis revealed that age >60 years (p = .003; odds ratio [OR] 9.41; confidence interval [CI] 2.52-41.05) was associated with a higher risk for the primary outcome, while administration of mAbs as early treatment (p = .030; OR 0.23; CI 0.06-0.87) was associated with a lower risk. No effect of vaccination and SARS-CoV-2 variant was observed. Forced expiratory volume in 1 s and forced vital capacity values did not decrease among 37 patients who had spirometry performed 1 month after COVID-19. CONCLUSIONS: We observed a relatively low morbidity and mortality of COVID-19 in LTR. mAb administration was associated with a better outcome.

Outcome of COVID-19 in Kidney Transplant Recipients Through the SARS-CoV-2 Variants Eras: Role of Anti-SARS-CoV-2 Monoclonal Antibodies.

Kidney transplant recipients (KTR) are at increased risk for COVID-19-associated complications. We aimed to describe the evolving epidemiology and outcome of PCR-documented SARS-CoV-2 infection in KTR followed at our institution from March 2020 to May 2022. The primary endpoint was hospitalization for COVID-19-related symptoms or death within 28 days from diagnosis. Overall, 243 cases were included of which 68 (28%) developed the primary outcome. A significant decrease in the incidence of the primary outcome was observed (p < 0.001, r -0.342) during the study period. Anti-Spike monoclonal antibodies (mAbs) were administered as early treatment (within 5-7 days of onset of symptoms) in 101 patients (14 with casirivimab/imdevimab and 87 with sotrovimab). Among 145 patients who had received at least one vaccination dose before infection, 109 patients were considered as adequately vaccinated. Multivariate analysis revealed that the Charlson Comorbidity Index (P 0.001; OR 1.28, CI 1.11-1.48) was associated with the primary outcome, while early administration of mAbs (P 0.032; OR 0.39, CI 0.16-0.92) was associated with a better outcome, but not infection during the period of the omicron variant predominance or adequate vaccination.

[COVID-19, how to treat the disease during Fall 2022?] / Covid-19 : quelle prise en charge pour l'automne 2022 ?

Since the arrival of COVID-19, we have witnessed a series of new variants and new therapies, and it is therefore becoming difficult to stay up to date on the best management of an outpatient infected with SARS-CoV-2. In a patient at risk of an unfavorable evolution in the first 5 days of illness, the antiviral Paxlovid is recommended. Evusheld, administered in the hospitals, is recommended in patients with a documented negative serology, for treatment in early disease or as a pre-exposure prophylaxis. The activity of monoclonal antibodies seems to be reduced with the new variants. Dexamethasone is reserved for the hospital management of an oxygen-dependent patient. There is no place for antibiotic therapy apart from additional bacterial infection.

Depuis l'arrivée du Covid-19, nous avons assisté à l'apparition simultanée de nouveaux variants et de nouvelles thérapies, de ce fait, il devient difficile de rester à jour sur la prise en charge d'un patient infecté par le SARS-CoV-2. En ambulatoire, chez un patient à risque d'évolution défavorable dans les 5 premiers jours de maladie, l'antiviral Paxlovid est proposé. L'Evusheld est administré dans les centres spécialisés et conseillé chez des patients avec sérologie négative après vaccination, en traitement précoce ou en prophylaxie préexposition. L'activité des anticorps monoclonaux semble néanmoins réduite avec les nouveaux variants. La dexaméthasone est réservée à la prise en charge hospitalière d'un patient oxygénodépendant et une antibiothérapie n'a pas sa place en dehors d'une surinfection bactérienne.

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents.

Administration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell-depleting agents that impair humoral immunity. However, little is known on the impact of anti-CD20 pre-exposition on the kinetics of SARS-CoV-2-specific antibodies. Here, we evaluated the relationship between anti-spike immunoglobulin G (IgG) kinetics and the clinical status or intra-host viral evolution after plasma therapy in 36 eligible hospitalized COVID-19 patients, pre-exposed or not to B-cell-depleting treatments. The majority of anti-CD20 pre-exposed patients (14/17) showed progressive declines of anti-spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B-cell-depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS-CoV-2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA-vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow-up in the management of COVID-19 patients with B-cell lymphopenia.

Anti-SARS-CoV-2 Titers Predict the Severity of COVID-19.

Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is associated with a wide spectrum of disease, ranging from asymptomatic infection to acute respiratory distress syndrome. Some biomarkers may predict disease severity. Among them, the anti-SARS-CoV-2 antibody response has been related to severe disease. The aim of this study was to assess the correlation between the anti-SARS-CoV-2 serological response and COVID-19 outcome. Demographic, clinical, and biological data from nasopharyngeal-PCR confirmed COVID-19 hospitalized patients were prospectively collected between April and August 2020 at our institution. All patients had serial weekly serology testing for a maximum of three blood samples or until discharge. Two different serological assays were used: a chemiluminescent assay and an in-house developed Luminex immunoassay. Kinetics of the serological response and correlation between the antibody titers and outcome were assessed. Among the 70 patients enrolled in the study, 22 required invasive ventilation, 29 required non-invasive ventilation or oxygen supplementation, and 19 did not require any oxygen supplementation. Median duration of symptoms upon admission for the three groups were 13, 8, and 9 days, respectively. Antibody titers gradually increased for up to 3 weeks since the onset of symptoms for patients requiring oxygen supplementation with significantly higher antibody titers for patients requiring invasive ventilation. Antibody titers on admission were also significantly higher in severely ill patients and serology performed well in predicting the necessity of invasive ventilation (AUC: 0.79, 95% CI: 0.67-0.9). Serology testing at admission may be a good indicator to identify severe COVID-19 patients who will require invasive mechanical ventilation.

Anti-SARS-CoV-2 Titers Predict the Severity of COVID-19

Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 is associated with a wide spectrum of disease, ranging from asymptomatic infection to acute respiratory distress syndrome. Some biomarkers may predict disease severity. Among them, the anti-SARS-CoV-2 antibody response has been related to severe disease. The aim of this study was to assess the correlation between the anti-SARS-CoV-2 serological response and COVID-19 outcome. Demographic, clinical, and biological data from nasopharyngeal-PCR confirmed COVID-19 hospitalized patients were prospectively collected between April and August 2020 at our institution. All patients had serial weekly serology testing for a maximum of three blood samples or until discharge. Two different serological assays were used: a chemiluminescent assay and an in-house developed Luminex immunoassay. Kinetics of the serological response and correlation between the antibody titers and outcome were assessed. Among the 70 patients enrolled in the study, 22 required invasive ventilation, 29 required non-invasive ventilation or oxygen supplementation, and 19 did not require any oxygen supplementation. Median duration of symptoms upon admission for the three groups were 13, 8, and 9 days, respectively. Antibody titers gradually increased for up to 3 weeks since the onset of symptoms for patients requiring oxygen supplementation with significantly higher antibody titers for patients requiring invasive ventilation. Antibody titers on admission were also significantly higher in severely ill patients and serology performed well in predicting the necessity of invasive ventilation (AUC: 0.79, 95% CI: 0.67–0.9). Serology testing at admission may be a good indicator to identify severe COVID-19 patients who will require invasive mechanical ventilation.

Solid organ transplantation from donors with recent or current SARS-CoV-2 infection: A systematic review.

BACKGROUND: Solid-organ transplantation (SOT) from SARS-CoV-2 positive donors could be a life-saving opportunity worth grasping. We perform a systematic review to evaluate the recipient outcomes of SOT from donors with recent or current SARS-CoV-2 infection. METHODS: Search strategy was performed in PubMed, Cochrane COVID-19 Study Register, and Web of Science databases from the 1st of January 2019 to the 31st of December 2021. SOT adult recipients from a donor with past or current SARS-CoV-2 infection were elegible for inclusion. Outcomes were viral transmission, COVID-19 symptoms, mortality, hospital stay, and complications. PROSPERO Register Number: CRD42022303242 FINDINGS: Sixty-nine recipients received 48 kidneys, 18 livers and 3 hearts from 57 donors. Six additional transplants from positive lungs were identified. IgG+ anti-SARS-CoV-2 titers were detected among 10/16 recipients; only 4% (3/69) recipients were vaccinated. Non-lung transplant recipients received organs from 10/57 (17.5%) donors with persistent COVID-19. In 18/57 donors, SARS-CoV-2 RNA was detected (median 32 Cycle threshold [Ct]) at procurement. Among non-lung transplant recipients, SARS-CoV-2 viral transmission was not documented. Four patients presented delayed graft dysfunction, two patients acute rejection, and two patients died of septic shock. The median (IQR) hospital stay was 18 (11-28) days in recipients from symptomatic donors. Viral transmission occurred from three lung donors to their recipients, who developed COVID-19 symptoms. One of the recipients subsequently died. CONCLUSION: Use of non-lung (kidney, liver and heart) organs from SARS-CoV-2 positive donors seem to be a safe practice, with a low risk of transmission irrespective of the presence of symptoms at the time of procurement. Low viral replication (Ct > 30) was safe among non-lung donors, even if persistently symptomatic at procurement.

Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019.

BACKGROUND: Remdesivir is efficacious for severe coronavirus disease 2019 (COVID-19) in adults, but data in pregnant women are limited. We describe outcomes in the first 86 pregnant women with severe COVID-19 who were treated with remdesivir. METHODS: The reported data span 21 March to 16 June 2020 for hospitalized pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection and room air oxygen saturation ≤94% whose clinicians requested remdesivir through the compassionate use program. The intended remdesivir treatment course was 10 days (200 mg on day 1, followed by 100 mg for days 2-10, given intravenously). RESULTS: Nineteen of 86 women delivered before their first dose and were reclassified as immediate "postpartum" (median postpartum day 1 [range, 0-3]). At baseline, 40% of pregnant women (median gestational age, 28 weeks) required invasive ventilation, in contrast to 95% of postpartum women (median gestational age at delivery 30 weeks). By day 28 of follow-up, the level of oxygen requirement decreased in 96% and 89% of pregnant and postpartum women, respectively. Among pregnant women, 93% of those on mechanical ventilation were extubated, 93% recovered, and 90% were discharged. Among postpartum women, 89% were extubated, 89% recovered, and 84% were discharged. Remdesivir was well tolerated, with a low incidence of serious adverse events (AEs) (16%). Most AEs were related to pregnancy and underlying disease; most laboratory abnormalities were grade 1 or 2. There was 1 maternal death attributed to underlying disease and no neonatal deaths. CONCLUSIONS: Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.

Prevention of viral infections in solid organ transplant recipients in the era of COVID-19: a narrative review.

INTRODUCTION: In solid organ transplant (SOT) recipients, viral infections are associated with direct morbidity and mortality and may influence long-term allograft outcomes. Prevention of viral infections by vaccination, antiviral prophylaxis, and behavioral measures is therefore of paramount importance. AREAS COVERED: We searched Pubmed to select publications to review current preventive strategies against the most important viral infections in SOT recipients, including SARS-CoV-2, influenza, CMV, and other herpesvirus, viral hepatitis, measles, mumps, rubella, and BK virus. EXPERT OPINION: The clinical significance of the reduced humoral response following mRNA SARS-CoV-2 vaccines in SOT recipients still needs to be better clarified, in particular with regard to the vaccines' efficacy in preventing severe disease. Although a third dose improves immunogenicity and is already integrated into routine practice in several countries, further research is still needed to explore additional interventions. In the upcoming years, further data are expected to better delineate the role of virus-specific cell mediated immune monitoring for the prevention of CMV and potentially other viral diseases, and the role of the letermovir in the prevention of CMV in SOT recipients. Future studies including clinical endpoints will hopefully facilitate the integration of successful new influenza vaccination strategies into clinical practice.

A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®.

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.

SARS-CoV-2 vaccination in solid-organ transplant recipients: What the clinician needs to know.

In response to the COVID-19 pandemic, SARS-CoV-2 vaccines have been developed at an unparalleled speed, with 14 SARS-CoV-2 vaccines currently authorized. Solid-organ transplant (SOT) recipients are at risk for developing a higher rate of COVID-19-related complications and therefore they are at priority for immunization against SARS-CoV-2. Preliminary data suggest that although SARS-CoV-2 vaccines are safe in SOT recipients (with similar rate of adverse events than in the general population), the antibody responses are decreased in this population. Risk factors for poor vaccine immunogenicity include older age, shorter time from transplantation, use of mycophenolate and belatacept, and worse allograft function. SOT recipients should continue to be advised to maintain hand hygiene, use of facemasks, and social distancing after SARS-CoV-2 vaccine. Vaccination of household contacts should be also prioritized. Although highly encouraged for research purposes, systematic assessment in clinical practice of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, since correlation between immunological findings and clinical protection from severe COVID-19, and cutoffs for protection are currently unknown in SOT recipients. Alternative immunization schemes, including a booster dose, higher doses, and modulation of immunosuppression during vaccination, need to be assessed in the context of well-designed clinical trials.

Viral infections in lung transplantation.

Viral infections account for up to 30% of all infectious complications in lung transplant recipients, remaining a significant cause of morbidity and even mortality. Impact of viral infections is not only due to the direct effects of viral replication, but also to immunologically-mediated lung injury that may lead to acute rejection and chronic lung allograft dysfunction. This has particularly been seen in infections caused by herpesviruses and respiratory viruses. The implementation of universal preventive measures against cytomegalovirus (CMV) and influenza (by means of antiviral prophylaxis and vaccination, respectively) and administration of early antiviral treatment have reduced the burden of these diseases and potentially their role in affecting allograft outcomes. New antivirals against CMV for prophylaxis and for treatment of antiviral-resistant CMV infection are currently being evaluated in transplant recipients, and may continue to improve the management of CMV in lung transplant recipients. However, new therapeutic and preventive strategies are highly needed for other viruses such as respiratory syncytial virus (RSV) or parainfluenza virus (PIV), including new antivirals and vaccines. This is particularly important in the advent of the COVID-19 pandemic, for which several unanswered questions remain, in particular on the best antiviral and immunomodulatory regimen for decreasing mortality specifically in lung transplant recipients. In conclusion, the appropriate management of viral complications after transplantation remain an essential step to continue improving survival and quality of life of lung transplant recipients.

SARS-CoV-2 seroprevalence in healthcare workers of a Swiss tertiary care centre at the end of the first wave: a cross-sectional study.

OBJECTIVE: To assess the SARS-CoV-2 transmission in healthcare workers (HCWs) using seroprevalence as a surrogate marker of infection in our tertiary care centre according to exposure. DESIGN: Seroprevalence cross-sectional study. SETTING: Single centre at the end of the first COVID-19 wave in Lausanne, Switzerland. PARTICIPANTS: 1874 of 4074 responders randomly selected (46% response rate), stratified by work category among the 13 474 (13.9%) HCWs. MAIN OUTCOME MEASURES: Evaluation of SARS-CoV-2 serostatus paired with a questionnaire of SARS-CoV-2 acquisition risk factors internal and external to the workplace. RESULTS: The overall SARS-CoV-2 seroprevalence rate among HCWs was 10.0% (95% CI 8.7% to 11.5%). HCWs with daily patient contact did not experience increased rates of seropositivity relative to those without (10.3% vs 9.6%, respectively, p=0.64). HCWs with direct contact with patients with COVID-19 or working in COVID-19 units did not experience increased seropositivity rates relative to their counterparts (10.4% vs 9.8%, p=0.69 and 10.6% vs 9.9%, p=0.69, respectively). However, specific locations of contact with patients irrespective of COVID-19 status-in patient rooms or reception areas-did correlate with increased rates of seropositivity (11.9% vs 7.5%, p=0.019 and 14.3% vs 9.2%, p=0.025, respectively). In contrast, HCWs with a suspected or proven SARS-CoV-2-infected household contact had significantly higher seropositivity rates than those without such contacts (19.0% vs 8.7%, p<0.001 and 42.1% vs 9.4%, p<0.001, respectively). Finally, consistent use of a mask on public transportation correlated with decreased seroprevalence (5.3% for mask users vs 11.2% for intermittent or no mask use, p=0.030). CONCLUSIONS: The overall seroprevalence was 10% without significant differences in seroprevalence between HCWs exposed to patients with COVID-19 and HCWs not exposed. This suggests that, once fully in place, protective measures limited SARS-CoV-2 occupational acquisition within the hospital environment. SARS-CoV-2 seroconversion among HCWs was associated primarily with community risk factors, particularly household transmission.

Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.

Burden, epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide, multi-season prospective cohort study.

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.