ABSTRACT
Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a "normalized" configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases. One-sentence summarySOT recipients showed distinct immune states at baseline associated with different profiles of vaccine-associated immune response.
Subject(s)
COVID-19ABSTRACT
Abstract text Background Front-line healthcare workers (HCWs) could be at-risk for Monkeypox infections. Vaccine hesitancy also affects HCWs and has an impact on their own attitudes toward vaccination. In the context of the exhaustion due to COVID-19 pandemic, we aimed to evaluate intentions to get vaccinated against Monkeypox in HCWs in France and Belgium. Methods We performed a cross-sectional study (snowball sampling) using a self-administered online questionnaire to evaluate intentions to get vaccinated against Monkeypox in HCWs if a recommendation for HCWs vaccination was made. We compared demographics characteristics, vaccine readiness, eagerness for COVID-19 vaccine, and confidence in HCW with Chi-square tests, student-t and performed a binary regression. Results Amon the 397 respondents, if a specific recommendation was made for HCWs vaccination against Monkeypox was made, 55.4 % will probably get the vaccine, while 79 % would accept the vaccine if recommended to the general population. COVID-19 vaccine eagerness and having concerns about Monkeypox epidemics were associated with favorable attitude toward Monkeypox vaccination in HCWs with respective adjusted odds ratio and 95 % Confidence Interval 2.5 (1.03-6.1), 2.6 (1.3-5.3). Forty-four HCWs (11 %) self-identified as at-risk for Monkeypox infections. Conclusion Acceptance of Monkeypox vaccination in HCWs is probably moderate, HCWs are probably complacent and did not perceive the risk of Monkeypox infections in the context of professional exposure.
Subject(s)
COVID-19 , MonkeypoxABSTRACT
Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.
Subject(s)
COVID-19ABSTRACT
Purpose: SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. Methods: : A multidisciplinary international panel of 33 specialists judged statements through a 2-rounds modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. Results: : Of the 13 statements, 7 reached consensus or strong consensus, 2 reached noConsensus and 2 reached near-consensus. According to the statements with strong consensus Otorhinolaryngologists – Head & Neck Surgeons who are pregnant, breastfeeding or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. Conclusion: Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information.
Subject(s)
COVID-19 , Otorhinolaryngologic Diseases , Joint DiseasesABSTRACT
Background: Zoonotic coronaviruses have repeatedly taken the spotlight leading to severe global epidemics over the last two decades. In addition, seasonal coronaviruses (sCoVs) broadly circulate in humans. Their epidemiology could have broad impacts on the spread of emerging coronaviruses, but has been neglected so far.Methods: Clinical samples and data were collected from hospitalized patients with severe acute respiratory infection (SARI) and primary care patients with influenza-like illness (ILI), recruited through the national influenza surveillance networks in Belgium. Multiplex RT-qPCRs for respiratory viruses, including sCoVs OC43, NL63 and 229E, and SARS-CoV-2 were performed. Incidence rates of sCoV infection between 2015-2020 were estimated by season and age group. The impact of co-infections and comorbidities on the outcome of hospitalized patients was assessed.Findings: Hospitalized children under five carry the highest burden of disease for OC43 (IR =9·0, 95%CI 7·2-11·2 per 100,000 person-months) and NL63 (IR=5·2, 95%CI 3·9-6·9 per 100,000 person-months), while adults over 65 carry the highest burden of disease for 229E (IR=1·7, 95%CI 1·3-2·2 per 100,000 person-months). In hospitalized children under five, complications were associated with co-infections (p=0·02). Overall, comorbidities were strongly associated with a severe outcome following sCoV infection (p=0·006). In early March 2020, the SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case without travel history to China. The ILI surveillance system captured two peaks in the number of primary care visits at weeks five (influenza) and 12 (SARS-CoV-2).Interpretation: We show that sCoVs can cause severe complications and death, especially in combination with pre-existing comorbidities and/or co-infections. Furthermore, we encourage the leverage of national influenza surveillance systems for early detection and monitoring of emerging coronaviruses such as SARS-CoV-2.Funding: Federal Public Service ‘Health, Food Chain Safety, and Environment’, National Insurance Health Care (INAMI/RIZIV), Regional Health Authorities (Flanders: AZG, Brussels: COCOM, Wallonia: AVIQ).Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study surveillance protocol was approved by a central Ethical Committee (reference AK/12-02- 11/4111; in 2011: Centre Hospitalier Universitaire St-Pierre, Brussels, Belgium; since 2014: Universitair Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium) and the local ethical committees of each participating hospital. Informed consent was obtained from all participants or parents/guardians.
Subject(s)
COVID-19 , Influenza, Human , Respiratory Tract InfectionsABSTRACT
Early evidence during the COVID-19 pandemic indicated high levels of IL-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 and several inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α and INF-γ) and of IL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 and may explain why TCZ has failed to improve survival in critically ill COVID-19 patients when given alone.
Subject(s)
COVID-19ABSTRACT
Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion: This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.