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1.
American Journal of Transplantation ; 22(Supplement 3):767, 2022.
Article in English | EMBASE | ID: covidwho-2063510

ABSTRACT

Purpose: Emerging evidence suggests that 3 doses of SARS-CoV-2 mRNA vaccine enhance immunity in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines. Here we report the results of humoral response in KT recipients in comparison with healthy control group after homologous and heterologous regimens with inactivated virus (Coronavac) and mRNA vaccine BNT162b2. Method(s): A multicenter prospective study was conducted. KT recipients received heterologous vaccine schedule (2 doses of Coronavac and a booster of mRNA BNT162b2, n= 136) or homologous (3 doses of BNT162b2 n=19). Healthy control group received 2 doses or Coronavac (n=67) or BNT162b2 (n=15). Serum IgG antibodies against Receptor Binding Domain of SARS-CoV-2 Spike protein were determined 30 and 40 days after last dose. Result(s): Seroconversion was 52.2% and 57,9% with heterologous and homologous vaccination schedules in KT, p=0.789, figure 1. Among KT patients with seroconversion, antibody levels against RBD of SARS-CoV-2 were [1012 (183-3111) and 603 (41-1255) BAU/mL, with heterologous and homologous schedule, respectively. Levels were higher in KT compared to heathy control with 2 doses of inactivated virus 308 (209-335), p=0.03 and lower than heathy control with 2 doses of BNT162b2: 2638 (2608-3808) BAU/mL, p=0.001]. Conclusion(s): Seroconversion improves after a third dose with homologous or heterologous vaccine schedules. Among patients with seroconversion antibody levels were higher than in heathy control with two doses of inactivated virus. Measurement of antibody levels could help to improve vaccination policies.

2.
Topics in Antiviral Medicine ; 30(1 SUPPL):72-73, 2022.
Article in English | EMBASE | ID: covidwho-1880801

ABSTRACT

Background: Critical COVID-19 occurs ca. 7d from symptoms onset, and is associated to immune dysregulation as well as SARS-CoV-2 detection in plasma (i.e. viremia). We hereby sought to detail the association between SARS-CoV-2 viremia measured at the end of the first week of disease and immune phenotypes/function in COVID-19 patients. Methods: We consecutively enrolled patients hospitalized in the acute phase of ascertained SARS-CoV-2 pneumonia. In this disease stage, we studied SARS-CoV-2 viremia (RT-PCR) and cytokines (MACSPlex), HLA-DR+CD38+ activated, GRZB+PRF+ pro-cytolitic T-cells, intracellular cytokine production (IL-2, IFNγ, TNFα, IL-4, IL-17A) after SARS-CoV-2 challenge (S-N-M-peptide pool). Simultaneous Th1-cytokines production (polyfunctionality) and amount (iMFI) was assessed. Humoral response: anti-S1/S2 IgG, anti-RBD total-Ig, IgM, IgA, IgG1 and IgG3 (ELISA), pseudoviruses neutralization (ID50) and Fc-mediated functions (%ADCC). Results: Out of 54 patients, 27 had detectable viremia (V+). Albeit comparable age and co-morbidities, V+ patients more frequently required non-invasive/invasive ventilatory support (p=0.035), with a trend to higher death (p=0.099) vs patients with undetectable viremia (V-)(Fig.1A). V+ displayed higher circulating IFN-α (p=0.002) and IL-6 (0.003), lower activated HLA-DR+CD38+CD4 (p=0.01) and CD8 (p=0.02), with no differences in GRZB+PRF+ T-cells. V+ featured reduced SARS-CoV-2-specific cytokine-producing T-cells, reaching significance for IFNγ+CD4 (p=0.02), TNFα+CD8, IL-4+CD8 (p=0.04) (Fig.1B-C), with lower bi-and tri-functional SARS-CoV-2-specific CD4 Th1, reaching significance for IL-2+TNFα+CD4 (p=0.03) (Fig.1D). A trend towards lower cytokines iMFI in bi-and tri-functional SARS-CoV-2-specific CD4 Th1 was observed in V+, reaching significance for IL-2+TNFα+CD4, p=0.004. V+ displayed lower anti-S IgG, anti-RBD total-Ig, IgM, IgG1 and IgG3 (Fig.1E), with lower ID50 and %ADCC vs V-(Fig.1F-G). Conclusion: Hospitalized COVID-19 patients with detectable plasma SARS-CoV-2 RNA in the acute phase of disease present worse outcome, higher inflammatory cytokines, fewer activated and SARS-CoV-2-specific polyfunctional T-cells, suggesting a link between SARS-CoV-2 viremia at the end of the first stage of disease and immune dysregulation. Whether high ab initium viral burden and/or intrinsic host factors contribute to a delayed and/or exhausted immune response in severe COVID-19 remains to be elucidated, to further inform strategies of targeted therapeutic interventions.

3.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-337383

ABSTRACT

Sotrovimab (VIR-7831) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sotrovimab and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. Sotrovimab and VIR-7832 neutralize wild-type and variant pseudotyped viruses and authentic virus in vitro. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to previously authorized mAbs. The sotrovimab/VIR-7832 epitope continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with sotrovimab had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that sotrovimab and VIR-7832 are key agents in the fight against COVID-19.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330329

ABSTRACT

Introduction Shared characteristics between COVID-19 and pulmonary fibrosis, including symptoms, genetic architecture, and circulating biomarkers, suggests interstitial lung disease (ILD) development may be associated with SARS-CoV-2 infection. Methods The UKILD Post-COVID study planned interim analysis was designed to stratify risk groups and estimate the prevalence of Post-COVID Interstitial Lung Damage (ILDam) using the Post-HOSPitalisation COVID-19 (PHOSP-COVID) Study. Demographics, radiological patterns and missing data were assessed descriptively. Bayes binomial regression was used to estimate the risk ratio of persistent lung damage >10% involvement in linked, clinically indicated CT scans. Indexing thresholds of percent predicted DLco, chest X-ray findings and severity of admission were used to generate risk strata. Number of cases within strata were used to estimate the amount of suspected Post-COVID ILDam. Results A total 3702 people were included in the UKILD interim cohort, 2406 completed an early follow-up research visit within 240 days of discharge and 1296 had follow-up through routine clinical review. We linked the cohort to 87 clinically indicated CTs with visually scored radiological patterns (median 119 days;interquartile range 83 to 155, max 240), of which 74 people had ILDam. ILDam was associated with abnormal chest X-ray (RR 1.21 95%CrI 1.05;1.40), percent predicted DLco<80% (RR 1.25 95%CrI 1.00;1.56) and severe admission (RR 1.27 95%CrI 1.07;1.55). A risk index based on these features suggested 6.9% of the interim cohort had moderate to very-high risk of Post-COVID ILDam. Comparable radiological patterns were observed in repeat scans >90 days in a subset of participants. Conclusion These interim data highlight that ILDam was not uncommon in clinically indicated thoracic CT up to 8 months following SARS-CoV-2 hospitalisation. Whether the ILDam will progress to ILD is currently unknown, however health services should radiologically and physiologically monitor individuals who have Post-COVID ILDam risk factors.

5.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326626

ABSTRACT

VIR-7831 (sotrovimab) and VIR-7832 are dual action monoclonal antibodies (mAbs) targeting the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). VIR-7831 and VIR-7832 were derived from a parent antibody (S309) isolated from memory B cells of a 2003 severe acute respiratory syndrome coronavirus (SARS-CoV) survivor. Both mAbs contain an “LS” mutation in the Fc region to prolong serum half-life. In addition, VIR-7832 encodes an Fc GAALIE mutation that has been shown previously to evoke CD8+ T-cells in the context of an in vivo viral respiratory infection. VIR-7831 and VIR-7832 potently neutralize wild-type and variant authentic virus in vitro as well as variant pseudotyped viruses including the Omicron variant. In addition, they retain activity against monoclonal antibody resistance mutations conferring reduced susceptibility to currently authorized mAbs. The VIR-7831/VIR-7832 epitope continues to be highly conserved among circulating sequences consistent with the high barrier to resistance observed in vitro. Furthermore, both mAbs can recruit effector mechanisms in vitro that may contribute to clinical efficacy via elimination of infected host cells. In vitro studies with these mAbs demonstrated no enhancement of infection. In a Syrian Golden hamster proof-of concept wildtype SARS-CoV-2 infection model, animals treated with VIR-7831 had less weight loss, and significantly decreased total viral load and infectious virus levels in the lung compared to a control mAb. Taken together, these data indicate that VIR-7831 and VIR-7832 are key agents in the fight against COVID-19.

6.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326613

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.

7.
Radiotherapy and Oncology ; 161:S784-S786, 2021.
Article in English | EMBASE | ID: covidwho-1492799

ABSTRACT

Purpose or Objective To assess the intrafraction accuracy of a frameless stereotactic linac-based radiosurgery (SRS) for brain metastases (BM) using a homemade mouth-bite thermoplastic mask in combination with cone-beam computed tomography (CBCT) and six-degrees of freedom (6-DOF) couchtop. Materials and Methods Covid-19 restrictions resulted in significant delays in the supply of the dedicated devices for BM SRS. A frameless approach using a homemade mouth-bite thermoplastic mask was implemented to offer BM SRS in a period of limited mobility (figure 1). All patients were immobilized and treated at the same institution with 6 MV FFF VMAT radiosurgery, with a 2 mm isotropic expansion from the GTV to the PTV. Before treatment delivery, patients underwent a low-dose CBCT to check position accuracy. Through image co-registration, translational (x, y, z) and rotational errors (roll, pitch, and yaw) were determined. The 6-DOF couchtop was used to automatically relocate the patient with sub-millimetric precision. Immediately after irradiation, patients underwent a second CBCT to verify any translational or rotational errors occurring during therapy (intrafraction motion). $Φg Results From February 2020 to January 2021 sixteen patients (29 lesions) received BM SRS (14-21 Gy). The whole procedure, from the first CBCT scan to the end of irradiation and subsequent CBCT, required a median time of 9 minutes [6-13]. Mean translational error was 0.0 ± 0.3 mm [-0.7;0.9] in lateral direction, and -0.1 ± 0.5 mm [-1.4;1.0] in longitudinal direction. A 2.2 mm maximum shift was recorded on the vertical axis, nevertheless the mean translation error was 0.1 ± 0.6 mm. Roll, pitch and yaw registered a mean value of -0.1 ± 0.3° [-0.8;0.2], 0.0 ± 0.2° [-0.8;0.2], and -0.1 ± 0.3° [-0.8;0.4], respectively. The results are summarized in figure 2. Conclusion This study demonstrated that homemade mouth-bite thermoplastic masks combined with CBCT, 6-DOF couchtop, and fast FFF treatment delivery allow minimal intra-fraction uncertainties in BM SRS, confirming the accuracy of PTV margin definition. The results are comparable to the declared specifics of SRS dedicated commercial frameless mask, while improving patient's comfort compared to the invasive fixed frame. However, the moulding procedure requires improved RTT skills and expertise. Our findings show that SRS can be safely delivered in radiotherapy units without dedicated expensive installations, such as CyberKnife and Gamma Knife, thus reducing patient mobility according to Covid-19 restrictions.

8.
Psychiatria Danubina ; 33(Suppl 9):158-163, 2021.
Article in English | MEDLINE | ID: covidwho-1439130

ABSTRACT

BACKGROUND: Suicidality is a widespread phenomenon with a dramatic burden worldwide. The Coronavirus disease 2019 (Covid-19) pandemic determined a relevant impact on mental health, due to the infection itself and its socio-economic consequences. The present study is aimed at analyzing the prevalence of suicidality during the Covid-19 pandemic among subjects requiring a psychiatric consultation in an emergency setting. SUBJECTS AND METHODS: Socio-demographic and clinical information was collected at the emergency department of the General Hospital of Perugia from June 1st, 2020 to January 31st, 2021. Data was entered into an electronic datasheet and retrospectively analysed. Pearson's bivariate correlation was performed in order to assess significant associations between suicide-related variables and specific socio-demographic and clinical features (p<0.05). RESULTS: Among 447 subjects included in the analysis, 109 (24.4%) showed suicidality-related phenomena, particularly suicide attempts (SA) (n=44, 9.8%), suicidal ideation (SI) (n=41, 9.2%), non suicidal self-injury (NSSI) (n=31, 6.9%), that in some cases co-occurred. A statistically significant association was detected between NSSI and living with marital family (p=0.024) and between suicidality-related phenomena and adjustment disorders (p=0.018). None of the examined subjects reported a previous positivity for Covid-19 and neither did their relatives. CONCLUSIONS: The present study confirms the impact of the Covid-19 pandemic on suicide-related phenomena. Consultation psychiatry fulfills a key role in the early detection and clinical management of these conditions, that require targeted intervention strategies.

9.
Healthcare ; 9(4):12, 2021.
Article in English | MEDLINE | ID: covidwho-1208876

ABSTRACT

The COVID-19 pandemic literally stopped most human movement and activities as it initially spread, which included dental practices and dental education. This defined the need for significative changes in teaching and learning with the use of "e-learning" methods, also for traineeships. This study was designed to determine the undergraduate student perception of these new methods as part of their education. This involved 353 students attending the Dental School of the G. D'Annunzio University of Chieti-Pescara, from the first to the sixth years. A questionnaire in Italian and was set-up using "Google Forms" and sent by email to the students. The questionnaire was divided into three parts: the first part included questions for general information, including age, sex and year of course;the second part had multiple choice questions related to their evaluation of the e-learning teaching, using a scale of opinion in the replies to each question (e.g., "scarce", "fair", "satisfying", "very good" and "excellent");and the third part included two open questions to indicate the strengths and limitations of these new teaching and learning approaches. The categorical variables in the first and second parts of the questionnaire were evaluated using Chi squared tests, setting significance at p < 0.05, while the comments were evaluated qualitatively. The student feedback showed significant appreciation (p < 0.05) of the new methods and the efforts that the lecturers put in to provide lectures of as high a quality as possible. However, a lack of practical training was significantly perceived as an important problem in the structure of their new curriculum (p < 0.05). COVID-19 has been an epic tragedy that has hit the human population not only in terms of health and healthcare, but also quality of life. This includes the quality of dental education within universities. However, the pandemic can be seen to also represent motivation to invest in the necessary technological innovation to deliver the best possible education to our future dentists.

10.
Finance Research Letters ; 38:12, 2021.
Article in English | Web of Science | ID: covidwho-1102893

ABSTRACT

Using the multifractional Brownian motion as a model of the price dynamics, we analyze the impact of the COVID-19 pandemic on the efficiency of fifteen financial markets from Europe, US and Asia. We find that Asian markets (Hang Seng, Nikkei 225, Kospi) have recovered full efficiency, while European and US markets after an initial rebound have not yet returned to the pre-crisis level of efficiency. The inefficiency that currently characterizes US and European markets originates moderately high levels of volatility.

11.
Thorax ; 76(Suppl 1):A46-A47, 2021.
Article in English | ProQuest Central | ID: covidwho-1050407

ABSTRACT

S75 Figure 1Difference between the fibrotic and inflammatory groups in mean 129Xe ADC (a) and LmD (b) at baseline study visit[Figure omitted. See PDF]Conclusions129Xe DW-MRI could have a role in differentiating changes in the airway microstructure between fibrotic and inflammatory ILD. 129Xe RBC:TP has sensitivity to longitudinal change with a decline in gas exchange observed in the fibrotic group but not in the inflammatory group.

12.
Annals of Oncology ; 31:S1000, 2020.
Article in English | EMBASE | ID: covidwho-804901

ABSTRACT

Background: During the SARS-COV-2 pandemic, cancer patients (pts) who are infected may develop severe disease if their systemic treatment is not temporarily stopped. Nasopharyngeal swab was not extensively available to screen cancer pts for SARS-COV-2 infection in northern Italy, the most area in the country most affected by the pandemic. From the beginning of the outbreak onwards, all pts admitted to the Medical Oncology Unit at Spedali Civili Hospital, Brescia, underwent a triage investigating the presence of symptoms and signs suggestive of SARS-COV-2 infection. Triage results were used to decide which pts should continue antineoplastic treatments. Methods: All consecutive cancer pts being admitted for systemic treatment from February 24th to April 21st 2020 were considered. Triage, performed by a trained nurse, consisted of questions regarding the presence of fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhoea, nausea and vomiting, measurement of body temperature and pulse oximetry. All enrolled pts were followed-up for overt SARS-COV-2 development until May 18th. Results: Overall, 1180 pts were included, 54% female and median age 65 years. Most represented primary malignancies were breast (32%), gastroenteric (18%) and lung (16.5%). Thirty-one (2.5%) presented with clinically evident SARS-COV-2 disease and infection was proven by positive nasopharyngeal swab and/or radiological imaging. The triage identified 69 (6%) “grey zone” pts, with suspicious symptoms (i.e. fever 41%, cough 30%, dyspnea 19%). The nasopharyngeal swab was negative in 48% of them and was not performed in the remaining 52% of pts, as well as in all pts who were triage negative. Both SARS-COV-2 positive and “grey zone” pts did not receive treatment and were addressed to hospitalisation or home quarantine. All the 1080 pts (91.5%) who resulted negative at triage continued their antineoplastic therapy as scheduled, none of them presenting symptoms of SARS-COV-2 infection during the follow-up. Conclusions: Accurate triage allowed safe continuation of anticancer treatment in 91.5% of pts during the SARS-COV-2 outbreak. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

13.
BJOG ; 127(9): 1116-1121, 2020 08.
Article in English | MEDLINE | ID: covidwho-125441

ABSTRACT

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Delivery, Obstetric/adverse effects , Infectious Disease Transmission, Vertical , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pregnancy Complications, Infectious/diagnosis , Adult , COVID-19 , Female , Humans , Infant, Newborn , Italy , Male , Pandemics , Pregnancy , Pregnancy Complications, Infectious/virology , Retrospective Studies , SARS-CoV-2 , Vagina/virology
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