ABSTRACT
Background: Established SARS-CoV-2 NAb tests are labor-intensive. We prospectively measured NAbs vs Wuhan-1 and Omicron BA.2 using the novel GenScript cPass assay and examined correlations with responses measured by gold-standard plaque reduction neutralisation test (PRNT) (Cotugno, Ruggiero et al. Cell Rep 2021) and with anti-Spike IgG quantified by Roche Elecsys. Given the paucity of data, we selected BNT162b2 vaccine recipients with a history of advanced HIV infection (prior AIDS-defining conditions and/or nadir CD4 <200 cells). Method(s): In Mar 2021-Apr 2022, 55 PWH received 2 vaccine doses median 3 weeks apart [IQR 3-3] and a 3rd dose 27 weeks later [23-31]. Plasma samples (n=147) were stored immediately before dose-1 (T0), median 4 weeks [3-5] after dose-2 (T1) and median 13 weeks [9-19] after dose-3 (T2) for batch testing. Result(s): Participants' characteristics: 74% male, 85% white, all on ART, 82% HIV-RNA <50 cps/ml;median age 55 years, ART duration 7 years, nadir CD4 83 cells [36-211], current CD4 440 cells [270-710], CD4:CD8 ratio 0.6 [0.4-1.0];73% had a history of advanced HIV infection;15% received a COVID-19 diagnosis during the study. At T0, T1 and T2, proportions with quantifiable anti-S IgG (>0.8 U/ml) were 11/49 (22%), 50/54 (93%) and 43/43 (100%), respectively;their median anti-S IgG titres were 30 [15-124], 15949 [596-3389] and 8527 [3146-17190] U/ml. Proportions showing Wuhan-1 neutralisation by cPass were 6/50 (12%), 45/53 (85%) and 40/43 (93%), with median neutralisations of 67% [47-70], 97% [91-98] and 98% [98-98] and corresponding NAb titres of 1332 [792-1436], 5354 [3529-6187] and 6242 [5765-6766] U/ml. At T2, 25/28 (89%) showed BA.2 neutralisation by cPass (median 83% [68-93];NAb titre 7836 [3172-12173] U/ml) (Fig 1A). Two participants lacking NAbs at T2 had a history of advanced HIV infection. cPass data were highly correlated with anti-S IgG titres (rho 0.82;p<0.0001) and with PRNT data for both Wuhan-1 (n=27, Fig 1B) and Omicron BA.2 (n=28, Fig 1C). Conclusion(s): cPAss offers a simple methodology for measuring SARS-CoV-2 NAbs. Despite prior advanced HIV infection, neutralising activity improved with successive vaccinations and most participants showed NAbs against both Wuhan-1 and Omicron BA.2 after 3 vaccine doses. (Figure Presented).
ABSTRACT
Background: mRNA vaccines elicit a durable humoral response to SARS-CoV-2 in adults, whereas evidence in children is lacking. This study aimed to evaluate the early and long-term immunological response after the BNT162b2 vaccine in children with or without a previous SARS-CoV-2 infection. Method(s): In a multicenter, prospective, observational study we profiled the immune response to the BNT162b2 vaccine in children aged 5-11 years attending the Pediatric Departments at the University of Padua and Bambino Gesu Children's Hospital in Rome (Italy). Forty-four healthy children (HC), 20 immune compromised (IC), and 18 children who previously developed MIS-C (MIS-C) were included in the study. Blood samples were collected pre-, 1, and 6 months after a 2-doses vaccination schedule. Neutralizing antibodies (NAbs) and anti-S-RBD IgG titers were analyzed through Plaque Reduction Neutralization Test (PRNT) and chemiluminescent immune-enzymatic assay (CLIA), respectively. B and T cell phenotypes were analyzed by flow cytometry. Geometric mean titers (GMTs) and 95% confidence intervals and median and interquartile range (IQR) of variables were evaluated according to pre-existing confirmed COVID-19. Result(s): Eighty-two children were studied;60 with a molecular-documented previous COVID-19 (Group A) and 22 without previous infection defined as the absence of antigen-specific antibodies before the vaccination (Group B). Overall, in Group A we observed higher NAbs GMTs, anti-S-RBD titers, and T- and B-reg cells than in Group A, at both 1 and 6 mo after vaccination (table);Nabs against the parental virus resulted to be greater in Group A than in Group B by a factor of 18 and 11, at 1 and 6 mo after vaccination, respectively. Both Groups recorded a decrease in antibody titers of approximately 50-70% between 1 and 6 months. A significant difference for Omicron NAbs (p=0.02) and anti-S-RBD (p=0.07) titers decay was observed between Group A and B;in contrast, Parental NAbs titers appeared to have similar trends in the 2 groups (p=0.47). Comparable antibody titers at 1 and 6 mo. (p=0.37) were detected across the three categories of HC, IC, and MIS-C (table). Conclusion(s): mRNA vaccination triggers a higher humoral response in children with a previous history of COVID-19, regardless of the immune deficiency or previous MIS-C, at least up to 6 mo, providing insight into boosting preexisting immunity with mRNA vaccines.
ABSTRACT
Background: Clinical manifestations of children's coronavirus disease-2019 (COVID-19) were initially considered less severe compared with adult patients. However, there is now increasing evidence of a “long-tail” of COVID-19 related symptoms lasting for several months after recovery from the acute infection. Long COVID-19-related symptoms and mechanisms are poorly characterized and understood, with several phenotypes reported, often driven by long-term tissue damage (such as lung, heart and brain) and pathological inflammation due to viral persistence and/or immune deregulation. Purpose: The objective of this study was to evaluate atrio-ventricular mechanics, by means of two-dimensional speckle-tracking echocardiography, in previously healthy children recovered from asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a long-term follow-up. Methods: We analysed a cohort of 157 paediatric patients, mean age 7±4 years, who had a confirmed diagnosis of SARS-CoV-2 infection and were asymptomatic or mildly symptomatic for COVID-19. Patients underwent standard transthoracic echocardiogram and speckle tracking echocardiographic study 148±68 days after diagnosis. One hundred seven age, sex, and body surface area comparable healthy subjects were used as control group. Results: Left ventricular ejection fraction was within normal limits in postCOVID-19 cases and CTRL with no significant differences between the two groups (postCOVID-19: 65.6±4% vs CTRL: 65.0±5%, p=0.182).Left ventricular (LV) global longitudinal strain (postCOVID-19: −20.5±2.9%;CTRL: −21.8±1.7%;p<0.001) was significantly reduced in cases compared with CTRLs. An amount of 11 (7%) postCOVID-19 cases showed impaired GLS values < −17% and 95 subjects (60%) presented with a strain lower than −16% in more than 2 segments. These subjects did not show any difference regarding symptoms or serological findings. Moreover, GLS was significantly reduced in children with disease's onset during the second wave of COVID-19 pandemic, compared with those during the first wave (second wave: −20.2±2.6%;first wave: −21.2±3.4%;p=0.048). Finally, peak left atrial systolic strain was within the normal range in the postCOVID-19 group with no significant differences compared to CTRL (postCOVID-19: 49.1±12%;CTRL: 49.5±18%). Conclusions: SARS-CoV-2 infection may affect left ventricular deformation in children despite an asymptomatic or only mildly symptomatic acute illness. Our data show an amount of 60% of children, recovering from asymptomatic or mildly symptomatic COVID-19, with still mild subclinical systolic cardiac impairment in the mid- and long-term follow-up after the infection. This subtle impairment was seen to be worse in children recovering from the second wave of COVID-19 compared to the first one.A follow-up is needed to verify the reversibility of these alterations and their impact on long-term outcomes. Funding Acknowledgement: Type of funding sources: None.
ABSTRACT
Wastewater-based epidemiology is now widely used as an indirect tool to monitor the spread of SARS-CoV-2. In this study, five different sample matrices representing diverse phases of the wastewater treatment process were collected during the second wave of SARS-CoV-2 from two wastewater treatment plants (WWTPs) serving the Civil Hospital and Sacca Fisola island in Venice, Italy. Positive SARS-CoV-2 detections occurred at both WWTPs, and data on viral genome detection rate and quantification suggest that the pellet (i.e., the particulate resulting from the influent) is a sensitive matrix that permits reliable assessment of infection prevalence while reducing time to results. On the contrary, analysis of post-treatment matrices provides evidence of the decontamination efficacy of both WWTPs. Finally, direct sequencing of wastewater samples enabled us to identify B.1.177 and B.1.160 as the prevalent SARS-CoV-2 lineages circulating in Venice at the time of sampling. This study confirmed the suitability of wastewater testing for studying SARS-CoV-2 circulation and established a simplified workflow for the prompt detection and characterization of the virus.
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Background: COVID-19 is a worldwide emergency;hospitals are subjected to intense workloads, reduced compared to the previous waves, for advent of vaccination and use of immunomodulators Aim: to evaluate the clinical outcome of patients during the last wave in a Spoke hospital and compare the results with those of the end of 2020. Methods: In the period Dec. 21-Jan. 22 we treated 105 patients (62 men, average age 68.4 y, range 30-99, 51 polipathological), 56 of them with complete vaccination cycle ;the mean age of the vaccinated was lower (65.2+-15.1 vs 71.8+-15.7);in addition to therapy with EBPM and dexamethasone if indicated, 23 with risk factors were treated with casirivimab and indevimab 1200+1200 mg, 33 with remdesivir and 9 baricitinib;6 patients with combination therapies. The mean hospital stay was 7.9 days, range 3-24. Results: 10 patients died (5 unvaccinated) and 13 needed UTI (10 NIV support, 6 unvaccinated, and 3 IOT, 2 unvaccinated) but with a favorable evolution in over 2/3 of the cases;the other patients were discharged at home. Considering then other 75 hospitalized patients between Dec 20-Jan21, 53 men, average age 69.5 y, range 36-91, treated only with standard therapy (EBPM and steroid), the average stay had been 12.6 days and the previous outcome was 23 transferred UTI (8 intubated) and total of 17 deaths. Conclusions: With advent of vaccines, monoclonal antibodies, antivirals and immunomodulators, hospitalization times, the need for intensive care (13 vs 23) and deaths (10 vs 17) have been approximately halved.
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Background: Remdesivir (REM) is authorized to cure COVID-19 pneumonia with low oxygen supplementation. We evaluated the effect of combination of REM and usual treatment with enoxaparin and dexamethasone on clinical outcome. Methods: A prospective open study with REM (200 mg first day and then 100 mg /day for four days) was performed in a medical unit with critical sector in the period of half november 2021 and half January 2022 . All COVID-19 patients requiring supplemental low O2 therapy were treated with enoxaparin (4000 unit/day for almost patients) and dexamethasone (6 mg);three patients were treated even with baricitinib for rapid pulmonary deterioration. The primary endpoint was the final outcome with discharge from Hospital. Results: 33 COVID-19 patients were enrolled, 20 men, mean age 66 y (range 41-87);14 patients with a complete vaccinal schedule;therapy was started 1-2 days after entering the hospital. The lenght of hospitalization was 7.5 days with a range of 7-25;mortality in two patients (one not vaccinated), need of intensive care in 10 patients with favorouble evolution (3 with oral intubation and seven with non invasive ventilation support);at the end, 31 patients were discharged or at home or at sub acute unit. We did not observe major side effects, cough, headache, moderate increase of transaminases Conclusions: REM treatment, associated with heparin, dexamethasone and oxigen supplement, especially if started early, is safety and associated with reduced length of hospitalization and reduction mortality.
ABSTRACT
Background: Many CoViD-19-infected patients may die due to an over-response of the immune system (IS) characterized by the abnormal release of circulating cytokines. The SARS-CoV-2 virus binds to alveolar cells, activating the IS, with the release of numerous cytokines, including interleukin 6 (IL-6), which is responsible for the increase of the reactive C protein (PCR). PCR is useful for assessing the trend of acute inflammation in patients with CoViD-19 pneumonia, while the dosage of IL-6 is not routine. Materials and Methods: In 35 consecutive patients coming from the Emergency Room and then admitted to our division, we dosed IL-6 and PCR at the entrance (T0) and after 5 days (T5), to understand if the combination of the 2 values could be more predictive of the course of the disease. The degree of clinical stability was assessed using the Modified Early Warning Score (Mews). Results: At T0 the subjects with MEWS score 0 were 9, score 1 were 11, score 2 were 12, 1 score 3, 1 score 4. The average value of IL-6 of the subjects to T0 was 52.6 (range 16-150), with higher values in subjects with higher MEWS, from score 0 to 3 respectively: 16.9, 46.8, 76.4, 150.0. Values of IL-6 at T5 remain increasing as the MEWS score increases, with average values=24.3 for MEWS 0-2 and 138.7 for MEWS 3-5 (p=0.07). Similar trends presented PCR values: with average values of 41.0 for MEWS 0-2 and 144.4 for MEWS 3-5 (p<0.05). Conclusions: Preliminary data from our study, limited by the small sample, suggest that high values of IL-6 and PCR are present in patients with more severe clinical scores, and should be confirmed by larger-scale studies.