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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):377-378, 2022.
Article in English | EMBASE | ID: covidwho-1880557

ABSTRACT

Background: During the COVID-19 pandemic, HIV care providers urgently adopted telemedicine as an alternative to routine in-person person visits to ensure continuity of care. We examined how introducing televisits at a community and an academic outpatient HIV clinic during the COVID-19 pandemic affected technical quality of care for persons with HIV (PWH). Methods: The study included all non-pregnant adult PWH who had at least two visits for HIV care in the 18 months prior to 3/13/2020 at the Howard Brown Health Centers (HB) and Northwestern University Infectious Disease Center (NU-IDC) and in Chicago, Illinois. HIV care quality indicators (described in Table) were calculated using data extracted from electronic medical records during 4 different time periods: 1. pre-pandemic (1/1/19-3/1/2020), 2. early pandemic (7/1/2019-9/1/2020), 3. mid-pandemic (1/1/2020-3/1/2021), and 4. current (7/1/2020-9/1/2021). Measures were compared between intervals 2-4 and interval 1 (pre-pandemic) using generalized linear mixed models to estimate differences in indicators across intervals within each site while controlling for multiple observations of individuals. Differences by age group, race, and sex at birth were also compared. Results: 6,447 PWH were included in the analysis. The proportion of televisits peaked between April-June 2020 (71-75% at HB 53-89% at NU-IDC) then declined by July-September (33-35%at HB, 10-15% at NU). Changes in quality care measures are shown in Table 1. There were significant declines in care utilization and disease monitoring measures in intervals 2,3 &4 compared to interval 1. The largest declines were observed in STI screening. Measures of HIV virologic suppression, BP control, and HbA1C <7% (in both persons with and without diabetes) were stable with no significant differences noted in these measures between interval 4 and 1. Similar trends were observed across all age, race and sex subgroups. Conclusion: During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and disease monitoring decreased compared to pre-pandemic levels. Despite these reductions, proportions with virologic, BP, and glycemic control remained stable among PWH. The effect of televisits as well as other patient factors on HIV quality indicators and their changes over time during COVID-19 need to be further examined.

2.
Topics in Antiviral Medicine ; 30(1 SUPPL):102-103, 2022.
Article in English | EMBASE | ID: covidwho-1880510

ABSTRACT

Background: COVID-19 clinical manifestations range from asymptomatic to severe disease. Prior immune responses to human coronaviruses may affect individual responses to SARS-CoV-2. We surveyed coronavirus responses pre-pandemic in individuals from Kenya, Nigeria, Tanzania, Uganda and Thailand;81% were people living with HIV. Methods: Specimens were screened for SARS-CoV-2 Spike S2 subunit IgG responses. Selected samples were tested using a bead-based immunoassay that profiled the specificity, isotype and subclass of antibody responses to coronavirus, flavivirus and HIV antigens. Wilcoxon rank sum tests were performed to compare responses across antigens and participant group. Results: We screened 1,875 samples (one per individual) collected between 2013 and October 2019: 1,630 samples were from Africa (87%) and 245 from Thailand. 6.99% of participants (n=131, 116 from Africa (89%) and 15 from Thailand) showed responses above the naïve signal threshold and were further tested. Using a signal to noise ratio of >10 as a cut-off value, 44, 27 and 42 samples showed IgG responses to the Spike protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV respectively, while 7, 9 and 4 samples showed responses to Nucleocapsid for these same antigens. Some individuals had higher responses than those seen in SARS-CoV-2 convalescent individuals. We found a strikingly different pattern of reactivity in Africa compared to Thailand (Figure 1). Antibody responses were significantly higher in the African participants compared to Thai participants across antigens corresponding to SARS-CoV-2 (p<0.001), SARS-CoV-1 (p<0.001) and MERS-CoV (p<0.01). Similar patterns were seen for IgG subclasses, IgA and IgM. The difference was less pronounced for the four endemic coronaviruses, nonetheless anti-Spike responses were significantly higher in African participants for HKU1 and OC43 (p≤0.018). In addition, mapping responses to 21 flavivirus antigens showed the highest reactivity in Thailand and in Nigeria. Conclusion: Our serosurvey of pre-pandemic samples showed that there were significantly higher antibody responses against coronaviruses, including SARS-CoV-2, in Africa than in Thailand. Profiling flavivirus responses showed that the difference between the two regions was not due to a higher background reactivity across African samples. Further analysis is needed to explain pre-pandemic SARS-CoV-2-like antibody responses among African participants and explore implications for geographic diversity in disease severity.

3.
Topics in Antiviral Medicine ; 30(1 SUPPL):78, 2022.
Article in English | EMBASE | ID: covidwho-1880481

ABSTRACT

Background: The aim of this study was to identify the cause of lymphopenia, strongly predictive of survival in COVID-19. Methods: We recruited PCR-positive SARS-CoV-2-infected patients upon admission to Intensive Care Units (ICU, n = 29) and to the Infectious Diseases Department (non-ICU, n = 29) at Nîmes University Hospital, as well as age-and sex-matched healthy controls (HC). Their Angiotensin II plasma levels were measured by ELISA and their monocytic reactive oxygen species (ROS) production and T-cell apoptosis were measured by flow cytometry using dichloro-dihydro-fluorescein diacetate and fluorescent annexin V, respectively. DNA damage and double strand breaks were quantified in immunofluorescence using antibodies specific for-γ-H2AX and 53BP1, respectively. Results: The monocytes of certain COVID-19 patients spontaneously released ROS able to induce DNA damage and apoptosis in neighboring cells. High ROS production was predictive of death. Indeed, in most patients we observed the presence of DNA damage in up to 50% of their peripheral mononuclear blood cells, with double-strand DNA breaks, and T-cell apoptosis. The intensity of this DNA damage was linked to lymphopenia. SARS-CoV-2 is known to induce the internalization of its receptor, Angiotensin Converting Enzyme 2, a protease able to catabolize Angiotensin II. Accordingly, we observed high plasma levels of Angiotensin II in ROS-producing patients. In search of the stimulus responsible for their ability to release ROS, we unveiled that Angiotensin II triggers ROS production by monocytes via Angiotensin receptor I (AT1). ROS released by Angiotensin II-activated monocytes induced DNA damage and apoptosis in neighboring cells. Conclusion: Mononuclear cell apoptosis provoked via DNA damage due to the release of monocytic ROS could play a major role in COVID-19 pathogenesis, inasmuch as ROS are also known to trigger inflammatory cytokine production. Unveiling this new pathogenic pathway opens up new therapeutic possibilities for COVID-19 based on the early association of AT1 antagonists and antioxidants.

4.
Topics in Antiviral Medicine ; 30(1 SUPPL):122, 2022.
Article in English | EMBASE | ID: covidwho-1880385

ABSTRACT

Background: More than 10% of patients infected with SARS-CoV-2 experience a Long COVID syndrome, characterized by the persistence of a diverse array of symptoms where fatigue predominates. The role of the adaptive immune response in Long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response that would trigger autoimmune damage. To address this issue, we set to characterize humoral and cellular responses in Long COVID patients prior to SARS-CoV-2 vaccination. Methods: Long COVID patients (n=36) were included based on (1) an initial SARS-CoV-2 infection documented by PCR or the conjunction of two major signs of COVID-19 and (2) the persistence or resurgence of symptoms for over 3 months. They were compared to convalescent COVID patients with resolved symptoms (n=23) and uninfected control individuals (n=20). IgG and IgA antibodies specific to the SARS-CoV-2 spike were detected by a sensitive S-flow assay, which measures antibody binding to spike-expressing 293T cells. For CD4+ T cell response analyses, cytokine production was measured by intracellular staining on primary T cell lines stimulated by immunodominant peptides derived from the S, M, and N viral proteins. Results: Antibody analyses revealed either strong or very low/undetectable amounts of spike-specific IgG in sera from Long COVID patients, thus distinguishing a seropositive and a seronegative group. Seropositive Long COVID patients (n=21) showed strong CD4 responses that tended to be of higher magnitude than those of convalescents (P<0.05 for 2 immunodominant peptides). In contrast, seronegative Long COVID patients (n=15) showed low or undetectable CD4+ T cells responses, with 4/15 patients showing responses above those observed in healthy donors. CD4+ T cell responses correlated with spike-specific IgG responses in seropositive Long COVID patients (P≤0.002) but not in convalescents, pointing to differences in immune memory persistence. Conclusion: These findings highlight divergent adaptive immune responses among Long COVID patients, with a group characterized by seroconversion and particularly strong CD4+ T cell responses, and a second group characterized by low or undetectable antibody and cellular responses. Further studies are warranted to determine whether the etiology and the duration of symptoms differ in these two groups of Long COVID patients.

5.
Topics in Antiviral Medicine ; 30(1 SUPPL):8, 2022.
Article in English | EMBASE | ID: covidwho-1880303

ABSTRACT

Background: The continuing spread of SARS-CoV-2 provides opportunities for the virus to evolve. Compared to ancestral strains, the 4 major variants of concern (VOC) exhibit Spike mutations that improve entry and/or diminish antibody neutralization. However, mutations have arisen in other viral genes. Several of these genes may counteract innate immunity mediated by antiviral interferons (IFNs). IFNs show extensive diversity, but only IFNα2 and IFNβ are approved for clinical use. We showed previously that diverse IFNs exhibit variable activities against HIV-1 and trigger distinct transcriptomes. Methods: To assess whether SARS-CoV-2 acquired human IFN resistance over time, isolates representing early lineages A, B, B.1, and VOC lineages B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) were tested for sensitivity to multiple IFNs in an alveolar type II epithelial cell (AT2) line, A549, overexpressing ACE2. Cells were pre-treated with IFNs for 18 h in triplicate, then infected to yield ∼105 copies/reaction. Virus copy numbers were evaluated at 24 h by qPCR. We compared the sensitivity of 5 SARS-CoV-2 isolates to 12 IFNα subtypes, IFNβ, IFNω and 3 IFNa;subtypes at 2 pM, within the dynamic range of preliminary IFN inhibition curves. IC50s for IFNβ and IFNa;1 were compared between lineage B and VOC isolates. Results: Among the 17 IFNs tested, IFNβ, IFNα8, IFNω and IFNα5 most potently inhibited SARS-CoV-2 in A549-ACE2 cells. Inhibition curves with a delta variant isolate showed that IFNα2 and IFNa;1 had >10-fold and >1000-fold higher IC50 than IFNβ, respectively. Interestingly, the antiviral activity patterns of diverse IFNα subtypes against SARS-CoV-2 and HIV-1 were different and did not significantly correlate. Compared to the ancestral lineage B, the alpha, beta, gamma and delta variants exhibited on average 5.2-fold (range: 1.9-8.2) and 6.7-fold (range: 1.3-21) fold higher IC50s for IFNβ and IFNa;1, respectively. The alpha and delta isolates were also more resistant to IFNβ and IFNa;1 than a lineage B.1 isolate in another AT2 cell line, Calu-3. Conclusion: Our findings suggest that diverse IFNs may have evolved to restrict distinct virus families. Emerging SARS-CoV-2 variants are more effective than earlier pandemic viruses at antagonizing antiviral IFN responses. These data have implications for deploying IFNs for early COVID-19 therapy and suggest that innate immunity may be a driving force for SARS-CoV-2 evolution.

6.
Topics in Antiviral Medicine ; 30(1 SUPPL):67, 2022.
Article in English | EMBASE | ID: covidwho-1880292

ABSTRACT

Background: Human immunodeficiency virus (HIV) and Influenza A virus (IAV) remain a global health concern. Further, emergence of novel coronavirus SARS-CoV-2, which rapidly became global pandemic, increases the concern in biomedical research field for antiviral treatment. To develop new antiviral therapy, we must need to understand the molecular and cellular mechanisms involved in assembly and replication. It is known for some viruses (HIV and IAV) that the host actin cytoskeleton has been involved in various stages of the virus life cycle. Regulation of actin cytoskeleton requires several actin binding proteins, which organize the actin filaments (F-actin) into higher order structures such as actin bundles, branches, filopodia and microvilli, for further assistance in viral particle production. Thus, our objective for this work is to understand the role of these actin regulator proteins, like cofilin and one of its cofactor WDR1, in viral particle assembly and release. Methods: Here we used a combination of different experimental methods like RNA interference, immunoblot, immunoprecipitation, immunofluorescence coupled to confocal and STED fluorescence microscopy. In order to study only virus release, and bypass viral entry, we set up a minimal system for virus-like particles production in transfected cells, giving HIV-1 Gag-VLP, Influenza M1-VLP and SARS-CoV-2 MNE-VLP (developed by D. Muriaux lab). For image analysis, we used Image J software. Statistical analysis was performed with non-parametric t-tests or one-way Anova test. Results: Using siRNA strategy, we have shown that upon knock down of actin protein cofilin or WDR1, HIV-1 and IAV particles production increases in contrario to SARS-CoV-2 VLP release. Further, using immunoprecipitation, we report that HIV-1 Gag is able to form an intracellular complex with WDR1 and cofilin. Similarly, IAV-M1, which like HIV Gag-MA binds with plasma membrane phospholipids, is able to form an intracellular complex with cofilin. These results suggested that virus budding from the host cell plasma membrane seemed restricted by the cofilin/WDR1 complex. Finally, using confocal/STED microscopy on cell producing VLP, we observed actin fibers rearrangement with cell protrusions, suggesting a role for actin in viral particles assembly and release. Conclusion: In conclusion, regulators of actin dynamic are involved in HIV-1 Gag, IAV-M1 and SARS-CoV-2 VLP production but play a differential role in assembly and release of these RNA enveloped viruses.

7.
Topics in Antiviral Medicine ; 30(1 SUPPL):118, 2022.
Article in English | EMBASE | ID: covidwho-1880283

ABSTRACT

Background: Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied clinical presentations from mild subclinical to severe disease with high mortality. Our aim was to determine whether examining immune-related gene expression early in infection could predict progression to severe disease. Methods: In subjects of the All Ireland Infectious Diseases Cohort study, we analysed expression of 579 genes with the NanoString nCounter Immunology panel in peripheral blood mononuclear cells in those with confirmed SARS-CoV-2 infection collected within 5 days of symptom onset and matched SARS-CoV-2 negative controls with respiratory infection. Subsequent maximum COVID19 disease severity was classified as mild or severe. Read counts were normalized using panel housekeeping genes. Expression changes in severity groups were estimated against control baseline. Results: Between April and July of 2020, we recruited 120 subjects, 62 with COVID19 and 58 controls, with average age 59 y.o. (IQR 34-88), 66% males and 69% Caucasian ethnicity. Maximal disease severity was used to separate COVID19 cases into mild (n=31) and severe (n=31). We identified 20 significantly deregulated genes between those with COVID19 and controls (;log2 fold;>0.5, p<0.05, Benjamin-Yekutieli p-adjustment). Function of 12 of these genes related to cytokine signaling, 9 upregulated genes to type I interferon signaling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1), while 7 downregulated genes mapped to innate immune function (IRF7, ICAM2, SERPING1, IFI16, BST2, FCER1A, PTK2). Expression in the severe group showed downregulation of FCER1A (innate immunity regulation), IL1B and TNF (inflammatory cytokines), and PTGS2 (inflammatory mediator) and greater upregulation of TNFSF4 (cytokine signaling) and PTK2 (innate immunity). Mild cases presented higher upregulation of IFIT2 (type I interferon signaling). Conclusion: Observed early downregulation of regulators and mediators of inflammation in those who developed severe COVID19, suggested dysregulation of inflammation. Specifically, IFIT2 upregulation in mild cases and FCER1A downregulation in severe cases, points to early differences in host responses centered on deregulation of the interferon and inflammation responses. Whether these patterns reflect delayed interferon involvement in pathways to control the infection and contribute to pathological inflammation and cytokine storms observed in severe COVID19 requires further research.

8.
Topics in Antiviral Medicine ; 30(1 SUPPL):331-332, 2022.
Article in English | EMBASE | ID: covidwho-1880280

ABSTRACT

Background: SARS-CoV2 antibody testing is an important auxillary test especially for retrospective diagnosis or in patients with long COVID-19 or multisystem inflammatory syndrome of childhood. Epidemiological serology studies may also assist public health planning. Access to formal laboratory testing is not universal in many low-and middle-income (LMIC) countries and rapid lateral flow antibody tests are an attractive alternative. Performance of these tests has been inconsistent. A large-scale study was undertaken in South Africa, during the beta and delta waves, to assess the field-based performance of rapid point of care (POC) COVID-19 antibody tests. Methods: Symptomatic, ambulatory persons under investigation (PUIs) aged 18 years and older, presenting for SARS-CoV-2 diagnosis at public health facilities in three provinces, South Africa were enrolled at baseline. All patients completed a questionnaire regarding symptoms. Nasopharyngeal swabs were taken and processed for SARS-CoV-2 PCR testing using a GeneXpert (Cepheid, USA), or manual assay (ThermoFisher TaqPath assay or Seegene Allplex assay) on a real-time platform at routine accredited National Health Laboratory Service laboratories as per routine national protocols. Concomitantly, trained study staff performed three facility-based POC lateral flow antibody tests on a on a fingerstick sample and blood was collected for formal serology. POC tests were selected following a rapid in-laboratory evaluation. Asymptomatic contacts of people with confirmed COVID-19 were recruited into the asymptomatic study arm and rapid tests and PCR were performed. PCR and rapid positive patients and 500 negative controls were followed up at 5-14 days. Antibody tests were compared with formal serology performed on 2 platforms-Euroimmun (Euroimmun, Lubeck) IgA and IgG anti-S antibodies and Abbott Architect IgG test. Results: The sensitivity (S), specificity (Sp), positive (PPV) and negative predictive (NPV) values of tests for PUIs and contacts were calculated (Table 1)∗. Analyses using serology as a reference are forthcoming. Conclusion: Compared with PCR, performance of rapid POC COVID-19 antibody tests was poor with low sensitivity. This may reflect the patient cohort tested as humoral responses typically develop from day 7-14. The tests are unlikely to be useful for acute diagnosis but sensitivity may improve at later timepoints and further follow up data will be analysed by duration of symptom onset, severity of symptoms and wave (beta versus delta).

9.
Topics in Antiviral Medicine ; 30(1 SUPPL):76, 2022.
Article in English | EMBASE | ID: covidwho-1880244

ABSTRACT

Background: Interferons play a pivotal role as a first line of the innate immune host response to viral infections, including COVID-19. Accumulating data suggests dysregulated interferon (IFN) responses in COVID-19. However, the clinical relevance of circulating levels of interferon to COVID-19 disease severity remains unclear Methods: In plasma from individuals with PCR confirmed SARS-CoV-2 infection recruited to the All Ireland Infectious Diseases Cohort, collected within 10 days from onset of symptoms, we measured levels of type I (IFN-α2a and IFN-β), type II (IFN-γ), and type III (IFN-a;1) interferons by electro-chemiluminescence immunoassays. Subsequent maximum COVID-19 disease severity was classified according to World Health Organization guidance (Critical, Severe, Moderate and Mild). We used Kruskal-Wallis tests to explore differences in IFN levels between COVID-19 severity groups, and logistic regression to determine associations, adjusting for demographics (age, sex at birth, ethnicity), comorbidities (obesity, hypertension, respiratory disease, heart disease) and medical management (antibiotics, immunosuppressants, anticoagulants, invasive ventilation) Results: Out of the 335 subjects with early infection and available samples, 319 had data on disease severity, 33 (10.3%) Critical, 37 (11.6%) Severe, 76 (23.8%) Moderate and 173 (54.2%) Mild. The population was predominantly Caucasian (79.3%), with a median [IQR] age of 64 [53,77] and male (52.7%). There was a significant difference between the 4 groups for the levels of Type I IFN-α2a (p=0.0028) and Type 3 IFN-a;1 (p=0.0001), both being higher in the critical group. In adjusted analyses, higher levels of Type I IFN-α2a but not Type 3 IFN-a;1 remained significantly associated with the development of Critical COVID-19 (Odds Ratio: 5.911/95% CI: 0.608, 52.388/p=0.029). (Fig 1) Conclusion: Increased circulating Type I IFN-α2a, but not other IFN classes, measured in the early stages of SARS-CoV-2 infection was associated with higher odds of Critical COVID-19 infection. These data point to specific differences in host responses that may lead to more targeted interventions to prevent development of severe COVID-19 infection.

10.
Topics in Antiviral Medicine ; 30(1 SUPPL):295-296, 2022.
Article in English | EMBASE | ID: covidwho-1880228

ABSTRACT

Background: Children generally develop asymptomatic or mild COVID-19 disease, despite the exact mechanisms that protect them from severity are yet to be defined. Since humoral response to SARS-CoV-2 infection in children is still poorly investigated, we aimed to analyze circulating levels of anti-Spike IgA and IgG in pediatric population up to 8 months after SARS-CoV-2 infection, to delineate whether COVID-19 outcomes could impact on antibody (Ab) levels. Methods: A total of 115 COVID-19 young patients (mean age: 11.5 years, range 1-19 years) were enrolled between October 2020 and March 2021. All cases were confirmed SARS-CoV-2 infection by use of a diagnostic molecular assay on nasopharyngeal swabs. Circulating anti-SARS-CoV-2 IgG and IgA were measured using ELISA assays at one-month (T1), two-month (T2) and eight-month (T3) follow-up blood samples of young partecipants. Results: Longitudinal observation of COVID-19 children showed a decreased circulating level of IgA at T2 and T3 respectively compared to T1 (p<0.001). Persistent levels of anti-Spike IgG were observed at least two-month post infection but they significantly decreased at T3 (p<0.001). Stratifying children in two age-classes (1-9 and 10-19 years old) we found significantly higher levels of IgA in younger children at T1, T2 and T3 than in children older than 10 years old (p=0.012;p=0.041;p=0.036, respectively). Differently, younger children had a significantly higher level of IgG at T2 (p=0.029) and at T3 (p=0.049), but not at T1. Stratifying children based on the presence or absence of SARS-CoV-2 correlated symptoms or on the basis of underlying diseases, we did not observe differences in blood levels of IgA and IgG in all time points analyzed. Conclusion: Our longitudinal data indicated that younger children are characterized by an elevated peak of early IgA and are also defined by a robust induction of IgG, with respect to the older. These results contrast with what is common in SARS-CoV-2 infection in adults that elicit higher levels of polyfunctional Abs in severe disease. If confirmed in larger groups, these data would suggest that pediatric patients that usually have an efficient control of SARS-CoV-2 infections without inflammation would also elicit a humoral immune response protective from reinfections.

11.
Topics in Antiviral Medicine ; 30(1 SUPPL):266-267, 2022.
Article in English | EMBASE | ID: covidwho-1880059

ABSTRACT

Background: There are limited data on how COVID-19 disease severity and vaccination throughout different trimesters in pregnancy impact maternal neutralizing antibody responses and transplacental transfer to the neonate at birth. Further characterization of the antibody response of in utero SARS-CoV-2 may inform vaccination schedules in pregnancy in order to optimize maternal and neonatal protection. Methods: The COVID-19 Outcomes in Mother-Infant Pairs (COMP) study is a longitudinal cohort of mother-infant dyads diagnosed with PCR-confirmed SARS-CoV-2 at any point during pregnancy. Maternal and cord sera from delivery, as well as infant sera collected at 24 hours of life, were analyzed by enzyme-linked immunosorbent assay (ELISA) for IgA, IgG, and IgM targeting receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Neutralizing antibody (NAb) activity against the original L strain was evaluated in a subset of unvaccinated mother-infant dyads with evidence of IgG transfer or history of severe/critical COVID-19 in pregnancy. Results: Among 115 pregnant women, the NIH COVID-19 severity of illness categories were: 12% asymptomatic, 70% mild/moderate, 11% severe/critical disease, and 7% vaccinated prior to delivery following recovery. Fifty percent of the cohort was diagnosed in the 3rd trimester, and the median diagnosis date to delivery was 61.5 days (IQR 27.75-122.25). The majority (74%) of the cohort produced all three anti-SARS-CoV-2 isotypes, although 5% had no detectable antibody class. Transplacental transfer ratios increased with increasing duration between onset of infection and delivery (Figure 1, r2=0.17). Infant IgG levels (ng/mL) were the highest among neonates born to vaccinated mothers (Figure 1), and maternal IgG levels increased with disease severity, although vaccination elicited a comparable maternal antibody response to severe/critical disease (Figure 1). Among 50 maternal specimens, 80% demonstrated in vitro neutralization activity, and 52% of 33 neonatal specimens had NAb. Conclusion: While transplacental transfer of IgG was high with natural infection and correlates with increasing duration between onset of infection and delivery, only half of analyzed neonatal specimens demonstrated in vitro neutralization activity. Further research is needed to characterize the functionality and kinetics of both maternal and neonatal antibody responses elicited by in utero SARS-CoV-2 natural infection compared with COVID-19 vaccination.

12.
Topics in Antiviral Medicine ; 30(1 SUPPL):266, 2022.
Article in English | EMBASE | ID: covidwho-1879920

ABSTRACT

Background: Knowledge about SARS-CoV2 infection in pregnancy and exposed newborns is deficient. We performed a longitudinal analysis of innate immune system status and determined soluble cytokines of women infected with SARS-CoV2 during pregnancy and their newborns Methods: Women with confirmed SARS-CoV2 infection (RT-PCR+ or SARS-CoV2 anti-IgM/IgG+) (COVID MOTHER group, CM n=29, median age of 31 years) and their SARS-CoV2 exposed uninfected newborns were recruited from Hospital Gregorio Marañón, Spain. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later (n=15). The immunophenotyping of innate components (natural killer cells [NK] and monocytes) was studied on cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma and cord plasma by ELISA assay. CM was compared to a healthy non-SARS-CoV2 infected mothers' group matched by age (SARS-CoV2 PCR-and SARS-CoV2 anti-IgM/IgG-)(Uninfected Mothers, UM n=16) and their newborns (n=16) Results: On NK cell assays, CM show at baseline lower percentage of CD16++ subset, higher NKG2D and lower NKG2A expression on CD16++ and CD56++ subsets and reduced CD57 expression compared to UM;proportion of CD16++ subset and percentage of NKG2D reverted after 6 months(A). Regarding monocytes, CM show increased levels of CD62L and decreased CD49d expression on classical subset, elevated intermediate monocytes proportion and decreased CD40 expression on patrolling subset(B). No differences were found 6 months later. No newborn was infected by SARS-CoV2 and the phenotype analyzed on cord cells shows lower frequency of NK subsets compared with unexposed children and increased CD16++ subset after 6 months(C). In monocytes distribution, exposed children present lower frequency of total monocytes and its subsets than unexposed. Classical monocytes show significant changes at follow-up time-point(D). Increased TNFα and IL10 levels were found on CM compared to UM. Strong and direct correlations were observed between the age and IL6(E). No differences were observed in soluble cytokine levels comparing both groups of newborns Conclusion: SARS-CoV2 infection during pregnancy shows differences in activation, maturation and endothelial markers on innate immune system that could lead newborns clinical implications at birth. However, altered cell proportions and phenotypes found at SARS-CoV2 at birth time and on their exposed newborns is later reverted.

13.
Laboratory Diagnostics. Eastern Europe ; 10(3):372-382, 2021.
Article in Russian | Scopus | ID: covidwho-1879828

ABSTRACT

The article describes the methodology and technology of laboratory research using the methods of "dry" chemistry that are are implemented using test strips of the first and second generation. The modern information about the design of test systems of different generations and the distinctive features of the chemical-analytical processes performed in them is presented. An idea of the equipment used for objective registration of the results of analytical research is given. The sequence of its implementation is given;attention is paid to the factors that can distort the results of the study. The areas of possible application of test systems for diagnostics of various somatic diseases are characterized. An idea is given about the laboratory diagnostic panels as combinations of indicators of laboratory tests traditionally used for laboratory diagnostics of diseases of the vital organs and various forms of infectious pathology. The set of different panels created in the second generation test strips that implement the immunochromatographic analysis makes a kind of "laboratory in a pocket" that can be used by a general practitioner directly at the patient’s location. © The Authors.

14.
Theory and Practice in Language Studies ; 12(6):1145-1156, 2022.
Article in English | ProQuest Central | ID: covidwho-1879698

ABSTRACT

Effective verbal communication in the English language poses many challenges for Malaysian students. As English is not their first language, the average Malaysian finds it difficult to attain the required speaking proficiency. COVID has only exacerbated this problem. Moving from a traditional classroom setting to an online one limits cohesive and effective verbal communication between the spreader and listener (s). Both students and teachers had to switch from traditional classroom instruction to online classroom instruction with various devices and technologies as their main means of communication. As a result, this study provides a systematic review of pertinent existing research into Investigating Speaking Challenges among English Language Learners (ESL) in Online Classrooms. We concentrated on 51 articles from the year 2006 to the year 2021, from a few databases. Google Scholar, L1 - https://media.proquest.com/media/hms/PFT/1/iT9BN?_a=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&_s=SfsIJYuCrgMB5UVgq5tFHz5FTUY%3D ERIC, Microsoft Academic, and ResearchGate were referred to. The review begins with a search and scanning of suitable articles related to this study before selection. Most of these articles disclosed speaking challenges and provided positive solutions to overcome them during the COVID-19 pandemic. Both students and teachers dealt effectively with psychological issues such as shyness, lack of confidence, and anxiety, as well as technological aspects. Overall, this review gave some insights into the difficulties that ESL students have when they speak, as well as many ways to deal with them when learning online.

15.
Transbound Emerg Dis ; 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1879106

ABSTRACT

The ongoing coronavirus disease 2019 pandemic and its overlap with the influenza season lead to concerns over severe disease caused by the influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infections. Using a Syrian hamster co-infection model with SARS-CoV-2 and the pandemic influenza virus A/California/04/2009 (H1N1), we found (a) more severe disease in co-infected animals, compared to those infected with influenza virus alone but not SARS-CoV-2 infection alone; (b) altered haematological changes in only co-infected animals and (c) altered influenza virus tropism in the respiratory tracts of co-infected animals. Overall, our study revealed that co-infection with SARS-CoV-2 and influenza virus is associated with altered disease severity and tissue tropism, as well as haematological changes, compared to infection with either virus alone.

16.
J Trop Pediatr ; 68(4)2022 06 06.
Article in English | MEDLINE | ID: covidwho-1878823

ABSTRACT

Fever without a source (FWS) is common clinical status in the young infants. The aim of this study was to evaluate the clinical and laboratory findings of coronavirus disease (COVID-19) infection in well-appearing infants with FWS. Well-appearing febrile infants between 30 and 90 days who were evaluated as FWS in the pediatric emergency department and tested for COVID-19 were divided into two groups: COVID-19 (+) and (-). The clinical and laboratory findings of the patients were compared. The study included 95 febrile infants with FWS, and the mean age was 59.62 ± 16.82 days. The nasopharyngeal COVID-19 polymerase chain reaction test results of 29/95 (30.5%) patients were positive, while 66/95 (69.5%) were negative. The complaints of irritability and nasal congestion were found to be significantly more common in COVID-19-positive patients (p = 0.04 and p = 0.041, respectively). The hospitalization rate (p = 0.009), length of hospital stay (p = 0.026), initiation of antibiotic treatment (p < 0.001) and duration of antibiotic treatment (p = 0.036) were significantly lower in the COVID-19 (+) patients. The C-reactive protein (CRP, p < 0.001), absolute neutrophil count (ANC, p < 0.001), absolute lymphocyte count (ALC, p = 0.015), white blood cell (WBC, p < 0.001) and systemic immune-inflammation index (SII, p < 0.001) were found to be significantly lower in the COVID-19 (+) patient group. There was no significant difference between the groups in terms of neutropenia, lymphopenia or leukopenia.COVID-19 infection may present as an FWS. During the pandemic period, testing for COVID-19 among infants who were evaluated as FWS may reduce unnecessary hospitalizations and antibiotic treatments, and shorten hospital stays and duration of antibiotics.


Subject(s)
COVID-19 , Adult , Aged , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19 Testing , Child , Fever/drug therapy , Fever/etiology , Humans , Infant , Leukocyte Count , Middle Aged
17.
Autophagy ; : 1-19, 2022 Jun 19.
Article in English | MEDLINE | ID: covidwho-1878703

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.

18.
Micromachines (Basel) ; 13(5)2022 Apr 30.
Article in English | MEDLINE | ID: covidwho-1872096

ABSTRACT

Extracellular vesicles (EVs) are a group of communication organelles enclosed by a phospholipid bilayer, secreted by all types of cells. The size of these vesicles ranges from 30 to 1000 nm, and they contain a myriad of compounds such as RNA, DNA, proteins, and lipids from their origin cells, offering a good source of biomarkers. Exosomes (30 to 100 nm) are a subset of EVs, and their importance in future medicine is beyond any doubt. However, the lack of efficient isolation and detection techniques hinders their practical applications as biomarkers. Versatile and cutting-edge platforms are required to detect and isolate exosomes selectively for further clinical analysis. This review paper focuses on lab-on-chip devices for capturing, detecting, and isolating extracellular vesicles. The first part of the paper discusses the main characteristics of different cell-derived vesicles, EV functions, and their clinical applications. In the second part, various microfluidic platforms suitable for the isolation and detection of exosomes are described, and their performance in terms of yield, sensitivity, and time of analysis is discussed.

19.
8th International Conference on Decision Support System Technology, ICDSST 2022 ; 447 LNBIP:139-150, 2022.
Article in English | Scopus | ID: covidwho-1877769

ABSTRACT

The study demonstrates the flexible functioning of the FITradeoff method that integrates the Holistic Evaluation with the Elicitation by Decomposition. For that purpose, the new features of the FITradeoff method in which integrates the two paradigms of preference modeling have been explored to solve a real multi-criteria decision problem. In this paper, a truck acquisition problem, at a midsize carrier faced with an uncertain and turbulent scenario due to the Coronavirus pandemic, was solved using the FITradeoff method. In this problem, seven criteria were considered to represent the Decision-Maker objectives. Also, six trucks (alternatives) have been examined by the Decision-Maker (Financial Director). The FITradeoff DSS supported the company as to obtain, through the combination of Holistic Evaluation and Elicitation by Decomposition, a ranking of all the trucks based on the preferences expressed during the decision process to ensure lower costs and higher profits in the long run, also guaranteeing a quicker (more efficient) resolution of the problem. © 2022, Springer Nature Switzerland AG.

20.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338083

ABSTRACT

Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute to long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide SARS-CoV-2 immunoprofiling in COVID-19 convalescents combining serological, cellular and monoclonal antibody explorations, revealed humoral immunity coordination. Detailed characterization of a hundred SARS-CoV-2 spike memory B-cell monoclonal antibodies uncovered diversity in their repertoire and antiviral functions. The latter were influenced by the targeted spike region with strong Fc-dependent effectors to the S2 subunit and potent neutralizers to the receptor binding domain. Amongst those, Cv2.1169 and Cv2.3194 antibodies cross-neutralized SARS-CoV-2 variants of concern including Omicron BA.1 and BA.2. Cv2.1169, isolated from a mucosa-derived IgA memory B cell, demonstrated potency boost as IgA dimers and therapeutic efficacy as IgG antibodies in animal models. Structural data provided mechanistic clues to Cv2.1169 potency and breadth. Thus, potent broadly neutralizing IgA antibodies elicited in mucosal tissues can stem SARS-CoV-2 infection, and Cv2.1169 and Cv2.3194 are prime candidates for COVID-19 prevention and treatment.

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