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1.
iScience ; 25(8): 104779, 2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-2000474

ABSTRACT

Bats perform important ecological roles in our ecosystem. However, recent studies have demonstrated that bats are reservoirs of emerging viruses that have spilled over into humans and agricultural animals to cause severe diseases. These viruses include Hendra and Nipah paramyxoviruses, Ebola and Marburg filoviruses, and coronaviruses that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the recently emerged SARS-CoV-2. Intriguingly, bats that are naturally or experimentally infected with these viruses do not show clinical signs of disease. Here we have reviewed ecological, behavioral, and molecular factors that may influence the ability of bats to harbor viruses. We have summarized known zoonotic potential of bat-borne viruses and stress on the need for further studies to better understand the evolutionary relationship between bats and their viruses, along with discovering the intrinsic and external factors that facilitate the successful spillover of viruses from bats.

2.
Viruses ; 14(7)2022 06 24.
Article in English | MEDLINE | ID: covidwho-1911653

ABSTRACT

The implementation of vaccination among healthcare workers (HCWs) allowed the management of the pandemic in a manner that differed from that in the first waves. It has been demonstrated that the mRNA vaccines elicit good humoral responses but that there are still breakthrough infections. In summer 2021, a fifth wave emerged, despite the good coverage of HCWs in Spain. We aimed to study the SARS-CoV-2 IgG antibody levels as a marker to predict the possibility of Delta variant infections after vaccination after a seroepidemiological campaign. Of the 5000 participants, a total of 4902 (98.04%) showed a positive result in the serological anti-S test and only 98 (1.96%) were negative. Among the 4368 fully vaccinated participants, only in five cases was the serology negative. Of the total number of participants that received antibody results during the study, 162 were PCR positive in the subsequent two months. Among these, 151 were fully vaccinated (two doses). Significant differences between antibody BAU/mL levels were found between PCR positive and non-PCR positive participants (p < 0.01). The median of BAU/mL was higher in those vaccinated patients with no infection (1260 BAU/mL; 465-2080) versus infected patients (661 BAU/mL; 361-2080). These data support the idea that vaccines play an important role in the control of the pandemic, especially among HCWs at the time of the Delta variant circulation. More studies with other variants of concern must be performed in order to establish a correlation between the levels of IgG and the new infections.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/prevention & control , Follow-Up Studies , Health Personnel , Humans , SARS-CoV-2/genetics , Vaccination
3.
J Virol ; 96(14): e0048822, 2022 07 27.
Article in English | MEDLINE | ID: covidwho-1909580

ABSTRACT

Species A rotavirus (RVA) vaccines based on live attenuated viruses are used worldwide in humans. The recent establishment of a reverse genetics system for rotoviruses (RVs) has opened the possibility of engineering chimeric viruses expressing heterologous peptides from other viral or microbial species in order to develop polyvalent vaccines. We tested the feasibility of this concept by two approaches. First, we inserted short SARS-CoV-2 spike peptides into the hypervariable region of the simian RV SA11 strain viral protein (VP) 4. Second, we fused the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, or the shorter receptor binding motif (RBM) nested within the RBD, to the C terminus of nonstructural protein (NSP) 3 of the bovine RV RF strain, with or without an intervening Thosea asigna virus 2A (T2A) peptide. Mutating the hypervariable region of SA11 VP4 impeded viral replication, and for these mutants, no cross-reactivity with spike antibodies was detected. To rescue NSP3 mutants, we established a plasmid-based reverse genetics system for the bovine RV RF strain. Except for the RBD mutant that demonstrated a rescue defect, all NSP3 mutants delivered endpoint infectivity titers and exhibited replication kinetics comparable to that of the wild-type virus. In ELISAs, cell lysates of an NSP3 mutant expressing the RBD peptide showed cross-reactivity with a SARS-CoV-2 RBD antibody. 3D bovine gut enteroids were susceptible to infection by all NSP3 mutants, but cross-reactivity with SARS-CoV-2 RBD antibody was only detected for the RBM mutant. The tolerance of large SARS-CoV-2 peptide insertions at the C terminus of NSP3 in the presence of T2A element highlights the potential of this approach for the development of vaccine vectors targeting multiple enteric pathogens simultaneously. IMPORTANCE We explored the use of rotaviruses (RVs) to express heterologous peptides, using SARS-CoV-2 as an example. Small SARS-CoV-2 peptide insertions (<34 amino acids) into the hypervariable region of the viral protein 4 (VP4) of RV SA11 strain resulted in reduced viral titer and replication, demonstrating a limited tolerance for peptide insertions at this site. To test the RV RF strain for its tolerance for peptide insertions, we constructed a reverse genetics system. NSP3 was C-terminally tagged with SARS-CoV-2 spike peptides of up to 193 amino acids in length. With a T2A-separated 193 amino acid tag on NSP3, there was no significant effect on the viral rescue efficiency, endpoint titer, and replication kinetics. Tagged NSP3 elicited cross-reactivity with SARS-CoV-2 spike antibodies in ELISA. We highlight the potential for development of RV vaccine vectors targeting multiple enteric pathogens simultaneously.


Subject(s)
COVID-19 , Rotavirus , Amino Acids/metabolism , Animals , Antibodies, Viral/metabolism , Cattle , Epitopes/genetics , Epitopes/metabolism , Humans , Reverse Genetics/methods , Rotavirus/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins/metabolism
4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335199

ABSTRACT

We aimed to implement a pilot intervention based on offering online COVID-19 selftest kits addressed to healthcare and education professionals in Spain during the peak of the 6 th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention;and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible. Key findings We implemented a pilot intervention based on offering online COVID-19 selftest kits in Spain. We demonstrated the feasibility of the intervention during the peak of the 6th wave caused by Omicron variant. The intervention counted with high acceptability among healthcare and education professionals in Spain. Our results may contribute to define screening strategies addressed to key populations, particularly during peaks of high community transmission of SARS-CoV-2.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331365

ABSTRACT

Human rotavirus (RV) vaccines used worldwide have been developed using live attenuated platforms. The recent development of a reverse genetics system for RVs has delivered the possibility of engineering chimeric viruses expressing heterologous peptides from other virus species to generate polyvalent vaccines. We tested the feasibility of this using two approaches. Firstly, we inserted short SARS-CoV-2 spike peptides into the hypervariable region of the simian SA11 RV strain viral protein (VP) 4. Secondly, we fused the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, or the shorter receptor binding motif (RBM) nested within the RBD, to the C-terminus of non-structural protein (NSP) 3 of the bovine RF strain RV, with or without an intervening T2A peptide. Mutating the hypervariable region of SA11 VP4 impeded viral replication, and for these mutants no cross-reactivity with spike antibodies was detected. To rescue NSP3 mutants, we established a plasmid-based reverse genetics system for the bovine RF strain. Except for the RBD mutant, all NSP3 mutants delivered endpoint titres and replication kinetics comparable to that of the WT virus. In ELISAs, cell lysates of an NSP3 mutant expressing the RBD peptide showed cross reactivity with a SARS-CoV-2 RBD antibody. 3D bovine gut enteroids were susceptible to infection by all NSP3 mutants but only RBM mutant showed cross reactivity with SARS-CoV-2 RBD antibody. The tolerability of large peptide insertions in the NSP3 segment highlights the potential for this approach in the development of vaccine vectors targeting multiple enteric pathogens simultaneously. IMPORTANCE We explored the use of rotaviruses (RVs) to express heterologous peptides, using SARS-CoV-2 as an exemplar. Small SARS-CoV-2 peptide insertion (<34 amino acids) into the hypervariable region of the viral protein 4 (VP4) of RV SA11 strain resulted in reduced viral titre and replication, thus limiting its use as a potential vaccine expression platform. To test RF strain for its tolerance for peptide insertions, we constructed a reverse genetics system. NSP3 was C-terminally tagged with SARS-CoV-2 spike peptides of up to 193 amino acids. With a T2A-separated 193 amino acid tag on NSP3, there was little effect on the viral rescue efficiency, titre and replication. Tagged NSP3 elicited cross-reactivity with SARS-CoV-2 spike antibodies in ELISA. This is the first report describing epitope tagging of VP4, and of a reverse genetics system for the RF strain. We highlight the potential for development of RV vaccine vectors targeting multiple enteric pathogens simultaneously.

6.
Front Public Health ; 9: 788581, 2021.
Article in English | MEDLINE | ID: covidwho-1648288

ABSTRACT

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antigen (Ag) tests have been widely employed to identify patients for a rapid diagnosis and pandemic control. Rapid lateral-flow techniques are currently the most used, but automated technologies have emerged as another viable alternative to molecular methods. We aimed to evaluate the analytical performance of the DiaSorin Liaison SARS-CoV-2 Ag test in asymptomatic population and close contacts, for its use as a tool in pandemic control efforts. Material and Methods: A retrospective study was conducted. A total of 861 samples were included, 291 (34%) were positive for SARS-CoV-2 with cycle threshold (Ct) <40, and 570 (66%) were negative. Results: A strong correlation was observed between reverse transcriptase-PCR (RT-PCR) Ct and Ag 50% Tissue Culture Infectious Dose per milliliter (TCID50/ml; r = 0.6486; p < 0.0001) and all RT-PCR negative samples tested negative for the 200 TCID50/ml SARS-Cov-2 Ag cutoff, i.e., a specificity of 100% was reached (95% CI: 99.4-100.0%). Samples with <25 Ct and/or >106 extrapolated copies/ml were reached a sensitivity of 100% (95% IC 97.0-100.0%). For intermediate viral loads (>105 extrapolated copies/ml or <30 Ct), the sensitivity value still exceeded 80%. As with other Ag methods, samples between 30 and 40 Ct could not be detected with a reliable sensitivity. Conclusions: The LIAISON® SARS-CoV-2 Ag assay displays an acceptable sensitivity and a very high specificity that is useful for detecting the presence of SARS-CoV-2 in nasal swabs (NPS) of asymptomatic population or to regular monitoring of risk groups in controlled settings. Additionally, the flexibility in processing different samples and in the sampling preparation process makes this test an option for its use in high throughput laboratories. Automated tests may facilitate result reporting and yield consistent data, while avoiding some of the pitfalls of rapid lateral-flow techniques, such as observer variability.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Retrospective Studies , Sensitivity and Specificity
7.
CHEST ; 160(4):A888-A888, 2021.
Article in English | Academic Search Complete | ID: covidwho-1460757
8.
Nutr Hosp ; 38(6): 1119-1125, 2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1431211

ABSTRACT

INTRODUCTION: Introduction: the COVID-19 pandemic put the world's population at risk. As the relationship between nutritional risk and clinical outcomes in critically ill patients with COVID-19 is still poorly understood, a multidisciplinary research team of the Argentine Society of Intensive Care (SATI) conducted a multicenter study aimed to define nutritional features, and to evaluate the relationship between nutritional risk and relevant clinical outcomes for COVID-19 patients in an intensive care unit (ICU). Methods: a multicenter, prospective, observational study including twelve Argentinian ICUs was conducted between March and October 2020. Inclusion criteria were: adult patients older than 18 years who were admitted to the ICU with a COVID-19 diagnosis were included. Clinical data included comorbidities scores, and nutritional screening tools such as the Subjective Global Assessment (SGA), the Nutritional Risk Screening (NRS) 2002, and the modified NUTRIC score (mNUTRIC SCORE) were used. In addition, clinical outcomes including overall mortality, mechanical ventilation (MV) days, and ICU and hospital length of stay (LOS) were recorded. Results: a total of 285 ICU patients met our inclusion criteria. Mean age was 61.24 (SD = 14.6) years; APACHE-II, 14.2 (SD = 6.6); Charlson Comorbidity Index (CCI), 2.3 (SD = 2.3). Most patients were admitted from the emergency room to the ICU. Hypertension, obesity, and diabetes were the most common comorbidities. Nutritional assessment showed that 36.9 % were SGA B+C, and 46 % were obese. Mean ICU LOS was 22.2 (SD = 19.5), and hospital LOS was 28.1 (SD = 21.9) days. Of all patients, 90.2 % underwent MV, and MV days were 20.6 (SD = 15.6). The univariate and multivariate analyses showed that risk factors for COVID-19 mortality were (odds ratio [95 % confidence interval]): SGA score of B or C: 2.13 [1.11-4.06], and NRS 2002 ≥ 3: 2.25 [1.01-5.01]. Conclusions: in the present study, nutritional status (SGA) and NRS 2002 were major mortality risk factors for CODIV-19 patients in the ICU.


INTRODUCCIÓN: Introducción: la pandemia de COVID-19 puso en riesgo a la población mundial. Dado que la relación entre el riesgo nutricional y los resultados clínicos en pacientes críticos con COVID-19 es aún poco conocida, un equipo de investigación multidisciplinario de la Sociedad Argentina de Cuidados Intensivos (SATI) realizó un estudio multicéntrico con el objetivo de definir las características nutricionales y evaluar la relación entre el riesgo nutricional y los resultados clínicos relevantes para los pacientes de la unidad de cuidados intensivos (UCI) de COVID-19. Métodos: entre marzo y octubre de 2020 se realizó un estudio observacional prospectivo y multicéntrico que incluyó 12 UCI argentinas. Criterios de inclusión: se incluyeron pacientes adultos mayores de 18 años que habían ingresado en la UCI con diagnóstico de COVID-19. Se utilizaron datos clínicos que incluían scores de comorbilidades, herramientas de cribado nutricional como la Evaluación Global Subjetiva (EGS) y el Cribado de Riesgo Nutricional (NRS) 2002, y la puntuación NUTRIC. Además. Se registraron los resultados clínicos, incluida la mortalidad, los días de ventilación mecánica (VM) y la duración de la estancia en la UCI y hospitalaria en general. Resultados: en total, 285 pacientes en UCI cumplieron nuestros criterios de inclusión. La edad media fue de 61,24 (DE = 14,6) años, la puntuación APACHE-II de 14,2 (DE = 6,6) y el índice de comorbilidad de Charlson (ICC) de 2,3 (DE = 2,3). La mayoría de los pacientes ingresaron desde la sala de emergencias a la UCI. La hipertensión, la obesidad y la diabetes fueron las comorbilidades más frecuentes. La evaluación nutricional mostró que el 36,9 % eran VGS B + C y el 46 % eran obesos. La estancia en la UCI fue de 22,2 (DE = 19,5) y la hospitalaria de 28,1 (DE = 21,9) días. El 90,2 % se sometieron a VM, siendo la media de días de VM de 20,6 (DE = 15,6). El análisis univariado y multivariado mostró que los factores de riesgo de mortalidad por COVID-19 eran (razón de posibilidades [intervalo de confianza del 95 %]): puntuación SGA de B o C: 2,13 [1,11-4,06], y NRS 2002 ≥ 3: 2,25 [1,01-5,01]. Conclusiones: en el presente estudio, el estado nutricional (EGS) y el NRS 2002 fueron los principales factores de riesgo de mortalidad para los pacientes con COVID-19 en la UCI.


Subject(s)
COVID-19/mortality , Nutrition Assessment , Nutritional Status , APACHE , Aged , Argentina/epidemiology , COVID-19/complications , Comorbidity , Critical Illness , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Intensive Care Units , Length of Stay , Male , Malnutrition/mortality , Middle Aged , Obesity/epidemiology , Prospective Studies , Respiration, Artificial/statistics & numerical data , Risk Factors
10.
J Med Cases ; 11(10): 299-302, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1227206

ABSTRACT

The rapid outbreak of coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to infection with variable clinical presentations and a wide clinical spectrum. The disease was first reported in Wuhan, China in 2019 and has rapidly spread worldwide. Despite reports of dynamic changes in disease progression, clinical predictors of disease severity have been difficult to identify. The following case describing identical twins with laboratory confirmed COVID-19 who had very different disease courses. These patients resided in the same home and shared many of the same comorbidities, including type 2 diabetes mellitus, hypertension and morbid obesity. Although twin 1 had higher inflammatory markers, white blood cell (WBC) and an arguably more complicated medical history in comparison to their identical twin, the patient experienced a milder and shorter disease course. This case highlights the need for identifying proper disease markers and predictors early in the clinical course in order to direct future management guidelines and timely treatment.

11.
Molecules ; 26(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1154456

ABSTRACT

Bats are unique in their potential to serve as reservoir hosts for intracellular pathogens. Recently, the impact of COVID-19 has relegated bats from biomedical darkness to the frontline of public health as bats are the natural reservoir of many viruses, including SARS-Cov-2. Many bat genomes have been sequenced recently, and sequences coding for antimicrobial peptides are available in the public databases. Here we provide a structural analysis of genome-predicted bat cathelicidins as components of their innate immunity. A total of 32 unique protein sequences were retrieved from the NCBI database. Interestingly, some bat species contained more than one cathelicidin. We examined the conserved cysteines within the cathelin-like domain and the peptide portion of each sequence and revealed phylogenetic relationships and structural dissimilarities. The antibacterial, antifungal, and antiviral activity of peptides was examined using bioinformatic tools. The peptides were modeled and subjected to docking analysis with the region binding domain (RBD) region of the SARS-CoV-2 Spike protein. The appearance of multiple forms of cathelicidins verifies the complex microbial challenges encountered by these species. Learning more about antiviral defenses of bats and how they drive virus evolution will help scientists to investigate the function of antimicrobial peptides in these species.


Subject(s)
Cathelicidins/chemistry , Cathelicidins/pharmacology , Chiroptera/genetics , Spike Glycoprotein, Coronavirus/metabolism , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Binding Sites , Cathelicidins/genetics , Cathelicidins/metabolism , Computational Biology/methods , Computer Simulation , Genome , Molecular Docking Simulation , Phylogeny
12.
PLoS One ; 15(12): e0244348, 2020.
Article in English | MEDLINE | ID: covidwho-999840

ABSTRACT

BACKGROUND: The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world has caused a global pandemic, infecting millions of individuals, with an unprecedented impact in health care systems worldwide. Healthcare workers are one of the risk groups that need to be well protected, due to their strategic role in patient management, presently and in prevention of healthcare needs for future outbreaks. Here, we present the results of the first SARS-CoV-2 seroprevalence study in the Northern Metropolitan Area of Barcelona, Spain. METHODS: IgG SARS-CoV-2 antibodies were analyzed in serum samples from 7563 healthcare workers of the Northern Metropolitan Area of Barcelona. Samples were collected after the first pandemic wave (from May 4th to May 22nd, 2020) and were analyzed by automated chemiluminescence assays. All samples were tested for IgG anti-S1/S2. Participant samples with negative or equivocal results but with analytical signals above the limit of detection and/or previously confirmed COVID-19 diagnosis were also tested for IgG anti-Nucleocapsid. RESULTS: A total of 779 of 7563 (10.3%) healthcare workers were positive for anti-SARS-CoV-2 IgG (specific for either S1/S2 or N antigens). No significant differences were observed between those working at primary care or at the reference hospital. Interestingly, among 341 participants with a confirmed COVID-19 diagnosis, 36 (10.55%) tested negative for SARS-CoV-2 IgG (both S1/S2 and recombinant N antigen). CONCLUSION: Seroprevalence of anti-SARS-CoV-2 IgG in the healthcare workers of the North Metropolitan Area of Barcelona was higher than in the general population in the same geographical area. Safety measures have to be stressed in order to protect these essential workers from future pandemic waves.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Female , Health Personnel , Humans , Male , Middle Aged , Pandemics/prevention & control , Seroepidemiologic Studies , Spain , Young Adult
13.
Vaccines (Basel) ; 8(3)2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740501

ABSTRACT

In the current worldwide pandemic situation caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the newest coronavirus disease (COVID-19), therapeutics and prophylactics are urgently needed for a large population. Some of the prophylaxis strategies are based on the development of antibodies targeting viral proteins. IgY antibodies are a type of immunoglobulin present in birds, amphibians, and reptiles. They are usually obtained from egg yolk of hyper-immunized hens and represent a relatively inexpensive source of antibodies. Specific IgY can be produced by immunizing chickens with the target antigen and then purifying from the egg yolk. Chicken IgY has been widely explored as a clinical anti-infective material for prophylaxis, preventive medicine, and therapy of infectious diseases. Administered non-systemically, IgY antibodies are safe and effective drugs. Moreover, passive immunization with avian antibodies could become an effective alternative therapy, as these can be obtained relatively simply, cost-efficiently, and produced on a large scale. Here, we highlight the potential use of polyclonal avian IgY antibodies as an oral prophylactic treatment for respiratory viral diseases, such as COVID-19, for which no vaccine is yet available.

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