RESUMEN

The pharmacological space comprises all the dynamic events that determine the bioactivity (and/or the metabolism and toxicity) of a given ligand. The pharmacological space accounts for the structural flexibility and property variability of the two interacting molecules as well as for the mutual adaptability characterizing their molecular recognition process. The dynamic behavior of all these events can be described by a set of possible states (e.g., conformations, binding modes, isomeric forms) that the simulated systems can assume. For each monitored state, a set of state-dependent ligand- and structure-based descriptors can be calculated. Instead of considering only the most probable state (as routinely done), the pharmacological space proposes to consider all the monitored states. For each state-dependent descriptor, the corresponding space can be evaluated by calculating various dynamic parameters such as mean and range values.The reviewed examples emphasize that the pharmacological space can find fruitful applications in structure-based virtual screening as well as in toxicity prediction. In detail, in all reported examples, the inclusion of the pharmacological space parameters enhances the resulting performances. Beneficial effects are obtained by combining both different binding modes to account for ligand mobility and different target structures to account for protein flexibility/adaptability.The proposed computational workflow that combines docking simulations and rescoring analyses to enrich the arsenal of docking-based descriptors revealed a general applicability regardless of the considered target and utilized docking engine. Finally, the EFO approach that generates consensus models by linearly combining various descriptors yielded highly performing models in all discussed virtual screening campaigns.

Asunto(s)

Simulación del Acoplamiento Molecular , Ligandos , Humanos , Unión Proteica , Proteínas/química , Proteínas/metabolismo , Descubrimiento de Drogas/métodos , Sitios de Unión

RESUMEN

ABSTRACT Unvaccinated identical twins developed bilateral anterior uveitis soon after the onset of coronavirus disease 2019 symptoms. During follow-up, both patients developed choroiditis, and one twine developed posterior scleritis and serous retinal detachment. Prompt treatment with oral prednisone ameliorated the lesions, and no recurrence was observed at the 18-month follow-up. Choroiditis may rarely be associated with severe acute respiratory syndrome coronavirus 2 infection, and it responds well to corticosteroid therapy. Although the exact mechanism is unknown, we hypothesize that the virus may act as an immunological trigger for choroiditis.

RESUMEN

BACKGROUND: Health workers were at higher risk for SARS-CoV-2 infection during the COVID-19 pandemic due to occupational risk factors. As part of the WHO Unity Studies initiative, we aimed to characterise these risk factors. METHODS: This global, multicentre, nested, case-control study was conducted in 121 healthcare facilities in 21 countries. Cases were health workers who tested positive for SARS-CoV-2 infection with a documented occupational exposure to COVID-19 patients in the 14 days pre-enrolment. Controls were enrolled from the same facility with a similar exposure but negative serology. Case and control status was confirmed with serological testing at baseline and after 3-4 weeks. Demographic and infection risk factor data were collected using structured questionnaires. FINDINGS: Between June 2020 and December 2021, data were obtained for 1213 cases and 1844 controls. SARS-CoV-2 infection risk was associated with non-adherence to personal protective equipment (PPE) guidelines (aOR 1·67 [95% CI 1·32-2·12]) and not consistently performing hand hygiene after patient contact (aOR 2·52 [1·72-3·68]). Direct close contact with COVID-19 patients was also associated with an increased risk, particularly during prolonged contact (>15 min.). Items associated with a lower risk were respirators during aerosol-generating procedures and gloves, gowns or coveralls during contact with contaminated materials/surfaces. No difference was observed among health workers using respirators versus surgical masks for routine care. CONCLUSION: Appropriate implementation of infection prevention and control measures and PPE use remain a priority to protect health workers from SARS-CoV-2 infection.

RESUMEN

BACKGROUND: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6'-Hydroxy justicidin B (6'-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties. HYPOTHESIS/PURPOSE: The aim of the present study was to assess the effectiveness and safety of 6'-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. METHODS: The efficacy of 6'-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. RESULTS: The anti-SARS-CoV-2 efficacy of 6'-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6'-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6'-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6'-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6'-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6'-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. CONCLUSION: This research highlights both the antiviral efficacy and safety profile of 6'-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6'-HJB was demonstrated using modern scientific methodologies and standards.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , Género Justicia , SARS-CoV-2 , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Células Vero , Chlorocebus aethiops , Humanos , SARS-CoV-2/efectos de los fármacos , Género Justicia/química , Hurones , Masculino , Lignanos/farmacología , Lignanos/uso terapéutico , Alanina/análogos & derivados , Alanina/farmacología , Alanina/uso terapéutico , Femenino , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/farmacología , Adenosina Monofosfato/uso terapéutico , COVID-19 , Perros , Dioxolanos

RESUMEN

TMPRSS13, a member of the Type II Transmembrane Serine Proteases (TTSP) family, is involved in cancer progression and in cell entry of respiratory viruses. To date, no inhibitors have been specifically developed toward this protease. In this study, a chemical library of 65 ketobenzothiazole-based peptidomimetic molecules was screened against a proteolytically active form of recombinant TMPRSS13 to identify novel inhibitors. Following an initial round of screening, subsequent synthesis of additional derivatives supported by molecular modelling, uncovered important molecular determinants involved in TMPRSS13 inhibition. One inhibitor, N-0430, achieved low nanomolar affinity towards TMPRSS13 activity in a cellular context. Using a SARS-CoV-2 pseudovirus cell entry model, we further show the ability of N-0430 to block TMPRSS13-dependent entry of the pseudovirus. The identified peptidomimetic inhibitors and the molecular insights of their potency gained from this study will aid in the development of specific TMPRSS13 inhibitors.

RESUMEN

OBJECTIVES: COVID-19, caused by the SARS-CoV-2 virus, has generated a global pandemic with a wide range of clinical manifestations. Cardiovascular complications are frequently observed in individuals with COVID-19, particularly those with preexisting cardiovascular risk factors or diseases. Cardiac biomarkers, including troponin, natriuretic peptides, and inflammatory markers, play a vital role in risk stratification, diagnosis, monitoring, and prognosis in COVID-19 patients. These biomarkers provide valuable insights into cardiac injury, myocardial stress, inflammation, and the prediction of adverse cardiovascular outcomes. This review aims to provide better understanding of how Cardiac biomarkers correlate to clinical manifestation of COVID-19. METHODS: We retrieved studies from PubMed, Medline, and Google Scholars that included results on cardiac biomarkers in COVID-19. Total of 14 studies were reviewed. RESULTS: 8 studies showed evidence of poor progression of the disease when there is increased troponin. 6 studies out of the 14 mentioned in this review showed positive correlation between mortality and elevation in cardiac biomarkers. This shows the significance of cardiac biomarkers in predicting the mortality in patients with COVID-19. CONCLUSION: It was shown that elevated cardiac biomarkers were associated significantly to poor outcome of covid-19 infection. The outcomes that were linked to increased cardiac biomarkers included increased length of hospitalization, need of life sustaining treatment, myocarditis, invasive and non-invasive respiratory support, and even death were linked to elevated cardiac biomarkers levels.

RESUMEN

This study investigates the effect of daily consumption of a concentrated garlic and onion extract on COVID-19 symptoms among elderly nursing home residents. Volunteers consumed a daily capsule of the concentrated powder rich in organosulfur compounds over 36 weeks during lunch. The incidence and severity of COVID-19 symptoms between the treatment and control groups were compared, along with monitoring the safety of consumption, incidence of other diseases, and medicine usage. The treatment group showed a significant reduction in both the number and severity of COVID-19 symptoms compared to the control group, with no significant adverse effects observed. No significant reduction in symptom duration was detected. This study provides preliminary evidence that concentrated garlic and onion extract may aid in the treatment of COVID-19 among older adults. These findings suggest potential public health benefits, emphasizing the need for further research to explore the immunomodulatory properties of these natural compounds.

RESUMEN

Furin, a serine protease enzyme located in the Golgi apparatus of animal cells, plays a crucial role in cleaving precursor proteins into their mature, active forms. It is ubiquitously expressed across various tissues, including the brain, lungs, gastrointestinal tract, liver, pancreas, and reproductive organs. Since its discovery in 1990, furin has been recognized as a significant therapeutic target, leading to the active development of furin inhibitors for potential use in antiviral, antibacterial, anticancer, and other therapeutic applications. This review provides a comprehensive overview of the progress in the development and characterization of furin inhibitors, encompassing peptides, linear and macrocyclic peptidomimetics, and non-peptide compounds, highlighting their potential in the treatment of both infectious and non-infectious diseases.

Asunto(s)

Furina , Furina/antagonistas & inhibidores , Furina/metabolismo , Humanos , Animales , Peptidomiméticos/farmacología , Peptidomiméticos/química , Peptidomiméticos/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Antivirales/química , Péptidos/uso terapéutico , Péptidos/química , Péptidos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , Desarrollo de Medicamentos

RESUMEN

Here, we report the synthesis of a series of oxyacanthine derivatives and evaluation for their anti-SARS-CoV-2 activity in Vero E6 cells. In order to eliminate the potential metabolic activation caused by para-methylene phenol moiety in oxyacanthine, totally 29 derivatives were designed and synthesized, resulting in 23 compounds with antivirus IC50 below 5.00 µM and 9 compounds with antivirus IC50 below 1.00 µM. Among them, amides compound 4a and 4d exhibited potent anti-SARS-CoV-2 activity and the most favorable selectivity index (SI) in vitro with the SI values of 115 and 70, respectively. The pharmacokinetic properties of 4a and 4d were also assessed. Much more improved exposure in mice, longer half-life (T1/2), and increased oral bioavailability were observed for both compounds 4a and 4d compared with oxyacanthine.

RESUMEN

BACKGROUND: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes. METHODS: We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r. RESULTS: We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs. 54.5% no rebound), Black race (12.5% rebound vs. 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs. 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs. 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound. CONCLUSIONS: COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Ritonavir , SARS-CoV-2 , Humanos , Femenino , Ritonavir/uso terapéutico , Masculino , Persona de Mediana Edad , Anciano , Antivirales/uso terapéutico , COVID-19/epidemiología , Indazoles/uso terapéutico , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Lactamas , Leucina , Nitrilos , Prolina

RESUMEN

BACKGROUND: Hybrid immunity provides better protection against COVID-19 than vaccination or prior natural infection alone. It induces high magnitude and broadly cross-reactive neutralising anti-Spike IgG antibodies. However, it is not clear how long these potent antibodies last, especially in the context of adenovirus-based COVID-19 vaccines. METHODS: We conducted a longitudinal cohort study and enrolled 20 adults who had received an adenovirus-based COVID-19 vaccine before a laboratory-confirmed SARS-CoV-2 infection. We followed up the study participants for 390 days post the initial breakthrough infection. We assessed the longevity and cross-reactive breadth of serum antibodies against SARS-CoV-2 variants of concern (VOCs), including Omicron. RESULTS: The binding anti-Spike IgG antibodies remained within the reported putative levels for at least 360 days and were cross-neutralising against Beta, Gamma, Delta, and Omicron. During the follow up period, a median of one SARS-CoV-2 re-infection event was observed across the cohort, but none resulted in severe COVID-19. Moreover, the re-exposure events were associated with augmented anti-Spike and anti-RBD IgG antibody titres. CONCLUSIONS: This study confirms that hybrid immunity provides durable broadly cross-reactive antibody immunity against SARS-CoV-2 variants of concern for at least a year (360 days), and that it is further augment by SARS-CoV-2 re-exposure.

Asunto(s)

Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Reacciones Cruzadas , Inmunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Adulto , Estudios Longitudinales , Persona de Mediana Edad , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Reacciones Cruzadas/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adenoviridae/inmunología , Anciano , Estudios de Cohortes

RESUMEN

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Eficacia de las Vacunas , Humanos , Adolescente , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , Femenino , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Hong Kong/epidemiología , SARS-CoV-2/inmunología , Esquemas de Inmunización , Miocarditis/prevención & control , Miocarditis/epidemiología , Niño , Vacunas de ARNm , Modelos de Riesgos Proporcionales , Vacunación/métodos

RESUMEN

The aim of this study was to determine the antiviral activity of cannabidiol (CBD) against SARS-CoV-2 infection. CBD is the second most studied cannabinoid obtained from Cannabis plants. We investigated the potential use of CBD, which has so far proven to have a positive effect on different diseases, in the SARS-CoV-2 infection. To test this, in vivo studies were carried out using K18-hACE2 transgenic mice. To reveal the potential therapeutic effect of the CBD at the histopathological and molecular level challenge experiments were performed. The study was designed with two groups (n = 10) and in the treatment group animals were infected with SARS-CoV-2 virus strain B.1.1.7 alpha before the administration of CBD. While the disease progressed and resulted in death in the control group that was infected by the virus alone, it was observed that the infection slowed down and the survival rate increased in the mice treated with CBD along with the virus. In this study, K18-hACE2 transgenic mice infected with the wild SARS-CoV-2 virus were used to investigate and prove the antiviral activity of CBD.

Asunto(s)

Enzima Convertidora de Angiotensina 2 , Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Cannabidiol , SARS-CoV-2 , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/farmacología , Antivirales/uso terapéutico , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , COVID-19/virología , COVID-19/patología , Modelos Animales de Enfermedad , Pulmón/virología , Pulmón/patología , Pulmón/efectos de los fármacos , Ratones Transgénicos , SARS-CoV-2/efectos de los fármacos , Carga Viral/efectos de los fármacos

RESUMEN

SpikoGen® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen® vaccine 25 µg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 µg/mL, 95% CI; 3.72-8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 µg/mL, 95% CI; 16.57-26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection.

Asunto(s)

Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Femenino , Masculino , Adulto , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Método Doble Ciego , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Adyuvantes de Vacunas , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Anciano

RESUMEN

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose significant global health challenges. The results demonstrated that GB-2 at 200 µg/mL effectively increased the population of 293T-ACE2 cells with low RBD binding for both SARS-CoV-2 Omicron EG.5.1 and HV.1 variants by dual-color flow cytometry, indicating its ability to inhibit virus attachment. Further investigation revealed that (+)-catechin at 25 and 50 µg/mL did not significantly alter the ACE2-RBD interaction for the EG.5.1 variant. In contrast, theaflavin showed inhibitory effects at both 25 and 50 µg/mL for EG.5.1, while only the higher concentration was effective for HV.1. Notably, theaflavin 3-gallate exhibited a potent inhibition of ACE2-RBD binding for both variants at both concentrations tested. Molecular docking studies provided insight into the binding mechanisms of theaflavin and theaflavin 3-gallate with the RBD of EG.5.1 and HV.1 variants. Both compounds showed favorable docking scores, with theaflavin 3-gallate demonstrating slightly lower scores (-8 kcal/mol) compared to theaflavin (-7 kcal/mol) for both variants. These results suggest stable interactions between the compounds and key residues in the RBD, potentially explaining their inhibitory effects on virus attachment. In conclusion, GB-2, theaflavin, and theaflavin 3-gallate demonstrate significant potential as inhibitors of the ACE2-RBD interaction in Omicron variants, highlighting their therapeutic promise against COVID-19. However, these findings are primarily based on computational and in vitro studies, necessitating further in vivo research and clinical trials to confirm their efficacy and safety in humans.

Asunto(s)

Enzima Convertidora de Angiotensina 2 , Antivirales , Biflavonoides , Catequina , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Catequina/análogos & derivados , Catequina/farmacología , Catequina/química , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Humanos , Biflavonoides/farmacología , Biflavonoides/química , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Antivirales/farmacología , Antivirales/química , Simulación del Acoplamiento Molecular , Células HEK293 , COVID-19/virología , Tratamiento Farmacológico de COVID-19 , Acoplamiento Viral/efectos de los fármacos , Enterovirus Humano B/efectos de los fármacos , Ácido Gálico/análogos & derivados

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies of other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors have been discovered. Their functioning may provide an explanation for some of the events observed in severe COVID-19 that cannot be directly explained by the model in which ACE2 constitutes the central point of infection. Diabetes mellitus type 2 (T2D) can induce severe COVID-19 development. Although many mechanisms associated with ACE2 can lead to increased SARS-CoV-2 virulence in diabetes, proteins such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster of differentiation 4 (CD4), transferrin receptor (TfR), integrins α5ß1/αvß3, or ACE2 co-receptors neuropilin 2 (NRP2), vimentin, and even syalilated gangliosides may also be responsible for worsening the COVID-19 course. On the other hand, some others may play protective roles. Understanding how diabetes-associated mechanisms can induce severe COVID-19 via modification of virus receptor functioning needs further extensive studies.

Asunto(s)

Enzima Convertidora de Angiotensina 2 , COVID-19 , Diabetes Mellitus Tipo 2 , Chaperón BiP del Retículo Endoplásmico , SARS-CoV-2 , COVID-19/metabolismo , COVID-19/virología , COVID-19/complicaciones , Humanos , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Enzima Convertidora de Angiotensina 2/metabolismo , Chaperón BiP del Retículo Endoplásmico/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/virología , Internalización del Virus , Receptores Virales/metabolismo

RESUMEN

Background/Objectives: Although articles and reviews have been published on the effect of SARS-CoV-2 infection on pregnancy outcomes, they show mixed results with different hypotheses, and no work has focused specifically on the prevalence of thrombocytopenia. The objective of this systematic review and meta-analysis was to synthesize previous evidence and estimate the prevalence of thrombocytopenia in pregnant women with COVID-19. Methods: This systematic review was conducted according to the PRISMA-2020 and MOOSE guidelines. The Medline and Web of Science databases were searched in February 2024, and a meta-analysis of the overall prevalence of thrombocytopenia in pregnant women with COVID-19 was performed. The risk of bias was assessed using the Joanna Briggs Institute checklists. A leave-1-out sensitivity analysis was performed to test for disproportionate effect. Publication bias was assessed by visual inspection of funnel plots and Egger's test. Results: A total of 23 studies met the inclusion criteria, of which 8 were included in the meta-analysis. There was significant (Q = 101.04) and substantial heterogeneity among the studies (I2 = 93.07%). There were no quality-based exclusions from the review of eligible studies. The combined effect of the studies showed a prevalence of thrombocytopenia of 22.9% (95%CI 4.8-41.0%). Subgroup analysis revealed no statistically significant difference in the pooled prevalence of thrombocytopenia ([16.5%; 30.3%]; p = 0.375. Egger's test for bias was not significant, indicating that smaller studies did not report larger estimates of prevalence (t = 1.01, p = 0.353). Moreover, no potential publication bias was found. Our results are consistent with those obtained in pregnant women without COVID-19 infection and extend those of previous reviews of the effect of COVID-19 infection on pregnancy outcomes. Conclusions: Infection during pregnancy does not seem to be an additional risk factor for platelet count, although monitoring platelet count in pregnant women with COVID-19 may be of great importance to determine possible therapeutic strategies, especially in emergency cases.

RESUMEN

Objectives: The objectives were to investigate the clinical characteristics and course of long COVID, defined as the persistence of symptoms at least one month after the onset of COVID-19, in outpatients and to clarify differences in symptoms between SARS CoV-2 mutant strains. Methods: Our observational study in a primary care institution in Japan included 1053 patients with long COVID who visited our outpatient clinic between April 2021 and March 2023. Symptom distribution, performance status, and patient background at the time of the first outpatient visit were compared between infectious strains (Delta and before group and Omicron group). Background factors and symptoms related to time to remission were also analyzed. Results: The severity of COVID-19 in the acute phase was mild, moderate, and severe in 82.2%, 14.9%, and 2.9% in the Delta and before group; and in 97.6%, 1.7%, and 0.4% in the Omicron group, respectively. Vaccination coverage was significantly different between the Delta and before (37.1%) and Omicron groups (73.1%) (p < 0.001), probably due to the period of vaccine unavailability in the former group. Symptoms of fatigue and headache occurred most frequently, irrespective of infectious strain. The mean number of symptoms per patient was significantly higher in the Delta and before group than the Omicron group (3.4 vs. 2.7, p < 0.0001). The median time overall to remission of long COVID was 169 days. Cox hazard model analysis identified female sex, high body mass index, and dyspnea (but not infectious strain) as significant factors prolonging the time to remission (p < 0.05). Conclusions: Differences in the number of symptoms between infectious strains may be related to differences in viral virulence and/or vaccination coverage. However, the clinical course was found to be minimally influenced by the infectious strain. The present results should improve the understanding of prognosis in patients with long COVID from both the clinical and social perspectives.

RESUMEN

Objectives: As the COVID-19 pandemic wanes, understanding maternal-fetal antibody transfer remains crucial for optimizing vaccination strategies. This study evaluates anti-SARS-CoV-2 antibody levels in amniotic fluid following maternal BNT162b2 mRNA vaccination and/or COVID-19 infection during early pregnancy, focusing on the first and second trimesters. Methods: A retrospective cohort study was conducted at a tertiary university-affiliated hospital, involving 149 pregnant women who underwent amniocentesis. Anti-SARS-CoV-2 spike IgG levels were measured in amniotic fluid samples. Participants were categorized based on vaccination and infection status: vaccine-only, infection-only, vaccine + infection, and no vaccine/infection. Correlations between antibody levels and the time since vaccination or infection were analyzed. Results: The vaccine + infection group had a higher proportion of positive antibody levels compared to the vaccine-only group (63.6% vs. 35.9%, p = 0.029). Median SARS-CoV-2 IgG levels were significantly higher in the vaccine + infection group (283.0 AU/mL) than in the vaccine-only group (64.1 AU/mL, p = 0.006). Women who received three vaccine doses had higher antibody levels and more positive antibody rates compared to those with one or two doses. A significant negative correlation was found between antibody levels and the interval since the last vaccine dose or infection. Conclusions: Our results indicate the presence of anti-SARS-CoV-2 antibodies in the amniotic fluid, reflecting antibody transfer during early pregnancy. However, a noticeable decrease in immunity was observed, as indicated by declining amniotic fluid antibody levels over time. Further studies are needed to determine the optimal timing and number of boosters required to protect against new variants of SARS-CoV-2.

RESUMEN

Objective: Knowledge of the role of hospital conditions in SARS-CoV-2 transmission should inform strategies for the prevention of nosocomial spread of this pathogen and of similarly transmitted viruses. This study aimed to identify risk factors for nosocomial acquisition of SARS-CoV-2. Methods: We ran a nested case-control study with incidence density sampling among adult patients hospitalized for >7 days (August-December 2020). Patients testing positive for SARS-CoV-2 after the 7th day of hospitalization were defined as cases and matched with controls (1:4) by date of admission, hospitalization duration until index date, and type of department. Individual and contextual characteristics were gathered, including admission characteristics and exposures during the risk period. Conditional logistic regression was used to estimate the odds ratios (ORs) with respective 95% confidence intervals (CI) separately for probable (diagnosed on day 8-13) and definitive (diagnosed after day 14) nosocomial sets. Results: We identified 65 cases (31 probable; 34 definitive) and 219 controls. No individual characteristic was related to nosocomial acquisition of SARS-CoV-2. Contextual risk factors for nosocomial acquisition were staying in a non-refurbished room (probable nosocomial: OR = 3.6, 1.18-10.87), contact with roommates with newly diagnosed SARS-CoV-2 (probable nosocomial: OR = 9.9, 2.11-46.55; definitive nosocomial: OR = 3.4, 1.09-10.30), and contact with roommates with a first positive test 21-90 days before the beginning of contact (probable nosocomial: OR = 10.7, 1.97-57.7). Conclusions: Hospital conditions and contact with recently infected patients modulated nosocomial SARS-CoV-2 transmission. These results alert us to the importance of the physical context and of agile screening procedures to shorten contact with patients with recent infection.