The constant mutation of SARS-CoV-2 has led to the continuous appearance of viral variants and their pandemics and has improved the development of vaccines with a broad spectrum of antigens to curb the spread of the virus. The work described here suggested a novel vaccine with a virus-like structure (VLS) composed of combined mRNA and protein that is capable of stimulating the immune system in a manner similar to that of viral infection. This VLS vaccine is characterized by its ability to specifically target dendritic cells and/or macrophages through S1 protein recognition of the DC-SIGN receptor in cells, which leads to direct mRNA delivery to these innate immune cells for activation of robust immunity with a broad spectrum of neutralizing antibodies and immune protective capacity against variants. Research on its composition characteristics and structural features has suggested its druggability. Compared with the current mRNA vaccine, the VLS vaccine was identified as having no cytotoxicity at its effective application dosage, while the results of safety observations in animals revealed fewer adverse reactions during immunization.

We conducted a randomized, Phase 2 trial to assess the safety and humoral immunogenicity of reduced doses/dose volume of the standard dose of Ad26.COV2.S COVID-19 vaccine (5 × 1010 viral particles [vp]) in healthy adolescents aged 12-17 years. Participants were randomly assigned to receive Ad26.COV2.S at reduced dose levels of 0.625 × 1010 (0.5 mL), 1.25 × 1010 (0.5 mL) or 2.5 × 1010 (0.5 mL or low volume 0.25 mL) vp in a 1- or 2-dose (56-day interval) primary schedule. Adolescents who received a 1-dose primary schedule received a 2.5 × 1010 vp booster dose 6 months later. Safety and humoral immunogenicity were assessed up to 6 months post-last vaccination. All regimens were well tolerated, with no safety concerns identified. Local and systemic solicited AEs in adolescents were consistent with the known safety profile in adults. All 1- and 2-dose Ad26.COV2.S primary schedules elicited robust peak Spike-binding antibody responses and virus neutralizing titers against the reference strain, in participants with and without preexisting SARS-CoV-2 immunity. Immune responses were durable for at least 6 months. Spike-binding antibody responses were comparable to those elicited in young adults aged 18-25 years who received a standard dose of Ad26.COV2.S in Phase 3 efficacy studies Reduced doses/dose volume of Ad26.COV2.S had an acceptable safety profile and elicited robust humoral immune responses in adolescents aged 12-17 years. All 1- and 2-dose schedules elicited Spike-binding antibody responses that were comparable to an adult population in whom efficacy has been demonstrated using a higher vaccine dose. (clinicaltrials.gov NCT05007080).

NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.

COVID-19 is a human respiratory syndrome caused by the infection of the SARS-CoV-2 virus that has a high rate of infection and mortality. Viruses modulate the host machinery by altering cellular mechanisms that favor their replication. One of the mechanisms that viruses exploit is the protein folding and processing of post-translational modifications that occur in the endoplasmic reticulum (ER). When ER function is impaired, there is an accumulation of misfolded proteins leading to endoplasmic reticulum stress (ER stress). To maintain homeostasis, cells trigger an adaptive signaling mechanism called the Unfolded Protein Response (UPR) which helps cells deal with stress, but under severe conditions, can activate the apoptotic cell death mechanism. This study elucidated an activation of a diversity of molecular mechanisms by Brazilian variants of SARS-CoV-2 by a time-resolved and large-scale characterization of SARS-CoV-2-infected cells proteomics and immunoblotting. Furthermore, it was shown that pharmacological UPR modulation could reduce viral release by counteracting the different viral activations of its cellular response. Analysis of human clinical specimens and disease outcomes focusing on ER stress reinforces the importance of UPR modulation as a host regulatory mechanism during viral infection and could point to novel therapeutic targets. SIGNIFICANCE: Since the emergence of SARS-CoV-2 and the consequent COVID-19 pandemic, the rapid emergence of variants of this new coronavirus has been a cause for concern since many of them have significantly higher rates of transmissibility and virulence, being called Variants of Concern (VOC). In this work, we studied the VOCs Gamma (P.1) and Zeta (P.2), also known as Brazilian variants. Constant evidence has reported that there are particularities related to each variant of SARS-CoV-2, with different rates of transmissibility, replication and modulation of host biological processes being observed, in addition to the mutations present in the variants. For this reason, this work focused on infections caused by the Brazilian variants of SARS-CoV-2 in different cell lines, in which we were able to observe that the infections caused by the variants induced endoplasmic reticulum stress in the infected cells and activated the UPR pathways, presenting specific modulations of each variant in this pathway. Furthermore, transcriptome analysis of patients revealed a correlation between ER-related genes and COVID-19 progression. Finally, we observed that the use of UPR modulators in host cells decreased viral release of all variants without affecting cell viability. The data presented in this work complement the observations of other studies that aim to understand the pathogenicity of SARS-CoV-2 VOCs and possible new therapeutic strategies, mainly targeting biological processes related to the endoplasmic reticulum.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to a significant burden on global healthcare systems. COVID-19-induced acute kidney injury (AKI) is among one of the complications, that has emerged as a critical and frequent condition in COVID-19 patients. This AKI among COVID-19 patients is associated with poor outcomes, and high mortality rates, especially in those with severe AKI or requiring renal replacement therapy. COVID-19-induced AKI represents a significant complication with complex pathophysiology and multifactorial risk factors. Indeed, several pathophysiological mechanisms, including direct viral invasion of renal cells, systemic inflammation, endothelial and thrombotic abnormalities as well as nephrotoxic drugs and rhabdomyolysis are believed to underlie this condition. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include acute tubular necrosis, glomerular injury, and the presence of viral particles within renal tissue and urine. Identified risk factors for developing AKI vary among studies, depending on regions, underlying conditions, and the severity of the disease. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include show acute tubular necrosis, glomerular injury, and viral particles within renal tissue and urine. While, identified risk factors for developing AKI vary among studies, according to regions, underlying conditions, and the gravity of the disease. This narrative review aims to synthesize current knowledge on the incidence, pathophysiology, risk factors, histopathology, and outcomes of AKI induced by COVID-19.

Coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused secondary pandemic, which still poses a serious threat to physical health and economic development. Herein, the target-driven functionalized DNA hydrogel capillary sensor based on cascade signal amplification and carbon coated cobalt manganese modified by prussian blue and platinum nanoparticles (MnCo@C-Pt-PB NPs) has been successfully developed for dual-mode detection of SARS-CoV-2. The cascade signal amplification triggered by target RNA causes the permeability of the DNA hydrogel loaded in the capillary to be destroyed, thereby releasing the embedded MnCo@C-Pt-PB NPs as signal molecules into 3,3',5,5'-tetramethylbenzidine/hydrogen peroxide (TMB/H2O2) solution under the driving of capillarity. The colorless TMB is then catalyzed to blue oxidation products (oxTMB) due to peroxidase-like activity of MnCo@C-Pt-PB NPs, and MnCo@C-Pt-PB NPs and oxTMB with photothermal properties synergistically increase the system temperature under near-infrared irradiation, which are recorded by portable devices to achieve dual-mode detection. Signals intensity are proportional to the logarithm of T-RNA concentration in a wide detection range (100 aM-100 pM), with a detection limit of 100 aM. Moreover, the reliability of the developed method in oropharyngeal swabs samples has also been validated. The signal conversion and amplification function of functionalized DNA hydrogel enhances the convenience, sensitivity and versatility of the developed method, which is promising to be applied in environmental safety, molecular diagnostic assays and disease prevention.

People with chronic illnesses are vulnerable to stress and psychopathology during population-level disasters, as a subset of individuals with disabilities. We aimed to examine the relationships between chronic illness, cumulative and specific stressors, and probable depression, probable anxiety, and post-traumatic stress in an under-resourced urban population in New York City during the COVID-19 pandemic. Using cross-sectional survey data collected in April 2020, we utilized bivariate chi-square analyses and multivariable logistic regression models to estimate differences in and adjusted odds of stressor endorsement and diagnostic prevalence between people with and without chronic illness. We also assessed effect modification of the relationship between stressor exposure and psychopathology by chronic illness status. Compared to people without chronic illness, those who reported having a chronic illness experienced increased odds of probable depression, probable anxiety, and post-traumatic stress. They were also more likely to report high cumulative COVID-19-related stress exposure, death of someone close to them due to coronavirus or COVID-19, family problems, feeling alone, supply shortages, and financial problems. Chronic illness was found to be an effect modifier in the relationship between the death of someone close due to coronavirus or COVID-19 and probable depression and between household job loss and probable anxiety.

Pregnant women are at heightened risk for severe COVID-19 outcomes. However, treatment options during pregnancy remain limited due to concerns over their safety and efficacy.

This systematic review and meta-analysis assessed the safety and efficacy of nirmatrelvir-ritonavir in pregnant women diagnosed with mild-to-moderate COVID-19. The analysis focused on cases where the treatment was initiated within five days of symptom onset. A single-arm meta-analysis was performed to comprehensively evaluate outcomes across maternal, delivery, and neonatal domains.

In line with PRISMA guidelines, six studies involving a total of 427 pregnant patients were included in the analysis. Hospitalization was reported in 2% of patients (95% CI: 1%-5%), with low heterogeneity across studies (I2 = 21.9%). Drug discontinuation and new-onset gestational diabetes (NOGDM) had a pooled estimate of 0.7% (95% CI: 3% to 15%) and 4.0% (95% CI: 1% to 16%), respectively, with substantial heterogeneity (I2 = 64.7% and 66.5%), respectively. New-onset gestational hypertension (NOGHTN) had a pooled estimate of 4% (95% CI: 1% to 26%), with considerable heterogeneity (I2 = 78.81%). For neonatal outcomes, the pooled estimate for birth weight was 3186 g (95% CI: 3123-3248 g; I2 = 0%), and no maternal or neonatal deaths were reported across the included studies.

Nirmatrelvir-ritonavir appears safe and effective for mild-to-moderate COVID-19 in pregnant women, with low rates of hospitalization and adverse maternal outcomes. Larger, randomized studies are crucial to confirm these findings and ensure safety in diverse populations.

To study the prevalence and timing of neurological manifestations, including cognitive involvement, in patients hospitalized for Coronavirus disease 2019 (COVID-19). To analyze the pathogenic mechanisms and any association they have with disease severity.

Longitudinal cohort study with prospective follow-up of patients who required hospitalization. Patients under 65 who had no pre-existing cognitive impairment and did not require an ICU stay were evaluated 3 and 12 months after discharge using a battery of neuropsychological tests.

Of 205 patients hospitalized for COVID-19, 153 (74.6%) presented with neurological manifestations. The most frequent were myalgia (32.7%), headache (31.7%), dysgeusia (29.2%), and anosmia (24.9%). Patients with more severe illness at the time of hospitalization presented fewer neurological manifestations. Of the 62 patients who underwent neuropsychological examination 3 months after discharge, 22.6% had impaired attention, 19.4% impaired working memory, 16.1% impaired learning and retrieval, 9.7% impaired executive functions, and 8.2% impaired processing speed. Patients with anosmia also presented with more headache (OR 5.45; p < 0.001) and greater risk of working memory impairment (OR 5.87; p 0.03). At follow-up 12 months after hospital discharge, 14.3% of patients still showed impaired attention, 2.4% impaired working memory, 2.5% impaired executive functions, and 2.5% impaired processing speed.

Neurological manifestations are common in patients hospitalized for COVID-19 regardless of severity. The high prevalence of anosmia and its association with headache and working memory impairment at 3 months, suggest potential direct or indirect damage to the prefrontal cortex via invasion of the olfactory bulb by COVID-19.

In May 2023 the World Health Organization (WHO) declared the end of COVID-19 as a public health emergency. Seroprevalence studies performed in African countries, such as Cameroon, depicted a much higher COVID-19 burden than reported by the WHO. To better understand humoral responses kinetics following infection, we enrolled 333 participants from Yaoundé, Cameroon between March 2020 and January 2022. We measured the levels of antibodies targeting the SARS-CoV-2 receptor-binding-domain (RBD) and the Spike glycoproteins of Delta, Omicron BA.1 and BA.4/5 and the common cold coronavirus HCoV-OC43. We also evaluated plasma capacity to neutralize authentic SARS-CoV-2 virus and to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC). Most individuals mounted a strong antibody response against SARS-CoV-2 Spike. Plasma neutralization waned faster than anti-Spike binding and ADCC. We observed differences in humoral responses by age and circulating variants. Altogether, we show a global overview of antibody dynamics and functionality against SARS-CoV-2 in Cameroon.

New-onset psychiatric disorders are frequent after COVID-19. We aim to determine whether acute COVID-19 severity markers can predict post-COVID new-onset psychiatric disorders. We conducted an electronic health records (EHR) cohort study of patients hospitalized for COVID-19 and without any known history of psychiatric disorders. Patients were included between January 2020 and September 2022 in one of the 36 university hospitals of the Assistance Publique - Hôpitaux de Paris. Acute COVID-19 clinical and biological severity markers were recorded during hospitalization for COVID-19. Psychiatric ICD-10 diagnoses were recorded up to 2 years and 9 months after hospitalization for COVID-19. Predictors of post-COVID new-onset psychiatric disorders were identified based on Cox regression models and sensitivity analyses. Predictive scores were built and tested in age- and sex-stratified populations. A total 34,489 patients hospitalized for COVID-19 were included; 3717 patients (10.8%) had at least one post-COVID new-onset psychiatric disorder. Hospital stay >7 days (HR = 1.72, 95%CI [1.59-1.86], p < 0.001), acute delirium (HR = 1.49, 95%CI [1.28-1.74], p < 0.001), elevated monocyte count (HR = 1.14, 95%CI [1.06-1.23], p < 0.001) and elevated plasma CRP (HR = 0.92, 95%CI [0.86-0.99], p = 0.04) independently predicted post-COVID new-onset psychiatric disorders. Sensitivity analyses confirmed hospital stay >7 days, acute delirium, and elevated monocyte count as predictors. Predictive scores based on these variables had good 12-month positive predictive values, up to 7.5 times more accurate than random in women < 65 years. In conclusion, hospital stay >7 days, acute delirium, and elevated monocyte count during acute COVID-19 predict post-COVID new-onset psychiatric disorders.

The COVID-19 pandemic affected healthcare management for people with multiple sclerosis (PwMS), leading to alterations in disease-modifying therapies (DMTs) due to concerns about COVID-19 outcomes and vaccine efficacy.

To compare DMT prescription patterns in PwMS before, during, and after the COVID-19 pandemic.

PwMS from the German MS Register, between 2019 and 2024, either newly diagnosed (Cohort A) or who discontinued or switched DMT (Cohort B), were analyzed over a follow-up period of 3 months. Data from the pre-pandemic period were compared to early-, late-, and post-pandemic periods. DMTs were categorized as medium efficacy (meDMT) or high efficacy (heDMT).

In Cohort A (n = 1810), pre-pandemic 46% had no DMT within 3 months of diagnosis, 39% received meDMT, and 15% heDMT (7.5% B cell-depleting therapies (BCD)). heDMT use increased during later periods ("early" 19%, "late" 29%, "post" 41%), with a shift toward BCD. In cohort B (n = 4246), pre-pandemic 47% paused DMT, 19% switched to meDMT, and 34% to heDMT (17% BCD). heDMT use also rose during the pandemic ("early" 37%, "late" 47%, "post" 48%), with increased BCD use.

There were no delays in DMT initiation or resumption during the pandemic with a notable increase in heDMT and BCD use, reflecting growing confidence in these treatment options.

Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease that needs further clinical investigation. Characterizing the temporal pattern of combined infections in patients with COVID-19 may help clinicians understand the clinical nature of this disease and provide valuable diagnostic and therapeutic guidelines.

We retrospectively analyzed COVID-19 patients isolated in four study hospitals in Korea for one year period from May 2021 to April 2022 when the delta and omicron variants were dominant. The temporal characteristics of combined infections based on specific diagnostic tests were analyzed.

A total of 16,967 COVID-19 patients were screened, 2,432 (14.3%) of whom underwent diagnostic microbiologic tests according to the clinical decision-making, 195 of whom had positive test results, and 0.55% (94/16,967) of whom were ultimately considered to have clinically meaningful combined infections. The median duration for the diagnosis of combined infections was 15 (interquartile range [IQR], 5-25) days after admission. The proportion of community-acquired coinfections (≤ 2 days after admission) was 11.7% (11/94), which included bacteremia (10/94, 10.63%) and tuberculosis (1/94, 1.06%). Combined infections after 2 days of admission were diagnosed at median 16 (IQR, 9-26) days, and included bacteremia (72.3%), fungemia (19.3%), cytomegalovirus (CMV) diseases (8.4%), Pneumocystis jerovecii pneumonia (PJP, 8.4%) and invasive pulmonary aspergillosis (IPA, 4.8%).

Among COVID-19 patients with risk factors for severe complications, 0.55% had laboratory-confirmed combined infections, which included community and nosocomial pathogens in addition to unusual pathogens such as CMV disease, PJP and IPA.

This retrospective study aimed to investigate the effect of mild-to-moderate COVID-19 on the risk of deep vein thrombosis (DVT) in patients with hip fractures. Hip fractures are common in the elderly, and previous research has shown that they accounted for 58.3% of traumatic fractures in older inpatients during the COVID-19 pandemic in China. Meanwhile, the relationship between COVID-19 and DVT is complex. Some studies have reported that the incidence of DVT in critically ill COVID-19 patients can be as high as 46%, and 20% in those with moderate-to-severe cases. However, the impact of mild-to-moderate COVID-19 on DVT risk in hip fracture patients remains unclear.

Adult patients who underwent surgery for hip fractures between December 8, 2022, and January 9, 2023, were included in the study. All patients were tested for SARS-CoV-2 nucleic acid and were assessed for DVT preoperatively using doppler ultrasonography (DUS). Logistic regression was used to identify risk factors for DVT.

The records of 98 patients with hip fractures, were included in the analysis, of whom 63 were SARS-CoV-2 positive and 35 were SARS-CoV-2 negative. Pre-operative DUS showed that 36/98 patients (37%) had DVT, including 25/63 (40%) patients with COVID-19, and 11/35 (31%) patients without COVID-19. Multivariable logistic regression analysis showed that pre-operative leukocyte count and platelet-to-lymphocyte ratio (PLR) were independent risk factors for DVT, whereas mild-to-moderate COVID-19 was not an independent risk factor for DVT. In patients with hip fractures, COVID-19 did not significantly increase the risk of DVT.

Therefore, in patients with hip fractures, DVT prevention measures should be implemented routinely, regardless of COVID-19 status.

Coronavirus disease 2019 (COVID-19) survivors are concerned about the likelihood of developing further diseases. This study examines the global trends in scientific research on diabetes associated with COVID-19 from several perspectives. Bibliometric analyses are used to undertake a scientific review of the literature. The Web of Science Core Collection (WoSCC) database was used to acquire bibliographic information on diabetes related to COVID-19 from Jan 2020 to Dec. 2023. The visual map was built via advanced CiteSpace 6.2.R6. 7,348 papers were found. Khunti Kamlesh and Rizzo-Manfredi are the most well-known high-yield authors in this area, and the top ten authors collaborate extensively. Most of these papers came from universities. Harvard Medical School has the most publications, followed by Wuhan University and Huazhong University of Science and Technology. China and the United States are the countries with the most publications. Angiotensin-converting enzymes, chronic disease, intensive care unit, viral infection, and gestational diabetes mellitus were scored 0-11, 2, 3, and 4, respectively. Zhou et al.'s work on this topic, which appeared in the prominent medical journal The Lancet, was cited 1,366 times, highlighting its importance. "clinical characteristics," "diabetes mellitus," "metabolic syndrome," and "angiotensin-converting enzyme" were used as keywords for reference co-citation and clustering data identify. Over the last four years, related investigations have focused primarily on observing clinical aspects. This report is important for developing treatment strategies, directing future research, and guiding clinical practice.

After the COVID-19 pandemic, nonhuman primate (NHP) models, which are necessary for the rapid development of vaccines and new medical therapies, have become important in studies on infectious diseases because of their genetic, metabolic, and immunological similarities to humans. Our group has long been using NHP models in studies on infectious diseases including H1N1 influenza pandemic and COVID-19. Despite limitations such as the limited number of animals and the husbandry requirements, NHP models have contributed to the prediction of the pathogenicity of emerging viruses and the evaluation of the efficacy of vaccines and therapeutics due to the similarity of NHP models to humans before starting clinical trials to select good candidates of vaccines and drugs. In this review, the findings obtained in NHP infectious disease models of influenza and COVID-19 are summarized to clarify the benefits of NHP models for studies on infectious diseases. We believe that this review will support future research in exploring new perspectives for the development of vaccines and therapies targeting influenza, COVID-19, and infectious diseases in future pandemics.

We aimed to evaluate the effects of both the expression and serum levels of Epidermal growth factor (EGF) and Transforming growth factor-β1 (TGF-β1) genes in patients with different degrees of cellular damage as mild, moderate, severe, and critical illness that can lead to fibrosis caused by SARS-CoV-2. Totally 45 individuals (male: 21(46.67%); female: 24(53.33%)) with COVID-19 infection were included in this study. Four groups were constituted as mild (n = 16)], moderate (n = 10), severe (n = 10), and critical (n = 9) according to the severity of the disease. Blood samples were drawn from the patients, and all of the hemograms, EGF and TGFβ1 gene expression, and serum levels were evaluated. The mean age of individuals was 57.311 ± 18.383 (min: 28, max: 94). Significant differences were found among the groups for PLT (χ2 = 9.955; p = 0.019), CRP (χ2 = 7.693; p = 0.053), Ferritin (χ2 = 22.196; p < 0.001), D-dimer (χ2 = 21.982; p = 0.000), LDH (χ2 = 21.807; p < 0.001) and all these parameters (exclude PLT in severe groups) was increased depending on the severity of the disease. Additionally, significant differences were detected for EGF (χ2 = 29.528; p < 0.001), TGFB1 (χ2 = 28.981; p < 0.001) expression (that increased depending on the disease severity), and EGF (χ2 = 7.84; p = 0.049), TGFB1 (χ2 = 17.451; p = 0.001) serum concentration levels (that decreased depending on the disease severity). This study found statistically significant differences for both EGF 2-ΔΔCt. TGFβ1 2-ΔΔCt and EGF, TGFβ1 serum concentration values among all patient groups. As disease severity increased, EGF 2-ΔΔCt. TGFβ1 2-ΔΔCt levels increased, while EGF and TGFβ1 serum concentration levels decreased. Perhaps this study will be useful in managing COVID-19 infection severity and pulmonary fibrosis cases secondary to COVID-19.

SARS-CoV-2, the third major coronavirus of the 21st century, causing COVID-19 disease, profoundly impacts public health and workforces worldwide. Identifying individuals at heightened risk of SARS-CoV-2 infection is crucial for targeted interventions and preparedness. This study investigated 35 SNVs within viral infection-associated genes in SARS-CoV-2 patients and uninfected controls from the Basque Country (March 2020-July 2021). Its primary aim was to uncover genetic markers indicative of SARS-CoV-2 susceptibility and explore genetic predispositions to infection. Association analyses revealed previously unreported associations between SNVs and susceptibility. Haplotype analyses uncovered novel links between haplotypes and susceptibility, surpassing individual SNV associations. Descriptive modelling identified key susceptibility factors, with rs11246068-CC (IFITM3), rs5742933-GG (ORMDL1), rs35337543-CG (IFIH1), and GGGCT (rs2070788, rs2298659, rs17854725, rs12329760, rs3787950) variation in TMPRSS2 emerging as main infection-susceptibility indicators for a COVID-19 pandemic situation. These findings underscore the importance of integrated SNV and haplotype analyses in delineating susceptibility to SARS-CoV-2 and informing proactive prevention strategies. The genetic markers profiled in this study offer valuable insights for future pandemic preparedness.

COVID-19 manifests with a wide range of severities, from asymptomatic to critical conditions. Immunological profiles in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may serve as early indicators of disease severity, aiding in prioritizing patient care.

Archived patient plasma samples were retrieved from the Molecular Lab Bio-repository, ensuring equal representation of males, females, and various disease severities. Socio-demographic and disease severity data were obtained from patient health records. Levels of pro-inflammatory cytokines (interferon-gamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], interleukin-2 [IL-2], and interleukin-17 [IL-17]) and anti-inflammatory cytokines (interleukin-4 [IL-4], interleukin-6 [IL-6], and interleukin-10 [IL-10]) were measured using the BD FACSCalibur flow cytometer. Data analysis involved comparing cytokine levels across different disease severities, with demographic data expressed as means ± standard deviation (SD). Statistical significance was set at P ≤ 0.05.

The mean ages for males and females were 49.6 ± 22.7 and 48.4 ± 23.7, respectively. Mean ages for disease severity categories were 33 ± 19 (asymptomatic), 45.2 ± 21.5 (moderate), 56.8 ± 18.7 (severe), and 61.95 ± 22 (critical). Comorbidities were present in 25 % of patients, with cardiovascular disease (41 %) and pulmonary disease (31 %) being the most common. Predominant symptoms in critical patients included dyspnea (63 %) and myalgia (60 %), while rhinorrhea (46.2 %) and chest pain (45.7 %) were common in severe cases. Gastrointestinal symptoms were observed only in severe and critical groups. Levels of the pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-17) increased linearly with disease severity. Among anti-inflammatory cytokines, IL-6 and IL-10 levels also rose significantly with increasing severity.

Levels of TNF-α, IL-17, and IL-6 correlated with disease severity and may serve as prognostic biomarkers. Advanced age and underlying comorbidities were independently associated with higher disease severity.

Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected global health, economies, and societies, necessitating a deeper understanding of the factors influencing its spread and severity. Methods: This study employed text network analysis to examine relationships among various risk factors associated with severe COVID-19. Analyzing a dataset of published studies from January 2020 to December 2021, this study identifies key determinants, including age, hypertension, and pre-existing health conditions, while uncovering their interconnections. Results: The analysis reveals five thematic clusters: biomedical, occupational, demographic, behavioral, and complication-related factors. Temporal trend analysis reveals distinct shifts in research focus over time. In early 2020, studies primarily addressed immediate clinical characteristics and acute complications of COVID-19. By mid-2021, research increasingly emphasized long COVID, highlighting its prolonged symptoms and impact on quality of life. Concurrently, vaccine efficacy became a dominant topic, with studies assessing protection rates against emerging viral variants, such as Alpha, Delta, and Omicron. This evolving landscape underscores the dynamic nature of COVID-19 research and the adaptation of public health strategies accordingly. Conclusions: These findings offer valuable insights for targeted public health interventions, emphasizing the need for tailored strategies to mitigate severe outcomes in high-risk groups. This study demonstrates the potential of text network analysis as a robust tool for synthesizing complex datasets and informing evidence-based decision-making in pandemic preparedness and response.

Real-time and precise evaluation of human body temperature offers crucial insights for health monitoring and disease diagnosis, while integration of high-performance and miniaturized sensors remains a challenge. Inspired by the thermal sensory pathway of skin, here we developed a new route for scalable fabrication of rapid-response and miniaturized thermoreceptor sensors using self-aligned in-plane silicon nanowire (SiNW) arrays as sensitive channels. These SiNW arrays, with a diameter of 100 ± 14 nm, were integrated into temperature sensors with a density of 445 devices/cm2 without using any high-precision lithography. The sensors exhibited an excellent temperature coefficient of resistance of -1.8%/°C, enabling the precise spatial identification of heat sources. They achieved real-time monitoring of temperature changes during breathing and blowing activities, with a rapid response time of ∼0.2 s and recovery time of ∼1 s. This study provides a robust foundation for the integration of advanced miniaturized temperature sensors for biological monitoring applications.

Severe coronavirus outbreaks, including SARS, MERS, and COVID-19, have underscored the urgent need for effective antiviral therapies. This study evaluated the antiviral activity of biflavanones isolated from Ouratea spectabilis-specifically ouratein (Our-) A, B, C, and D-against murine hepatitis virus (MHV-3) and human SARS-CoV-2. Cells infected with MHV-3 or SARS-CoV-2 were treated with ourateins, and viral replication was assessed using plaque assays. Mice infected with MHV-3 were treated with Our-D either orally or intraperitoneally. Key assessments included leukocyte counts, cytokine and chemokine levels, histological analysis, and survival rates. The mechanism of action was explored through in silico and in vitro studies focused on the binding and inhibition of the main protease (Mpro). Our-D significantly inhibited the replication of both viruses, with a selective index of 2.5 for MHV-3 and 14.9 for SARS-CoV-2. In vivo, Our-D reduced leukocyte infiltration in the lungs, decreased CCL2 levels, increased IL-10, and lowered plasma IL-6 and CXCL1 levels. Additionally, Our-D mitigated lung damage, partially restored betacoronavirus-induced lymphopenia, and reduced viral loads in the lungs, heart, and spleen, ultimately improving survival in mice. In silico studies revealed that Our-A and Our-C had strong binding affinity for Mpro, and both significantly inhibited Mpro activity in vitro, unlike Our-D. Our-D protected mice from coronavirus infection by modulating the inflammatory response and reducing viral loads, with minimal effect on Mpro inhibition, suggesting alternative mechanisms for its antiviral activity.

Sustainable development represents a significant and pressing challenge confronting the global community at present. A wide variety of macroscopic engineering systems has been developed to promote sustainable development. Recent advancements in DNA materials have showcased their substantial contributions toward achieving sustainable development goals (SDGs). Compared to nonbiological materials, DNA materials possess exceptional properties such as genetic functionality, molecular programmability, recognition capabilities, and biocompatibility. These unique characteristics enable DNA materials to serve as general and versatile substrates beyond their genetic role. Consequently, they can be used to develop DNA-based engineering systems that offer versatile solutions to support sustainable development. In this Perspective, we critically examine the opportunities that DNA-based engineering systems present in contributing to the achievement of the SDGs within various real-world scenarios. We establish direct relationships between DNA-based engineering systems and the SDGs, highlighting their inherent merits in accelerating sustainable development. Furthermore, in order to successfully achieve SDGs, we address the challenges associated with these systems and emphasize the urgent need for developing multifunctional, reliable, biosafe, and intelligent DNA-based engineering systems to overcome these challenges.

Introduction: Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, in vitro, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Methods: Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Results: Urine exosomal podocalyxin levels were significantly high at 10 week (n = 18; P = 0.001), 6 month (n = 25; P = 0.003) and 12 month (n = 14; P = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (n = 18; P = 0.001) and 12 month (n = 14; P = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Conclusion: Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.

Following several waves of the COVID-19 pandemic, we are now facing a lower but persistent rate of SARS-CoV-2 infections, with seasonal resurgences often coinciding with other respiratory tract infections.

We aimed to identify early clinico-biological variables predictive of an unfavorable outcome in patients with primary SARS-CoV-2 infection. We also evaluated the role of suPAR, an innovative biomarker, in predicting disease severity.

We included 255 patients with PCR-confirmed primary SARS-CoV-2 infection and with a 30-day follow-up minimum. Blood samples were collected within the first 24 h of hospitalization to measure suPAR levels. Comprehensive data from medical records were analyzed to assess their predictive value in stratifying patients into seven severity groups, with groups 1 to 3 representing severe COVID-19 (death, intubation, ECMO, or non-invasive ventilation).

Early plasma suPAR levels were significantly associated with severe disease progression, as evidenced by ANOVA and logistic regression models, highlighting suPAR as a persistent predictive factor for unfavorable outcomes.

Our findings suggest that a single suPAR measurement, performed early after a positive PCR test for SARS-CoV-2, holds strong predictive value for patient outcomes. This biomarker, alongside pulse oximetry and CT scan results, could be instrumental in early patient triage during seasonal COVID-19 resurgences.

High-affinity and specific binding toward the human angiotensin-converting enzyme 2 (hACE2) receptor by severe acute respiratory syndrome coronavirus (SARS)-related coronaviruses (SARSr-CoVs) remains incompletely understood. We report cryo-electron microscopy structures of eight different S-proteins from SARSr-CoVs found across Asia, Europe, and Africa. These S-proteins all adopt tightly packed, locked, prefusion conformations. These structures enable the classification of SARSr-CoV S-proteins into three types, based on their receptor-binding motif (RBM) structures and ACE2 binding characteristics. Type-2 S-proteins often preferentially bind bat ACE2 (bACE2) over hACE2. We report a structure of a type-2 BtKY72-RBD in complex with bACE2 to understand ACE2 specificity. Structure-guided mutagenesis of BtKY72-RBD reveals that multiple synergistic mutations in four different regions of RBM are required to achieve high-affinity hACE2 binding. Similar RBM changes can also confer hACE2 binding to another type-2 BM48-31 S-protein, which is primarily non-ACE2 binding. These results provide an understanding of how high-affinity hACE2 binding may be acquired by SARSr-CoV S-proteins.

This systematic review evaluates the efficacy and safety of COVID-19 vaccines in individuals with cystic fibrosis (CF). A systematic search of major databases conducted between December 2019 and January 2024 identified eight cohort studies comprising 1,361 CF patients. Studies without subgroup analyses specific to CF patients were excluded, which may have limited the generalizability of findings, particularly for CF lung transplant recipients. COVID-19 vaccines generally induced robust serological responses following the second and third doses, although reduced antibody levels were observed in lung transplant recipients. Factors influencing humoral response included prior SARS-CoV-2 infection, age, inhaled corticosteroid use, and immunosuppressive therapy. Vaccination-related adverse events were predominantly mild. Although breakthrough infections were reported, severe COVID-19 outcomes were infrequent among vaccinated CF patients. The evidence supports the immunogenicity and safety of COVID-19 vaccines in the CF patients. However, individualized vaccination strategies may be necessary for CF lung transplant recipients and those on immunosuppressive therapies. Further research is essential to optimize vaccination strategies and to identify risk factors associated with breakthrough infections in this high-risk population.

The global pandemic of novel coronavirus pneumonia (COVID-19) has resulted in millions of deaths over the past three years. As one of the most commonly affected extra-pulmonary organs, numerous studies have reported varying degrees of liver injury in a significant proportion of patients with COVID-19, particularly in severe and critically ill patients. Early prediction of liver dysfunction in hospitalized patients would facilitate the clinical management of COVID-19 and improve clinical prognosis, but reliable and valid predictive models are still lacking.MethodsWe collected data from 286 patients with RT-PCR confirmed COVID-19 admitted to various ICUs from the case system. These patients were randomly divided into a training cohort (50%) and a validation cohort (50%). In the training cohort, we first used ROC curves to measure the predictive efficiency of each of the variables for the development of liver damage during hospitalization in patients with COVID-19, followed by LASSO regression analysis to screen the variables for predictive models and logistic regression analysis to identify relevant risk factors. A nomogram based on these variables was created following the above model. Finally, the efficiency of the prediction models in the training and validation cohorts was assessed using AUC, consistency index (C index), calibration curves and Decision Curve Analysis.ResultsOut of a total of 80 parameters for COVID-19 patients admitted to the ICUs, 10 were determined to be significantly associated with the occurrence of liver dysfunction during hospitalization. Based on these predictors, further prediction models were used to construct and develop a nomogram that was offered for practical clinical application. The C-index of the column line graphs for the training and validation cohorts was 0.956 and 0.844 respectively. in addition, the calibration curves for the model showed a high degree of agreement between the predicted and actual incidence of liver dysfunction in patients with COVID-19.ConclusionBy developing a predictive model and associated nomogram, we predicted the incidence of liver dysfunction during hospitalization in patients with COVID-19 in the ICU. The model's predictive performance was determined in both the training and validation cohorts, contributing to the clinical management of COVID-19.

Lipid nanoparticle (LNP)-mRNA vaccines have demonstrated protective capability in combating SARS-CoV-2. Their extensive deployment across the global population leads to the broad presence of T-cell immunity against the SARS-CoV-2 spike protein, presenting an opportunity to harness this immunological response as a universal antigen target for cancer treatment. Herein, we design and synthesize a series of amino alcohol- or amino acid-derived ionizable lipids (AA lipids) and develop an LNP-RNA-based antigen presentation platform to redirect spike-specific T-cell immunity against cancer in mouse models. First, in a prime-boost regimen, AA2 LNP encapsulating spike mRNA elicit stronger T-cell immunity against the spike epitopes compared to FDA-approved LNPs (ALC-0315 and SM-102), highlighting the superior delivery efficiency of AA2 LNP. Next, AA15V LNP efficiently delivers self-amplifying RNAs (saRNAs) encoding spike epitope-loaded single-chain trimer (sSE-SCT) MHC I molecules into tumor tissues, thereby inducing the presentation of spike epitopes. Our results show that a single intratumoral (i.t.) treatment of AA15V LNP-sSE-SCTs suppresses tumor growth and extends the survival of B16F10 melanoma and A20 lymphoma tumor-bearing mice vaccinated with AA2 LNP-spike mRNA. Additionally, AA15V LNP-sSE-SCTs enable SE-SCT expression in ex vivo human glioblastoma and lung cancer samples, suggesting its potential in clinical translation.

To describe the epidemiology pattern of the COVID-19 pandemic during all Spanish State of Alarm.

Retrospective, observational, cohort and multicenter study. Inclusion criteria: age ≥18 years old, admitted for COVID-19 pneumonia in any of the centers of the HM Hospitals Group. Exclusion criteria: voluntary discharge, death in the emergency department, transfer to centers outside the HM group or incomplete data. State of Alarm period: 31/01/2020 to 05/07/2023. Predominant COVID-19 variant was defined when it exceeded 50% of the total isolates.

During the study period, 2,992 patients were admitted due to a COVID-19 pneumonia, 295 patients (9.86%) non-survive. Survivors and non-survivors were different in age and comorbidities. However, both cohorts presented a similar net of interaction between comorbidities. Hospital admissions per week showed an evolution in "peaks" with "troughs". A total of 197 (6.48%) patients were admitted to the ICU, of whom 52 (26.39%) non-survive; this subgroup stood out for having a higher proportion of septic shock, orotracheal intubation and acute renal failure, as well as a lower proportion of pulmonary thromboembolism and delirium. Concerning the viral variants, the incidence for the original variant was 4.05 cases/day, for the alpha variant 3.82 cases/day, for the delta variant 1.16 cases/day and for the omicron variant 1.35 cases/day.

Almost 1 of 10 patients with COVID-19 pneumonia death, a proportion that increased to 1 of 4 in case of being admitted to the ICU. Unexpectedly, interaction between comorbidities did not differ between survivors and non-survivors patients. Predominant variants were associated with different hospital admission rates but not influence the presence of peak-troughs evolution of the pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the respiratory system but may induce hematological alterations such as anemia, lymphopenia and thrombocytopenia. Previous studies have reported that SARS-CoV-2 efficiently infects hematopoietic stem and progenitor cells (HSPCs); however, the subsequent effects on hematopoiesis and immune reconstitution have not yet been described. Here we evaluated the pathological effects of infection of umbilical-cord-blood-derived HSPCs with the SARS-CoV-2 Omicron variant pseudovirus (PsV). Transcriptomic analysis of Omicron PsV-infected HSPCs revealed the upregulation of genes involved in inflammation, aging and the NLRP3 inflammasome, suggesting a potential trigger of inflammaging. Omicron PsV-infected HSPCs presented decreased numbers of multipotential progenitors (granulocyte‒erythrocyte‒macrophage‒megakaryocyte colony-forming units) ex vivo and repopulated primitive hematopoietic stem cells (Ki-67-hCD34+ cells) in an HSPC transplantation NOD-scid IL2rγnull mouse model (Omicron mouse). Furthermore, Omicron PsV infection induced myeloid-biased differentiation of HSPCs. Treatment with nanographene oxide, an antiviral agent, partially mitigated the myeloid bias and inflammaging phenotype both in vitro and in vivo. These findings provide insights into the abnormal hematopoietic and immune effects of SARS-CoV-2 infection and highlight potential therapeutic interventions.

Steroids are used in management of coronavirus disease 2019 (COVID-19) patients with severe illness and their use has been demonstrated to decrease mortality. Although life-saving, steroids are well documented as risk factors for osteonecrosis. Osteonecrosis of the hip can be debilitating and surgery may be required to improve the quality of life. With the increasing number of COVID-19 cases, osteonecrosis of the hip and other joints resulting from steroid use is expected to show a sharp rise in the coming years. In this review we discuss the association between steroids and osteonecrosis, indications for steroid therapy in COVID-19 patients, and incidence, diagnosis, and treatment of osteonecrosis secondary to steroids in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Despite reports of liver injury during viral disease, the occurrence and detailed mechanisms underlying the development of secondary exogenous liver injury, particularly in relation to changes in metabolic enzymes, remain to be fully elucidated. Therefore, this study was aimed to investigate the mechanisms underlying SARS-CoV-2-induced molecular alterations in hepatic metabolism and the consequent secondary liver injury resulting from alcohol exposure. We investigated the potential effects of SARS-CoV-2 infection on alcohol-induced liver injury in Keratin 18 promoter-human angiotensin converting enzyme 2 (K18-hACE2) transgenic mice. Mice were intranasally infected with 1 × 102 PFU of SARS-CoV-2. Following a 14 d recovery period from infection, the recovered mice were orally administered alcohol at 6 g/kg. Prior SARS-CoV-2 infection aggravated alcohol-induced liver injury based on increased alanine aminotransferase levels and cytoplasmic vacuolation. Interestingly, infected mice exhibited lower blood alcohol levels and higher levels of acetaldehyde, a toxic alcohol metabolite, compared to uninfected mice after the same period of alcohol consumption. Along with alterations of several metabolic process-related terms identified through RNA sequencing, notably, upregulation of cytochrome P450 2E1 (CYP2E1) and CYP1A2 was observed in infected mice compared to control value prior to alcohol exposure, with no significant impact of SARS-CoV-2 on intestinal damage. Tumor necrosis factor-alpha persistently showed upregulated expression in the infected mice; it also enhanced aryl hydrocarbon receptor and Sp1 expressions and their binding activity to Cyp1a2 and Cyp2e1 promoters, respectively, in hepatocytes, promoting the upregulation of their transcription. Our findings suggest that SARS-CoV-2 infection exacerbates alcohol-induced liver injury through the transcriptional activation of Cyp1a2 and Cyp2e1, providing valuable insights for the development of clinical recommendations on long COVID.