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).

Persistent respiratory symptoms and impaired gas exchange are common in patients recovering from COVID-19 pneumonia. The Lung Diffusing Capacity for Carbon Monoxide (DLCO) and Carbon Monoxide Transfer Coefficient (KCO) do not adequately distinguish alveolar membrane dysfunction from vascular abnormalities. This study aimed to characterize persistent diffusion impairment in post-ICU patients with prior SARS-CoV-2 pneumonia and reduced DLCO.

After hospital discharge, patients underwent spirometry, DLCO measurement, and a 6-minute walking test every six months. If DLCO remained impaired at 18-24 months, a combined Lung Diffusing Capacity for Nitric Oxide (DLNO) and DLCO assessment was performed to differentiate alveolar-capillary membrane (DmCO) and pulmonary capillary blood volume (Vc) alterations.

Among 20 patients with persistent DLCO reduction, 3 had an obstructive ventilatory pattern, 6 had restriction, and 12 had low KCO. In restrictive cases, KCO was reduced but remained within normal limits without compensation. The DLNO/DLCO ratio exceeded 113.5% predicted in all patients. DmCO was impaired in 7 patients, while Vc was reduced in 16.

Both DLCO determinants were affected, with vascular impairment predominating. Vc reduction was present in most patients, with mean values below the lower limit of normality, whereas DmCO was less affected and often normal. The elevated DLNO/DLCO ratio suggests that persistent DLCO reduction is primarily driven by prolonged pulmonary capillary circulation dysfunction rather than alveolar membrane alterations, highlighting the vascular component as the primary site of long-term impairment.

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.

The emergence of the SARS-CoV-2 virus worldwide led to the call for the development of effective and safe vaccines to contain the spread and effects of COVID-19. Using information from 40 publications, including clinical trials and observational studies from 2019 to 2024, this review assesses the effectiveness, safety, and limitations of four major vaccines: Sinopharm (BBIBP-CorV), Moderna (mRNA-1273), Pfizer-BioNTech (BNT162b2), and CoronaVac. Pfizer-BioNTech and Moderna's mRNA vaccines proved to be more effective than others; Moderna's vaccines showed an efficacy of 94.1 % against symptomatic infection, while Pfizer-BioNTech's vaccines showed an efficacy of up to 95 %, against severe diseases and hospitalization. These vaccinations, which included protection against Omicron and Delta variants, offered notable protection against serious illness, hospitalization, and mortality. Severe adverse events were rare while most adverse events were mild to moderate, such as headaches, fatigue, and localized reactions. In contrast, inactivated virus vaccines such as Sinopharm and CoronaVac with efficacies ranging from 50 to 79 % against symptomatic infection showed lower levels of effectiveness. In Phase 3 trial, Sinopharm showed 72.8 % efficacy, whereas CoronaVac demonstrated roughly 67 % efficacy in population against hospitalization and severe disease. Booster doses were required for adequate immunological response, especially against novel strains, as these vaccinations proved to be less effective in older populations. They showed considerable safety profiles, with mild side effects, but their low immunogenicity is concerning. This review emphasizes the importance of continuously evaluating vaccines in response to the evolving virus, essential for improving international immunization programs.

Previous studies have shown that COVID-19 diagnosis increases rates of perioperative infection, readmission, and other complications following surgery. However, the effect of the COVID vaccine in such patients is unknown. We hypothesized that of the patients with COVID diagnosis, vaccinated patients with COVID-19 diagnosis would have lower rates of adverse complications compared to unvaccinated patients undergoing total joint arthroplasty (TJA).

Using a national database registry, patients aged less than 85 years undergoing elective primary total knee or total hip arthroplasty with at least 90 days of follow-up were included during the first year of COVID-19 pandemic from April 2020-April 2021. Patients were included in the COVID-19 cohort if they had a diagnosis on the day of surgery or within 30 days prior to surgery. Patients with a history of malignancy, joint injection, femoral neck fractures, tibial fractures, and those undergoing revision arthroplasty were excluded from the study. All comparisons were performed using multivariate logistic regression with significance set at P < .05. Odds ratio and 95% confidence interval were reported for all comparisons.

There were a total of 1280 patients with COVID-19 diagnosis matched with 3831 patients without COVID-19 diagnosis. Patients with a COVID-19 diagnosis were at an increased risk of pneumonia, acute kidney injury, urinary tract infection, and readmission following TJA compared to patients without COVID-19 diagnosis. However, there were no differences in any complications assessed between vaccinated patients and unvaccinated patients with COVID-19 diagnosis following TJA.

This study confirms that patients with a COVID-19 diagnosis in the 30 days prior to TJA, whether vaccinated or not, have increased risks of medical complications and hospital utilization. However, this study demonstrates that vaccination status does not appear to be associated with the incidence of adverse postoperative events in patients with a COVID-19 diagnosis prior to TJA.

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.

While most SARS-CoV-2 infections and reinfections in the era of widespread population immunity with omicron subsub-lineage variants are mild for immunocompetent individuals, any manifestation previously seen during the pandemic phase is still possible. COVID-19 may affect any organ system. Previous infections and prior vaccines protect against symptomatic future SARS-CoV-2 infections, though this protection wanes over time.

Early prediction of critical COVID-19 disease is crucial for an optimal clinical management. The objective of this study was to optimize predictive models for critical COVID-19 disease. Clinical data, laboratory data and genetic polymorphisms were integrated into AI models to compare the performance of different machine learning algorithms.

Data from 155 inpatients were analyzed, 23 of whom developed critical disease. A univariate analysis was performed to assess potential correlations between seven SNPs, nine clinical variables and 10 laboratory parameters at admission.

Of the 7 SNPs, only three SNPs demonstrated a significant association with critical disase, namely: rs77534576, rs10774671 and rs10490770. The ensemble models exhibited the best performance: Random Forest (AUC=0.989), XGBoost (AUC=0.954) and AdaBoost (AUC=0.927). Variable importance varied across models, with age, C-reactive protein, heart diseases and the three SNPs being the most influential features. The predictive power of models improved with the integration of the three SNPs, as compared to previous studies where genetic data were not included. Internal validation confirmed the superiority and stability of the ensemble models.

Machine learning models may help predict progression into critical COVID-19-disease. The predictive power of models improves when SNPs associated with COVID-19 severity are integrated with laboratory and clinical data. Prior to implementation in clinical practice, larger studies in different populations are needed to validate and support the generalization of these results.

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.

The COVID-19 disease has spread rapidly across the world within just six months, affecting 169 million people and causing 3.5 million deaths globally (2021). The most affected countries include the USA, Brazil, India, and several European countries such as the UK and Russia. Healthcare professionals face new challenges in finding better ways to manage patients and save lives. In this regard, more comprehensive research is needed, including genomic and proteomic studies, personalized medicines and the design of suitable treatments. However, finding novel molecular entities (NME) using a standard or de novo strategy to drug development is a time-consuming and costly process. Another alternate strategy is discovering new therapeutic uses for old/existing/available medications, known as drug repurposing. There are a variety of computational repurposing methodologies, and some of them have been used to counter the coronavirus disease pandemic of 2019 (COVID-19). This review article compiles recently published data on the origin, transmission, pathogenesis, diagnosis, and management of the coronavirus by drug repurposing and vaccine development approach. We have attempted to screen probable drugs in clinical trials by using literature survey. This systematic review aims to create priorities for future research of drugs repurposed and vaccine development for COVID-19.

Nirmatrelvir-Ritonavir (NR) has proven effective for mild to moderate COVID-19 patients at risk of disease progression. Following its emergency use authorization in Taiwan in January 2022, this study aims to evaluate its impact on severe COVID-19 outcomes across different patient demographics in Taiwan.

We performed a retrospective analysis of a database that includes data from three hospitals in Northern Taiwan. Patients with COVID-19 in 2022 were paired by propensity score matching based on NR prescription. Cox proportional hazard regression analysis calculated hazard ratios (HR), adjusting for confounding factors. Subgroup analysis determined HRs across patient characteristics.

Among 95,096 patients, 3329 were in the NR group, and 12,807 in the non-NR group. NR users demonstrated significantly better prevention of severe outcomes: intubation (HR=0.296 [95 % CI: 0.187-0.469], p = 0.0482); ICU admission (HR=0.327[0.108-0.991], p < 0.001); mortality (HR=0.195 [0.101-0.378], p < 0.001). Subgroup analysis revealed significantly lower intubation risks for NR users among both sexes, aged 18-65 or ≥ 65 years, BMI < 30, and patients with diabetes mellitus (DM), cardiovascular disease (CVD), or chronic obstructive pulmonary disease (COPD). ICU admission risk was lower for NR users among males, aged ≥ 65 years, and BMI < 30. Mortality risk was lower for NR users among both sexes, aged ≥ 65 years, BMI < 30, and patients with DM, CVD, or COPD.

NR significantly reduces the risk of severe COVID-19, particularly among older adults and those with pre-existing conditions, supporting NR as an essential treatment for high-risk COVID-19 patients.

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.

We present a rapid and highly sensitive immunoassay platform based on an ultra-thin immuno-wall microfluidic device with an easy-to-perform sequential fluorescence signal increment method. The ultra-thin immuno-wall was fabricated using a special type of water-soluble photopolymer mixed with streptavidin via photolithography. During photolithography, the photopolymer formed a three-dimensional cross-linked structure, and streptavidin was immobilized in the cross-linked structure based on the click chemistry reaction. The immobilized streptavidin was used to immobilize biotin-conjugated antibodies on the cross-linked structure to capture biomarkers, forming immune complexes on the surface, known as an "immuno-wall." A sequential fluorescence signal increment method utilizes two different fluorescence-labeled antibodies with high affinity that were incubated several cycles in the immuno-wall to enhance the fluorescence signal. Moreover, an ultra-thin immuno-wall was developed to reduce the nonspecific binding and increase the signal-to-noise ratio. To evaluate the performance of this immunoassay platform, the spike protein from the SARS-CoV-2 virus was selected as the target biomarker. This immunoassay platform exhibited a limit of detection of 0.01 ng/mL, and the detection time was 30 min, which is comparable to rapid antigen tests. This immunoassay platform demonstrates significant potential for early-phase disease diagnosis.

Despite the availability of vaccines, immunocompromised patients are still at high risk for severe COVID-19. Vaccination has been proven to be an effective measure in preventing severe SARS-CoV-2 infections; however, data on B- and T-cell responses are lacking. While vaccination schedules for the general population have been defined, achieving immunogenicity in patients who are immunocompromised remains a challenge.

The primary objective is to analyze anti-spike-immunoglobulin G (IgG) titers after repeated messenger ribonucleic acid vaccinations in patients who are immunocompromised. Further objectives are to analyze data on humoral immune responses and to evaluate data on cellular immune responses.

This multicenter, prospective, noninterventional study aims to determine the immunogenicity and reactogenicity of an implemented standard-of-care COVID-19 vaccination strategy in patients who are immunocompromised. A total of 100 patients will be recruited at three study sites. Patients are eligible for study inclusion when they are 18 years or older, vaccinated according to the recent version of the COVID-19 vaccination standard, and if the patient is immunocompromised according to stage 3 of the classification "Stages of Immunosuppression." The study analyzes B- and T-cell responses generated within the standard-of-care COVID-19 vaccination strategy. Additional blood samples will be drawn at each scheduled outpatient visit. Study-related blood samples will be used to extract ethylenediaminetetraacetic acid plasma and peripheral blood mononuclear cells for evaluation of B- and T-cell responses to COVID-19 vaccinations. For this study, no additional visits or invasive procedures will be performed in addition to standard care.

As of August 2024, the study has enrolled 32 patients. The recruitment phase is still ongoing.

Results will be used to optimize vaccination and booster schedules for patients who are immunocompromised and to increase rates of protection against severe SARS-CoV-2 infections. Further, results may identify risk and treatment factors, which lead to low immune responses in patients vaccinated against COVID-19, as well as the impact of repeated vaccination on B- and T-cell responses.

ClinicalTrials.gov NCT05597761; https://clinicaltrials.gov/study/NCT05597761.

DERR1-10.2196/60675.

The SARS-CoV-2 virus has continuously evolved, with new variants like Delta, Omicron-BA.5, and XBB-EG.5 posing challenges to vaccine efficacy. mRNA vaccines have emerged as a promising tool due to their rapid development and adaptability. This study evaluates the protective efficacy of six novel mRNA vaccine candidates against these variants using a golden hamster model.

Six mRNA vaccines were designed, targeting the spike (S) and nucleocapsid (N) proteins of SARS-CoV-2. The vaccines were tested on golden hamsters, which were immunized and then challenged with Delta, Omicron-BA.5, and XBB-EG.5 variants. Key outcomes measured included body weight, viral RNA loads in various tissues, cytokine levels, and lung tissue pathology.

Hamsters vaccinated with the novel mRNA vaccines showed reduced weight loss, lower viral RNA loads in throat swabs and lung tissues, and reduced levels of pro-inflammatory cytokines compared to control groups. Additionally, vaccinated animals exhibited significantly less lung damage as evidenced by both histological and immunofluorescence analyses, especially in groups vaccinated with RBD-Fe, RE-N, and COVID-19 epitope formulations.

These mRNA vaccines demonstrated broad protective efficacy against multiple SARS-CoV-2 variants. They elicited immune responses, reduced viral RNA loads, and mitigated inflammatory and pathological damage, highlighting their potential in combating rapidly evolving SARS-CoV-2 variants.

This study investigated the effects of the COVID-19 pandemic on cardiovascular disease (CVD) incidence among hypertensive patients without SARS-CoV-2 infection by changes in CVD incidence, all-cause mortality, blood pressure (BP) control, and healthcare utilization rates among this population from Hong Kong. Individuals diagnosed with hypertension from January 2010 to January 2020 were followed up until death, SARS-CoV infection, or April 2022. Interrupted time series analyses on 1,318,907 patients with hypertension, comparing outcomes across four periods: pre-pandemic (January 2012-January 2020), early pandemic (February 2020-February 2021), interwave (March-December 2021), and Omicron outbreak (January-April 2022). A significant increase in out-of-hospital mortality was found when the early pandemic started. Overall all-cause mortality increased progressively during the interwave period. CVD incidence decreased immediately in the early pandemic period, followed by a progressive increase, and surpassed the pre-pandemic level at the beginning of the interwave period. The proportion of patients with office-measured BP ≤ 140/90 mmHg remained below pre-pandemic levels across the pandemic periods. Healthcare utilization declined immediately in February 2020, while most utilization rebounded to the pre-pandemic level after March 2021 and declined again during the Omicron outbreak. Healthcare disruptions during the early pandemic likely delayed CVD diagnosis and treatment, driving an immediate rise in out-of-hospital mortality. When healthcare services gradually recovered in the interwave period, CVD incidence rebounded and both in and out-of-hospital all-cause mortality increased with a lag, possibly related to delayed treatment.

Between March 2020-June 2021, over 30 million COVID-19 cases were reported in India. We described the COVID-19 response across the US Mission India (US Embassy New Delhi, US Consulates - Mumbai, Hyderabad, Chennai, and Kolkata) to use the learnings for a possible future pandemic. We reviewed COVID-19 mitigation activities at five US Mission India posts from March 2020-July 2021. We also analyzed case investigation and contact tracing data from Health Units (outpatient clinics), including demographics, clinical findings, test results, contact positivity rate, and compared attack rates across the posts during the same period. The US Mission in India, comprising multiple US Government agencies, initiated COVID-19 mitigation in March 2020 with educational sessions, infection prevention training, health assessments, and standard operating procedures. The Health Unit and US CDC India office initiated COVID-19 case investigations and conducted contact tracing. During the study period, 636 COVID-19 cases (72% males), including 48 clusters (size range 2-10 cases), were reported. Overall case fatality rate was 1.5% (10). Of case patients, 82% (523) were Indians, and 18% (113) were Americans. On presentation, 22% (138/625) of cases were asymptomatic. The median time from symptom onset to notification to the Health Unit was three days (Interquartile range 1-5). The Health Unit identified 2,484 contacts with a 25% positivity rate. The attack rates ranged between 10-19%, with the highest at 19% in Delhi, which was lower compared to the estimated attack rate for respective cities but closely resembled the pattern of COVID-19 waves in India. Collaboration between medical providers and public health specialists during the COVID-19 response in US Mission India led to new organizational capabilities in contact tracing, community education, and workflows. These strategies helped reduce morbidity and mortality within the US Mission during the pandemic.

The epidemiological patterns of respiratory tract infections (RTIs) have experienced substantial changes due to the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a particular focus on acute respiratory infections (ARIs). Challenges in early diagnosis, inadequate triage strategies, and the inappropriate use of antimicrobials or antivirals have compounded the difficulties in accurately diagnosing and managing ARIs in the post-pandemic context. This study aimed to investigate the efficacy of fever clinics equipped with nucleic acid testing capabilities in the precise triage of ARIs. In a cohort of 604 individuals presenting with symptoms of ARIs, we utilized real-time reverse transcription polymerase chain reaction (RT-PCR) technology available in the fever clinic to perform nucleic acid testing for SARS-CoV-2, influenza A virus (Flu A), influenza B virus (Flu B), respiratory syncytial virus, adenovirus, human rhinovirus, and Mycoplasma pneumoniae. Subsequently, statistical methods were employed to analyze the distribution and types of ARIs associated with these pathogens. In fever clinics, most patients presenting with respiratory pathogen infections were diagnosed with non-SARS-CoV-2 respiratory pathogens, with a higher incidence noted among pediatric patients compared to adults. In contrast, SARS-CoV-2 primarily affected the adult population and was linked to more severe clinical outcomes. Consequently, the swift triage of patients exhibiting ARI symptoms in a fever clinic equipped with nucleic acid testing enables the rapid identification and precise treatment of pathogens. This approach alleviates patient discomfort and enhances the efficiency of healthcare resource utilization.

Procalcitonin (PCT) is recognized as an inflammatory biomarker, often elevated in COVID-19 pneumonia alongside other biomarkers. Understanding its association with severe outcomes and comparing its predictive ability with other biomarkers is crucial for clinical management.

This retrospective multicenter observational study aimed to investigate the association between PCT levels and adverse outcomes in hospitalized COVID-19 patients. Additionally, it sought to compare the predictive performance of various biomarkers.

The study analyzed data from the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry, comprising COVID-19 patients hospitalized across multiple Mayo Clinic sites between March 2020 and June 2022.

A total of 7851 adult COVID-19 patients were included. Patients were categorized into 6 groups based on the worst WHO ordinal scale. Multivariate models were constructed using peak biomarker levels within 72 hours of admission, adjusted for confounders.

Elevated PCT levels were independently associated with increased odds of adverse outcomes, including ICU admission (adjusted odds ratio [aOR] 1.32, 95%CI 1.27-1.38), IMV requirement (aOR 1.35, 95%CI: 1.28-1.42), and in-hospital mortality (aOR 1.30, 95%CI: 1.22-1.37). A 3.48-fold increase in IMV requirement and 3.55 times increase in in-hospital mortality were noted with peak PCT ⩾ 0.25 ng/ml. Similar associations were observed with other biomarkers like NLR (AUC 0.730), CRP, IL-6, LDH (AUC 0.800), and D-dimer (AUC 0.719). Models incorporating NLR, LDH, D-dimer, and PCT demonstrated the highest predictive accuracy, with a combined model exhibiting an area under the curve (AUC) of 0.826 (95%CI 0.803-0.849).

Higher PCT levels were significantly linked to worse outcomes in COVID-19 patients, emphasizing its potential as a prognostic marker. Biomarker-based predictive models, particularly those including PCT, showed promising utility for risk assessment and clinical decision-making. Further prospective studies are warranted to validate these findings on a larger scale.

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 purpose of this study is to compare and analyze the changes of CPET and pulmonary function indexes in patients with mild and moderate SARS-CoV-2 before infection and in the early recovery period, and to explore the influence of SARS-CoV-2 on cardiopulmonary fitness and its pathogenesis. Clinical data of 39 cases are collected, and paired analyses of CPET and pulmonary ventilation parameters before and after infection are performed using software SPSS. Bivariate correlations are analyzed for days post-infection, VO2peak decline rate, VO2peak/kg after infection, AHRR decline rate, and residual symptom count. The results show that VO2peak, VO2peak/kg, and AT significantly decreased after infection. The VE/VCO2 slope increased, while PetCO2, VEpeak, and VE/VCO2 minimum showed reductions. FVC, FEV1, and FEV1/FVC remained unchanged. OUES significantly declined, along with AHRR and HRpeak, although no significant differences are observed in HRrest, HRR-1 min, and HRR-2 min. The number of residual symptoms is significantly correlated with VO2peak/kg and its decline rate, but not with infection duration. Additionally, the decline rate of VO2peak/kg is strongly associated with post-infection time and post-infection VO2peak/kg. VO2/HR and power also decreased significantly. Moreover, after SARS-CoV-2 infection, cardiopulmonary function, including cardiac chronotropic and muscle function, is significantly impaired in mild and moderate patients. Residual symptoms are closely linked to cardiopulmonary function. Given the large proportion of mild and moderate cases, these findings offer valuable insights for developing targeted interventions to prevent further symptom progression and improve cardiopulmonary health in this population.

Objectives: Critically ill COVID-19 patients are at high risk of malnutrition; however, no study has directly compared the prognostic accuracy of different nutritional assessment tools. This study aimed to determine the optimal cutoff values for the Modified Nutrition Risk in the Critically Ill (mNUTRIC) score, Nutritional Risk Screening 2002 (NRS 2002), and Malnutrition Universal Screening Tool (MUST) and to evaluate their predictive value for ICU mortality. Method: A retrospective analysis was conducted on patients with laboratory-confirmed COVID-19 admitted to our ICU between 20 March 2020 and 15 June 2021. Clinical and laboratory data, as well as patient outcomes, were retrieved from electronic medical records and patient charts. The mNUTRIC, NRS 2002, and MUST scores were calculated at ICU admission. Results: The study included 397 patients, with 273 survivors and 124 non-survivors. The median age was 65 (55-76) years, and the median BMI was 26.1 (24.0-29.4). Non-survivors had significantly higher median scores in all three nutritional assessment tools compared to survivors (mNUTRIC: 5 vs. 3, NRS 2002: 4 vs. 3, MUST: 2 vs. 2; p < 0.01). At the optimal cutoff values, mNUTRIC ≥ 4 demonstrated the highest prognostic accuracy (sensitivity: 0.77, specificity: 0.74; AUC = 0.75, CI = 0.70-0.81), followed by NRS 2002 ≥ 4 (sensitivity: 0.63, specificity: 0.60; AUC = 0.62, CI = 0.56-0.67) and MUST ≥ 3 (sensitivity: 0.21, specificity: 0.91; AUC = 0.56, CI = 0.50-0.68). Higher scores were associated with increased disease severity, poorer patient performance, prolonged hospital stays, and elevated ICU, 28-day, and overall hospital mortality rates. Among the three assessment tools, only an mNUTRIC score of ≥ 4 was independently associated with ICU mortality (OR = 1.54, CI = 1.21-1.96, p < 0.01). Conclusions: At ICU admission, mNUTRIC ≥ 4, NRS 2002 ≥ 4, and MUST ≥ 3 were identified as the most accurate predictors of mortality in critically ill COVID-19 patients. However, only the mNUTRIC score was an independent predictor of ICU mortality.

We examined the association between air pollution and neutralizing antibody responses to COVID-19 vaccination in participants enrolled in a phase 3 clinical trial. Seventy-four adults were vaccinated with two doses of the AstraZeneca ChAdOx1 vectored vaccine (AZD1222) (5 x 1010 viral particles) at baseline and day 29, between Aug 28, 2020, to Jan 15, 2021, in Monroe County, NY. SARS-CoV-2 pseudovirus neutralizing ID50 titers (NAb) and total spike protein IgG were assessed at baseline and 15, 29, 43, 57 and 90 days after vaccination. In this pilot study, each participant's dates of neutralization titers were matched to Monroe County ambient concentrations of fine particles (PM2.5; ≤ 2.5 µm), black carbon (BC; marker of traffic), among other particulate and gaseous pollutants. Using linear mixed models, we estimated the association between each interquartile range (IQR) difference in air pollutant concentrations in the 14 days prior to blood collection and antibody responses at each post vaccination timepoint. Though not statistically significant, we observed a 23% reduction in NAb titer (95% CI: -67%, 79%) measured on day 43 (i.e., 14 days after second vaccination) associated with each 0.32 µg/m3 increase in BC concentrations in the prior 14 days. We also observed a 42% increase in spike protein IgG (95% CI: -16%, 141%) measured on day 15 (i.e., 14 days after primary vaccination) associated with each 0.26 µg/m3 increase in BC concentrations in the 14 days prior. A similar pattern for total spike protein IgG was observed at day 29 (42%; 95% CI: -22%, 157%) and 90 (43%; 95% CI: -11%, 127%). Future research will need to explore the possible association between air pollution exposure and antibody response to SARS-CoV-2 vaccination given the potential for compromised vaccine efficacy.

The novel coronavirus pandemic, SARS-CoV-2, has a variable clinical spectrum, ranging from asymptomatic to critical forms. High mortality and morbidity rates have been associated with risk factors such as comorbidities, age, sex, and virulence factors specific to viral variants. Material and Methods: We retrospectively evaluated imaging characteristics using the Brixia radiological score in relation to favorable or unfavorable outcomes in adult patients. We included COVID-19 cases, admitted between 2020 and 2022, in a specialized pulmonology hospital with no intensive care unit. We analyzed 380 virologically confirmed COVID-19 cases, with a mean age of 52.8 ± 13.02 years. The mean Brixia radiological score at admission was 5.13 ± 3.56, reflecting predominantly mild-to-moderate pulmonary involvement. Multivariate analysis highlighted the utility of this score as a predictive marker for COVID-19 prognosis, with values >5 correlating with other severity biomarkers, NEWS-2 scores, and a lack of vaccination and hospitalization delay of more than 6 days from symptom onset. Summarizing, the Brixia score is itself an effective tool for screening COVID-19 cases at risk of death for early recognition of clinical deterioration and for decisions regarding appropriate care settings. Promoting vaccination can reduce the severity of radiological lesions, thereby decreasing the risk of death. Technologies based on artificial intelligence could optimize diagnosis and management decisions.

COVID-19 can affect multiple organ systems beyond the respiratory tract, including the gastrointestinal tract, where gastrointestinal symptoms include nausea, vomiting, diarrhea, abdominal pain, and even serious manifestations such as ulcers, perforation, or gastrointestinal bleeding.

We report a case of a 45-year-old male patient with small bowel ulcers caused by chronic COVID-19 infection. Initially presenting with fever and transient unconsciousness, he developed ischemic necrosis and required a mid-thigh amputation. Despite treatment with anti-infection therapy, extracorporeal membrane oxygenation, and continuous renal replacement therapy, he experienced persistent abdominal pain and gastrointestinal bleeding. Imaging and colonoscopy confirmed partial small bowel obstruction and inflammation. After treatment with methylprednisolone and enteral nutrition, his symptoms improved. However, he suffered a gastrointestinal perforation requiring emergency surgery and later underwent a successful stoma reversal. The patient was subsequently discharged with improvement and was discharged with a primary diagnosis of "enterostomal status, perforation of small intestinal ulcer, viral myocarditis, COVID-19 infection, and post right lower extremity amputation". During the past year of follow-up, the patient has not experienced any recurrence of abdominal pain or rectal bleeding.

Although coronavirus pneumonia combined with small bowel ulcers is rare, it requires emergency treatment and has a high mortality rate. This case highlighted the severe gastrointestinal complications induced by COVID-19 infection and the effectiveness of comprehensive management strategies.

Background/Objectives: This study aimed to analyze optic nerve parameters, retinal nerve fiber layer thickness (RNFLT), ganglion cell layer thickness (GCLT), and subfoveal choroidal thickness (ChT) in patients who have recovered from coronavirus disease 2019 (COVID-19). Methods: This comparative study included 78 recovered COVID-19 patients (16 men, 62 women) and 56 age- and sex-matched healthy controls (18 men, 38 women). COVID-19 was confirmed in all patients, either through the detection of viral RNA in nasopharyngeal swabs via reverse transcriptase polymerase chain reaction or by serological testing for SARS-CoV-2 antibodies. Spectral-domain optical coherence tomography (SD-OCT) was used to assess optic nerve parameters, RNFLT, GCLT, and ChT. Results: The mean age was 35.0 ± 8.3 years in the COVID-19 group and 31.5 ± 8.3 years in the control group, with no statistically significant differences in age or sex distribution between groups (p = 0.41 and p = 0.16, respectively). Optic nerve parameters and RNFLT (overall and across the four peripapillary quadrants) did not differ significantly between the COVID-19 and control groups. However, the mean ganglion cell-inner plexiform layer (GC-IPL) thickness was significantly reduced in all quadrants in the COVID-19 group compared to the controls. No significant difference was observed in mean subfoveal ChT between groups. Conclusions: A significant reduction in ganglion GCLT was observed in recovered COVID-19 patients compared to healthy controls, suggesting a potential neurodegenerative effect of the disease on the optic nerve.

Severe COVID-19 is characterized by complex immunopathology that involves inflammation, endothelial dysfunction, and immunothrombosis. Neutrophil extracellular traps (NETs) have been recognized as key factors in the severity of the disease, with their emergence correlating to viral load, immmunothrombosis, and organ damage. In this study, we investigated the role of NETosis and macrophage activation in the course of severe COVID-19. We analyzed 23 autopsy samples from patients who died from COVID-19 and performed immunohistochemical staining and stereological point counting to quantify leukocyte infiltration and NET formation among other histopathological parameters. Our results showcase 2 evident immunophenotypes: lowNET and highNET. The lowNET group displayed lower NET formation, higher viral loads, and an increased incidence of secondary infections, as well as shorter survival times. In contrast, the highNET group exhibited increased neutrophil activation, pronounced endothelial damage and thrombotic complications, as well as prolonged survival times. Our data suggest a dual role of NETosis in COVID-19: initially protective, limiting viral replication, but later likely detrimental through immunothrombosis and tissue damage. These findings underline the need for tailored therapeutic actions, with early antiviral and immune-modulating interventions for lowNET patients and strategies aiming to limit excessive NETosis and coagulopathy in highNET patients. Further research is needed to define the timing of interventions based on the dynamics of NETosis.

If health impairments due to coronavirus disease 2019 (COVID-19) persist for 12 weeks or longer, patients are diagnosed with Post-COVID Syndrome (PCS), or Long-COVID. Although the COVID-19 pandemic has largely subsided in 2024, PCS is still a major health burden worldwide, and identifying potential genetic modifiers of PCS remains of great clinical and scientific interest. We therefore performed a case-control type genome-wide association study (GWAS) of three recently developed PCS (severity) scores in 2,247 participants of COVIDOM, a prospective, multi-centre, population-based cohort study of SARS-CoV-2-infected individuals in Germany. Each PCS score originally represented the weighted sum of the binary indicators of all, or a subset, of 12 PCS symptom complexes, assessed six months or later after the PCR test-confirmed SARS-CoV-2 infection of a participant. For various methodical reasons, however, the PCS scores were dichotomized along their respective median values in the present study, prior to the GWAS. Of the 6,383,167 single nucleotide polymorphisms included, various variants were found to be associated with at least one of the PCS scores, although not at the stringent genome-wide statistical significance level of 5 × 10- 8. With p = 6.6 × 10- 8, however, the genotype-phenotype association of SNP rs9792535 at position chr9:127,166,653 narrowly missed this threshold. The SNP is located in a region including the NEK6, PSMB7 and ADGRD2 genes which, however, does not immediately suggest an etiological connection to PCS. As regards functional plausibility, variants of a possible effect mapped to the olfactory receptor gene region (lead SNP rs10893121 at position chr11:123,854,744; p = 2.5 × 10- 6). Impairment of smell and taste is a pathognomonic feature of both, acute COVID-19 and PCS, and our results suggest that this connection may have a genetic basis. Three other genotype-phenotype associations pointed towards a possible etiological role in PCS of cellular virus repression (CHD6 gene region), activation of macrophages (SLC7A2) and the release of virus particles from infected cells (ARHGAP44). All other gene regions highlighted by our GWAS did not relate to pathophysiological processes currently discussed for PCS. Therefore, and because the genotype-phenotype associations observed in our GWAS were generally not very strong, the complexity of the genetic background of PCS appears to be as high as that of most other multifactorial traits in humans.

10-20% of people infected with the coronavirus infection have long COVID symptoms, therefore, current research is the first regional assessment in Saudi Arabia to determine the relationship between long-term health complaints of COVID-19 survivors and health-related quality of life (HRQoL).

The study population comprised COVID-19 infection cases registered in the Ha'il region of Saudi Arabia from the beginning of the COVID-19 pandemic until September 2022. A retrospective research design was employed, and 295 participants completed a self-report questionnaire to assess long COVID symptoms and the Arabic version of the European 5-Dimensional Quality of Life (EQ-5D). Multiple linear regression was used to evaluate the predictive role of long COVID symptoms on the HRQoL of patients by choosing (p-value < 0.05).

The mean (SD) age of the participants was 38 years, (67.1%) were male and (58.6%) were married. On the long COVID-19 symptoms, the highest mean values were fatigue (M=2.3; 95% CI 2.1-2.4) followed by headache (M=2.1; 95% CI 2.0-2.3) and persistent cough (M=1.9; 95% CI 1.8-2.1). Findings show that HRQoL was problematic in domains of pain/discomfort as depicted by a highest mean score on this domain (M=4.24; 95% CI 4.14-4.33) followed by anxiety/depression (M=4.17: 95% CI 4.08-4.27). Multiple regression analysis showed that marital status (p=0.05), irregular exercise (p<0.01), duration of hospitalization (p<0.01), and oxygen therapy (p<0.05) were the independent background factors affecting HRQoL post-COVID-19. Among the long-COVID-19 symptoms, fatigue (p=0.05), persistent cough (p=0.001), dyspnea (p=0.02), and sexual dysfunction (p<0.001) were the independent factors that impacted the HRQoL after controlling for background variables.

The study has significant implications for Saudi Arabia's Health Sector Transformation Program that could achieve its goals of human centric care and patient satisfaction though addressing the negative impacts of specific long-COVID symptoms such as fatigue, persistent cough, dyspnea and sexual dysfunction and improving the HRQoL in domains of pain/discomfort and anxiety/depression.

Pneumonia caused by SARS-CoV-2 is a public health problem. Older adults are vulnerable and the atypical presentation delays diagnosis and increases mortality. In this group the atypical clinical manifestations are more frequent.

To identify the clinical manifestations and mortality of COVID-19 pneumonia in hospitalized older adults.

A comparative cross-sectional observational study was carried out, from July 1, 2020, to December 31, 2021, in a general hospital of Mexico City. Patients aged 60 years or more who were hospitalized with a diagnosis of COVID-19 were included.

267 older adults participated; 53.9% were men, with a median age of 74 years. The most frequent comorbidities in this population were type 2 diabetes mellitus (T2DM), hypertension and chronic obstructive pulmonary disease (COPD). 41.2% showed atypical presentation of the disease; mortality in the studied population was 53.5%.

The atypical presentation of COVID-19 pneumonia is common in adults over 60 years of age and it increases significantly as they become older. The absence of typical symptoms of pneumonia and the ignorance of the most common signs could delay diagnosis and timely care in this age group, which may increase complications and mortality.

Severe COVID-19 typically results in pulmonary sequelae. However, current research lacks clarity on the differences in these sequelae among various clinical subtypes. This study aimed to evaluate the changing lung imaging features and predictive factors in patients with COVID-19 pneumonia in northern China over a 12-month follow-up period after the relaxation of COVID-19 restrictions in 2022.

Imaging and clinically relevant data from three groups (moderate, severe, and critical) of patients with varying severity were prospectively analyzed. Low-dose CT scans were conducted at 3, 6, and 12 months after discharge, with chest CT images evaluated at baseline and each follow-up using qualitative and quantitative analyses. Clinical symptoms and pulmonary function recovery at 12 months were documented. The correlation between lung function and CT results was analyzed. Univariate and multivariable logistic regression analyses were employed to examine factors influencing prognosis, while a post-hoc analysis model was utilized to investigate the relationships among different groups, time points, and chest CT findings.

Among the 103 hospitalized patients with COVID-19 pneumonia, 64 completed the 12-month evaluation. The median age was 63.70 ± 12.15%, and 62.5% (40/64) were men. During the follow-up period, while 67.19% (43/64) showed abnormalities, including fibrotic changes in 9.38% (6/64). Multivariable logistic regression identified age ≥ 65 (OR: 8.66; 95% CI: 1.86, 40.34; P = 0.006), length of hospital stays (OR: 1.23; 95% CI: 1.03, 1.47; P = 0.022), and baseline consolidation volume as a percentage of the whole lung (OR: 56.95; 95% CI: 1.198, 2706.782; P = 0.04) as independent risk factors for persistent CT lung abnormalities at 1 year. After 1 year, 34.38% (22/64) of patients still had abnormal lung function, and 9.38% (6/64) had pulmonary fibrosis and restrictive ventilatory dysfunction. The relationship between lung function and CT findings is weak correlation. The mixed model analysis revealed significant differences between groups, particularly between the moderate and severe groups, and significant changes in CT values over time.

One year after infection, more than one third of even moderate patients with mild symptoms had persistent pulmonary abnormalities. In our study, fibrotic changes were seen in severe and critically ill patients and remained stable 6 months after discharge from hospital. Imaging parameters can predict the prognosis. The larger the extent of baseline consolidation, the worse the prognosis of elderly patients.