Search Results (84)

Background: Despite the multiple waves of the COVID-19 pandemic, follow-up strategies for recovered patients remain inconclusive. This study aimed to evaluate chest computed tomography (CT) and pulmonary function test (PFT) abnormalities in convalescents six months after COVID-19 and to compare these findings with those from a representative population cohort. The goal was to support more individualized pulmonary management of post-COVID-19 sequelae. Methods: This study population consisted of 2 groups: I—232 post-COVID-19 patients and II—543 patients from a population cohort. Chest CT was performed during the acute phase of COVID-19 and six months after. The PFTs were conducted six months after COVID-19. Results: There were no significant differences in FEV1, FVC, TLC, and DLCO in the two study groups. A singular GGO in 24 patients (20%), a crazy paving pattern in 1 patient (0.8%), thickening of interlobular septa in 4 patients (3.5%), consolidations in 4 patients (3.5%), traction bronchiectasis in 6 patients (5%), fibrosis in 6 patients (5%), and singular nodular densities in 68 patients (58%) were observed in chest CT 6 months after COVID-19. Most radiological abnormalities were clinically insignificant and did not require further diagnostic evaluation. No significant differences in chest CT and PFT six months after infection were observed between patients differing in the severity of inflammation during the acute disease or SARS-CoV-2 variant. Conclusions: The majority of chest CT abnormalities resolved within six months of recovery, regardless of SARS-CoV-2 variant or initial disease severity. Pulmonary function tests should be prioritized in post-COVID-19 follow-up, as PFT results in convalescents were comparable to those observed in the general population. Full article

Certain strains of Influenza A virus (IAV), a primary cause of influenza, can lead to pneumonia. Patients recovering from influenza pneumonia may experience physical discomfort akin to post-acute sequelae of COVID-19 (PASC). Despite extensive clinical research on viral pneumonia during convalescence, animal model studies are scarce, highlighting the need for a reliable model for pharmaceutical research. In this study, BALB/c mice were divided into three groups: NC (control), MC (infected with IAV), and Model (treated with oseltamivir post-infection for five days). A fatigue model was then induced in the Model group through diet restriction and weight-bearing swimming. The results showed the MC group had a 75% survival rate, while the NC and Model groups had 100%. Both the MC and Model groups experienced rapid weight loss followed by gradual recovery, differing significantly from the NC group. From dpi (days post-inoculation) 6 to dpi9, the MC group lost more weight than the NC group. The MC group had the highest pulmonary index, but there was no significant difference in IAV Nucleoprotein (NP) expression across groups. The Model group had higher IL-10 levels than the NC and MC groups, while the MC group had the highest TNF-α expression. Hematoxylin and eosin (H&E) staining revealed pathological changes in the MC and Model groups, with severe damage and pulmonary fibrosis in the MC group. Oxidative stress markers showed the MC group had the highest lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and lowest superoxide dismutase (SOD) activity. Electron microscopy indicated mitochondrial damage in both the MC and Model groups. The Model group had the lowest splenic and thymic indices, with histological findings showing larger splenic nodules in the MC group and poor thymocyte density and atrophy in the Model group. The successful creation of this mouse model of influenza pneumonia convalescence phase fatigue, exhibiting fatigue syndrome with various symptoms, holds significance for PASC and other viral pneumonia convalescence phase animal model research. Full article

Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Geum japonicum var. chinense (GJC) is used as a traditional Chinese medicine to effectively treat various respiratory conditions. However, the protective effects of GJC against PF remains unclear. In the present study, the anti-PF effect of GJC aqueous extract was studied using a PF mouse model induced by bleomycin (BLM). To characterize the metabolite changes related to PF and reveal therapeutic targets for GJC aqueous extract, we performed metabolomic and network analysis on mice lungs. Finally, key targets were then validated by Western blotting. GJC aqueous extract effectively alleviated the onset and progression of lung fibrosis in PF mice by inhibiting inflammatory responses and regulating oxidative stress levels. Integrating serum metabolomics and network analyses showed the arachidonic acid (AA) pathway to be the most important metabolic pathway of GJC aqueous extract against PF. Further validation of AA pathway protein levels showed a significant rise in the levels of ALOX5, PTGS2, CYP2C9, and PLA2G2A in PF lungs. GJC aqueous extract treatment regulated the above changes in metabolic programming. In conclusion, GJC is a promising botanical drug to delay the onset and progression of PF mice. The primary mechanism of action is associated with the comprehensive regulation of metabolites and protein expression related to the AA metabolic pathway. Full article

Dengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore adults. Plasma samples from 48 dengue patients (24 severe and 24 non-severe) during acute and convalescent phases were selected from the prospective COhort study on progression of DENgue severity in Singapore adults (CODEN) cohort. The CODEN was conducted at the National Centre for Infectious Diseases, Tan Tock Seng Hospital, from June 2016 to January 2020. ANGPTL4 levels were measured and compared to 152 healthy controls. Logistic regression assessed the relationship between plasma ANGPTL4 concentrations and disease severity. There were no statistically significant differences in ANGPTL4 levels between severe and non-severe dengue patients during acute (677.4 vs. 909.1 pg/mL, p = 0.4) or convalescent phases (793.7 vs. 565.6 pg/mL, p = 0.96). Plasma ANGPTL4 levels were significantly elevated during acute dengue (4634.3 pg/mL) versus healthy controls (907.4 pg/mL), declining during convalescence. Compared to the lowest tertile, the adjusted odds ratios for severe dengue were 0.36 (95%CI: 0.08–1.65, p = 0.190) for medium tertile and 0.57 (95%CI: 0.13–2.49, p = 0.456) for high tertile. Among patients with high ANGPTL4 levels (>5000 pg/mL), 36.4% developed severe complications, including significant plasma leakage. Plasma ANGPTL4 levels were significantly higher in dengue patients than controls, suggesting its potential as a biomarker, which warrants future detailed investigations. Larger prospective studies with serial sampling, including pediatric populations, may clarify the role of ANGPTL4 in severe dengue. Full article

Background: During the acute phase of COVID-19, a number of immunological abnormalities have been reported, but few studies longitudinally analyzed the specific subsets of peripheral blood lymphocytes. Methods: In this observational, prospective, and longitudinal study, adult patients developing acute pneumonia during the COVID-19 pandemic have been followed up for 12 months. Peripheral blood lymphocyte subsets were assessed (with a specific focus on the memory markers) at 6 time points after the disease onset until 12 months. Results: A total of 76 patients with acute pneumonia (characterized by a prevalently interstitial pattern of lung inflammation) at the hospital admission (who completed the 12-month follow-up period) were recruited in this study. They were divided into two groups, namely positive (n = 31) and negative (n = 45) patients for the SARS-CoV-2 PCR test. In the acute phase, the general lymphocyte immunophenotyping profile was comparable for most parameters between these groups, except for B cells. When B and T cells were analyzed according to the expression of memory markers, a significant decrease in naïve CD8⁺ T cells was observed in the SARS-CoV-2-positive pneumonia group during the acute phase. Notably, this aspect was maintained during the follow-up period for at least 9 months. Conclusions: COVID-19 pneumonia seems to be associated with a lower number of naïve CD8⁺ T cells compared to pneumonia patients negative for this virus. This alteration can persist in the convalescent phase. Full article

The typical clinical signs of Nocardia seriolae infection include white nodules, ranging from 0.1 to 10 mm in diameter, distributed across various internal organs. However, the structural composition of nodules of different sizes remains unexplored. In this study, natural cases of largemouth bass (Micropterus salmoides) were collected, and pathogenic bacteria were isolated and confirmed through a re-infection experiment. The isolated bacteria were identified as N. seriolae through 16S rRNA and gyrB gene sequencing. Healthy largemouth bass were infected with the isolate using an immersion infection and observed continuously over 56 days. Samples were successfully obtained from the incubation, prodromal, symptomatic, and convalescent phases, allowing for gross, histological, and ultrastructural observations of nodular lesion progression. Results demonstrated two types of nodular lesions: necrotic foci and granulomas. Macroscopically visible nodules larger than 1 mm, observed primarily in the liver, spleen, kidney, and muscle tissues of moribund fish, exhibited coagulative necrosis and were identified as the principal cause of mortality. Conversely, granulomas, with diameters less than 1 mm, were consistently present in the spleen, kidney, and liver during the symptomatic and convalescent phases. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log₁₀ RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log₁₀ RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS. Full article

Background/Objectives: Leptospirosis is a zoonotic disease that is widely distributed around the world and presents symptoms similar to other febrile illnesses in tropical regions, which complicates clinical diagnosis. This study aimed to evaluate the performance and agreement between serological diagnostic tests for detecting both acute and convalescent human leptospirosis, using the micro agglutination test (MAT) as a reference in an endemic region of the Colombian Caribbean. Methods: A prospective descriptive study was conducted on 275 participants with suspected leptospirosis. Paired serum samples were obtained, and an epidemiological survey was conducted. Using the MAT as the gold standard, we calculated positive and negative predictive values, sensitivity, specificity, and kappa index. A Bayesian latent class model was also used to compare the diagnostic tests. Results: In 223 paired serum samples, the sensitivity values for various stages of the disease ranged between 10.8% to 54.1% in the acute and 6.1% to 66.7% during the convalescent phase compared to the MAT. According to the Bayesian model, sensitivity was 9.5% to 75.3% in the acute phase and 5.7% to 85.3% in the convalescent phase. The Kappa value, an indicator of agreement, was moderate for the IgM ELISA in the acute phase (0.553) and substantial in the convalescent phase (0.692). Conclusions: The MAT was the best confirmatory test in both acute and convalescent phases of leptospirosis. Despite the high specificity of ELISA, 21.62% of participants identified as negative by IgM-ELISA in both phases were subsequently confirmed as positive by the MAT. It is necessary to re-evaluate diagnostic guidelines that do not employ the MAT for confirmation and to enhance the diagnostic and clinical identification of leptospirosis within healthcare institutions and public health laboratories while providing a rapid and reliable test for its implementation. Full article

COVID-19, caused by SARS-CoV-2, triggers a complex immune response, with T regulatory cells (Tregs) playing a crucial role in maintaining immune homeostasis and preventing excessive inflammation. The current study investigates the function of T regulatory cells during COVID-19 infection and the subsequent recovery period, emphasizing their impact on immune regulation and inflammation control. We conducted a comprehensive analysis of Treg subpopulations in peripheral blood samples from COVID-19 patients at different stages: acute infection, early convalescence, and long-term recovery. Flow cytometry was employed to quantify Tregs including “naïve”, central memory (CM), effector memory (EM), and terminally differentiated CD45RA⁺ effector cells (TEMRA). Additionally, the functional state of the Tregs was assessed by the expression of purinergic signaling molecules (CD39, CD73). Cytokine profiles were assessed through multiplex analysis. Our findings indicate a significant decrease in the number of Tregs during the acute phase of COVID-19, which correlates with heightened inflammatory markers and increased disease severity. Specifically, we found a decrease in the relative numbers of “naïve” and an increase in EM Tregs, as well as a decrease in the absolute numbers of “naïve” and CM Tregs. During the early convalescent period, the absolute counts of all Treg populations tended to increase, accompanied by a reduction in pro-inflammatory cytokines. Despite this, one year after recovery, the decreased subpopulations of regulatory T cells had not yet reached the levels observed in healthy donors. Finally, we observed the re-establishment of CD39 expression in all Treg subsets; however, there was no change in CD73 expression among Tregs. Understanding these immunological changes across different T regulatory subsets and adenosine signaling pathways offers important insights into the disease’s pathogenesis and provides a broader view of immune system dynamics during recovery. Full article

Background: Self-amplifying mRNA vaccines have the potential to increase the magnitude and duration of protection against COVID-19 by boosting neutralizing antibody titers and cellular responses. Methods: In this study, we used the immunogenicity data from a phase 3 randomized trial comparing the immunogenicity of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, with BNT162b2 mRNA COVID-19 vaccine to estimate the relative vaccine efficacy (rVE) of the two vaccines over time in younger (<60 years) and older (≥60 years) adults. Results: By day 181 post-vaccination, the rVE against symptomatic and severe Wuhan-Hu-1 disease was 9.2–11.0% and 1.2–1.5%, respectively, across age groups whereas the rVE against symptomatic and severe Omicron BA.4/5 disease was 26.8–48.0% and 5.2–9.3%, respectively, across age groups. Sensitivity analysis showed that varying the threshold titer for 50% protection against severe disease up to 10% of convalescent sera revealed incremental benefits of ARCT-154 over BNT162b2, with an rVE of up to 28.0% against Omicron BA.4/5 in adults aged ≥60 year. Conclusions: Overall, the results of this study indicate that ARCT-154 elicits broader and more durable immunogenicity against SARS-CoV-2, translating to enhanced disease protection, particularly for older adults against Omicron BA.4/5. Full article

Objective: This study aimed to assess changes in the morphology of the retina and cornea in patients treated and hospitalized during the acute active phase of SARS-CoV-2 infection. Methods: A total of 24 patients with symptomatic early COVID-19 disease and 38 healthy participants from a control group were enrolled in our study. Among them, 20 received oxygen therapy at flow rates ranging from 1–10 L, while four received high-flow intranasal oxygen therapy (HFNOT). Some patients were treated with other types of therapy, such as Remdesivir, COVID-19 convalescent plasma therapy, or Tocilizumab. In the study, we focused on the analysis of optical coherence tomography (OCT) images of the cornea and retina including corneal thickness, central retinal thickness, retinal nerve fiber layer (RNFL), and optic disc parameters. The measurements were acquired using Spectral-domain OCT REVO FC 130. Results: The analysis did not show significant changes between the examined ophthalmological parameters before and after therapy. Furthermore, there were no detected significant differences between the tested parameters of the retina and cornea in COVID-19-positive patients compared to the control group. Conclusions: No ophthalmological manifestations of COVID-19 disease were observed during the study. Taking into account the results of other publications, the lack of an unambiguous position on this topic requires further research. Full article

HEV antibody detection constitutes the main screening test for HEV infection. The aim of this study is to compare the sensitivity and specificity of four techniques: LIAISON^® MUREX DiaSorin anti-HEV IgG and anti-HEV IgM assays, Hepatitis E VIRCLIA^® IgM and IgG monotests, WANTAI HEV-IgM and IgG ELISA and VIDAS^® anti-HEV IgM and IgG tests in five panels of samples configurated according to the immunoblot (RecomLine, Mikrogen, Neuss, Germany). Anti-HEV IgM sensitivity in the acute phase was 100% in all techniques, while sensitivity, including the immediate convalescence phase, was 96.74% for LIAISON^®, 83.14% for VIRCLIA^®, 84.78% for WANTAI and 88.04% for VIDAS^®. Anti-HEV IgM specificity was 100% for both LIAISON^® and VIRCLIA^®. Anti-HEV IgM WANTAI agreed with VIRCLIA^® with a good Kappa coefficient (κ = 0.71). Anti-HEV IgG post-infection sensitivity was 100% for LIAISON^®, VIDAS^® and VIRCLIA^® and 99% for WANTAI. Anti-HEV IgG specificity reached 97.17% for LIAISON and 88.68% for VIRCLIA^®. Our results demonstrated a better capacity of LIAISON^® MUREX anti-HEV IgM than that of competitors for detecting acute infections as well as accurate anti-HEV IgG results and in how to resolve them. Full article

A phase 1–2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were a ≥4-fold anti-RBD IgG seroconversion or a ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe—no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints. Full article

The emergence and spread of highly pathogenic avian influenza virus A subtype H5N1 (HP H5N1-IAV), particularly clade H5N1 2.3.4.4b, pose a severe global health threat, affecting various species, including mammals. Historically, cattle have been considered less susceptible to IAV, but recent outbreaks of H5N1-IAV 2.3.4.4b in dairy farms suggest a shift in host tropism, underscoring the urgency of expanded surveillance and the need for adaptable diagnostic tools in outbreak management. This study investigated the presence of anti-nucleoprotein (NP) antibodies in serum and milk and viral RNA in milk on dairy farms affected by outbreaks in Texas, Kansas, and Michigan using a multi-species IAV ELISA and RT-qPCR. The analysis of ELISA results from a Michigan dairy farm outbreak demonstrated a positive correlation between paired serum and milk sample results, confirming the reliability of both specimen types. Our findings also revealed high diagnostic performance during the convalescent phase (up to 96%), further improving sensitivity through serial sampling. Additionally, the evaluation of diagnostic specificity using serum and milk samples from IAV-free farms showed an excellent performance (99.6%). This study underscores the efficacy of the IAV NP-blocking ELISA for detecting and monitoring H5N1-IAV 2.3.4.4b circulation in dairy farms, whose recent emergence raises significant animal welfare and zoonotic concerns, necessitating expanded surveillance efforts. Full article

Background/Objectives: Monkeypox (mpox) is currently the most common orthopoxvirus (OPXV) zoonotic disease, and, since 2022, there has been atypical person-to-person transmission observed in non-endemic countries. The present study aimed to investigate the frequency of monkeypox virus (MPXV) and OPXV DNA detection in recommended and alternative clinical materials taken during the acute and convalescent phases of infection in Bulgarian patients. Methods: The study included laboratory investigation by real time PCR of 181 clinical samples from 42 Bulgarian patients with possible mpox infections. Results: MPXV DNA was detected in 23/181 (12.71%), and OPXV DNA in 20/181 (11.05%) clinical samples. There were six mpox-confirmed patients aged 23 to 44. At the highest frequency, MPXV and OPXV DNA were detected in samples of vesicular contents (6/6) and nasal/oropharyngeal secretions (5/6 and 4/6) during the first three days from the appearance of clinical symptoms. We demonstrated MPXV and OPXV DNA in alternative samples (urine, feces, ejaculate, and saliva), and in follow-up patient samples, taken two weeks after mpox confirmation in the convalescent phase (vesicular contentsand urine). Conclusions: Our findings suggested that MPXV may be detected in a larger set of clinical materials, including alternatives, where the virus can persist for more than two weeks. Full article