The End of the COVID-19 Pandemic—What Is Currently Known and What Could Have Been Useful Four Years Ago? (2nd Edition)

Background: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have generated major public health concerns worldwide. Young adults represent a critical group for viral transmission due to their high proportion of asymptomatic infections. Objective: To characterize the dynamics of SARS-CoV-2-specific antibodies in individuals aged 20–29 years from Bogotá, Colombia, across two longitudinal phases. Methods: Phase I assessed seroprevalence, seroconversion, spatial clustering, symptoms associated with seropositivity and antibody kinetics following natural infection. Phase II evaluated vaccine-induced antibodies, immune memory, and neutralizing capacity. Analyses included Functional Principal Component Analysis, survival analysis, clustering, and predictive modeling. Results: In Phase I, a seroprevalence of 15.59% (17/109 participants enrolled) was observed, while seroconversion among those who completed all six sampling points was 30.18% (16/53), with clusters of positive cases in different areas of Bogotá. The symptoms most associated with seropositivity included mucus hypersecretion, fever, and respiratory difficulty. Antibody responses were heterogeneous: naturally infected individuals generally showed high titers during the first 1–2 months, remaining detectable up to 4 months. The reduction in dimensionality suggested dominant humoral patterns, and clustering revealed two immune profiles differing in the risk of seroconversion. Predictive modeling indicated diverse antibody trajectories over 12 months. In Phase II (2024), three long-term immune memory clusters (low, medium, high) were observed; post-vaccination IgG titers were observed, although in most cases they lacked neutralizing activity. Conclusions: This longitudinal exploratory observational study provides an initial characterization of antibody dynamics in young adults, suggesting their potential epidemiological relevance and offering preliminary insights into post-infection and post-vaccination immunity. Full article

Background/Objectives: Severe COVID-19 is marked by IL-6-driven inflammation, endothelial injury, and dysregulated coagulation. Although IL-6 antagonists improve clinical outcomes, their effects on the temporal evolution of coagulation and fibrinolysis remain insufficiently defined. This study characterizes inflammatory, endothelial, coagulation, and fibrinolytic trajectories following IL-6 receptor blockade in critically ill COVID-19 patients. Methods: In this prospective, exploratory multicenter case series (ClinicalTrials.gov NCT05218369), 15 ICU patients with PCR- or antigen-confirmed COVID-19 received tocilizumab per protocol. Serial sampling at five timepoints (T0–T4) included routine laboratories, comprehensive viscoelastic hemostatic assays (ClotPro^®), and ELISA-based endothelial and fibrinolytic biomarkers. Analyses were primarily descriptive, emphasizing temporal patterns through boxplots; paired Wilcoxon tests with FDR correction contextualized within-patient changes. Results: Patients exhibited marked inflammation, hyperfibrinogenemia, endothelial activation, and delayed fibrinolysis at baseline. IL-6 blockade induced rapid suppression of CRP and PCT, progressive declines in fibrinogen, and modest platelet increases. In contrast, vWF antigen and activity further increased, indicating persistent endothelial dysfunction. Viscoelastic testing showed preserved thrombin generation and sustained high clot firmness, while biochemical markers (rising PAI-1, modest PAP increase, and progressively increasing D-dimer) and VHA indices suggested ongoing antifibrinolytic activity despite resolution of systemic inflammation. Conclusions: IL-6 antagonism was associated with rapid attenuation of systemic inflammation but was not accompanied by normalization of endothelial activation or fibrinolytic resistance. The observed hemostatic profile was consistent with attenuation of inflammation-associated coagulation features, while endothelial and prothrombotic alterations appeared to persist during follow-up, warranting further investigation in larger controlled studies. Full article

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article

Background: Patients with systemic lupus erythematosus (SLE), particularly those with lupus nephritis (LN), are at increased risk of severe COVID-19 outcomes due to immune dysregulation and immunosuppressive therapy. Renal transplant recipients with prior LN (LN-RTX) combine chronic immunosuppression with residual autoimmune risk. This study aimed to evaluate renal function trajectories and disease activity in LN patients during the COVID-19 pandemic, comparing transplant recipients with conservatively managed patients (LN-CT), and to assess the potential effects of COVID-19 vaccination. Methods: A retrospective cohort of 111 biopsy-confirmed LN patients followed between 2019 and 2023 was analyzed at four time points: pre-pandemic (T0), first pandemic year (T1), second pandemic year (T2), and post-pandemic (T3). Changes in renal function, disease activity markers, and treatment patterns were compared between LN-CT (n = 100) and LN-RTX (n = 11) groups, with additional analysis by vaccination status. Results: Renal function declined significantly in LN-CT (median eGFR: from 76.5 to 66.5 mL/min/1.73 m²; p < 0.001) but remained stable in LN-RTX patients despite higher comorbidity rates. LN activity (proteinuria, erythrocyturia) and glucocorticoid/MMF use decreased over time. Vaccinated patients showed a statistically significant decline in eGFR (p = 0.00046), though causality remains uncertain. Conclusions: Renal outcomes during the pandemic differed by treatment modality, with LN-RTX patients maintaining stable function despite higher risk. Adjusted immunosuppression and vigilant monitoring may have supported these outcomes. Further prospective studies should clarify vaccine-related renal effects in LN populations. Full article

Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53–196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03–1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset. Full article

Background: The long-term impact of SARS-CoV-2 infection on pulmonary function remains insufficiently characterised, particularly among individuals who have experienced mild or asymptomatic disease. This study aimed to assess spirometric changes over a three-year period and evaluate potential associations with demographic and clinical variables. Methods: We retrospectively analysed spirometry data from 103 healthcare workers (HCWs) who underwent pulmonary function tests at three time points: before the pandemic (Time 0), one year post-pandemic (Time 1), and two years post-pandemic (Time 2). Linear regression models were employed to evaluate the impact of various factors, including age, BMI, gender, smoking status, history of SARS-CoV-2 infection, vaccination status prior to infection, and the number of infections, on changes in FVC and FEV₁. Results: A statistically significant decrease in both FVC and FEV₁ were observed at Time 1 and Time 2 compared to baseline (p < 0.05). Smoking habits were significantly associated with a greater decline in both FVC and FEV₁. Multiple infections were associated with larger reductions in FVC at Time 1. No significant associations were found with age, gender, BMI, or vaccination status. Even in the absence of severe symptoms of the disease, healthcare workers exhibited a measurable decline in pulmonary function over time. Smoking and reinfection emerged as relevant factors associated with reduced lung capacity. Conclusions: These findings emphasise the need for ongoing respiratory monitoring in occupational settings and the importance of targeted preventive measures. Full article

Background/Objectives: During the COVID-19 pandemic, several antivirals were approved or repurposed, but their safety profiles have not been fully compared. Pharmacovigilance data help clarify how these drugs perform in real-world use. Methods: This study performed a comparative pharmacovigilance analysis of eight antivirals used or tested during the COVID-19 pandemic, based on individual case safety reports (ICSRs) retrieved from the EudraVigilance database, reported up to 9 February 2025 and extracted from the official platform on 12 February 2025. Adverse reactions were assessed by system organ class (SOC), demographic patterns, and seriousness, and disproportionality analysis (reporting odds ratio (ROR)) was conducted to identify potential safety signals. Results: A total of 64,776 ICSRs were analyzed. Among approved antivirals, nirmatrelvir/ritonavir (NTV/r) accounted for 13.4% (n = 8693) of reports, while remdesivir (RDV) represented 6.3% (n = 4105). Repurposed antivirals such as ribavirin and lopinavir/ritonavir dominated the dataset, together making up over 80% (n = 51,978) of all reports. RDV was associated with a high proportion of serious adverse events (84%, n = 3448), and showed consistent ROR signals in hepatobiliary, renal, cardiac, and general disorders, with values exceeding 2 in several comparisons. NTV/r displayed a milder overall profile, but with positive RORs for psychiatric disorders, gastrointestinal disorders, and product-related issues. The most affected SOCs across all drugs included general disorders (31.6%, n = 20,493), gastrointestinal (19.5%, n = 12,625), nervous system (17.8%, n = 11,511), and investigations (20.4%, n = 13,219). Demographic analysis showed that most events occurred in adults aged 18–64, with RDV more often reported in elderly patients and NTV/r more frequently associated with reports from female patients and non-healthcare reporters. Conclusions: This study highlights distinct pharmacovigilance profiles of COVID-19 antivirals and supports the role of real-world data in guiding safer therapeutic choices. Full article

Background/Objectives: The present study aimed to analyze changes in symptom intensity during the recovery period of COVID-19 survivors and patients with post-COVID syndrome. Methods: Initially, we described a new remote patient monitoring system to track the intensity of specific symptoms in individuals’ home environments. Remote patient monitoring (RPM) was implemented over 15 days in a cohort of 133 individuals aged 20 to 78 years, divided into four groups: mild (MG, n = 40), Hospital Discharge Without Invasive Mechanical Ventilation (WIMV, n = 40), Hospital Discharge With Invasive Mechanical Ventilation (IMV, n = 13), and reinfected (RG, n = 40). Results: The most prevalent symptoms reported across all groups, based on average intensity, were shortness of breath, fatigue, cough, headache, and body pain. The WIMV group exhibited the highest average intensities in six symptoms (p < 0.01), while the IMV group reported the highest averages in four symptoms (p < 0.05). Fatigue was the symptom with the highest overall intensity, followed by memory lapses. The hospitalized groups demonstrated the highest intensities and most persistent symptoms (p < 0.05). Blood pressure was significantly higher in the MG group compared to the RG group (p < 0.0001), although all values remained within the normal range. Conclusions: These results provide novel insights, revealing distinct differences in the symptom profiles among the studied groups. These findings hold significant implications for developing more personalized care strategies and informing future pandemic preparedness and response efforts. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

Background/Objectives: SARS-CoV-2 has strained healthcare systems, emphasizing the need for biomarkers to predict disease severity. Recent studies suggest that soluble urokinase plasminogen activator receptor (suPAR) is a promising marker for COVID-19 pneumonia, though its utility alongside the CURB-65 score remains unstudied. This study evaluates the prognostic value of suPAR in comparison to leukocyte count and CURB-65, and its potential for enhancing risk stratification in a combined CURB-65 model. Methods: Biomarkers and CURB-65 scores were obtained for 240 immunocompetent patients hospitalised with COVID-19 pneumonia. Intensive care unit admission and in-hospital mortality were assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier analysis. Additionally, a Net Reclassification Improvement (NRI) analysis was performed to evaluate the predictive value of suPAR combined with the CURB-65 score for risk stratification. Results: suPAR demonstrated strong diagnostic accuracy, outperforming lymphocyte count and showing greater precision than the CURB-65 score for ICU admission. Notably, no patient with suPAR < 4 ng/mL experienced the studied outcomes. NRI analysis revealed a significant improvement in risk classification when suPAR was combined with CURB-65. Conclusions: The addition of the suPAR biomarker to the CURB-65 score represents a substantial improvement in the risk classification of patients with COVID-19 pneumonia, with a potential impact on daily clinical practice. Full article

Background/Objectives: The spread of the COVID-19 pandemic has spurred the development of advanced healthcare tools to effectively manage patient outcomes. This study aims to identify key predictors of mortality in hospitalized patients with some level of natural immunity, but not yet vaccinated, using machine learning techniques. Methods: A total of 363 patients with COVID-19 admitted to Río Hortega University Hospital in Spain between the second and fourth waves of the pandemic were included in this study. Key characteristics related to both the patient’s previous status and hospital stay were screened using the Random Forest (RF) machine learning technique. Results: Of the 19 variables identified as having the greatest influence on predicting mortality, the most powerful ones could be identified at the time of hospital admission. These included the assessment of severity in community-acquired pneumonia (CURB-65) scale, age, the Glasgow Coma Scale (GCS), and comorbidities, as well as laboratory results. Some variables associated with hospitalization and intensive care unit (ICU) admission (acute renal failure, shock, PRONO sessions and the Acute Physiology and Chronic Health Evaluation [APACHE-II] scale) showed a certain degree of significance. The Random Forest (RF) method showed high accuracy, with a precision of >95%. Conclusions: This study shows that natural immunity generates significant changes in the evolution of the disease. As has been shown, machine learning models are an effective tool to improve personalized patient care in different periods. Full article

Background/Objectives: People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. Methods: Among 1238 COVID-19 patients, hospitalized from 17 March 2020 to 15 June 2021, 247 survivors and 247 deceased within 90 days from hospitalization were matched 1:1 based on age, sex, and intensive care unit (ICU) admission within three days. Conditional logistic regression was used to estimate associations by means of odds ratio (OR) with a 95% confidence interval (CI). Results: A univariate regression analysis suggested that OAT, no differently from subcutaneous low-molecular-weight heparins (LMWHs) during hospitalization, has no significant impact (p value > 0.05) on medium-term mortality. A multivariate analysis, limited to baseline variables (i.e., comorbidities and pharmacotherapies at hospital admission) showing significant association (p < 0.05) to mortality in a univariate analysis, revealed that, compared to patients living at 90 days from hospitalization, deceased patients had cancer histories (OR 1.75, CI 1.06–2.90, p = 0.029) or suffered from asthma (OR 2.25, CI 1.13–4.47, p = 0.021). In contrast, heart failure (HF), atrial fibrillation (AF), arteriopathy, chronic obstructive pulmonary disease (COPD), and kidney failure (KF), which, in a univariate analysis, were found to be associated with the endpoint (p < 0.05), lost significance in a multivariate analysis. Therapy at admission with aldosterone antagonists also appeared to be associated with medium-term mortality (OR 2.49, CI 1.52–4.08, p < 0.001); whereas, vitamin D supplementation during hospitalization appeared to be beneficial. Although not conclusive, a search into the Eudravigilance database, combined with consulting a digital predictive platform (PLATO, polypharmacology platform prediction), suggested potential off-target activities, which might contribute to increasing the severity of SARS-CoV-2 infection. Conclusions: This retrospective clinical study furnished evidences of the impact of OAT, comorbidities and other pharmacological treatments on COVID-19 clinical course. Full article

Background/Objectives: Respiratory diseases are common and result in high mortality, especially in the elderly, with pneumonia and chronic obstructive pulmonary disease (COPD). Auscultation of lung sounds using a stethoscope is a crucial method for diagnosis, but it may require specialized training and the involvement of pulmonologists. This study aims to assist medical professionals who are non-pulmonologist doctors in early screening for pneumonia and COPD by developing a smart stethoscope with cloud server-embedded machine learning to diagnose lung sounds. Methods: The smart stethoscope was developed using a Micro-Electro-Mechanical system (MEMS) microphone to record lung sounds in the mobile application and then send them wirelessly to a cloud server for real-time machine learning classification. Results: The model of the smart stethoscope classifies lung sounds into four categories: normal, pneumonia, COPD, and other respiratory diseases. It achieved an accuracy of 89%, a sensitivity of 89.75%, and a specificity of 95%. In addition, testing with healthy volunteers yielded an accuracy of 80% in distinguishing normal and diseased lungs. Moreover, the performance comparison between the smart stethoscope and two commercial auscultation stethoscopes showed comparable sound quality and loudness results. Conclusions: The smart stethoscope holds great promise for improving healthcare delivery in the post-COVID-19 era, offering the probability of the most likely respiratory conditions for early diagnosis of pneumonia, COPD, and other respiratory diseases. Its user-friendly design and machine learning capabilities provide a valuable resource for non-pulmonologist doctors by delivering timely, evidence-based diagnoses, aiding treatment decisions, and paving the way for more accessible respiratory care. Full article

Background/Objectives: The rapid viral spread observed in coronavirus disease 2019 (COVID-19) is capable of inducing the secretion of excessive inflammatory cytokines. The resulting multi-organ damage is a severe complication that can be attenuated through adequate nutrition. Formulae enhanced with either glutamine or arginine are conditionally essential amino acids that have been proven to improve the condition of hospitalized patients. This retrospective study aimed to investigate the effects of administering an immune-enhancing enteral formula enhanced with arginine and glutamine on the clinical signs and biomarkers of patients with severe COVID-19. Methods: After checking the data of 232 patients enrolled in the biobank for completeness and eligibility, 31 patients with severe COVID-19 in the intensive care unit at Taipei Tzu Chi Hospital were grouped based on the type of enteral formula used: 16 patients received the control formula, and 15 patients received the immune-enhancing formula. Baseline characteristics, clinical signs, and inflammatory markers were analyzed for differences. Results: An increase in IL-10 levels in the intervention group was observed (p = 0.048). Changes in other inflammatory cytokine levels were insignificant. Conclusions: Providing an enteral formula enriched with glutamine and arginine to severe COVID-19 patients may help improve their anti-inflammatory marker levels. Further interventional study utilizing enteral formula enriched with glutamine and arginine is needed to confirm the findings of this study. Full article

Background/Objectives: The impact of vaccines against SARS-CoV-2 on the immunity of patients with multiple sclerosis (PwMS) is still not fully known. Further clarification could help address medical concerns related to the use of immunosuppressive and immunomodulatory medications, known as disease-modifying therapies (DMTs), in PwMS, as well as ensure adequate protection against severe outcomes of COVID-19. Therefore, the aim of our study was to evaluate the humoral and cellular immune response in PwMS treated with DMTs. Methods: The concentrations of IgG Spike (S) anti-SARS-CoV-2 antibodies and IgG Nucleocapsid (N) anti-SARS-CoV-2 antibodies, as well as interferon-gamma (IFN-γ) titers were analyzed in PwMS groups treated with dimethyl fumarate (DMF), interferon beta (IFN), and healthy control group. Results: Almost 100% of PwMS experienced seroconversion, which resulted from either vaccination and/or prior infection. Additionally, there were no significant differences between the study and control groups in terms of IgG (S) and (N) anti-SARS-CoV-2 antibody levels. However, interferon-gamma titers were lower in both PwMS groups, which may indicate adequate humoral and decreased cellular response to the examined PwMS. Additionally, after the division of the whole study group into two subgroups according to the time since the last vaccination, IgG (S) anti-SARS-CoV-2 and IFN-γ concentrations were significantly lower in the case of patients who were immunized more than 200 days before sample collection. No differences were observed in the case of subgroups in which sample collection was less than 200 days after vaccination when compared to the control group. Conclusions: This could indicate a time-related decrease in immunity in PwMS treated with DMTs. Full article

Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS (n = 19), without MAS (n = 78), and probable MAS (n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2—ferritin > 469 μg/L or platelets < 114 × 10⁹/L—allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 10⁹/L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods. Full article

Background/Objectives: On-site diagnosis of infection in their early stages requires assays with high sensitivities that are compact and easy to operate out of the laboratory and hospital environments. However, current assay technologies fall short of these requirements and require highly skilled technicians to set up, operate, and interpret the results. Methods: To address these challenges, we developed and evaluated a Point-of-Care-Testing (PoCT) immunoassay platform called the D-strip. The D-strip platform combines the capabilities of a digital enzyme-linked immunoassay (ELISA) with a lateral flow assay (LFA). The D-strip sample flow cell is composed of the same components found in conventional LFAs, and its high sensitivity is due to its efficient implementation of ELISA. The fully integrated platform is simple and requires minimal user intervention to operate. Results: The D-strip exhibited a sample-to-result time of 15 min with a limit of detection (LOD) of 1.7 × 10³ copies/mL for severe acute respiratory syndrome coronavirus 2 (SARS-2-CoV) antigen. The LOD of the D-strip is 488-fold higher than that for conventional LFAs and is comparable to a clinical laboratory test. Conclusions: The D-strip is a compact and highly sensitive immunoassay platform with a strong potential for application as a confirmatory assay outside the clinical laboratory. Full article

Objectives: The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of radiographic pulmonary infiltrates and the clinical outcomes of COVID-19. Methods: The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study. Results: This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787–0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9–30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes. Conclusion: PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death. Full article

The breach of an interspecies barrier by RNA viruses has facilitated the emergence of lethal hCoVs, particularly SARS-CoV-2, resulting in significant socioeconomic setbacks and public health risks globally in recent years. Moreover, the high evolutionary plasticity of hCoVs has led to the continuous emergence of diverse variants, complicating clinical management and public health responses. Studying the evolutionary trajectory of hCoVs, which provides a molecular roadmap for understanding viruses’ adaptation, tissue tropism, spread, virulence, and immune evasion, is crucial for addressing the challenges of zoonotic spillover of viruses. Tracing the evolutionary trajectory of lethal hCoVs provides essential genomic insights required for risk stratification, variant/sub-variant classification, preparedness for outbreaks and pandemics, and the identification of critical viral elements for vaccine and therapeutic development. Therefore, this review examines the evolutionary landscape of the three known lethal hCoVs, presenting a focused narrative on SARS-CoV-2 variants under monitoring (VUMs) as of May 2025. Using advanced bioinformatics approaches and data visualization, the review highlights key spike protein substitutions, particularly within the receptor-binding domain (RBD), which drive transmissibility, immune escape, and potential resistance to therapeutics. The article highlights the importance of real-time genomic surveillance and intervention strategies in mitigating emerging variant/sub-variant risks within the ongoing COVID-19 landscape. Full article

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has imposed several medical and economic challenges since its onset in 2019. This is due to its ability to target the respiratory system as well as other organs, resulting in significant impacts and necessitating organ transplants. Our goal is to compile information from the existing literature to investigate how COVID-19 affects outcomes following organ transplantation. A comprehensive literature search was conducted to target studies reporting post-COVID-19 complications. We included 45 studies reporting data related to solid organ transplants, where either the recipient, organ, or donor was affected by SARS-CoV-2. The majority of the included studies concluded that organ transplantation following COVID-19 infection could be performed safely and with similar outcomes to non-COVID-19 patients, regardless of whether the organ, donor, or recipient was affected by COVID-19. No deviation from standard immunosuppression regimens or surgical protocols was necessary either, further re-assuring the feasibility of these transplants as viable treatment options. This applies to organ transplants involving the lungs, kidneys, liver, or heart. However, there was a limited number of studies in some areas, which warrants the need for additional research in order to reach more concrete conclusions pertaining to COVID-19’s effect on organ transplants. Full article

Introduction: The emergence of the SARS-CoV-2 virus and its subsequent global pandemic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed and Web of Science, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2-positive pregnant women compared to controls. The average incidence rate of preterm birth in infected patients was 18.5%, with a median of 12.75%, while non-infected women showed an average incidence of preterm birth of 10%, with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. The severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes. Full article

Background: During the coronavirus disease (COVID)-19 pandemic several drugs were used to manage the patients mainly those with a severe phenotype. Potential drugs were used off-label and major concerns arose from their applicability to managing the health crisis highlighting the importance of clinical trials. In this context, we described the mechanisms of the three repurposed drugs [Ivermectin-antiparasitic drug, Chloroquine/Hydroxychloroquine-antimalarial drugs, and Azithromycin-antimicrobial drug]; and, based on this description, the study evaluated the clinical efficacy of those drugs published in clinical trials. The use of these drugs reflects the period of uncertainty that marked the beginning of the COVID-19 pandemic, which made them a possible treatment for COVID-19. Methods: In our review, we evaluated phase III randomized controlled clinical trials (RCTs) that analyzed the efficacy of these drugs published from the COVID-19 pandemic onset to 2023. We included eight RCTs published for Ivermectin, 11 RCTs for Chloroquine/Hydroxychloroquine, and three RCTs for Azithromycin. The research question (PICOT) accounted for P—hospitalized patients with confirmed or suspected COVID-19; I—use of oral or intravenous Ivermectin OR Chloroquine/Hydroxychloroquine OR Azithromycin; C—placebo or no placebo (standard of care); O—mortality OR hospitalization OR viral clearance OR need for mechanical ventilation OR clinical improvement; and T—phase III RCTs. Results: While studying these drugs’ respective mechanisms of action, the reasons for which they were thought to be useful became apparent and are as follows: Ivermectin binds to insulin-like growth factor and prevents nuclear transportation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), therefore preventing cell entrance, induces apoptosis, and osmotic cell death and disrupts viral replication. Chloroquine/Hydroxychloroquine blocks the movement of SARS-CoV-2 from early endosomes to lysosomes inside the cell, also, this drug blocks the binding between SARS-CoV-2 and Angiotensin-Converting Enzyme (ACE)-2 inhibiting the interaction between the virus spike proteins and the cell membrane and this drug can also inhibit SARS-CoV-2 viral replication causing, ultimately, the reduction in viral infection as well as the potential to progression for a higher severity phenotype culminating with a higher chance of death. Azithromycin exerts a down-regulating effect on the inflammatory cascade, attenuating the excessive production of cytokines and inducing phagocytic activity, and acts interfering with the viral replication cycle. Ivermectin, when compared to standard care or placebo, did not reduce the disease severity, need for mechanical ventilation, need for intensive care unit, or in-hospital mortality. Only one study demonstrated that Ivermectin may improve viral clearance compared to placebo. Individuals who received Chloroquine/Hydroxychloroquine did not present a lower incidence of death, improved clinical status, or higher chance of respiratory deterioration compared to those who received usual care or placebo. Also, some studies demonstrated that Chloroquine/Hydroxychloroquine resulted in worse outcomes and side-effects included severe ones. Adding Azithromycin to a standard of care did not result in clinical improvement in hospitalized COVID-19 participants. In brief, COVID-19 was one of the deadliest pandemics in modern human history. Due to the potential health catastrophe caused by SARS-CoV-2, a global effort was made to evaluate treatments for COVID-19 to attenuate its impact on the human species. Unfortunately, several countries prematurely justified the emergency use of drugs that showed only in vitro effects against SARS-CoV-2, with a dearth of evidence supporting efficacy in humans. In this context, we reviewed the mechanisms of several drugs proposed to treat COVID-19, including Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin, as well as the phase III clinical trials that evaluated the efficacy of these drugs for treating patients with this respiratory disease. Conclusions: As the main finding, although Ivermectin, Chloroquine/Hydroxychloroquine, and Azithromycin might have mechanistic effects against SARS-CoV-2 infection, most phase III clinical trials observed no treatment benefit in patients with COVID-19, underscoring the need for robust phase III clinical trials. Full article