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This multidisciplinary composition of the contributors to this Special Issue provides the readers with multiple and original views and approaches, enriching the scientific debate on SARS-CoV-2 epidemiology and pathogenesis. Concerning the topics, the majority of the papers ( I n i = 11) dealt with the epidemiology of SARS-CoV-2 infection in various contexts, while 10 articles focused on specific aspects characterizing the pathogenesis of the disease. Since its emergence in 2019 in Wuhan City, Hubei Province, China, SARS-CoV-2 has spread across hundreds of countries and all continents. 10.3390/microorganisms9040800 4 Jo S., Kim S., Yoo J., Kim M.-S., Shin D.H. A Study of 3CLpros as Promising Targets against SARS-CoV and SARS-CoV-2. [Extracted from the article]

Graphene and its derivatives have lately been the subject of increased attention for different environmental applications of membrane technology such as water treatment and air filtration, exploiting their antimicrobial and antiviral activity. They are interesting candidates as membrane materials for their outstanding mechanical and chemical stability and for their thin two-dimensional (2D) nanostructure with potential pore engineering for advanced separation. All these applications have evolved and diversified from discovery to today, and now graphene and graphene derivatives also offer fascinating opportunities for the fight against infective diseases such as COVID-19 thanks to their antimicrobial and antiviral properties. This paper presents an overview of graphene-based 2D materials, their preparation and use as membrane material for applications in water treatment and in respiratory protection devices. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of the vaccination decline experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on the impacts of routine childhood vaccinations in low-income countries from 1 January 2020 to 8 February 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to discuss the impact of COVID-19 on patients with urological malignancies (prostate cancer, bladder and upper tract urothelial cancer, kidney cancer, penile and testicular cancer) and to review the available recommendations reported in the literature. Methods: A review was performed, through the PubMed database, regarding available recommendations reported in the literature, to identify studies examining the impact of COVID-19 on treatment and clinical outcomes (including upstaging, recurrence, and mortality) for uro-oncological patients. Results: The COVID-19 pandemic dramatically changed the urological guidelines and patients' access to screening programs and follow-up visits. Great efforts were undertaken to guarantee treatments to high-risk patients although follow up was not always possible due to recurrent surges, and patients with lower risk cancers had to wait for therapies. Conclusions: Physically and mentally, uro-oncological patients paid a heavy price during the COVID-19 pandemic. Long term data on the "costs" of clinical decisions made during the COVID-19 pandemic are still to be revealed and analyzed. [ABSTRACT FROM AUTHOR]

As of 2024, SARS-CoV-2 continues to propagate and drift as an endemic virus, impacting healthcare for years. The largest sequencing initiative for any species was initiated to combat the virus, tracking changes over time at a full virus base-pair resolution. The SARS-CoV-2 sequencing represents a unique opportunity to understand selective pressures and viral evolution but requires cross-disciplinary approaches from epidemiology to functional protein biology. Within this work, we integrate a two-year genotyping window with structural biology to explore the selective pressures of SARS-CoV-2 on protein insights. Although genotype and the Spike (Surface Glycoprotein) protein continue to drift, most SARS-CoV-2 proteins have had few amino acid alterations. Within Spike, the high drift rate of amino acids involved in antibody evasion also corresponds to changes within the ACE2 binding pocket that have undergone multiple changes that maintain functional binding. The genotyping suggests selective pressure for receptor specificity that could also confer changes in viral risk. Mapping of amino acid changes to the structures of the SARS-CoV-2 co-transcriptional complex (nsp7-nsp14), nsp3 (papain-like protease), and nsp5 (cysteine protease) proteins suggest they remain critical factors for drug development that will be sustainable, unlike those strategies targeting Spike. [ABSTRACT FROM AUTHOR]

The lack of a universally accepted definition of a pandemic hinders a comprehensive understanding of and effective response to these global health crises. Current definitions often lack quantitative criteria, rendering them vague and limiting their utility. Here, we propose a refined definition that considers the likelihood of susceptible individuals contracting an infectious disease that culminates in widespread global transmission, increased morbidity and mortality, and profound societal, economic, and political consequences. Applying this definition retrospectively, we identify 22 pandemics that occurred between 165 and 2024 AD and were caused by a variety of diseases, including smallpox (Antonine and American), plague (Justinian, Black Death, and Third Plague), cholera (seven pandemics), influenza (two Russian, Spanish, Asian, Hong Kong, and swine), AIDS, and coronaviruses (SARS, MERS, and COVID-19). This work presents a comprehensive analysis of past pandemics caused by both emerging and re-emerging pathogens, along with their epidemiological characteristics, societal impact, and evolution of public health responses. We also highlight the need for proactive measures to reduce the risk of future pandemics. These strategies include prioritizing surveillance of emerging zoonotic pathogens, conserving biodiversity to counter wildlife trafficking, and minimizing the potential for zoonotic spillover events. In addition, interventions such as promoting alternative protein sources, enforcing the closure of live animal markets in biodiversity-rich regions, and fostering global collaboration among diverse stakeholders are critical to preventing future pandemics. Crucially, improving wildlife surveillance systems will require the concerted efforts of local, national and international entities, including laboratories, field researchers, wildlife conservationists, government agencies and other stakeholders. By fostering collaborative networks and establishing robust biorepositories, we can strengthen our collective capacity to detect, monitor, and mitigate the emergence and transmission of zoonotic pathogens. [ABSTRACT FROM AUTHOR]

The clinical presentation, organ involvement, and severity of disease caused by SARS-CoV-2 are highly variable, ranging from asymptomatic or mild infection to respiratory or multi-organ failure and, in children and young adults, the life-threatening multisystemic inflammatory disease (MIS-C). SARS-CoV-2 enters cells via the angiotensin-converting enzyme-2 receptor (ACE-2), which is expressed on the cell surfaces of all organ systems, including the gastrointestinal tract. GI manifestations have a high prevalence in children with COVID-19. However, isolated terminal ileitis without other manifestations of COVID-19 is rare. In March 2023, two previously healthy boys (aged 16 months and 9 years) without respiratory symptoms presented with fever and diarrhea, elevated C-reactive protein levels, and low procalcitonin levels. Imaging studies revealed marked terminal ileitis in both cases. SARS-CoV-2 (Omicron XBB.1.9 and XBB.1.5 variants) was detected by nucleic acid amplification in throat and stool samples. Both patients recovered fast with supportive measures only. A differential diagnosis of acute abdominal pain includes enterocolitis, mesenteric lymphadenitis, appendicitis, and more. During SARS-CoV-2 epidemics, this virus alone may be responsible for inflammation of the terminal ileum, as demonstrated. Coinfection with Campylobacter jejuni in one of our patients demonstrates the importance of a complete microbiological workup. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the therapeutic efficacy of ursodeoxycholic acid (UDCA) and mesenchymal stem cells (MSCs) in patients with severe COVID-19. Methods: We included severe COVID-19 patients hospitalized at Shulan (Hangzhou) Hospital between December 2022 and June 2023. We used a logistic regression model to compare the use of UDCA and MSCs in the two distinct groups of improved and poor outcomes. It is noteworthy that the deterioration group encompassed instances of both death and abandonment of treatment. The receiver operating characteristic (ROC) curve was plotted to assess the performance of the model. The aim was to assess the therapeutic effect of UDCA and MSCs on the outcome of severe COVID-19 patients. Results: A total of 167 patients with severe COVID-19 were included in this study. The analysis revealed that out of 42 patients (25.1%), 17 patients (10.2%) had taken UDCA, and 17 patients (10.2%) had used MSCs. Following a multivariable logistic regression, the results indicated a negative association between UDCA treatment (OR = 0.38 (0.16–0.91), p = 0.029), MSCs treatment (OR = 0.21 (0.07–0.65), p = 0.007), and the risk of severe COVID-19 mortality. Additionally, age showed a positive association with the risk of mortality (OR = 1.03 (1.01–1.07), p = 0.025). Conclusions: UDCA and MSCs have shown potential in improving the prognosis of severe COVID-19 patients and could be considered as additional treatments for COVID-19 in the future. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) infected with SARS-CoV-2 indicate a higher risk of severe COVID-19 course, which is defined as the need for hospitalization in the intensive care unit, mechanical ventilation, or death. However, simple tools to stratify the risk in patients with COPD suffering from COVID-19 are lacking. The current study aimed to evaluate the predictive value of the C2HEST score in patients with COPD. A retrospective analysis of medical records from 2184 patients hospitalized with COVID-19 at the University Hospital in Wroclaw from February 2020 to June 2021, which was previously used in earlier studies, assessed outcomes such as mortality during hospitalization, all-cause mortality at 3 and 6 months, non-fatal discharge, as well as adverse clinical incidents. This re-analysis specifically examines the outcomes using a COPD split. In the COPD group, 42 deaths were recorded, including 18 in-hospital deaths. In-hospital mortality rates at 3 and 6 months did not significantly differ among C2HEST strata, nor did their impact on subsequent treatment. However, a notable association between the C2HEST score and prognosis was observed in the non-COPD cohort comprising 2109 patients. The C2HEST score's predictive ability is notably lower in COPD patients compared to non-COPD subjects, with COPD itself indicating a high mortality risk. However, C2HEST effectively identifies patients at high risk of cardiac complications during COVID-19, especially in non-COPD cases. [ABSTRACT FROM AUTHOR]

The evaluation of coronavirus disease 2019 (COVID-19) vaccine immunogenicity remains essential as the severe acute respiratory syncytial virus 2 (SARS-CoV-2) pandemic continues to evolve and as additional variants emerge. Neutralizing antibodies are a known correlate of protection for SARS-CoV-2 vaccines. A pseudovirus neutralization (PNT) assay was developed and validated at Novavax Clinical Immunology Laboratories to allow for the detection of neutralizing antibodies in vaccine clinical trial sera. The PNT assay was precise, accurate, linear, and specific in measuring SARS-CoV-2 neutralization titers in human serum for ancestral strain and the Omicron subvariants BA.5 and XBB.1.5, with an overall geometric coefficient of variation of ≤43.4%, a percent relative bias within the expected range of −60% to 150%, and a linearity value of R2 > 0.98 for all three strains. This pseudovirus assay will be useful for the analysis of vaccine clinical trial samples to assess vaccine immunogenicity. Future work will focus on modifying the assay for emerging variants, including XBB.1.16, EG.5.1, BA.2.86, and any other variants that emerge in the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients' cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6–7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella. [ABSTRACT FROM AUTHOR]

Background: Based on recent findings, we speculated the existence of the lung, heart, and kidney axis as the main pathway for the COVID-19 disease progression. Methods: This paper reports on an observational study conducted by a team of researchers and doctors of the 118-Pre-Hospital and Emergency Department of SG Moscati of Taranto City in Italy. The study was conducted on a totality of 185 participants that were divided into three groups. The study group included COVID-19 affected patients (PP n = 80), the first control group included patients with different pathologies (non-COVID-19 NNp n = 62) of the SG Moscati Hospital, and the second control group included healthy individuals (NNh n = 43). The core of the current trial was focused on assessing the level of the vitamin D (serum 25(OH) D concentration), IL-6, and the renal glomerular filtrate (eGFR) in COVID-19 disease and non-COVID-19 patients in both groups. Results: It was observed that the majority of COVID-19-infected patients showed a progressive multi-organ involvement, especially in regard to the lung, kidney, and heart. The majority of the COVID-19 patients exhibited preexisting comorbidities which include cardiovascular, respiratory, and renal disorders accompanied by a severely low level of vitamin D, extremely high level of IL-6, and low glomerular filtration rate (eGFR). The significant overall damages exerted by the immune-mediated responses under the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may be facilitated by either a decreased level of vitamin D or the ageing process. The reduced presence of vitamin D was often found together with a reduced functionality of renal activity, as revealed by the low eGFR, and both were seen to be concomitant with an increased mortality risk in patients with lung disorders and heart failure (HF), whether it is showed at baseline or it develops during manifestation of COVID-19. Therefore, the documentation of the modifiable risk factors related to SARS-CoV-2 and lung impairment in older patients with kidney and heart disease may help the clinician to better manage the situation. Conclusions: This paper addresses how a low level of vitamin D and older age may be indicative of systemic worsening in patients with COVID-19, with a goal of providing a broader context in which to view a better therapeutic approach. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies have been administered to kidney transplant recipients (KTRs) with a poor or non-responder status to SARS-CoV-2 vaccination. The cellular response to SARS-CoV-2 has been poorly studied in this context. We assessed the T cell response to SARS-CoV-2 in 97 patients on the day of the injection of tixagevimab/cilgavimab using an IFNγ enzyme-linked immunospot assay (ELISPOT). Among the 97 patients, 34 (35%) developed COVID-19 before the injection. Twenty-nine (85.3%) had an ELISPOT compatible with a SARS-CoV-2 infection. There was no difference between KTRs under belatacept or tacrolimus treatment. Sixty-three patients (64.9%) had no known COVID-19 prior to the ELISPOT, but nine (14.3%) had a positive ELISPOT. In 21 KTRs with a positive ELISPOT who received a booster dose of a bivalent mRNA vaccine, median antibody titers and spike-reactive T cells increased significantly in patients under tacrolimus but not belatacept. Our study emphasizes the potential usefulness of the exploration of immune cellular response to SARS-CoV-2 by ELISPOT. In KTRs with a positive ELISPOT and under CNI therapy, a booster dose of mRNA vaccine seems effective in inducing an immune response to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory generated during the SARS-CoV-2 pandemic, either by infection or vaccination, offer protection against future coronaviruses? Or rather than protection, could antibody-dependent enhancement have taken place, a mechanism by which circulating corona antibodies enhance the severity of COVID-19? Another related phenomenon, the original antigenic sin, would also predict that the effectiveness of the immune response to future coronaviruses would be impaired because of the reactivation of memory against irrelevant epitopes. The currently available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses. [ABSTRACT FROM AUTHOR]

Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially develop severe illnesses that could result in hospitalization or death in the worst case. The most common ARVs are the Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARV infection are a common symptom among patients. This review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need to understand the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients. [ABSTRACT FROM AUTHOR]

Neutralizing antibody responses from COVID-19 vaccines are pivotal in conferring protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Effective COVID-19 vaccines and assays measuring neutralizing antibodies against emerging variants (i.e., XBB.1.5, XBB.1.16, and XBB.2.3) are needed. The use of biosafety level (BSL)-3 laboratories for live virus assays results in higher costs and a longer turnaround time; therefore, a BSL-2–based pseudovirus neutralization assay (PNT) was developed. The pseudoviruses were produced by cotransfecting cells with plasmids encoding a lentiviral backbone-expressing luciferase reporter; non-surface proteins for lentiviral production; and ancestral or Omicron (BA.1 and BA.5) SARS-CoV-2 spike (S) proteins. The PNT was developed and optimized in dose and kinetics experiments. The representative serum samples (COVID-19–convalescent or NVX-CoV2373–vaccinated participants enrolled in the 2019nCoV-101 trial) demonstrated a wide dynamic range. The neutralization data showed robust correlation with validated anti-recombinant spike IgG levels and angiotensin-converting enzyme 2 inhibition titers (ancestral). This assay is suitable for measurement of the neutralization ability in clinical samples from individuals infected with SARS-CoV-2 or immunized with a COVID-19 vaccine. The results suggest that this PNT provides a lower cost, high-throughput, rapid turnaround alternative to BSL-3–based microneutralization assays and enables the discovery and development of effective vaccines against emerging variants. [ABSTRACT FROM AUTHOR]

Introduction: The multifaceted impact of COVID-19 extends beyond the respiratory system, encompassing intricate interactions with various physiological systems. This study elucidates the potential association between SARS-CoV-2 infection and anemia, with a particular emphasis on the deformability of red blood cells (RBCs), stability of hemoglobin, enzymatic activities, and proteomic profiles. Methods: The study encompasses a cohort of 74 individuals, including individuals positive for COVID-19, a control group, and patients with other viral infections to discern the specific effects attributable to COVID-19. The analysis of red blood cells was focused on deformability measured by osmotic gradient ektacytometry, hemoglobin stability, and glycolytic enzyme activity. Furthermore, membrane proteins were examined using advanced proteomics techniques to capture molecular-level changes. Results: Findings from the study suggest a correlation between anemia and exacerbated outcomes in COVID-19 patients, marked by significant elevations in d-dimer, serum procalcitonin, creatinine, and blood urea nitrogen (BUN) levels. These observations suggest that chronic kidney disease (CKD) may play a role in the development of anemia in COVID-19 patients, particularly those of advanced age with comorbidities. Furthermore, the proteomic analyses have highlighted a complex relationship between omics data and RBC parameters, enriching our understanding of the mechanisms underlying the disease. Conclusions: This research substantiates the complex interrelationship between COVID-19 and anemia, with a specific emphasis on the potential repercussions of SARS-CoV-2 infection on RBCs. The findings contribute to the growing body of evidence supporting the extensive impact of COVID-19 on RBCs. [ABSTRACT FROM AUTHOR]

Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET and ATO, commonly prescribed for diabetes and dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory and antiviral capabilities, as well as their cost-effectiveness and ubiquitous availability, they are highly suitable options for treating the virus. MET's effect extends beyond managing blood sugar, impacting pathways that can potentially decrease the severity and fatality rates linked with COVID-19. It can partially block mitochondrial complex I and stimulate AMPK, which indicates that it can be used more widely in managing viral infections. ATO, however, impacts cholesterol metabolism, a crucial element of the viral replicative cycle, and demonstrates anti-inflammatory characteristics that could modulate intense immune reactions in individuals with COVID-19. Retrospective investigations and clinical trials show decreased hospitalizations, severity, and mortality rates in patients receiving these medications. Nevertheless, the journey from observing something to applying it in a therapeutic setting is intricate, and the inherent diversity of the data necessitates carefully executed, forward-looking clinical trials. This review highlights the requirement for efficacious, easily obtainable, and secure COVID-19 therapeutics and identifies MET and ATO as promising treatments in this worldwide health emergency. [ABSTRACT FROM AUTHOR]

The global pandemic was caused by the SARS-CoV-2 virus, known as COVID-19, which primarily affects the respiratory and intestinal systems and impacts the microbial communities of patients. This systematic review involved a comprehensive search across the major literature databases to explore the relationship between lactobacilli and COVID-19. Our emphasis was on investigations employing NGS technologies to explore this connection. Our analysis of nine selected studies revealed that lactobacilli have a reduced abundance in the disease and an association with disease severity. The protective mechanisms of lactobacilli in COVID-19 and other viral infections are likely to be multifaceted, involving complex interactions between the microbiota, the host immune system, and the virus itself. Moreover, upon closely examining the NGS methodologies and associated statistical analyses in each research study, we have noted concerns regarding the approach used to delineate the varying abundance of lactobacilli, which involves potential biases and the exclusion of pertinent data elements. These findings provide new insight into the relationship between COVID-19 and lactobacilli, highlighting the potential for microbiota modulation in COVID-19 treatment. [ABSTRACT FROM AUTHOR]

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic. [ABSTRACT FROM AUTHOR]

Severe SARS-CoV-2 elicits a hyper-inflammatory response that results in intravascular inflammation with endothelial injury, which contributes to increased mortality in COVID-19. To predict the outcome of severe SARS-CoV-2 infection, we analyzed the baseline level of different biomarkers of vascular disorders in COVID-19 subjects upon intensive care unit (ICU) admission and prior to any vaccination. A total of 70 severe COVID-19 patients (37 survivors and 33 non-survivors) were included with 16 age- and sex-matched controls. Vascular dysfunction was monitored via soluble VCAM-1, E-selectin, ACE2 and Lp-PLA2, while abnormal platelet activation was evaluated by soluble P-selectin and CD40L in parallel. These results were correlated with routine laboratory parameters and disease outcomes. Among these parameters, VCAM-1 and ACE2 showed significantly higher serum levels in COVID-19 patients with early death vs. convalescent subjects. VCAM-1 was significantly correlated with the Horowitz index (r = 0.3115) and IL-6 (r = 0.4599), while ACE2 was related to E-selectin (r = 0.4143) and CD40L (r = 0.2948). Lp-PLA2 was altered in none of these COVID-19 subcohorts and showed no relationship with the other parameters. Finally, the pre-treatment level of VCAM-1 (≥1420 ng/mL) and ACE2 activity (≥45.2 μU/mL) predicted a larger risk for mortality (Log-Rank p = 0.0031 and p = 0.0117, respectively). Vascular dysfunction with endothelial cell activation is linked to lethal COVID-19, and highly elevated soluble VCAM-1 and ACE2 at admission to ICU may predict unfavorable outcomes. [ABSTRACT FROM AUTHOR]

We study the experience with COVID-19 vaccination of an initially naïve population, which can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, very few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE) and waning effectiveness over time and the relative effectiveness of the four principal vaccines used in developed Western countries: BNT162b2 (Pfizer-BioNTech), mRNA1273 (Moderna), Ad26.CoV2.S (Johnson&Johnson), and ChAdOx1-S (AstraZeneca). As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through 15 August 2022, reporting VE against four endpoints for these four vaccines: any infection, symptomatic infection, hospitalization, and death. The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines outperformed the viral vector vaccines (Ad26.CoV2.S and ChAdOx1-S). A third "booster" dose, roughly six months after the initial doses, substantially reduced symptomatic infection, hospitalization, and death. In hindsight, a third dose should be seen as part of the normal vaccination schedule. Our analysis highlights the importance of the real-time population-level surveillance needed to assess evidence for waning, and the need for rapid regulatory response to this evidence. [ABSTRACT FROM AUTHOR]

Naturally occurring SARS-CoV-2 variants mutated in genomic regions targeted by antiviral drugs have not been extensively studied. This study investigated the potential of the RNA-dependent RNA polymerase (RdRp) complex subunits and non-structural protein (Nsp)5 of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to accumulate natural mutations that could affect the efficacy of antiviral drugs. To this aim, SARS-CoV-2 genomic sequences isolated from 4155 drug-naive individuals from southern Italy were analyzed using the Illumina MiSeq platform. Sequencing of the 4155 samples showed the following viral variant distribution: 71.2% Delta, 22.2% Omicron, and 6.4% Alpha. In the Nsp12 sequences, we found 84 amino acid substitutions. The most common one was P323L, detected in 3777/4155 (91%) samples, with 2906/3777 (69.9%) also showing the G671S substitution in combination. Additionally, we identified 28, 14, and 24 different amino acid substitutions in the Nsp5, Nsp7, and Nsp8 genomic regions, respectively. Of note, the V186F and A191V substitutions, affecting residues adjacent to the active site of Nsp5 (the target of the antiviral drug Paxlovid), were found in 157/4155 (3.8%) and 3/4155 (0.07%) samples, respectively. In conclusion, the RdRp complex subunits and the Nsp5 genomic region exhibit susceptibility to accumulating natural mutations. This susceptibility poses a potential risk to the efficacy of antiviral drugs, as these mutations may compromise the drug ability to inhibit viral replication [ABSTRACT FROM AUTHOR]

The presence of symptoms after an acute SARS-CoV-2 infection (long-COVID) has become a worldwide healthcare emergency but remains underestimated and undertreated due to a lack of recognition of the condition and knowledge of the underlying mechanisms. In fact, the prevalence of post-COVID symptoms ranges from 50% during the first months after the infection up to 20% two-years after. This perspective review aimed to map the existing literature on post-COVID symptoms and to identify gaps in the literature to guide the global effort toward an improved understanding of long-COVID and suggest future research directions. There is a plethora of symptomatology that can be due to COVID-19; however, today, there is no clear classification and definition of this condition, termed long-COVID or post-COVID-19 condition. The heterogeneity in the symptomatology has led to the presence of groups/clusters of patients, which could exhibit different risk factors and different mechanisms. Viral persistence, long-lasting inflammation, immune dysregulation, autoimmune reactions, reactivation of latent infections, endothelial dysfunction and alteration in gut microbiota have been proposed as potential mechanisms explaining the complexity of long-COVID. In such an equation, viral biology (e.g., re-infections, SARS-CoV-2 variants), host biology (e.g., genetics, epigenetics) and external factors (e.g., vaccination) should be also considered. These various factors will be discussed in the current perspective review and future directions suggested. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PJP) is an invasive fungal infection (IFI) that occurs mainly in immunocompromised hosts. After observing a high prevalence of PJP as a complication of COVID-19 in immunocompetent patients, we conducted a study to evaluate the prevalence of P. jirovecii colonization with PCR on oral washing samples (OWS) among non-immunocompromised and non-critical patients admitted with COVID-19 pneumonia at our university hospital. Methods: All patients over 18 years of age admitted to the Infectious Diseases Unit for SARS-CoV-2 pneumonia between July 2021 and December 2022 were included. Patients undergoing invasive mechanical ventilation or ECMO, those with risk factors for developing PJP, and those receiving prophylaxis for P. jirovecii were excluded. Samples were collected by gargling with 10 mL of 0.9% NaCl on day 14 of the hospital stay or at discharge. Results: Of 290 screened patients, 59 (20%) met the inclusion criteria and were enrolled. Only 1 of 59 patients (1.7%) tested positive for P. jirovecii detection with PCR, and the same patient was the only one to develop PJP in the follow-up period. Conclusions: Our results are in line with the previous findings of other studies that confirmed a very low prevalence of P. jirovecii colonization on OWS in the immunocompetent population. Despite the limitations of the study, the fact that the only patient who tested positive for P. jirovecii was the only one in our cohort to develop PJP leads us to reflect on the role of this non-invasive sample in predicting the risk of PJP in patients with COVID-19. [ABSTRACT FROM AUTHOR]

COVID-19 patients show characteristic over-expression of different cytokines that may interfere with the interferon (IFN) response, delaying its production. Within the overexpressed cytokines, IL-8 plays a key role, and it may impede IFN-I activation. PBMC from eight healthy donors were exposed to 2019-nCoV/Italy-INMI1 isolate and supernatants/cells were collected at different time points; the production of either IFN-alpha or IL-8 was assessed. The same analysis was performed on plasma samples obtained from 87 COVID-19 patients. Antagonism between IFN-alpha and IL-8 was observed, since in those PBMC with medium or high IL-8 levels, IFN-α levels were low. The same scenario was observed in SARS-CoV-2-infected patients that were divided into three groups based on IL-8 low, medium and high levels; the correlation between low levels of IFN-α and high levels of IL-8 was statistically significant in both the IL-8 medium and IL-8 high group. Overall, our results showed a crosstalk/antagonism between IL-8 and IFN-alpha in PBMC from healthy donors challenged with SARS-CoV-2 and inversely proportional IFN-alpha levels to IL-8 concentrations detected in plasma samples from COVID-19 patients, suggesting that the impairment of the innate immune response in COVID-19 patients may be linked to a dysregulated cytokine response, namely through IL-8 production. [ABSTRACT FROM AUTHOR]

Universal history is characterized by continuous evolution, in which civilizations are born and die. This evolution is associated with multiple factors, among which the role of microorganisms is often overlooked. Viruses and bacteria have written or decisively contributed to terrible episodes of history, such as the Black Death in 14th century Europe, the annihilation of pre-Columbian American civilizations, and pandemics such as the 1918 Spanish flu or the current COVID-19 pandemic caused by the coronavirus SARS-CoV-2. Nevertheless, it is clear that we could not live in a world without these tiny beings. Endogenous retroviruses have been key to our evolution and for the regulation of gene expression, and the gut microbiota helps us digest compounds that we could not otherwise process. In addition, we have used microorganisms to preserve or prepare food for millennia and more recently to obtain drugs such as antibiotics or to develop recombinant DNA technologies. Due to the enormous importance of microorganisms for our survival, they have significantly influenced the population genetics of different human groups. This paper will review the role of microorganisms as "villains" who have been responsible for tremendous mortality throughout history but also as "friends" who help us survive and evolve. [ABSTRACT FROM AUTHOR]

Since COVID-19 might have a lasting impact on global public health, it is crucial to analyze its effect on drug-resistant bacterial infections in the respiratory system for the prevention and control of hospital infections. This work aimed to investigate the impact of the COVID-19 outbreak on the clinical distribution and antibiotic resistance of bacterial infection among hospitalized patients in the respiratory unit in order to establish strategies to control antibiotic-resistant infections. Electronic clinical data registry records from 2018 to 2022 were retrospectively analyzed. A total of 36,829 clinical specimens, including sputum, bronchoalveolar lavage fluid, blood, and urine, were collected from 16,073 patients admitted to the Guangzhou First People's Hospital from January 2018 to December 2022. Among them, 2209 samples were culture-positive. The bacterial isolation rates of different types of samples showed a similar trend from 2019 to 2022, with an increase in 2020 and 2022 and a decrease in 2021. Different bacterial species were separated from different types of samples. The most reported pathogens were identified in sputum samples. Gram-positive isolates were prevalent in urine samples, while Gram-negative bacilli were the predominant pathogenic bacteria isolated from respiratory tract and blood samples. Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii) complex, and Klebsiella pneumoniae (K. pneumoniae) were the most abundant Gram-negative bacteria in sputum samples, of which A. baumannii complex had the highest resistance to all tested antibiotics except colistin. Notably, there has been a substantial prevalence of carbapenem-resistant P. aeruginosa, A. baumannii, and K. pneumoniae in the past five years. This alarming situation calls for greater attention and precaution with prescribed antibiotics to limit the generation and spread of new multidrug-resistant bacteria and improve therapeutic management. [ABSTRACT FROM AUTHOR]

The long-distance spreading and transport of airborne particulate matter (PM) of biogenic or chemical compounds, which are thought to be possible carriers of SARS-CoV-2 virions, can have a negative impact on the incidence and severity of COVID-19 viral disease. Considering the total Aerosol Optical Depth at 550 nm (AOD) as an atmospheric aerosol loading variable, inhalable fine PM with a diameter ≤2.5 µm (PM2.5) or coarse PM with a diameter ≤10 µm (PM10) during 26 February 2020–31 March 2022, and COVID-19's five waves in Romania, the current study investigates the impact of outdoor PM on the COVID-19 pandemic in Bucharest city. Through descriptive statistics analysis applied to average daily time series in situ and satellite data of PM2.5, PM10, and climate parameters, this study found decreased trends of PM2.5 and PM10 concentrations of 24.58% and 18.9%, respectively compared to the pre-pandemic period (2015–2019). Exposure to high levels of PM2.5 and PM10 particles was positively correlated with COVID-19 incidence and mortality. The derived average PM2.5/PM10 ratios during the entire pandemic period are relatively low (<0.44), indicating a dominance of coarse traffic-related particles' fraction. Significant reductions of the averaged AOD levels over Bucharest were recorded during the first and third waves of COVID-19 pandemic and their associated lockdowns (~28.2% and ~16.4%, respectively) compared to pre-pandemic period (2015–2019) average AOD levels. The findings of this research are important for decision-makers implementing COVID-19 safety controls and health measures during viral infections. [ABSTRACT FROM AUTHOR]

Respiratory viral infections have been found to have a negative impact on neurological functions, potentially leading to significant neurological impairment. The SARS-CoV-2 virus has precipitated a worldwide pandemic, posing a substantial threat to human lives. Growing evidence suggests that SARS-CoV-2 may severely affect the CNS and respiratory system. The current prevalence of clinical neurological issues associated with SARS-CoV-2 has raised significant concerns. However, there needs to be a more comprehensive understanding of the specific pathways by which SARS-CoV-2 enters the nervous system. Based on the available evidence, this review focuses on the clinical neurological manifestations of SARS-CoV-2 and the possible mechanisms by which SARS-CoV-2 invades the brain. [ABSTRACT FROM AUTHOR]

Long COVID-19 is a recognized entity that affects millions of people worldwide. Its broad clinical symptoms include thrombotic events, brain fog, myocarditis, shortness of breath, fatigue, muscle pains, and others. Due to the binding of the virus with ACE-2 receptors, expressed in many organs, it can potentially affect any system; however, it most often affects the cardiovascular, central nervous, respiratory, and immune systems. Age, high body mass index, female sex, previous hospitalization, and smoking are some of its risk factors. Despite great efforts to define its pathophysiology, gaps remain to be explained. The main mechanisms described in the literature involve viral persistence, hypercoagulopathy, immune dysregulation, autoimmunity, hyperinflammation, or a combination of these. The exact mechanisms may differ from system to system, but some share the same pathways. This review aims to describe the most prevalent pathophysiological pathways explaining this syndrome. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections (LRTIs) occur when there is a lower airway tract infection. They are well-known for increasing the susceptibility of patients to bacterial/fungal co-infections and super-infections. In this study, we present the results of our investigation, which involved 381 consecutive patients admitted to our hospital during the Influenza season from October 2022 to April 2023. Among the 381 specimens, 75 were bronchoalveolar (BAL), and 306 were nasopharyngeal swabs (NPSs). Notably, 34.4% of the examined samples tested positive for SARS-CoV-2. Of these, we observed that 7.96% of NPSs showed positivity only for other respiratory viruses, while a substantial percentage (77%) of BAL specimens exhibited positive results only for bacterial co-infections. The results of our study not only confirm the importance of co-infections in COVID-19 but also emphasize the significance of utilizing rapid diagnostic tests (RDTs) for the timely diagnosis of LRTIs. In fact, RDTs allow for the identification of multiple pathogens, providing clinicians with useful and timely information to establish effective therapy. [ABSTRACT FROM AUTHOR]

Since its emergence in early 2020, the SARS-CoV-2 infection has had a significant impact on the entire eye care system. Ophthalmologists have been categorized as a high-risk group for contracting the virus due to the belief that the eye may be a site of inoculation and transmission of the SARS-CoV-2 infection. As a result, clinical ophthalmologists, optometrists, and eyecare professionals have had to familiarize themselves with the ocular manifestations of COVID-19, as well as its treatments and vaccines. The implementation of measures to prevent the transmission of the virus, such as restrictions, lockdowns, telemedicine, and artificial intelligence (AI), have led to substantial and potentially irreversible changes in routine clinical practice, education, and research. This has resulted in the emergence of a new mode of managing patients in a routine clinical setting. This brief review aims to provide an overview of various aspects of COVID-19 in ophthalmology, including the ocular manifestations related to the disease, the modes of transmission of SARS-CoV-2 infection, precautions taken in ophthalmic practice to prevent the spread of the virus, drugs, and vaccines used in the treatment of COVID-19, the impact of the pandemic on patients, clinicians, and the eye care system as a whole, and the future of ophthalmology conditioned by this global pandemic experience. [ABSTRACT FROM AUTHOR]

Remdesivir is the first FDA-approved drug for treating severe SARS-CoV-2 infection and targets RNA-dependent RNA polymerase (RdRp) that is required for viral replication. To monitor for the development of mutations that may result in remdesivir resistance during prolonged treatment, we sequenced SARS-CoV-2 specimens collected at different treatment time points in two transplant patients with severe COVID-19. In the first patient, an allogeneic hematopoietic stem cell transplant recipient, a transient RdRp catalytic subunit mutation (nsp12:A449V) was observed that has not previously been associated with remdesivir resistance. As no in vitro study had been conducted to elucidate the phenotypic effect of nsp12:A449V, its clinical significance is unclear. In the second patient, two other transient RdRp mutations were detected: one in the catalytic subunit (nsp12:V166A) and the other in an accessory subunit important for processivity (nsp7:D67N). This is the first case report for a potential link between the nsp12:V166A mutation and remdesivir resistance in vivo, which had only been previously described by in vitro studies. The nsp7:D67N mutation has not previously been associated with remdesivir resistance, and whether it has a phenotypic effect is unknown. Our study revealed SARS-CoV-2 genetic dynamics during remdesivir treatment in transplant recipients that involved mutations in the RdRp complex (nsp7 and nsp12), which may be the result of selective pressure. These results suggest that close monitoring for potential resistance during the course of remdesivir treatment in highly vulnerable patient populations may be beneficial. Development and utilization of diagnostic RdRp genotyping tests may be a future direction for improving the management of chronic COVID-19. [ABSTRACT FROM AUTHOR]

To prospectively study the kinetics of immune responses after immunization with the BNT162b2 mRNA COVID-19 vaccine and their association with epidemiological parameters and breakthrough infection (BI), we measured total (TAbs-WT) and neutralizing antibodies against wild-type (NAbs-WT) and Omicron (NAbs-O) SARS-CoV-2 spike proteins in healthcare workers (HCWs) after the second (4 and 8 months) and third dose (1 and 8 months). Vaccinated HCWs (n = 486), with a median age (IQR) of 49 years (38–56), were included in this prospective cohort study. BI was observed 4 and 8 months after the second dose in 8/486 (1.6%) and 15/486 (3.1%) HCWs, respectively, and 1 and 8 months after the third dose in 17/486 (3.5%) and 152/486 (31.3%) HCWs, respectively. A comparison of immune responses 1 month after the third dose in vaccinated HCWs without a BI or with a BI in the next 7 months did not detect any statistically significant differences in the TAbs-WT (median (IQR): 16,611.0 (13,011.0) U/mL vs. 17,572.5 (14,501.0) U/mL, p = 0.529) and NAbs-WT (median (IQR): 96.5% (1.7) vs. 96.7% (1.9), p = 0.555). After infection, HCWs with a BI had significantly increased TAbs-WT levels at all time points compared to healthy HCWs. The findings of the present study indicate that antibody levels after three doses of the BNT162b2 vaccine are not directly associated with the possibility of a BI. [ABSTRACT FROM AUTHOR]

Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection. The answer to this question is consequential, not only to the understanding of how anti-SARS-CoV-2 vaccines work, but also to public health efforts against existing and novel pathogens. In this review, we argue that immune system sensitization-desensitization rather than sterilizing immunity may explain vaccine-mediated protection against severe COVID-19 illness even when the SARS-CoV-2 viral load is high. Through the lessons learned from COVID-19, we make the case that in the disease's aftermath, public health agencies must revisit healthcare policies, including redefining the term "vaccine effectiveness." [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects. Methods: a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects. Results: Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens' lungs. At present, a modulation of the dose-effect posology for children and infants is necessary. Conclusions: Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects. [ABSTRACT FROM AUTHOR]

The recent global emergence of the SARS-CoV-2 pandemic has accelerated research in several areas of science whose valuable outputs and findings can help to address future health challenges in the event of emerging infectious agents. We conducted a comprehensive shotgun analysis targeting multiple aspects to compare differences in bacterial spectrum and viral presence through culture-independent RNA sequencing. We conducted a comparative analysis of the microbiome between healthy individuals and those with varying degrees of COVID-19 severity, including a total of 151 participants. Our findings revealed a noteworthy increase in microbial species diversity among patients with COVID-19, irrespective of disease severity. Specifically, our analysis revealed a significant difference in the abundance of bacterial phyla between healthy individuals and those infected with COVID-19. We found that Actinobacteria, among other bacterial phyla, showed a notably higher abundance in healthy individuals compared to infected individuals. Conversely, Bacteroides showed a lower abundance in the latter group. Infected people, regardless of severity and symptoms, have the same proportional representation of Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteriales. In addition to SARS-CoV-2 and numerous phage groups, we identified sequences of clinically significant viruses such as Human Herpes Virus 1, Human Mastadenovirus D, and Rhinovirus A in several samples. Analyses were performed retrospectively, therefore, in the case of SARS-CoV-2 various WHO variants such as Alpha (B.1.1.7), Delta (B.1.617.2), Omicron (B.1.1.529), and 20C strains are represented. Additionally, the presence of specific virus strains has a certain effect on the distribution of individual microbial taxa. [ABSTRACT FROM AUTHOR]

The clinical aspects of SARS-CoV-2 infection, as well as the COVID-19 vaccines' safety, efficacy and effectiveness in pediatric patients with asthma, are crucial to adapting clinical management in this fragile population and for prevention strategies. The aim of this narrative review was to evaluate the impact of SARS-CoV-2 infection in children with asthma and the impact of COVID-19 vaccination. Systematic research using the principal medical databases was conducted using specific search query strings from the early spreading of COVID-19 globally until March 2023; further relevant data were drawn from the main national and supranational institutions. No significant differences in SARS-CoV-2 incidence and morbidity were found in asthmatic pediatric patients compared to non-asthmatic ones; however, subjects with uncontrolled asthma were found to be at increased risk of developing a serious disease during SARS-CoV-2 infection. Regarding COVID-19 vaccines, accumulating data support their safety, efficacy and effectiveness on asthmatic children regardless of asthma severity. Further cohort-based studies are needed as the evidence of new epidemic waves caused by new viral variants makes the current knowledge outdated. [ABSTRACT FROM AUTHOR]

To study the differences in the immune response to SARS-CoV-2 infection compared to the response to vaccination, we characterized the humoral immune kinetics of these situations. In this prospective longitudinal study, we followed unvaccinated COVID-19-recovered individuals (n = 130) and naïve, two-dose BNT162b2-vaccinated individuals (n = 372) who were age- and BMI-matched for six months during the first pandemic year. Anti-RBD-IgG, neutralizing antibodies (NAbs), and avidity were assessed monthly. For recovered patients, data on symptoms and the severity of the disease were collected. Anti-RBD-IgG and NAbs titers at peak were higher after vaccination vs. after infection, but the decline was steeper (peak log IgG: 3.08 vs. 1.81, peak log NAbs: 5.93 vs. 5.04, slopes: −0.54 vs. −0.26). Peak anti-RBD-IgG and NAbs were higher in recovered individuals with BMI > 30 and in older individuals compared to individuals with BMI < 30, younger population. Of the recovered, 42 (36%) experienced long-COVID symptoms. Avidity was initially higher in vaccinated individuals compared with recovered individuals, though with time, it increased in recovered individuals but not among vaccinated individuals. Here, we show that while the initial antibody titers, neutralization, and avidity are lower in SARS-CoV-2-recovered individuals, they persist for a longer duration. These results suggest differential protection against COVID-19 in recovered-unvaccinated vs. naïve-vaccinated individuals. [ABSTRACT FROM AUTHOR]

African Swine Fever (ASF) has threatened the swine industry of Southeast Asian countries, including the Philippines, since 2019. Given the severity and the economic impact of the ASF epidemic, understanding the spatial and temporal patterns of the disease is crucial for devising effective control measures. Here, data on 19,697 ASF farm outbreaks reported in the Philippines between August 2019 and July 2022 were analyzed to estimate the space–time clustering, seasonal index, and directional spread of the disease. Central Luzon was the region with the largest number of reported outbreaks, followed by Regions I and II, whereas Western and Central Visayas remained ASF-free throughout the study period. ASF outbreaks were temporally and spatially clustered and exhibited a distinct seasonal pattern, with highest and lowest frequencies reported between August and October, and April and May, respectively. This seasonal pattern may be explained, at least in part, by a combination of environmental and anthropogenic factors, such as rain and cultural practices leading to disease spread. The results here will help inform decisions intended to mitigate the impact of ASF in the Philippines and will contribute to the understanding of the epidemiological dynamics of one of the most important emerging swine diseases globally. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is the causal agent of COVID-19; the first report of SARS-CoV-2 infection was in December 2019 in Wuhan, China. This virus has since caused the largest pandemic in history, and the number of deaths and infections has been significant. Nevertheless, the development of vaccines has helped to reduce both deaths and infections. Comorbidities such as diabetes, hypertension, heart and lung diseases, and obesity have been identified as additional risk factors for infection and the progression of COVID-19. Additionally, latent toxoplasmosis has been reported to be a risk factor for acquiring COVID-19 in some studies, but other studies have suggested a negative association between these two infections. Furthermore, in patients after vaccination or with COVID-19 and coinfection, an increase in the lethality and mortality of toxoplasmosis has been observed. Therefore, the objective of the current study is to determine the association of toxoplasmosis with COVID-19 in patients diagnosed with COVID-19. Serum samples from 384 patients previously diagnosed with COVID-19 using IgG antibodies against the S1/S2 antigens of SARS-CoV-2 were collected. Subsequently, anti-Toxoplasma IgG and IgM antibodies were analyzed with ELISA. Statistical analysis was performed using SPSS Version 20.0 frequencies, percentages, 2 × 2 tables, and the Pearson correlation coefficient. IgG and IgM anti-Toxoplasma antibodies were positive in 105/384 (27.34%) and (26/191) 13.6% of patients, respectively. The positivity for both infections was higher in patients aged >40 years old. Subjects who were overweight or obese were mainly positive for both IgG antibodies against S1/S2 SARS-CoV-2 and Toxoplasma antibodies. In conclusion, the coinfection rate was 21.7%. The prevalence of S1/S2 SARS-CoV-2 was 308/384 (80.2%), and the percentage of Toxoplasma antibodies was 27.34%. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) remain the most common infections diagnosed in outpatients and hospitalized patients. This study was designed to determine the patterns of antibiotic resistance and the prevalence of uropathogens causing UTIs in pediatric patients hospitalized between 1 January 2020 and 31 December 2022 at Teaching Hospital in Warsaw. The most frequent species isolated from urine samples were E. coli (64.5%), Klebsiella spp. (11.6%), and Enterococcus spp. (6.1%). UTIs caused by Enterobacter spp., Enterococcus spp., and Klebsiella spp. were significantly more common in children younger than three months of age than in children older than three months (p < 0.001). Trimethoprim and trimethoprim–sulfamethoxazole were the least active compounds against Enterobacterales with the resistance of E. coli, Klebsiella spp., P. mirabilis, and Enterobacter spp. in the range of 26.7/25.2%, 48.4/40.4%, 51.1/40.4%, and 15.8/13.2% respectively. Ampicillin was also found to have resistance rates for E. coli of 54.9% and P. mirabilis of 44.7%. Cefalexin and cefuroxime were highly active towards Enterobacterales except for Klebsiella spp., in which the resistance level reached 40%. Regarding third- and fourth- generation cephalosporins, resistance in E. coli and P. mirabilis was observed in approximately 2–10% of the isolates, but in Klebsiella spp. and Enterobacter spp. ranged over 30%. The resistance of Enterobacterales to carbapenems, nitrofurantoin, and fosfomycin was below 1%. The quinolones resistance was very high for Klebsiella spp. (31.1%) and P. mirabilis (29.8%) and three times lower for E. coli (11.9%), P. aeruginosa (9.3%), Enterobacter spp. (2.6%), and E. faecalis (4.6%). Resistance to multiple antibiotic classes was identified in 396 Enterobacterales strains, 394 of which were multi-drug resistant (MDR) and 2 were extensive drug-resistant (XDR). In the case of E. coli, 30% of isolates were MDR, with the proportion of strains having this exact resistance pattern similar in all of the analyzed years; no E. coli XDR strains were isolated. The number of Klebsiella spp. MDR strains was much higher in 2022 (60%) than in 2021 (47.5%). In the analyzed time, only one strain of K. pneumonia XDR, producing New Delhi metallo-β-lactamase, was isolated. Monitoring infection trends is essential to improve control and limit the rise of bacterial resistance. [ABSTRACT FROM AUTHOR]

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs. [ABSTRACT FROM AUTHOR]

Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of SARS-CoV-2 infection, with various advantages and weaknesses to each. In this paper, we summarize promising methods, such as reverse transcription-polymerase chain reaction (RT-PCR), serological testing, point-of-care testing, smartphone surveillance of infectious diseases, nanotechnology-based approaches, biosensors, amplicon-based metagenomic sequencing, smartphone, and wastewater-based epidemiology (WBE) that can also be utilized for the detection of SARS-CoV-2. In addition, we discuss principles, advantages, and disadvantages of these detection methods, and highlight the potential methods for the development of additional techniques and products for early and fast detection of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Since its outbreak, Coronavirus disease 2019 (COVID-19), a life-threatening respiratory illness, has rapidly become a public health emergency with a devastating social impact. Lately, the Omicron strain is considered the main variant of concern. Routine blood biomarkers are, indeed, essential for stratifying patients at risk of severe outcomes, and a huge amount of data is available in the literature, mainly for the previous variants. However, only a few studies are available on early routine biochemical blood biomarkers for Omicron-afflicted patients. Thus, the aim and novelty of this study were to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality. Methods: 449 COVID-19 patients from Sapienza University Hospital of Rome were divided into four groups: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients that after the admission in the emergency department were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency department required intensive assistance); (4) the deceased group (patients that after the admission in the emergency department had a fatal outcome). Results: ANOVA and ROC data showed that high-sensitivity troponin-T (TnT), fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin for both men and women may predict lethal outcomes already at the level of the emergency department. Conclusions: Compared to previous Delta COVID-19 parallel emergency patterns of prediction, Omicron-induced changes in TnT may be considered other early predictors of severe outcomes. [ABSTRACT FROM AUTHOR]

For three years, the novel coronavirus disease 2019 (COVID-19) pandemic, caused by infection of the SARS-CoV-2 virus, has completely changed our lifestyles and prepared us to live with this novel pneumonia for years to come. Given that pre-existing flu is caused by the influenza A virus, we have begun unprecedently co-coping with two different respiratory diseases at the same time. Hence, we draw a comparison between SARS-CoV-2 and influenza A virus based on the general characteristics, especially the main variants' history and the distribution of the two viruses. SARS-CoV-2 appeared to mutate more frequently and independently of locations than the influenza A virus. Furthermore, we reviewed present clinical trials on combined management against COVID-19 and influenza in order to explore better solutions against both at the same time. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection. (2) Methods: A single-center, prospective observational study was conducted at the University Clinical Hospital Center in Belgrade, Serbia, from January 2019 to December 2021. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented. (3) Results: The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI–COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p < 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p < 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p < 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p < 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p < 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p < 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005). (4) Conclusion: Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic. [ABSTRACT FROM AUTHOR]