Viruses modulate various aspects of host physiology, including carbon metabolism, redox balance, and mitochondrial bioenergetics to acquire the building blocks for replication and regulation of the immune response. Understanding how SARS-CoV-2 alters the host metabolism may lead to treatments for COVID-19. We report that a ubiquitous gaseous molecule, hydrogen sulfide (H2S), regulates redox, metabolism, and mitochondrial bioenergetics to control SARS-CoV-2. Virus replication is associated with down-regulation of the H2S-producing enzymes cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CTH), and 3-mercaptopyruvate sulfurtransferase (3-MST) in multiple cell lines and nasopharyngeal swabs of symptomatic COVID-19 patients. Consequently, SARS-CoV-2-infected cells showed diminished endogenous H2S levels and a protein modification (S-sulfhydration) caused by H2S. Genetic silencing or chemical inhibition of CTH resulted in SARS-CoV-2 proliferation. Chemical supplementation of H2S using a slow-releasing H2S donor, GYY4137, diminished virus replication. Using a redox biosensor, metabolomics, transcriptomics, and XF-flux analyzer, we showed that GYY4137 blocked SARS-CoV-2 replication by inducing the Nrf2/Keap1 pathway, restoring redox balance and carbon metabolites and potentiating mitochondrial oxidative phosphorylation. Treatment of SARS-CoV-2-infected mice or hamsters with GYY4137 suppressed viral replication and ameliorated lung pathology. GYY4137 treatment reduced the expression of inflammatory cytokines and re-established the expression of Nrf2-dependent antioxidant genes in the lungs of SARS-CoV-2-infected mice. Notably, non-invasive measurement of respiratory functions using unrestrained whole-body plethysmography (uWBP) of SARS-CoV-2-infected mice showed improved pulmonary function variables, including pulmonary obstruction (Penh), end-expiratory pause (EEP), and relaxation time (RT) upon GYY4137 treatment. Together, our findings significantly extend our understanding of H2S-mediated regulation of viral infections and open new avenues for investigating the pathogenic mechanisms and therapeutic opportunities for coronavirus-associated disorders.

Long COVID, characterized by persistent symptoms following COVID-19 infection, significantly impacts individuals' health and daily functioning due to fatigue and pain. Focusing on pain, this review addresses nociplastic and chronic pain conditions. Interventions designed to reduce inflammation, oxidative stress, and enhance vagal activity may offer a promising approach to managing post-pandemic pain. This review presents individual components of food supplements with demonstrated efficacy in one or more pain conditions, focusing on their proposed mechanisms and clinical activity in pain, including their use in post-COVID-19 pain when available. Many of these substances have a long history of safe use and may offer an alternative to long-term analgesic drug treatment, which is often associated with potential side effects. This review also explores the potential for synergistic effects when combining these substances with each other or with conventional analgesics, considering the advantages for both patients and the healthcare system in using these substances as adjunctive or primary therapies for pain symptoms related to long COVID. While preclinical scientific literature provides a mechanistic basis for the action of several food supplements on pain control mechanisms and signaling pathways, clinical experience, particularly in the field of long COVID-associated pain, is still limited. However, the reviewed literature strongly suggests that the use of food supplements in long COVID-associated pain is an attainable goal, provided that rigorous clinical trials are conducted.

At the end of 2022, the COVID-19 wreaked havoc in China as well as around the world. Here, we focused on the dynamic changes in platelet kinetics and psychological state in ITP patients before and after infection with COVID-19.

A questionnaire survey was designed to retrospectively investigate the COVID-19-related symptoms, changes in platelet count, and psychological changes in ITP patients infected with Omicron variant during November 2022 to January 2023, with a healthy population survey conducted as a control.

A total of 90 ITP patients and 69 healthy individuals were included in the study. The results showed that only in terms of low-grade fever, the proportion of ITP patients was significantly higher than that of healthy individuals, 31% vs. 17% (p = 0.04). Interestingly, it was found that there was a transient elevation in platelet counts (PC) of ITP patients after COVID-19 infection, which then gradually decreased to the previous level after recovering from virus, including three subgroups comparation: PC >100 × 109/L vs. PC <100 × 109/L; ITP treatment vs. non-ITP treatment; and vaccination vs. non-vaccination. Additionally, the platelet-to-lymphocyte ratio (PLR) showed the same trend. The fear and concerns related to COVID-19 infection were also compared between the two population. For ITP patients, they are more concerned that COVID-19 will worsen the condition of ITP and delay its recovery. It should be pointed out that the limitations of this study include the small sample size in the retrospective survey and the possibility of selection bias in ITP patients.

Some ITP patients showed transiently elevated platelet counts after COVID-19 infection, and the specific mechanism requires further exploration. Additionally, ITP patients experienced heightened anxiety and tension after COVID-19 infection, needing for more mental health support.

Fibrosis-4 (FIB-4) score and D-dimer (DD) have emerged as prognostic markers in coronavirus disease 2019 (COVID-19). However, precise cutoff points remain undefined, and their combined use has been scarcely studied. We aimed to analyze FIB-4 and DD performance, individually and combined, to predict outcomes among COVID-19 patients.

From March to December 2020, hospitalized COVID-19 patients were evaluated based on clinical and laboratory tests from their first day of hospitalization. Primary outcome was inhospital mortality, and secondary outcomes included hospital stay length, ICU admission and duration, need for hemodialysis, ventilatory support, and extent of lung involvement. Optimal FIB-4 and DD cutoff points to predict mortality were established to maximize sensitivity and specificity. A sequential diagnostic strategy using both markers was subsequently evaluated.

Among 518 patients (61 ± 16 years, 64% men), the inhospital mortality rate was 18%. FIB-4 outperformed DD in predicting mortality (area under the receiver operating characteristic curve: 0.76 vs. 0.65, P = 0.003) and was chosen as the first step in sequential analysis. Mortality was higher in patients with FIB-4 ≥1.76 vs. FIB-4 <1.76 (26 vs. 5%, P < 0.001) and DD ≥2000 ng/ml vs. DD <2000 ng/ml (38 vs. 16%, P < 0.001). Using FIB-4 as a screening test (cutoff = 1.76, 90% sensitivity) followed by DD (cutoff = 2000 ng/ml; 90% specificity) identified a subgroup with higher mortality when compared with FIB-4 alone (48 vs. 26%, P < 0.001), missing the identification of only 2% of deaths.

Sequential use of FIB-4 and DD represents a comprehensive strategy to identify high-risk COVID-19 patients at hospital admission, potentially minimizing unnecessary DD tests in those deemed low-risk by FIB-4.

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review.

The COVID-19 pandemic presents a significant challenge to the global health and the world economy, with humanity engaged in an extended struggle against the virus. Notable advancements have been achieved in the development of vaccines and therapeutic interventions, including the application of neutralizing antibodies (NAbs) and convalescent plasma (CP). While antibody-dependent enhancement (ADE) has not been observed in human clinical studies related to SARS-CoV-2, the potential for ADE remains a critical concern and challenge in addressing SARS-CoV-2 infections. Moreover, the causal relationship between ADE and viral characteristics remains to be clearly elucidated. Viruses that present with severe clinical manifestations of ADE have demonstrated the capacity to replicate in macrophages or other immune cells, or to alter the immunological status of these cells, which induces abortive infections characterized by systemic inflammation. In this review, we summarize experimental observations and clinical evidence concerning the ADE effect associated with coronaviruses. We critically examine the potential mechanisms through which coronaviruses mediate ADE, and propose strategies to mitigate this phenomenon in the context of viral infection treatment. Our aim is to offer informed recommendations for the containment of the COVID-19 pandemic and to strengthen the response to SARS-CoV-2, as well as to prepare for potential future coronavirus threats.

The fibrosis 4 (FIB-4) index is typically used in assessing liver fibrosis, and has shown potential in predicting the outcome in various diseases. This study aims to evaluate the predictive power of the FIB-4 index for mortality in COVID-19 patients admitted to a reference hospital in Tehran, Iran.

In this prospective cohort study, 387 patients with COVID-19 without diabetes, were categorized into deceased and surviving groups. We compared anthropometric and demographic data, liver function tests, CT scores, and FIB-4 indices between the groups. Multivariate logistic regression assessed the independent association of FIB-4 with mortality.

Among the 387 patients, (all non-diabetics), 58 (15%) died, with a higher mortality rate observed in patients with a FIB-4 index≥2.6 (63.4%) compared to those with FIB-4<2.6 (29.7%). Deceased patients were considerably older and more likely to be hypertensive (P values<0.001). After adjustment of confounding factors, a FIB-4 index≥2.6 was found to be independently associated with increased mortality (OR: 13.511, 95% CI: 1.356-134.580, P=0.026).

The FIB-4 index, calculable by routine laboratory tests, may be a valuable prognostic factor for COVID-19 mortality. This easily obtainable marker could help identify high-risk patients early, potentially allowing for more rapid intervention and treatment prioritization.

Current evidence is inconsistent on whether vitamin D supplementation can prevent COVID-19 infection or improve its clinical outcomes. To better understand and look into the issue, we went through the background knowledge of COVID-19 and vitamin D, searched in Pubmed [by using key words in the title containing "randomized clinical trial", "COVID-19", and "vitamin D (25-hydroxyvitamin D, or cholecalciferol, or calcidiol, or calcifediol) supplementation"] for publications of studies on vitamin D/supplementation in COVID-19 patients, especially those about the randomized clinical trials (RCTs). After reviewing these papers, we did a short background review of vitamin D and the pathophysiology of COVID-19, summarized the key features of the 25 RCTs in text and tabulated in a table of some of the features, commented, compared and discussed the differences between RCTs (for example, change the serum 25-hydroxyvitamin D concentration from nmol/L to ng/mL, making the comparison easier). The take-home question of the review is that serum 25-hydroxyvitamin D concentration is an important indicator of the supplementation effect of vitamin D correction but may not be reliable in predicting the supplementation effect on the clinical outcomes of COVID-19.

The literature review presents an analysis of the pathogenesis and pathological anatomy of liver damage in COVID-19. Liver damage with the steatosis, vascular disorders, mild portal and lobular inflammatory infiltration, cholestasis and clinically - liver failure is observed in majority of the patients with COVID-19. Chronic liver diseases with infection SARS-CoV-2 tend to decompensate, which significantly worsens the prognosis of the disease. Pathogenesis of liver damage in COVID19 is unclear. There was no convincing evidence for the hypothesis of cytotoxicity for hepatocytes or cholangiocytes by SARS-CoV-2. Similar liver morphological changes described by different authors suggest their nonspecific nature and multifactorial pathogenesis related to hypoxia, cytokin storm, systemic inflammatory response syndrome, sepsis and shock, Covid-associated angio- and coagulopathy, as well as drug-induced hepatotoxicity. Further research is needed to clarify the pathogenesis and pathological anatomy of the liver pathology in COVID-19.

It was in 2019 that the world experienced the devastation caused by SARS-CoV-2, contributing to a large number of deaths. This contagious virus not only challenged the health care system but has also hit the economy very badly. There has been a lot of research on effective vaccine development, and there has been some success in the same, but no effective antiviral drugs are available in the market. No doubt vaccination can prevent the disease, but it doesn't have the potential to cure an infected person, for which there is a dire need to develop some effective drug. Angiotensin convertase enzyme 2 (ACE2) played a substantial role in SARS-CoV-2 pathogenesis and thus has gained much attention during the pandemic. Moreover, it has opened up new avenues for the cure of COVID-19.

To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19.

The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2. The binding of rucaparib to spike protein was tested by molecular modelling and microcalorimetry. The anti-inflammatory properties of rucaparib were demonstrated in cell-based models upon challenging with recombinant spike protein or SARS-CoV-2 RNA vaccine.

We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients, both of which negatively correlated with lymphocytopaenia. Interestingly, rucaparib, unlike other tested PARP inhibitors, reduced the SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein and viral RNA-induced overexpression of cytokines was down-regulated by the inhibition of PARP1 by rucaparib at pharmacologically relevant concentrations.

These results point towards repurposing rucaparib for treating inflammatory responses in COVID-19.

This review has focused on the development of mRNA nano-vaccine and the biochemical interactions of anti-COVID-19 mRNA vaccines with various disease conditions and age groups. It studied five major groups of individuals with different disease conditions and ages, including allergic background, infarction background, adolescent, and adult (youngsters), pregnant women, and elderly. All five groups had been reported to have background-related adverse effects. Allergic background individuals were observed to have higher chances of experiencing allergic reactions and even anaphylaxis. Individuals with an infarction background had a higher risk of vaccine-induced diseases, e.g. pneumonitis and interstitial lung diseases. Pregnant women were seen to suffer from obstetric and gynecological adverse effects after receiving vaccinations. However, interestingly, the elderly individuals (> 65 years old) had experienced milder and less frequent adverse effects compared to the adolescent (<19 and >9 years old) and young adulthood (19-39 years old), or middle adulthood (40-59 years old) age groups, while middle to late adolescent (14-17 years old) was the riskiest age group to vaccine-induced cardiovascular manifestations.

Infectious diseases are a global public health problem that poses a threat to human society. Since the 1970s, constantly mutated new infectious viruses have been quietly attacking humanity, and at least one new type of infectious disease is discovered every year. Therefore, early warning of infectious diseases will greatly reduce the socio-economic harm of infectious diseases. This study is based on the data of COVID-19 epidemic in China (except Macau and Taiwan Province) from 2020 to 2022. Firstly, we used ArcGIS software to analyze the spatial agglomeration pattern of the number of patients in various regions of China through global spatial autocorrelation analysis, local spatial autocorrelation analysis, center of gravity trajectory migration algorithm and other statistical tools; In addition, the areas with serious COVID-19 epidemic and requiring special attention were screened out. Then, autoregressive integrated moving average model (ARIMA), extreme learning machine (ELM), support vector regression (SVR), wavelet neural network (Wavelet), recurrent neural network (RNN) and long short-term memory (LSTM) were used to predict COVID-19 epidemic data in Guangdong Province, China; And the prediction performance of each model was compared through prediction accuracy indicators. Finally, a multi algorithm fusion learning model based on stacking technology is proposed to address the problem of poor generalization ability of single algorithm models in prediction; Furthermore, radial basis function network (RBF) was used as a two-level meta learner to fuse the above models, and particle swarm optimization (PSO) was used to optimize RBF parameters to reduce generalization error. The experimental results show that the performance of the integrated model is better than that of the single model in the COVID-19 dataset. In order to better apply the stacking model to the prediction of new infectious diseases, we applied the prediction model based on the COVID-19 dataset to the prediction of the number of AIDS and pulmonary tuberculosis (PTB) cases, and verified the wide applicability of our model in the prediction of infectious diseases.

Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.

Spontaneous regression (SR) of cancer remains a rare phenomenon, particularly in hepatocellular carcinoma (HCC), where limited literature exists. This case report emphasizes the significance of SR in advanced HCC, shedding light on the proposed mechanisms and addressing the scarcity of documented cases in current medical literature.

We present the case of a 67-year-old female with a history of localized HCC who underwent right hepatectomy. Surveillance imaging 4 months later revealed tumor recurrence with tumor thrombus in the main portal vein. Radioembolization was deemed unsuitable, leading to the recommendation of systemic therapy with atezolizumab and bevacizumab. Prior to receiving any treatment, the patient tested positive for coronavirus disease 2019 (COVID-19), having previously received both the messenger RNA (mRNA)-1273 vaccine series and a booster. Surprisingly, subsequent imaging 10 months after initial diagnosis showed SR of the previously identified lesions, suggesting a potential link between viral exposure, vaccination, and the observed regression. The patient eventually received treatment with atezolizumab and bevacizumab and has sustained disease control to date, 12 months after initiating treatment.

This unique case highlights SR of advanced HCC following COVID-19 infection, raising intriguing questions about the interplay between viral infections, vaccinations, and cancer outcomes. The patient's response in the absence of systemic therapy further underscores the complexity of HCC management and prompts further investigation into the potential immunomodulatory effects of viral infections and vaccinations on cancer regression. Understanding these interactions could have implications for tailoring treatment approaches and improving outcomes in patients with advanced HCC.

The emergence of the SARS-CoV-2 virus has highlighted the importance of genomic epidemiology in understanding the evolution of pathogens and guiding public health interventions. The Omicron variant in particular has underscored the role of epistasis in the evolution of lineages with both higher infectivity and immune escape, and therefore the necessity to update surveillance pipelines to detect them early on.

In this study, we apply a method based on mutual information between positions in a multiple sequence alignment, which is capable of scaling up to millions of samples. We show how it can reliably predict known experimentally validated epistatic interactions, even when using as little as 10,000 sequences, which opens the possibility of making it a near real-time prediction system. We test this possibility by modifying the method to account for the sample collection date and apply it retrospectively to multiple sequence alignments for each month between March 2020 and March 2023. We detected a cornerstone epistatic interaction in the Spike protein between codons 498 and 501 as soon as seven samples with a double mutation were present in the dataset, thus demonstrating the method's sensitivity. We test the ability of the method to make inferences about emerging interactions by testing candidates predicted after March 2023, which we validate experimentally.

We show how known epistatic interaction in SARS-CoV-2 can be detected with high sensitivity, and how emerging ones can be quickly prioritized for experimental validation, an approach that could be implemented downstream of pandemic genome sequencing efforts.

The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing the endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis and secretion of mature, bioactive forms of IL-1β and IL-18. The NLRP3 inflammasome is essential in the genesis and progression of infectious illnesses. Herein, we provide a comprehensive review of the NLRP3 inflammasome in infectious diseases, focusing on its two-sided effects. As an essential part of host defense with a protective impact, abnormal NLRP3 inflammasome activation, however, result in a systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence of small molecules, biologics, and phytochemicals acting on the NLRP3 inflammasome has been reviewed. We believe that the NLRP3 inflammasome helps us understand the pathological mechanism of different stages of infectious diseases and that inhibitors targeting the NLRP3 inflammasome will become a new and valuable research direction for the treatment of infectious diseases.

COVID-19 has caused a worldwide pandemic, creating an urgent need for early detection methods. Breath analysis has shown great potential as a non-invasive and rapid means for COVID-19 detection. The objective of this study is to detect patients infected with SARS-CoV-2 and even the possibility to screen between different SARS-CoV-2 variants by analysis of carbonyl compounds in breath. Carbonyl compounds in exhaled breath are metabolites related to inflammation and oxidative stress induced by diseases. This study included a cohort of COVID-19 positive and negative subjects confirmed by reverse transcription polymerase chain reaction between March and December 2021. Carbonyl compounds in exhaled breath were captured using a microfabricated silicon microreactor and analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). A total of 321 subjects were enrolled in this study. Of these, 141 (85 males, 60.3%) (mean ± SD age: 52 ± 15 years) were COVID-19 (55 during the alpha wave and 86 during the delta wave) positive and 180 (90 males, 50%) (mean ± SD age: 45 ± 15 years) were negative. Panels of a total of 34 ketones and aldehydes in all breath samples were identified for detection of COVID-19 positive patients. Logistic regression models indicated high accuracy/sensitivity/specificity for alpha wave (98.4%/96.4%/100%), for delta wave (88.3%/93.0%/84.6%) and for all COVID-19 positive patients (94.7%/90.1%/98.3%). The results indicate that COVID-19 positive patients can be detected by analysis of carbonyl compounds in exhaled breath. The technology for analysis of carbonyl compounds in exhaled breath has great potential for rapid screening and detection of COVID-19 and for other infectious respiratory diseases in future pandemics.

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.

The virus called SARS-CoV-2 emerged in 2019 and quickly spread worldwide, causing COVID-19. It has greatly impacted on everyday life, healthcare systems, and the global economy. In order to save as many lives as possible, precautions such as social distancing, quarantine, and testing policies were implemented, and effective vaccines were developed. A growing amount of data collected worldwide allowed the characterization of this new disease, which turned out to be more complex than other common respiratory tract infections. An increasing number of convalescents presented with a variety of nonspecific symptoms emerging after the acute infection. This possible new global health problem was identified and labelled as long COVID. Since then, a great effort has been made by clinicians and the scientific community to understand the underlying mechanisms and to develop preventive measures and effective treatment. The role of autoimmunity induced by SARS-CoV-2 infection in the development of long COVID is discussed in this review. We aim to deliver a description of several conditions with an autoimmune background observed in COVID-19 convalescents, including Guillain-Barré syndrome, antiphospholipid syndrome and related thrombosis, and Kawasaki disease highlighting a relationship between SARS-CoV-2 infection and the development of autoimmunity. However, further studies are required to determine its true clinical significance.

It is not yet possible to estimate the proportion of patients with COVID-19 who present distinguishable classical neurological symptoms and syndromes. The objective of this study is to estimate the incidence of sensory symptoms (hypoaesthesia, paraesthesia, and hyperalgesia) in physicians who have presented the disease at Hospital Universitario Fundación Alcorcón (HUFA) in Madrid; to establish the relationship between sensory symptoms and the presence of other signs of infection; and to study their association with the severity of COVID-19.

We conducted a descriptive, cross-sectional, retrospective, observational study. HUFA physicians who presented SARS-CoV-2 infection between 1 March and 25 July 2020 were included in the study. A voluntary, anonymous survey was distributed via corporate email. Sociodemographic and clinical characteristics were collected from professionals with PCR- or serology-confirmed COVID-19.

The survey was sent to 801 physicians and we received 89 responses. The mean age of respondents was 38.28 years. A total of 17.98% presented sensory symptoms. A significant relationship was found between the presence of paraesthesia and cough, fever, myalgia, asthaenia, and dyspnoea. A significant relationship was also found between paraesthesia and the need for treatment and admission due to COVID-19. Sensory symptoms were present from the fifth day of illness in 87.4% of cases.

SARS-CoV-2 infection can be associated with sensory symptoms, mostly in severe cases. Sensory symptoms often appear after a time interval, and may be caused by a parainfectious syndrome with an autoimmunity background.

This multicenter, prospective study is designed to investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the Middle Ear Effusion (MEE) of patients developing Otitis Media with Effusion (OME) subsequent to an Omicron infection. The objective is to elucidate any potential association between the virus and the condition.

This study, conducted from January to June 2023, spanned the Otolaryngology departments of two medical institutions in Eastern China. Patients manifesting OME subsequent to Omicron infection from both hospitals were subjected to comprehensive otolaryngological assessments, including pure-tone audiometry (PTA), tympanometry, otoscopic examination, and nasopharyngolaryngoscopy. Subsequently, MEE samples extracted from these patients were analyzed through RT-PCR to detect SARS-CoV-2.

In this study, 23 patients (32-84 years; 57.5 ± 14.8 mean age; 47.8 % male) presented OME in 25 ears post-Omicron infection, with 21 (91.3 %) exhibiting unilateral symptoms. The median duration from infection to MEE sampling was 21 days (IQR: 25-46; range: 11-150). Predominantly, 64.0 % exhibited Type B tympanograms, and fluid accumulation was observed in 88.0 % of ears. SARS-CoV-2 was detected in 3 MEE samples (12.0 %), with cycle threshold values ranging between 25.65 and 33.30.

Our study highlights the potential effects of COVID-19 on the middle ear, suggesting a link between SARS-CoV-2 and OME onset. The virus, a significant contributor to OME, is detectable in the MEE nearly a month post-Omicron infection, indicating a potential alteration in OME treatment strategies and a risk of recurrence, emphasizing the necessity for otolaryngologist vigilance.

The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response to viral infections, monocytes are recruited into the lung and subsequently differentiate into dendritic cells (DCs). DCs are critical players in the development of acute lung inflammation that causes ARDS. Here, we focus on the interaction of a specific SARS-CoV-2 open reading frame protein, ORF8, with DCs. We show that ORF8 binds to DCs, causes pre-maturation of differentiating DCs, and induces the secretion of multiple proinflammatory cytokines by these cells. In addition, we identified DC-SIGN as a possible interaction partner of ORF8 on DCs. Blockade of ORF8 leads to reduced production of IL-1β, IL-6, IL-12p70, TNF-α, MCP-1 (also named CCL2), and IL-10 by DCs. Therefore, a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.

Multiple genetic, environmental, and immunological variables cause neuropsychiatric disorders (NPDs). The induced inflammatory immune response is also connected to the severity and treatment outcomes of various NPDs. These reactions also significantly impact numerous brain functions such as GABAergic signaling and neurotransmitter synthesis through inflammatory cytokines and chemokines. Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic counterparts are flavonoids with various biological characteristics including anti-inflammatory activity. Several pure chalcones have been clinically authorized or studied in humans. Chalcones are favored for their diagnostic and therapeutic efficacy in neuroinflammation due to their tiny molecular size, easy manufacturing, and flexibility for changes to adjust lipophilicity ideal for BBB penetrability. These compounds reached an acceptable plasma concentration and were well-tolerated in clinical testing. As a result, they are attracting increasing attention from scientists. However, chalcones' therapeutic potential remains largely untapped. This paper is aimed at highlighting the causes of neuroinflammation, more potent chalcone congeners, their mechanisms of action, and relevant structure-activity relationships.

In the face of the global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), researchers are tirelessly exploring novel therapeutic approaches to combat coronavirus disease 2019 (COVID-19) and its associated complications. Nitric oxide (NO) has appeared as a multifaceted signaling mediator with diverse and often contrasting biological activities. Its intricate biochemistry renders it a crucial regulator of cardiovascular and pulmonary functions, immunity, and neurotransmission. Perturbations in NO production, whether excessive or insufficient, contribute to the pathogenesis of various diseases, encompassing cardiovascular disease, pulmonary hypertension, asthma, diabetes, and cancer. Recent investigations have unveiled the potential of NO donors to impede SARS-CoV- 2 replication, while inhaled NO demonstrates promise as a therapeutic avenue for improving oxygenation in COVID-19-related hypoxic pulmonary conditions. Interestingly, NO's association with the inflammatory response in asthma suggests a potential protective role against SARS-CoV-2 infection. Furthermore, compelling evidence indicates the benefits of inhaled NO in optimizing ventilation-perfusion ratios and mitigating the need for mechanical ventilation in COVID-19 patients. In this review, we delve into the molecular targets of NO, its utility as a diagnostic marker, the mechanisms underlying its action in COVID-19, and the potential of inhaled NO as a therapeutic intervention against viral infections. The topmost significant pathway, gene ontology (GO)-biological process (BP), GO-molecular function (MF) and GO-cellular compartment (CC) terms associated with Nitric Oxide Synthase (NOS)1, NOS2, NOS3 were arginine biosynthesis (p-value = 1.15 x 10-9) regulation of guanylate cyclase activity (p-value = 7.5 x 10-12), arginine binding (p-value = 2.62 x 10-11), vesicle membrane (p-value = 3.93 x 10-8). Transcriptomics analysis further validates the significant presence of NOS1, NOS2, NOS3 in independent COVID-19 and pulmonary hypertension cohorts with respect to controls. This review investigates NO's molecular targets, diagnostic potentials, and therapeutic role in COVID-19, employing bioinformatics to identify key pathways and NOS isoforms' significance.

The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic effects remain unclear. Here, we studied the antiviral mechanisms of their synergistic use in vitro and in vivo. We selected the SARS-CoV-2 pseudovirus for viral studies and found that synergistic andrographolide and baicalein significantly reduced angiotensin-converting enzyme 2 protein level and viral entry of SARS-CoV-2 into cells compared to singal compound individually and inhibited the major protease activity of SARS-CoV-2. This mechanism is essential to reduce the pathogenesis of SARS-CoV-2. In addition, their synergistic use in vivo also inhibited the elevation of pro-inflammatory cytokines, including IL-6 and TNF-α-the primary cytokines in the development of acute respiratory distress syndrome (the main cause of COVID-19 deaths). In conclusion, this study shows that synergistic andrographolide and baicalein treatment acts as potent inhibitors of coronavirus mechanisms in vitro and in vivo-and is more effective together than in isolation.

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity. Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically. The humoral response to SARS-CoV-2 infection has been the focus of intense research, and the role of the innate immune system has received significantly less attention. Here, we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems. We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

The coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection continues to affect the daily life of communities worldwide. Nutrition is a vital determinant of overall health. Given the lack of specific drugs for COVID-19 and incomplete vaccination coverage, optimizing nutrition appears to be one of the most cost-effective means of enhancing immunity. Therefore, this study was designed to evaluate nutrition-related knowledge, attitudes, and practices (KAP) to offer insights into the personal determinants of dietary behavior during COVID-19 pandemic in four major cities within the Northeast region.

This cross-sectional study was conducted between January and December 2022 using a self-administered questionnaire. The data were entered in EpiData V-3.02 and analyzed using SPSS version 26. Binary logistic regression analysis was also employed to examine the association between dependent and independent variables.

A total of 4,092 respondents were included in the study. Most of the respondents demonstrated had inadequate nutrition knowledge, 26% of them provided ≥60% of correct answers. About one-third of the respondents were knowledgeable about the daily levels of oil, salt, milk, water, vegetables and fruits for adults. Furthermore, our results showed that 60.6% of participants held positive attitudes toward healthy eating. Additionally, only 54.6% of the participants have heathy dietary practices during COVID-19 pandemic. Binary logistic regression analysis showed that the following characteristics were associated with displaying unhealthy dietary behaviors: being men, having a lower education level, having a family income of 10,000-19,999 and more than 20,000, being resided in Harbin, Shenyang, and Changchun. Importantly, the strongest associations were observed between poor dietary knowledge and unhealthy eating behaviors. Similarly, dietary attitudes were strongly associated with healthy dietary behaviors when the effects of other factors were excluded; responders with negative attitudes were more likely to exhibit unhealthy eating behaviors.

Our findings suggest that residents in the Northeast China possessed a relatively low level of nutritional knowledge, which directly influenced their dietary practices during the COVID-19 pandemic. This study provides valuable insights into the cross-sectional description and key factors related to nutrition-related KAP, serving as a basis for future policymaking to respond more effectively to health crises.

The widespread occurrence of SARS-CoV-2 infections and the diverse range of symptoms have placed significant strain on healthcare systems worldwide. Pregnancy has also been affected by COVID-19, with an increased risk of complications and unfavorable outcomes for expectant mothers. Multiple studies indicate that SARS-CoV-2 can infiltrate the placenta, breach its protective barrier, and infect the fetus. Although the precise mechanisms of intrauterine transmission remain unclear, factors such as perinatal infection, macrophages, sexual intercourse, and the virus' interaction with host angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP-1) proteins appear to play a role in this process. The integrity of the placental barrier fluctuates throughout pregnancy and appears to influence the likelihood of fetal transmission. The expression of placental cell receptors, like ACE2, changes during pregnancy and in response to placental damage. However, due to the consistent presence of others, such as NRP-1, SARS-CoV-2 may potentially enter the fetus at different stages of pregnancy. NRP-1 is also found in macrophages, implicating maternal macrophages and Hofbauer cells as potential routes for viral transmission. Our current understanding of SARS-CoV-2's vertical transmission pathways remains limited. Some researchers question the ACE2-associated transmission model due to the relatively low expression of ACE2 in the placenta. Existing studies investigating perinatal transmission and the impact of sexual intercourse have either involved small sample sizes or lacked statistical significance. This review aims to explore the current state of knowledge regarding the potential mechanisms of COVID-19 vertical transmission, identifying areas where further research is needed to fill the gaps in our understanding.

The global coronavirus disease 2019 (COVID-19) pandemic has a detrimental impact on public health. COVID-19 usually manifests as pneumonia, which can progress into acute respiratory distress syndrome (ARDS) related to uncontrolled TH17 immune reaction. Currently, there is no effective therapeutic agent to manage COVID-19 with complications. The currently available anti-viral drug remdesivir has an effectiveness of 30% in SARS-CoV-2-induced severe complications. Thus, there is a need to identify effective agents to treat COVID-19 and the associated acute lung injury and other complications. The host immunological pathway against this virus typically involves the THαβ immune response. THαβ immunity is triggered by type 1 interferon and interleukin-27 (IL-27), and the main effector cells of the THαβ immune response are IL10-CD4 T cells, CD8 T cells, NK cells, and IgG1-producing B cells. In particular, IL-10 exerts a potent immunomodulatory or anti-inflammatory effect and is an anti-fibrotic agent for pulmonary fibrosis. Concurrently, IL-10 can ameliorate acute lung injury or ARDS, especially those caused by viruses. Owing to its anti-viral activity and anti-pro-inflammatory effects, in this review, IL-10 is suggested as a possible treatment agent for COVID-19.

Increasing evidence has been pointing towards the existence of a bi-directional interplay between mental health condition and immunity. Data collected during the COVID-19 outbreak suggest that depressive symptoms may impact the production of antibodies against SARS-CoV-2, while a previous infection could affect the immune response and cause neuropsychological disturbances. A prospective observational study was designed to investigate the association between mental health conditions and immune response over time. We analyzed the mental health at baseline and the antibodies before and after immunization with the COVID-19 mRNA vaccine in a cohort of healthcare professionals in southern Switzerland. One-hundred and six subjects were enrolled. Anxiety, distress and depression correlated to each other. There were no correlations between the mentioned variables and the vaccine induced IgG antibodies against the receptor binding domain (RBD) of the spike protein. For those who had a previous COVID-19 infection, the antibodies increased according to the grade of depression. For those who did not, the anti-RBD IgG levels remained similar when comparing presence or absence of depression symptoms. Our results show that previous SARS-CoV-2 natural infection in subjects with mental health conditions enhances the immune response to COVID-19 mRNA vaccination. The correlation between immune response to COVID-19 vaccination, a previous exposure to the virus, and symptoms of mood disorders, makes it necessary to explore the direction of the causality between immune response and depressive symptoms.

Thrombocytopenia, characterized by a decrease in platelet count, is commonly observed in sepsis and COVID-19. In sepsis, thrombocytopenia can result from various mechanisms, including impaired platelet production in the bone marrow, accelerated platelet destruction due to increased inflammation, sequestration of platelets in the spleen, immune-mediated platelet destruction, or dysregulated host responses. Similarly, thrombocytopenia has been reported in COVID-19 patients, but the immune-related mechanisms underlying this association remain unclear. Notably, interventions targeting thrombocytopenia have shown potential for improving outcomes in both sepsis and COVID-19 patients. Understanding these mechanisms is crucial for developing effective treatments.

The COVID-19 pandemic has led to over 760 million cases and 6.9 million deaths worldwide. To mitigate the loss of lives, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with susceptible variants. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response anti-viral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

In a short time, several types of injectable and oral therapeutics have been developed and used to effectively manage patients with coronavirus disease 2019 (COVID-19). BEN815 is an improved mixture of three extracts (Psidium guajava, Camellia sinensis, and Rosa hybrida) recognized by the Ministry of Food and Drug Safety of Korea as a health food ingredient that alleviates allergic rhinitis. The current animal efficacy study was performed to assess its probability of improving COVID-19 symptoms. BEN815 treatment significantly increased the survival of K18-hACE2 transgenic mice and reduced viral titers in the lungs at 5 days post infection (DPI). Furthermore, the lungs of the treated mice showed mild tissue damage at 5 DPI and nearly complete recovery from COVID-19 at 14 DPI. BEN815 appears to be an effective and minimally toxic anti-SARS-CoV-2 agent in mice and has potential for clinical applications.

The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process.

The SARS-CoV-2 infection (COVID-19) pandemic created an unprecedented chain of events at a global scale, with European counties initially following individual pathways on the confrontation of the global healthcare crisis, before organizing coordinated public vaccination campaigns, when proper vaccines became available. In the meantime, the viral infection outbreaks were determined by the inability of the immune system to retain a long-lasting protection as well as the appearance of SARS-CoV-2 variants with differential transmissibility and virulence. How do these different parameters regulate the domestic impact of the viral epidemic outbreak? We developed two versions of a mathematical model, an original and a revised one, able to capture multiple factors affecting the epidemic dynamics. We tested the original one on five European countries with different characteristics, and the revised one in one of them, Greece. For the development of the model, we used a modified version of the classical SEIR model, introducing various parameters related to the estimated epidemiology of the pathogen, governmental and societal responses, and the concept of quarantine. We estimated the temporal trajectories of the identified and overall active cases for Cyprus, Germany, Greece, Italy and Sweden, for the first 250 days. Finally, using the revised model, we estimated the temporal trajectories of the identified and overall active cases for Greece, for the duration of the 1230 days (until June 2023). As shown by the model, small initial numbers of exposed individuals are enough to threaten a large percentage of the population. This created an important political dilemma in most countries. Force the virus to extinction with extremely long and restrictive measures or merely delay its spread and aim for herd immunity. Most countries chose the former, which enabled the healthcare systems to absorb the societal pressure, caused by the increased numbers of patients, requiring hospitalization and intensive care.