Inflammation-associated diseases have become widespread and pose a significant threat to human health, and the therapeutic methods for diverse diseases are inadequate due to the undesirable effects of synthetic ingredients. Recently, more and more evidence indicated that phytochemicals, plant secondary metabolites, have numerous therapeutic functions against human diseases via affecting a variety of mechanisms with their distinct advantages of high efficiency and low toxicity. Here, we highlight the mechanisms of phytochemicals to hinder inflammation-associated diseases (including Inflammatory diseases, cardiovascular diseases, metabolic syndrome, neurological disorders, skin diseases, respiratory diseases, kidney diseases, gastrointestinal diseases, retinal diseases, viral infections) by regulating the crosstalk among various signal cascades (including MicroRNAs, SIRT1, DNMTs, NF-κB, NLRP3, TGF-β, the Gasdermin-mediated pyroptosis pathway), which can be considered as a novel and potential therapeutic strategy. Furthermore, phytochemicals could prevent virus infection by disturbing different targets in the virus replication cycle. However, natural plants have shown limited bioavailability due to their low water solubility, the use of adjuvants such as liposomal phytochemicals, phytochemical nanoparticles and phytochemicals-phospholipid complex promote their bioavailability to exhibit beneficial effects against various diseases. The purpose of this review is to explore the molecular mechanisms and promising applications of phytochemicals in the fields of inflammation-associated diseases and virus infection to provide some direction.

As pivotal effectors of antiviral immunity, natural killer (NK) cells are crucial for controlling the spread of COVID-19. The nonstructural protein 13 of SARS-CoV-2 can encode a viral peptide (Nsp13232-240) preventing human leukocyte antigen E (HLA-E) from recognizing inhibitory receptor NKG2A, thereby activating NK cells. The underlying molecular mechanisms of Nsp13232-240 remain unclear. Therefore, we compared the interaction discrepancy between the self-peptide and Nsp13232-240, theoretically predicting its source. Results indicate that electrostatic interaction energy provides the main source of binding, and its attenuation greatly promotes binding affinity differences. Nsp13232-240 disrupts the hydrogen bond network between CD94 and HLA-E, impacting the binding of hot-spot residues, including Q112CD94 and E161HLA-E. Moreover, Nsp13232-240 breaks the salt bridges formed by K217NKG2A and K199NKG2A with HLA-E. Conformational changes induced by Nsp13232-240 lead to diminished atomic contacts and an unstable binding pattern. These findings provide novel insights into the immunomodulatory role of Nsp13232-240 and may inform future NK cell-mediated strategies targeting SARS-CoV-2.

The role of vitamin D supplementation in modulating clinical outcomes and inflammatory responses in COVID- 19 patients has garnered significant interest. This umbrella review consolidates current evidence to evaluate the association between vitamin D supplementation and COVID- 19-related outcomes.

A comprehensive search was conducted across multiple databases to identify relevant systematic reviews and meta-analyses. Studies assessing the impact of vitamin D supplementation on disease severity, mortality, hospitalization, and inflammatory markers in COVID- 19 patients were included. Methodological quality was assessed using standardized tools.

The findings suggest that vitamin D supplementation may be associated with reduced mortality and improved clinical outcomes in COVID- 19 patients. Several studies reported a decrease in inflammatory markers, such as C-reactive protein and interleukin- 6, following supplementation. However, variations in study design, dosage regimens, and baseline vitamin D status limit the generalizability of results.

Vitamin D supplementation appears to have a potential role in improving clinical outcomes and modulating inflammatory responses in COVID- 19 patients. Nevertheless, due to heterogeneity among studies, further high-quality randomized controlled trials are warranted to confirm these findings.

To determine the effect of Traditional Chinese Medicine (TCM) Fuzheng Xuanfei Huashi prescription (, FZXF) on lipopolysaccharide (LPS)-induced pneumonia in mice and identify the mechanism of FZXF in the treatment of LPS-induced lung inflammation.

The pneumonia model was established by intraperitoneal injection of 5 mg/kg LPS in mice. Cytokines were detected by enzyme-linked immune-osorbent assay (ELISA), macrophages in lung tissue were determined by immunofluorescence, and pathway-related data were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blot.

The liver, thymus, and spleen index values and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) obviously increased in LPS-treated mice. FZXF decreased the white blood cell count and reduced the increase in the lung wet weight/dry weight ratio caused by LPS. The hematoxylin-eosin staining result showed that FZXF could maintain the integrity of lung tissue structure, alleviate interstitial oedema and alveolar wall thickening, and reduce inflammatory cell infiltration. Moreover, FZXF markedly reduced the expression of proinflammatory cytokines. FZXF also significantly reduced LPS-induced malondialdehyde production and increased superoxide dismutase level in the lung. By immunofluorescence, we found that FZXF could reduce macrophage infiltration. The mRNA expression levels of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), toll-like receptor 4 (TLR4) and nuclear transcription factor κB (NF-κB) in the lung tissue of mice were decreased by treatment with FZXF. In addition, FZXF inhibited the protein expression of TLR4, p-p65 and COX-2. These results indicated that FZXF could inhibit the inflammatory response of LPS induced cytokine storm in mice through TLR4/NF-κB and COX-2/PGE2 signaling pathway.

These findings were suggested that FZXF prescription suppresses inflammation in LPS-induced pneumonia in mice via TLR4/NF-κB and COX-2/ PGE2 pathway.

The seroepidemiological characteristics of the SARS-CoV-2 were investigated along with the secondary infection rate in the household of confirmed patients in a high-risk population in Mashhad, Iran. The current descriptive cross-sectional study includes a total of 154 confirmed cases of SARS-CoV-2 infection in Mashhad, Iran, from March 2021 to December 2021. The participants' families were screened for SARS-CoV-2 secondary infection rate, and a standard checklist containing the research parameters was completed by all participants. The participants' average age was 43.19 ± 9.86 years, of which 80 (51.9%) were female and the rest were male. Of the participants, 147 (95.5%) reported using face masks, and 83 (53.9%) were using masks all the time. IgG and IgM of COVID-19 were positive in 43 (27.9%) and 8 (5.2%) individuals, respectively. The average positive rate in the participants was 0.12 ± 0.24. Wearing masks when contracting with an infected patient (p < 0.001 and r = -0.370), using a separate room (p < 0.001 and r = -0.663), a separate toilet (p < 0.001 and r = -0.663) and the number of family members (p = 0.013 and r = 0.201) were significantly correlated to the positive rate of infection among the participants. Adherence to wearing masks and using separate rooms, and toilets by households in contact with a COVID-19-confirmed patient reduces the secondary transmission rate of the disease among healthy family members. In addition, the probability of COVID-19 transmission is higher in larger families.

The online version contains supplementary material available at 10.1007/s13337-024-00903-9.

Lianhua Qingke (LHQK), a traditional Chinese medicine, has shown efficacy in treating acute and chronic bronchitis and bronchiolitis. However, the specific mechanism underlying the therapeutic effects of LHQK on severe pneumonia is not clear.

Severe pneumonia remains a critical health challenge, particularly in cases progressing to sepsis and septic shock, where host immune responses become dysregulated or dysfunctional. This study aims to evaluate the immunomodulatory effects of LHQK in severe pneumonia.

This research examined LHQK's therapeutic and immunomodulatory mechanisms in patients with severe pneumonia and a lipopolysaccharide (LPS)-induced mouse model of severe pneumonia. Patients with severe pneumonia were randomized into three groups: basal treatment, LHQK-Low dose (12 tablets/day), and LHQK-High dose (24 tablets/day). BALB/c mice were categorized into four groups: control, model, LHQK-Low dose (3.7 mg/kg), and LHQK-High dose (7.4 mg/kg). Clinical efficacy was evaluated by assessing parameters including the value and rate of change in APACHE II score, improvement in chest X-ray or CT, partial pressure of oxygen (PO2), oxygen saturation in arterial blood (SaO2), oxygenation index (OI), and the length of hospitalization after 7 days of treatment. The viscosity of sputum was measured by viscosimeter. Moreover, lung histopathology, airway barrier integrity, and immune cells in BALF, were assessed using hematoxylin and eosin staining, immunostaining, and Wright-Giemsa staining. Cytokine levels were measured using Luminex assay and Olink, while pulmonary immune cell patterns were analyzed using multiplex fluorescence and Cytometry by Time-Of-Flight (CyTOF).

In comparison to the basal treatment group of patients, LHQK treatment exhibited a reduction in the severity of severe pneumonia and inflammatory status, as evidenced by observations on Chest X-ray or CT scans. Additionally, LHQK treatment led to an elevation in OI, PO2, and SaO2 levels, and notably, a decreased duration of hospitalization. Further analysis revealed that LHQK enhanced the integrity of the airway epithelial barrier, reduced the viscosity of sputum, and significantly decreased inflammatory cells infiltration. The application of Luminex and Olink assay further confirmed the inhibitory impact of LHQK on the cytokine storm in mice. Moreover, multiplex fluorescence and CyTOF analysis demonstrated that LHQK effectively suppressed the activation of monocyte derived macrophages, neutrophils, and Treg cells, while preserved the levels of alveolar macrophages, B cells, and CD4+ and CD8+ T lymphocytes, therefore restoring immune homeostasis within the lung of severe pneumonia. These findings significantly substantiate the potential clinical application of LHQK in severe pneumonia treatment.

LHQK demonstrates therapeutic efficacy in severe pneumonia by maintaining structural integrity, suppressing cytokine storms, enhancing intrinsic immunity, reversing T cell exhaustion, and correcting lung immune disorders. These findings significantly substantiate LHQK's potential clinical application in severe pneumonia treatment.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.

COVID-19 pneumonia has spread across China and globally since late 2019, becoming a pandemic. Its extremely contagious nature as well as high morbidity and mortality rates have attracted widespread attention globally. For the treatment of SARS-CoV-2 pneumonia, two commonly used antiviral drugs in the clinic are nirmatrelvir/ritonavir(Paxlovid) and Azvudine, while the therapeutic efficacy of the two drugs and their impact on patient prognosis remain inconclusive. Therefore, the aim of this study is to investigate the effects of two antiviral drugs, Azvudine and Paxlovid, on the disease development and prognosis of patients with COVID-19.

This study collected and analyzed in Inner Mongolia hospital treated 267 cases of COVID - 19 patients. According to the use of antiviral medications, the participants in this experiment were split into the Azvudine and Paxlovid groups. The effectiveness of the medications was evaluated using the length of hospitalization, Nucleic acid into negative time for the first time, and laboratory indices such as total protein, lymphocytes, leukocytes, albumin, creatinine, and platelets.

Compared with the Azvudine group, patients in the Paxlovid group had a shorter recovery time, a higher degree of rise in lymphocytes, a faster recovery of the immune system, a lower rise in creatinine, and a lesser renal burden, but patients in the Paxlovid group had a greater decrease in total protein.

In assessing patient conditions for treatment selection, Paxlovid may be preferable for individuals with renal insufficiency or those exhibiting compromised immune responses. Conversely, for patients experiencing malnutrition or cirrhotic hypoproteinemia, Azvudine could be considered to mitigate the reduction in protein levels.

This study investigates the role of Annexin A1 (ANXA1) in regulating T cell function and its implications in bone marrow adiposity in aplastic anaemia (AA). Utilizing single-cell sequencing analysis, we compared bone marrow tissues from AA patients and healthy individuals, focusing on T cell subgroups and their impact on bone marrow pathology. Our findings reveal a significant activation of CD8+ T cells in AA, driven by reduced ANXA1 expression. This heightened T cell activity promotes adipogenesis in bone marrow-derived mesenchymal stem cells via IFN-γ secretion. Overexpression of ANXA1 was found to suppress this process, suggesting its therapeutic potential in AA treatment. The study highlights ANXA1 as a crucial regulator in the AA-associated immune microenvironment and bone marrow adiposity. KEY POINTS: This study found that ANXA1 is significantly downregulated in AA and provides detailed insights into its critical role in the disease. The study demonstrates the excessive activation of CD8+ T cells in the progression of AA. The research shows that the overexpression of ANXA1 can effectively inhibit the activation of CD8+ T cells. The study confirms that overexpression of ANXA1 reduces the secretion of the cytokine IFN-γ, decreases adipogenesis in bone marrow-derived mesenchymal stem cells and may improve AA symptoms. This research provides new molecular targets for the treatment of AA.

COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) represents the biggest global health emergency in recent decades. The host immune response to SARS-CoV-2 seems to play a key role in disease pathogenesis and clinical manifestations, with Natural Killer (NK) lymphocytes being among the targets of virus-induced regulation.

This study performed a single-cell multi-omics analysis of transcripts and proteins of NK lymphocytes in COVID-19 patients, for the characterization of the innate immunological response to infection. NK cells were isolated from peripheral blood samples collected from adult subjects divided into 3 study groups: (1) non-infected subjects (Naïve group, n = 3), (2) post COVID-19 convalescent subjects (Healed group, n = 3) and (3) patients that were vaccinated against SARS-CoV-2 (Vaccine group, n = 3). Cells were then analysed by the BD Rhapsody System for the single-cell multi-omics investigation of transcriptome and membrane proteins.

The bioinformatic analysis identified 5 cell clusters which differentially expressed gene/protein markers, defining NK cell subsets as "Active NK cells" and "Mature NK cells". Calculating the relative proportion of each cluster within patient groups, more than 40% of the Naïve group cell population was found to belong to Mature NKs, whereas more than 75% of the Vaccine group cell population belonged to the cluster of Active NKs. Regarding the Healed group, it seemed to show intermediate phenotype between Active and Mature NK cells. Differential expression of specific genes, proteins and signaling pathways was detected comparing the profile of the 3 experimental groups, revealing a more activated NK cell phenotype in vaccinated patients versus recovered individuals.

The present study detected differential expression of NK cell markers in relation to SARS-CoV-2 infection and vaccine administration, suggesting the possibility to identify key molecular targets for clinical-diagnostic use of the individual response to viral infection and/or re-infection.

The mental health of populations is usually affected after a disaster event. However, it is not known what the level of mental health of Chinese population 1 year after COVID-19, nor what factors influence it.

This study aimed to examine the mental health status of general population in Chengdu 1 year after COVID-19, and then analyse influencing factors.

This study is a cross-sectional survey based on the SCL-90 questionnaire. Continuous data were described as M and SD, and counting data were described as frequencies(n) and percentages (%). Chi-square test or Fisher's exact test were used for statistical inference, and significance variables were included in the binary logistic regression equation for multivariate analysis.

There were 172 participants with positive screening results. Age, marital status, number of kids, self-perceived health and the presence of chronic disease had an effect on screening results. Logistic regression analysis showed that age and self-perceived health were the main influencing factors.

Young people aged 18-19 and those who consider themselves not very healthy were at higher risk of poor mental health 1 year after the COVID-19 outbreak.

Community institutions and community workers should focus on the mental health status of people 1 year after COVID-19, with a focus on people with poor self-perceived health and younger age groups, and take early preventive measures.

Multiple concerning reports have emerged of cardiovascular complications, particularly thrombosis, following mRNA vaccination against the SARS-CoV-2 pathogen. The presence of serologically persistent anti-phospholipid antibodies is a characteristic of antiphospholipid syndrome, which presents with clinical manifestations including thrombosis or pregnancy morbidity. Anti-SARS-CoV-2 mRNA vaccines pose a theoretical risk of cross-reactivity between the SARS-CoV-2 spike protein and phospholipids in host tissues. In this study, serum anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination were compared among 184 hospital staff members. Although no significant differences were found in terms of antibody titers targeting cardiolipin and β2-glycoprotein I, post-vaccination antibody titers targeting phosphatidylethanolamine were found to be significantly increased compared to pre-vaccination levels (p = 0.008). Anti-phosphatidylethanolamine antibodies are the most common anti-phospholipid antibodies detected in patients with recurrent miscarriages at < 10 weeks of gestation. However, the association between vaccination and these types of adverse events remains unknown, thus warranting further investigation.

To investigate the relationship between cognitive complaints, systemic inflammatory biomarkers, and psychological general well-being (PGWB) after mild/asymptomatic SARS-CoV-2 infection, according to the presence of long COVID and work tasks.

University employees and metal workers were recruited in a cross-sectional study 4 months after SARS-CoV-2 infection to assess cognitive impairment, individual PGWB index, inflammatory biomarkers, namely platelet-lymphocyte, neutrophil-lymphocyte, and lymphocyte-monocyte ratios, and the presence of long COVID symptoms.

A significant increase in the levels of inflammatory biomarkers was observed in subjects with long COVID. Furthermore, the PGWB index was influenced by long COVID symptoms and subjective cognitive and depressive symptoms, but not by work activity.

In occupational settings, it is crucial to detect the presence of long COVID symptoms and systemic inflammation early, as they may be associated with lower PGWB.

Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment.

Plasma samples were taken at hospital admission (baseline) and on the 5th day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS.

127 patients, 17 with CAP and 110 with COVID-19, were included. The analysis revealed 87 altered metabolites, suggesting changes in the metabolism of arachidonic acid, glycerolipids, glycerophospholipids, linoleic acid, pyruvate, glycolysis, among others. Most of these metabolites are involved in inflammatory, hypoxic, and thrombotic processes. At baseline, the greatest differences were found in phosphatidylcholine (PC) 31:4 (p < 0.001), phosphoserine (PS) 34:3 (p < 0.001), and phosphatidylcholine (PC) 36:5 (p < 0.001), all of which were notably decreased in COVID-19 patients. At follow-up, the most dysregulated metabolites were monomethyl-phosphatidylethanolamine (PE-Nme) 40:5 (p < 0.001) and phosphatidylcholine (PC) 38:4 (p < 0.001).

Metabolic and lipidic alterations suggest inhibition of innate anti-inflammatory and anti-thrombotic mechanisms in COVID-19 patients, which might lead to increased viral proliferation, uncontrolled inflammation, and thrombi formation. Results provide novel targets for predictive biomarkers against CAP and COVID-19.

Not applicable.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.

This study aims to develop and apply multistate models to estimate, forecast, and manage hospital length of stay during the COVID-19 epidemic without using any external packages. Data from Bellvitge University Hospital in Barcelona, Spain, were analyzed, involving 2285 hospitalized COVID-19 patients with moderate to severe conditions. The implemented multistate model includes transition probabilities and risk rates calculated from transitions between defined states, such as admission, ICU transfer, discharge, and death. In addition to examining key factors like age and gender, diabetes, lymphocyte count, comorbidity burden, symptom duration, and different COVID-19 waves were analyzed. Based on the model, patients hospitalized stay an average of 11.90 days before discharge, 2.84 days before moving to the ICU, or 34.21 days before death. ICU patients remain for about 24.08 days, with subsequent stays of 124.30 days before discharge and 35.44 days before death. These results highlight hospital stays' varying durations and trajectories, providing critical insights into patient flow and healthcare resource utilization. Additionally, it can predict ICU peak loads for specific subgroups, aiding in preparedness. Future work will integrate the developed code into the hospital's Health Information System (HIS) following ISO 13606 EHR standards and implement recursive methods to enhance the model's efficiency and accuracy.

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Takotsubo Syndrome (TS) is a heart disease caused by extreme exposure of the body to physical or psychological stress. In the context of COVID-19, the virus can be a significant source of stress, with particular attention being paid to the cytokine storm as a cause of damage to the body. New research shows that the production of specific cytokines is linked to the activation of immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 on T cells. Although initially beneficial in combating infections, it can suppress defense and aid in disease progression. Therefore, checkpoint inhibitor therapy has been highlighted beyond oncological therapies, given its effectiveness in strengthening the immune system. However, this treatment can lead to excessive immune responses, inflammation, and stress on the heart, which can cause Takotsubo Syndrome in patients. Several studies investigate the direct link between this therapy and cardiac injuries in these patients, which can trigger TS. From this perspective, we must delve deeper into this treatment and consider its effects on the prognosis against SARS-CoV-2 infection.

Fluoride is unnecessary in the human body. Long-term fluoride exposure may lead to immune system abnormalities. However, the mechanism remains unclear. This study aim to explore the mechanism of fluoride interference in the immune system and also identify the key indicators of fluoride-induced immune damage. Questionnaires were used to collect basic information. Multiple linear analyses and other statistical methods were used in order to process the data. Flow cytometry was used to detect relevant immunomarkers and analyze immune damage. Simultaneously, Wistar rats and cell models exposed to fluoride were established to detect the effects of fluoride on immune homeostasis. The results showed that sex, residence time, smoking, and Corona Virus Disease 2019 (COVID-19) infection may indirectly influence fluoride-induced immune damage. In residents of fluoride-exposed areas, there was a significant decrease in CD3+ T lymphocytes and CD4+ and CD8+ cells and a downward trend in the CD4+/CD8+ cell ratio. CD4+CD8+/CD4+, regulatory T cells (Tregs), and Tregs/effector T cells (Teffs) ratios showed opposite changes. Fluoride inhibits T cell activation by inhibiting the expression and phosphorylation of Protein Kinase C-θ (PKC-θ), hinders the internalization of T cell receptors, and affects NF-kB and c-Jun protein expression, leading to homeostatic Treg/Teff imbalance in vivo and in vitro experiments. This study represents the first evidence suggesting that PKC-θ may be the key to immune imbalance in the body under fluoride exposure. It is possible that Tregs/Teffs cell ratio provide a reference point for the diagnosis and treatment of fluoride-induced immune damage.

Coronavirus disease 2019 (COVID-19) is a viral pneumonia that can result in serious respiratory illness. It is associated with extensive systemic inflammation, changes to the lung extracellular matrix, and long-term lung impairment such as interstitial lung disease (ILD). In this study, the aim was to investigate whether tissue remodelling, wound healing, and neutrophil activity is altered in patients with COVID-19 and how these relate to the development of post-COVID ILD.

Serum samples were collected from 63 patients three months after discharge as part of the Research Evaluation Alongside Clinical Treatment study in COVID-19 (REACT COVID-19), 10 of whom developed ILD, and 16 healthy controls. Samples were quantified using neo-epitope specific biomarkers reflecting tissue stiffness and formation (PC3X, PRO-C3, and PRO-C6), tissue degradation (C1M, C3M, and C6M), wound healing (PRO-FIB and X-FIB), and neutrophil activity (CPa9-HNE and ELP-3).

Mean serum levels of PC3X (p < 0.0001), PRO-C3 (p = 0.002), C3M (p = 0.009), PRO-FIB (p < 0.0001), CPa9-HNE (p < 0.0001), and ELP-3 (p < 0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Moreover, PC3X (p = 0.023) and PRO-C3 (p = 0.032) were significantly elevated in post-COVID ILD as compared to COVID-19.

Serological biomarkers reflecting type III collagen remodelling, clot formation, and neutrophil activity were significantly elevated in COVID-19 and type III collagen formation markers were further elevated in post-COVID ILD. The findings suggest an increased type III collagen remodelling in COVID-19 and warrants further investigations to assess the potential of tissue remodelling biomarkers as a tool to identify COVID-19 patients at high risk of developing ILD.

Whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be complicated by immune suppression is under debate, but the following case suggests decreased immune competence during and after a SARS-CoV-2 infection.

The patient is a 50-year-old woman with a previous history of transient hyperthyroidism, allergy against ambrosia, and burn-out syndrome, who experienced a mild infection with SARS-CoV-2 during which she developed candida pharyngitis, which was successfully treated with miconazole. Twenty-eight days after clinical recovery from the SARS-CoV-2 infection, she developed right-sided zoster oticus with vestibular neuronitis and was successfully treated with acyclovir.

The case suggests that infection with SARS-CoV-2 can weaken immune competence and precipitate the development of candidiasis and focal infection with the zoster virus. Even mild infections with SARS-CoV-2 may be complicated by immune-compromise and immune-concomitant superinfections, which is why coronavirus disease 2019 (COVID-19) patients should strengthen their immune system not only during but also after the infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

SARS-CoV-2 is a highly pathogenic respiratory virus that successfully initiates and establishes its infection at the respiratory mucosa. However, little is known about how SARS-CoV-2 antagonizes the host's mucosal immunity. Recent findings have shown a marked reduction in the expression of the polymeric Ig receptor (pIgR) in COVID-19 patients. This receptor maintains mucosal homeostasis by transporting the dimeric IgA (dIgA) and pentameric IgM (pIgM) across mucosal epithelial cells to neutralize the invading respiratory pathogens. By studying the interaction between pIgR and SARS-CoV-2 proteins, we discovered that the viral accessory protein Open Reading Frame 8 (ORF8) potently downregulates pIgR expression and that this downregulation activity of ORF8 correlates with its ability to interact with pIgR. Importantly, the ORF8-mediated downregulation of pIgR diminishes the binding of dIgA or pIgM, and the ORF8 proteins of the variants of concern of SARS-CoV-2 preserve the function of downregulating pIgR, indicating the importance of this conserved activity of ORF8 in SARS-CoV-2 pathogenesis. We further observed that the secreted ORF8 binds to cell surface pIgR, but that this interaction does not trigger the cellular internalization of ORF8, which requires the binding of dIgA to pIgR. These findings suggest the role of ORF8 in SARS-CoV-2 mucosal immune evasion.

Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients.

We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO.

The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection.

Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2.

This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE.

This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection.

This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19.

Concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios predict prognosis and the need for oxygen therapy in patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aims of the present study were to evaluate the changes of these biomarkers early in the course of infection, the association with the prior coronavirus disease (COVID-19) vaccination and therapeutic administration of Anti-SARS-CoV-2 monoclonal antibodies, investigation of other potential biomarkers including neuropilin, 8-hydroxy-2-deoxyguanosine and 8-hydroxyguanosine in patients hospitalized with SARS-CoV-2 infection and an assessment of these biomarkers and vitamins A, E and D in patients with post-COVID syndrome.

Urine and blood samples were obtained on the 1st to the 4th day and 4th to 7th day from 108 patients hospitalized with COVID-19. Chromatography tandem mass spectrometry methods were used to analyse neopterin, kynurenine, tryptophan, liposoluble vitamins, and DNA damage biomarkers.

A statistically significant decrease of neopterin, kynurenine and kynurenine/tryptophan ratios was observed on after 4th to 7th day of hospitalization, and concentrations of these biomarkers were increased in patients with poor prognosis and subsequent post-COVID syndrome. The concentrations of remaining biomarker and vitamins were not associated with outcomes, although markedly decreased concentrations of vitamin A, E and D were noted.

The concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios decrease during the course of infection SARS-CoV-2 and are associated with the post-COVID syndrome. No other prognostic biomarkers were identified.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

Background/Objective: Bearing in mind the relationship of transferrin (TRF) microheterogeneity with the biological activity of its isoforms, we propose, in this study, to determine the association of the profile of TRF isoforms with COVID-19 disease severity and to compare this profile to the profiles of other diseases. Methods: The disease group consisted of 96 patients from whom blood was collected twice, upon admission to the ward and after treatment (on average on the ninth day). TRF isoforms were separated by capillary electrophoresis. The analysis included disease severity, cytokine storm, comorbidities, patient survival, oxygen therapy, and modified early warning scores (MEWSs). Results: The concentration of 5-sialoTRF was higher in patients compared to controls at the beginning and during COVID-19 treatment. The concentration of this isoform varies with the severity of disease and was higher in critical patients than those with a moderate condition. Additionally, the level of 5-sialoTRF was lower and the level of 4-sialoTRF was higher in patients with comorbidities than that in patients without them. The concentration of 5-sialoTRF was lower and the concentration of 4-sialoTRF was higher in surviving patients than in non-surviving patients. There were no statistical changes in TRF isoforms according to presence of cytokine storm, MEWS, and oxygen therapy. Conclusions: We conclude that the profile of TRF isoforms in COVID-19 patients differs from that in other diseases. An increase in the concentration of a sialic acid-rich isoform, 5-sialoTRF, may be a compensatory mechanism, the goal of which is to increase oxygen delivery to tissues and is dependent on the severity of the disease. Additionally, the concentration of 5-sialoTRF may be a prognostic marker of the survival of COVID-19 patients.

DNA vaccines can be a potential solution to protect global health, triggering both humoral and cellular immune responses. DNA vaccines are valuable in preventing intracellular pathogen infections, and therefore can be explored against coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). This work explored different systems based on polyethylenimine (PEI), functionalized for the first time with both cholesterol (CHOL) and mannose (MAN) to deliver parental plasmid (PP) and minicircle DNA (mcDNA) vectors encoding the receptor-binding domain (RBD) of SARS-CoV-2 to antigen-presenting cells (APCs). For comparative purposes, three different systems were evaluated: PEI, PEI-CHOL and PEI-CHOL-MAN. The systems were prepared at various nitrogen-to-phosphate group (N/P) ratios and characterized in terms of encapsulation efficiency, surface charge, size, polydispersity index (PDI), morphology, and stability over time. Moreover, in vitro transfection studies of dendritic cells (JAWS II) and human fibroblast cells were performed. Viability studies assured the biocompatibility of all nanocarriers. Confocal microscopy studies confirmed intracellular localization of systems, resulting in enhanced cellular uptake using PEI-CHOL and PEI-CHOL-MAN systems when compared with the PEI system. Regarding the RBD expression, PEI-CHOL-MAN was the system that led to the highest levels of transcripts and protein expression in JAWS II cells. Furthermore, the nanosystems significantly stimulated pro-inflammatory cytokines production and dendritic cell maturation in vitro. Overall, mannosylated systems can be considered a valuable tool in the delivery of plasmid DNA or mcDNA vaccines to APCs.

COVID-19 has been notoriously unpredictable in its clinical course. Such unpredictability poses a challenge to clinicians in predicting patients who will develop severe cases and possibly die from the infection. This study aims to assess and compare the diagnostic value of the NLR and SII as biomarkers in predicting COVID-19 severity, represented by mortality, with a multicentre comparative study including 855 patients in Saudi Arabia. Descriptive and analytical statistics were used to compare haematological indices between survivors and non-survivors. The median age of patients included was 41 years old, with an almost equal ratio of men to women. Most participants were Saudis, and the mortality rate in the study cohort was 13.22%. Non-survivors, as compared to survivors, were significantly older, had lower RBC counts, haemoglobin and haematocrit levels, as well as significantly higher WBC and neutrophil counts. Both the NLR and SII were capable of differentiating between survivors and non-survivors, with the latter having significantly higher values. However, the NLR was superior to the SII in such differentiation, as it had a larger area under the curve. This study further confirms the diagnostic values of the NLR and SII as biomarkers in predicting COVID-19 severity and mortality, with the NLR being more sensitive and specific. Clinical guidelines on managing COVID-19 cases should benefit from these findings by harnessing the value of the NLR in COVID-19 management.

This study aimed to characterize the changes in serum inflammatory mediators in hospitalized patients with COVID-19 correlating with death. The study includes 58 participants: i) inpatients (n = 37): patients suffering from severe acute respiratory syndrome due to COVID-19, who were admitted at Intensive Care Unit (ICU) recovered and who died and ii) control group (n = 21): community volunteers. Inflammatory mediators evaluated interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-17 (IL-17), interferon-gamma (IFN-γ) and interferon-gamma protein levels (IFN-γ), as well as, Urea, LDH, D-dimer, TAP/INR, AST, ALT and lymphocytes. Our results suggest that high levels of inflammatory markers, such as pro-inflammatory cytokines, and laboratory parameters, such as low levels of lymphocytes and high levels of IL-6, are associated with disease severity, especially in individuals who died. Constant measurement and monitoring of these inflammatory parameters is an effective tool in clinical practice, and it can help choosing appropriate therapies during the course of the disease.

Sixty patients with COVID-19 infection were categorized into mild and severe groups, and their immune response was analyzed using flow cytometry and complete blood count. An observed increase in immune activation parameters, notably a higher percentage of CD4 lymphocytes co-expressing CD69 and CD25 molecules, and enhanced activity of the macrophage-monocyte cell line was noted in the mild group. Although Group 2 (severe COVID) had fewer CD4 cells, significant migration and proliferation were evident, with increased CD4CD69, CD8 HLA-DR+, and CD8CD69 lymphocytes. The CD4 to CD8 ratio in Group 1 suggested potential autoimmune reactions, while Group 2 indicated potential immunosuppression from severe infection and employing immunosuppressive drugs. Additionally, Group 2 exhibited an increased neutrophil count, hinting at possible bacterial co-infection. Group 1 showed differences in CD4RO and CD8RA lymphocyte populations, implying that cellular immunity plays a role in developing efficient postinfectious immunity. This intimation suggests that vaccination might mitigate the severity of the coronavirus infection and prevent complications, including long-term COVID-19.

The COVID-19 pandemic has left a lasting impact on global health, challenging communities, healthcare systems, and researchers worldwide. As we navigate this unprecedented crisis, this paper embarks on a multifaceted exploration of the pivotal role played by natural killer (NK) cells in the context of COVID-19. A significant portion of this paper is devoted to dissecting the nuanced role that NK cells assume in the context of COVID-19. From the initial acute infection to post-recovery immunity, NK cells emerge as critical players. We scrutinize the activation and dysregulation of NK cells during SARS-CoV-2 infection, shedding light on their potential contribution to disease severity. Moreover, we explore the fascinating landscape of post-COVID immunity, where NK cells are known to interact with adaptive immune responses, providing a foundation for long-term protection. In light of their central role, we investigate therapeutic strategies targeting NK cells in COVID-19 management, presenting an overview of current research efforts and their promise in mitigating disease progression. Lastly, we draw attention to research gaps, emphasizing the need for further investigation into NK cell dynamics during COVID-19. These gaps represent opportunities for advancing our understanding of NK cell biology and, by extension, enhancing our strategies for combating this global health crisis. This comprehensive exploration not only highlights the intricate interplay between NK cells and the COVID-19 pandemic but also underscores the importance of these innate immune warriors in shaping both the acute response and long-term immunity, ultimately contributing to the broader discourse surrounding the pandemic's pathophysiology and therapeutic approaches.

COVID-19 pneumonia is associated with SIRS and hypercatabolism. The aim of this study was to determine muscle loss during the acute phase of COVID-19 pneumonia and evaluate long-term sequelae in discharged patients.

A total of 16 patients with COVID-19 pneumonia and respiratory insufficiency were included in the study. Selected parameters (weight, BMI, LBM = lean body mass, albumin, CRP, NLR = neutrophil-to-lymphocyte ratio, ultrasound measured thickness of rectus femoris muscle = US RF and rectus femoris + vastus intermedius = US RF + VI, handgrip strength, quality of life = EQ-5D questionnaire, and activities of daily living = Barthel's ADLs) were recorded on admission, discharge, and 1, 3, and 6 months after discharge.

The most significant changes were between hospital admission and discharge: US RF and RF + VI (-1.28 ± 1.97 mm, p = 0.046; -1.76 ± 2.94 mm, p = 0.05), EQ-5D score (14.6 ± 19.2, p = 0.02), and ADLs (17.1 ± 22.6; p = 0.02). There was a significant positive correlation between US RF + VI and handgrip strength (p = 0.014) and a negative correlation between weight and Barthel index (p = 0.012). There was an association between muscle function with an EQ-5D score and ADLs during outpatient check-ups, most noticeably between handgrip strength, US RF+VI, and ADLs (p = 0.08; p = 0.1, respectively). Conclusions: In patients with COVID-19 pneumonia, there is a significant reduction of health-related quality of life, impaired even 6 months after hospital discharge, influenced mainly by muscle loss. During the hospital stay, there was a significant muscle mass reduction. Ultrasound measurement of thigh muscle thickness may be a useful method to monitor muscle loss.

Information on the performance of oxygenation indices (OIs) and risk scores in patients requiring invasive mechanical ventilation (IMV) is limited. We determine the performance of the OIs and risk scores in hospitalized patients with COVID-19 to predict the requirement of IMV and death at 28 days after admission.

A retrospective study of diagnostic tests in patients admitted to the emergency department, hospitalization, and intensive care unit diagnosed with COVID-19. The receiver operating characteristic curve (ROC-curve) were built with the OIs and risk scores to predict IMV and mortality.

A total of 1402 subjects entered the final analysis, of whom 19.5% (274/1402) received IMV and 23.0% (323/1402) died at 28 days. The ROC-curve of the delta PaO2/FiO2 ratio for the requirement of IMV and mortality at 28-day was 0.589 (95% CI: 0.546-0.632) and 0.567 (95% CI: 0.526-0.608), respectively. PaO2/FiO2 ≤ 300 shows a ROC curve of 0.669 (95% CI: 0.628-0.711) to predict IMV. PaO2/FiO2 ≤ 300 and 4 C mortality score in mortality at 28 days showed an ROC-curve of 0.624 (95% CI: 0.582-0.667) and 0.706 (95% CI: 0.669-0.742), respectively.

PaO2/FiO2 ≤ 300, 4 C mortality score ≥ 8, SOFA score ≥ 4 y SaO2/FiO2 ≤ 300 were weak predictors of the IMV requirement from admission, and 4 C mortality score ≥ 8 was weak predictors of the mortality from admission in patients with pulmonary involvement by COVID-19.

COVID-19 is a severe infectious disease caused by a SARS-CoV-2 infection. It has caused a global pandemic and can lead to acute respiratory distress syndrome (ARDS). Beyond the respiratory system, the disease manifests in multiple organs, producing a spectrum of clinical symptoms. A pivotal factor in the disease's progression is autoimmunity, which intensifies its severity and contributes to multi-organ injuries. The intricate interaction between the virus' spike protein and human proteins may engender the generation of autoreactive antibodies through molecular mimicry. This can further convolute the immune response, with the potential to escalate into overt autoimmunity. There is also emerging evidence to suggest that COVID-19 vaccinations might elicit analogous autoimmune responses. Advanced technologies have pinpointed self-reactive antibodies that target diverse organs or immune-modulatory proteins. The interplay between autoantibody levels and multi-organ manifestations underscores the importance of regular monitoring of serum antibodies and proinflammatory markers. A combination of immunosuppressive treatments and antiviral therapy is crucial for managing COVID-19-associated autoimmune diseases. The review will focus on the generation of autoantibodies in the context of COVID-19 and their impact on organ health.

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. It is essential to explore the immune response characteristics of peripheral circulation in COVID-19 patients to reveal pathogenesis and predict disease progression. In this study, the levels of total immunoglobulins (IgG, IgM, IgA), complement (C3, C4)，lymphocyte subsets (CD3+ cell，CD4+ cell，CD8+ cell, NK cell, CD19+ cell and CD45+ cell) and cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-12p, IL-1β, TNF-α, IFN-α and IFN-γ) were retrospectively analyzed in COVID-19 patients. A total of 513 patients were enrolled in this study, cases were distributed according to clinical status as mild or moderate (n = 212), severe survivors (n = 197) and severe non-survivors (n = 104). IL-6, IL-8, IL-10 and IFN-γ were increased in severe patients compared with non-severe patients, despite decreased CD45+ cell, CD3+ cell, CD4+ cell, CD8+ cell, CD19+ cell, and NK cell. Compared with severe survivors, the levels of L-6, IL-8 and IL-10 in non-survivors increased significantly, and levels of C3, CD45+ cell, CD3+ cell，CD4+ cell，CD8+ cell, and NK cell decreased. Moreover, age, IL-8, IL-10, CD8+cells and NK cell were independent risk factors for the severity of COVID-19. Multivariable regression showed increasing odds ratio of in-hospital death associated with tumor, older age, higher IL-8 level, and decreasing odds ratio of in-hospital death associated with increased levels of CD8+cell and NK cell. Finally, patients with tumor, or high IL-6 or high IL-10 expression and lower CD8+ or lower NK levels exhibited a significantly shorter survival time. In conclusion, our study provides findings of the immunological characteristics associated with disease severity to predict the progression of COVID-19. The immune inflammation factors, such as IL-6, IL-8, IL-10, CD8+ cell and NK cell, could serve as excellent biomarkers for monitoring or predicting COVID-19 progression therapeutic to COVID-19 patients.