Tuberculosis (TB), a leading cause of death from infectious diseases, faced considerable challenges during the coronavirus disease 2019 (COVID-19) pandemic. This review examines the impact of pandemic-related disruptions, including the diversion of healthcare resources, reduced access to TB diagnostics and treatment, and declining BCG vaccination rates, on TB trends. The aim is to forecast the post-COVID-19 TB burden, identify risk factors that exacerbate transmission, and propose strategies to prevent a global resurgence.

This narrative review incorporates epidemiological data, modeling research, and reports from the World Health Organization and national health systems. It examines TB trends before and after COVID-19, the outcomes of coinfection, and the pandemic's impact on immunology, socioeconomic factors, and health systems. The review also compares trends in India and South Africa-two countries facing significant challenges-to those observed during the COVID-19 pandemic.

COVID-19 disruptions in healthcare led to an 18% decrease in TB notifications in 2020, resulting in delayed diagnoses, increased household transmission, and higher mortality. Immune dysregulation, including T-cell depletion and cytokine storms, contributed to a 12.3% mortality rate in COVID-19-TB coinfections. Models predict a 5%-15% rise in TB incidence and an additional 1.4 million deaths by 2025. Individuals with HIV, diabetes, and malnutrition were particularly vulnerable. Factors such as overcrowding, air pollution, and reduced Bacillus Calmette-Guérin (BCG) coverage in endemic regions have further heightened susceptibility to TB.

COVID-19 has undone years of progress in TB control, highlighting the need for a unified health strategy. Early diagnosis, treatment of latent TB, and BCG catch-up initiatives are crucial. Strengthening health systems, addressing socioeconomic factors such as poverty and hunger, and utilizing pandemic advancements like telemedicine and vaccine research will be key to preventing a resurgence of TB. Continued financial support and international cooperation are essential to eliminating TB by 2030.

Monkeypox (Mpox) is a major global human health threat after COVID-19. Its treatment becomes complicated with type-2 diabetes (T2D). It may happen due to the influence of both disease-causing common host key genes (cHKGs). Therefore, it is necessary to explore both disease-causing cHKGs to reveal their shared pathogenetic mechanisms and candidate drugs as their common treatments without adverse side effect. This study aimed to address these issues. At first, 3 transcriptomics datasets for each of Mpox and 6 T2D datasets were analyzed and found 52 common host differentially expressed genes (cHDEGs) that can separate both T2D and Mpox patients from the control samples. Then top-ranked six cHDEGs (HSP90AA1, B2M, IGF1R, ALD1HA1, ASS1, and HADHA) were detected as the T2D-causing cHKGs that are associated with the complexity of Mpox through the protein-protein interaction network analysis. Then common pathogenetic processes between T2D and Mpox were disclosed by cHKG-set enrichment analysis with biological processes, molecular functions, cellular components and Kyoto Encyclopedia of Genes and Genomes pathways, and regulatory network analysis with transcription factors and microRNAs. Finally, cHKG-guided top-ranked three drug molecules (tecovirimat, vindoline, and brincidofovir) were recommended as the repurposable common therapeutic agents for both Mpox and T2D by molecular docking. The absorption, distribution, metabolism, excretion, and toxicity and drug-likeness analysis of these drug molecules indicated their good pharmacokinetics properties. The 100-ns molecular dynamics simulation results (root mean square deviation, root mean square fluctuation, and molecular mechanics generalized born surface area) with the top-ranked three complexes ASS1-tecovirimat, ALDH1A1-vindoline, and B2M-brincidofovir exhibited good pharmacodynamics properties. Therefore, the results provided in this article might be important resources for diagnosis and therapies of Mpox patients who are also suffering from T2D.

This study aims to identify early warning indicators of COVID-19 severity by integrating modern medical biomarkers with traditional Chinese medicine (TCM) tongue features.

A retrospective observational study was conducted on 409 hospitalized COVID-19 patients from two centers in China. Patients were stratified into severe (n = 50) and non-severe (n = 359) groups based on the 10th edition of China's diagnostic guidelines. Data included demographics, clinical symptoms, tongue characteristics, and laboratory parameters. Univariate analyses (chi-square/Fisher's exact tests) and stepwise logistic regression were performed to identify key predictors.

Age (p < 0.001), fever (p < 0.001), elevated procalcitonin (PCT, p < 0.001), thick tongue fur (p = 0.003), and fat tongue shape (p = 0.002) were significant predictors of severity. The combined model integrating these factors demonstrated superior predictive performance (Nagelkerke R 2 = 0.741).

Integrating TCM tongue features (thick fur and fat shape) with clinical biomarkers (age, fever, and PCT) enhances early identification of severe COVID-19, particularly in resource-limited settings.

Actinomycosis and mucormycosis are rare infections, and their coexistence in a single host is extremely uncommon. Actinomycosis of the trachea is a chronic septic condition caused by actinomycete infection, often misdiagnosed due to the difficulty of obtaining microbiological evidence. Mucormycosis, an invasive fungal infection, is characterised by rapid progression and high mortality, commonly occurring in immunocompromised patients. A 58-year-old woman with poorly controlled diabetes presented with a whitish mass in the main bronchus, identified via bronchoscopy. Pathological biopsy confirmed actinomycosis with mucormycosis. After treatment with cryotherapy, Holmium Laser, amphotericin B, and penicillin, she was successfully discharged. When imaging suggests intratracheal lesions, early bronchoscopy and etiological investigation are crucial to avoid misdiagnosis.

COVID-19, caused by SARS-CoV-2, has emerged as a global pandemic since its outbreak in 2019. As an increasing number of variants have emerged, especially concerning variants such as Omicron BA.1, BA.2, XBB.1, EG.5, which can escape the immune system and cause repeated infections, they have exerted significant pressure on monoclonal antibodies and the treatment approaches for COVID-19. Broad spectrum antiviral medication was urgently needed. In this study, we developed several bispecific antibodies based on the IgG-scFv format and one trispecific antibody containing Fab fragments with different anti-virus mechanisms studied previously. The Fab fragments are from h11B11, S2P6, and S309 respectively.

all recombinant antibodies were expressed by HEK 293. The pseudoviruses' neutralization assay and the virus challenge to BALB/c mice were deployed to assess the efficiency of recombinant antibodies in vitro and in vivo.

the bispecific antibodies exhibited a favorable pseudoviruses neutralization activity, with IC50 values ranging from 8 to 591 ng/mL. The trispecific antibody performed even better, with IC50 values ranging from 5 to 27 ng/mL. Furthermore, the virus challenge to mice confirmed that the bispecific antibodies, including the trispecific antibody, had decent therapeutic efficacy.

our study provided several supplements to the therapeutic measures of COVID-19 based on multispecific antibodies, supporting the great potential of the multispecific antibodies strategy in dealing with emerging pathogens.

Diabetes mellitus (DM) is recognized and classified as a group of conditions marked by persistent high blood glucose levels. It is also an inflammatory condition that may influence concurrent disease states, including Coronavirus Disease 2019 (COVID-19). Currently, no effective drug has been found to treat COVID-19, especially in DM patients. Many herbal medicines, such as the well-known Andrographis paniculata, have been explored as drugs and complementary therapies due to their antidiabetic, antibacterial, antiviral, anti-inflammatory, and immunomodulatory effects. This study aimed to examine the potential of herbal medicines as complementary therapy in DM patients with COVID-19 complications, drawing from in-vitro and in-vivo investigations. This study analyzed articles published within the last 15 years using keywords including "herbal medicines", "COVID-19", "Diabetes Mellitus", "antidiabetics", "antiviral", and "anti-inflammatory". The results showed that several herbal medicines could serve as complementary therapy for DM patients with COVID-19 complications. These include Andrographis paniculata, Ageratum conyzoides, Artocarpus altilis, Centella asiatica, Momordica charantia, Persea gratissima, Phyllanthus urinaria, Physalis angulata, Tinospora cordifolia, and Zingiber zerumbet. Herbal medicines may serve as a complementary therapy for DM patients with COVID-19, but these claims need experimental validation in infection models and among affected patients.

Yupingfeng powder (YPF) is a classic traditional Chinese medicine prescription with a long history of clinical application. However, there is a consensus on the clinical efficacy of YPF in the prevention and treatment of influenza, the underlying pharmacological mechanisms and functional substances have not been thoroughly investigated.

This study aimed to elucidate the functional substances and potential mechanisms of YPF against influenza infections by integrating network analysis, metabolomics, computational system pharmacology, and in vitro experiments.

In this study, the active ingredients, related targets, and potential mechanisms of YPF against influenza were identified through network pharmacology and GEO database mining. Combined with metabolomics to corroborate the results of network pharmacology analysis and construct C-T-P-D-M network. Based on this, the key network motifs (KNM) with significance were predicted by system pharmacology algorithm. Finally, the key components as functional substances in the KNM were validated by the coverage of influenza-causing genes and functional pathways, and in vitro experiments.

A total of 238 active components and 158 potential target genes intersecting with influenza infection differential genes were screened from YPF. KEGG enrichment analysis indicated that metabolism participated in YPF-provided prevention and treatment on influenza, and metabolomic results further corroborated the significance of the metabolic pathways intervened by YPF included pyruvate metabolism, Valine, leucine and isoleucine degradation, etc. The KNM prediction strategy was computed to include wogonin and isoimperaporin, a group of 48 potential functional components. This functional component group maintained a high degree of consistency with the corresponding C-T network in terms of the coverage of influenza pathogenic genes, and the coverage of functional pathways. Meanwhile, the in vitro results showed that wogonin and isoimperaporin had significant inhibitory effects on inflammation induced by influenza infection, confirming the reliability and accuracy of the KNM prediction strategy.

YPF against influenza has multi-target and multi-pathway effects, and the underlying mechanisms may be related to metabolism. The pharmacodynamic effects of core components such as wogonin and isoimperaporin on influenza prevention and treatment were confirmed, which represent promising functional candidates for subsequent influenza prevention and treatment, and provide references for the pharmacological and mechanistic analyses of subsequent formulas.

To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control.

Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM).

It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia.

Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.

The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era has been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship.

A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status.

The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB in people with DM was 2.7-fold higher among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19.

DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in past COVID-19 persons with DM. Future studies are warranted with a longitudinal design and larger sample size to confirm our findings.

As of the 7th of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15th of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.

The emergence of a new pandemic SARS-CoV-2 (COVID-19) resulted in a high mortality rate across the world. This study sought to comprehensively analyze the Case Fatality Rate (CFR) associated with COVID-19 in the Khuzestan province of Iran". The primary objective was to discern patterns and determinants influencing CFR, shedding light on the evolving impact of the pandemic on morbidity and mortality.

A retrospective examination was performed on a dataset encompassing confirmed COVID-19 cases and related fatalities in Khuzestan. Data, spanning from December 2020 to April 2022, underwent rigorous statistical analysis. Demographic variables, comorbidities, and temporal trends were scrutinized to identify key factors influencing CFR.

Preliminary findings revealed dynamic shifts in CFR, capturing the nuanced nature of the pandemic over time. Demographic nuances, particularly age and gender, emerged as significant determinants impacting CFR, the reported CFR of COVID-19 in Khuzestan province was 1.79%.

This study contributes critical insights into the CFR landscape of COVID-19 in Khuzestan, providing a foundation for evidence-based decision-making in public health. The identified factors influencing mortality rates offer valuable information for tailoring interventions and optimizing resource allocation. Continuous monitoring and further investigations are recommended to adapt strategies to the evolving nature of the pandemic.

Emerging evidence describes the high incidence and strong impact of hyperglycemia on the outcomes of critically ill patients with a diagnosis of COVID-19. Given resource limitations during the COVID-19 pandemic, clinicians moved away from using continuous IV infusions of insulin to manage hyperglycemia.

To evaluate glycemic control in critically ill patients receiving various medication regimens to manage their hyperglycemia.

This retrospective cohort study involved 120 mechanically ventilated adult patients (> 18 years) with COVID-19 who were admitted to the intensive care unit (ICU) between February 2020 and December 2021. The following data were collected for the first 14 days of the ICU admission: blood glucose values (up to 4 times daily), hypoglycemia events, and antihyperglycemic medication regimens.

The use of IV insulin infusions maintained glucose measurements within the target range of 4 to 10 mmol/L more often than any other medication regimen, with 60% of measured values falling within the target range. The use of a sliding-scale insulin regimen maintained 52% of glucose measurements within the target range. Oral hypoglycemic agents performed relatively poorly, with only 12% to 29% of glucose measurements within range. The coadministration of corticosteroids led to worse glycemic control across all medication regimens.

This study confirmed that ICUs should continue using the standard protocol of IV insulin infusion to achieve recommended blood glucose targets in critically ill patients with COVID-19, particularly those receiving corticosteroids.

The prolonged period of COVID-19 has ingrained physical inactivity as a habit, leading to a reluctance to move. This has resulted in a decline in physical fitness and the loss of a healthy body composition. While this trend is particularly noticeable among the older adults, its impact on the immune cell defense system, which is crucial for minimizing viral infections, remains unclear. This study aimed to investigate the physical fitness, body composition, cytokines and immunocytes of older adults who engaged in physical activity (PA) before the COVID-19 pandemic but had to stop it due to the lockdown. A total of 172 older adults aged 61 to 85 years participated in this study: 90 in non-PA group (NPAG, 34 men and 56 women), and 82 in PA group (PAG, 29 men and 53 women). Physical inactivity was 45.13 ± 5.67 weeks in the NPAG and 1.70 ± 0.43 weeks in the PAG. Although there was no significant difference in calorie intake, PA volume showed a significant decrease in NPGA (P < 0.001). VO₂max, strength, and sit-ups decreased in NPAG, whereas they maintained or increased in PAG (Ps < 0.001). NPAG experienced an increase in fat mass (∼33.0 %), along with a decrease in muscle mass (∼10.4 %), but PAG showed slight increases (∼1.1 % vs. ∼1.5 %, Ps < 0.001). Interleukin-6 (∼38.9 %), tumor necrosis factor-α (∼38.3 %), and C-reactive protein (∼33.6 %) increased, whereas immunocytes decreased in NPAG (Ps < 0.001). In contrast, those in PAG showed the opposite phenomenon. This study indicates that even during the COVID-19 situation, maintaining active PA in the older adults helps retain beneficial physical fitness and body composition, reduces inflammatory factors, and contributes to preserving or enhancing the function of immunocytes.

Diabetes has become one of the most prevalent global epidemics, significantly impacting both the economy and the health of individuals. Diabetes is associated with numerous complications, such as obesity; hyperglycemia; hypercholesterolemia; dyslipidemia; metabolic endotoxemia; intestinal barrier damage; insulin-secretion defects; increased oxidative stress; and low-grade, systemic, and chronic inflammation. Diabetes cannot be completely cured; therefore, current research has focused on developing various methods to control diabetes. A promising strategy is the use of probiotics for diabetes intervention. Probiotics are a class of live, non-toxic microorganisms that can colonize the human intestine and help improve the balance of intestinal microbiota. In this review, we summarize the current clinical studies on using probiotics to control diabetes in humans, along with mechanistic studies conducted in animal models. The primary mechanism by which probiotics regulate diabetes is improved intestinal barrier integrity, alleviated oxidative stress, enhanced immune response, increased short-chain fatty acid production, etc. Therefore, probiotic supplementation holds great potential for the prevention and management of diabetes.

Diabetes mellitus (DM) leads to impaired innate and adaptive immune responses. This renders individuals with DM highly susceptible to microbial infections such as COVID-19, tuberculosis and melioidosis. Melioidosis is a tropical disease caused by the bacterial pathogen Burkholderia pseudomallei, where diabetes is consistently reported as the most significant risk factor associated with the disease. Type-2 diabetes is observed in 39% of melioidosis patients where the risk of infection is 13-fold higher than non-diabetic individuals. B. pseudomallei is found in the environment and is an opportunistic pathogen in humans, often exhibiting severe clinical manifestations in immunocompromised patients. The pathophysiology of diabetes significantly affects the host immune responses that play a critical role in fighting the infection, such as leukocyte and neutrophil impairment, macrophage and monocyte inhibition and natural killer cell dysfunction. These defects result in delayed recruitment as well as activation of immune cells to target the invading B. pseudomallei. This provides an advantage for the pathogen to survive and adapt within the immunocompromised diabetic patients. Nevertheless, knowledge gaps on diabetes-infectious disease comorbidity, in particular, melioidosis-diabetes comorbidity, need to be filled to fully understand the dysfunctional host immune responses and adaptation of the pathogen under diabetic conditions to guide therapeutic options.

The effect of COVID-19 on the occurrence of type 1 diabetes and ketoacidosis in children and adolescent.

In this descriptive-analytical cross-sectional study, the records of all children and adolescents hospitalized due to type1 diabetes for two years ago and during the COVID-19 pandemic and its peaks were investigated (January 2018-2022). Also, the desired variables including the frequency of hospitalized patients (known and new cases), the frequency of DKA, the severity of DKA, the duration of discharge from DKA, age, body mass index, duration of hospitalization, clinical symptoms including cerebral edema, laboratory data and the total daily dose insulin required at the time of discharge were compared and statistically analyzed.

Out of the 334 hospitalized T1DM patients, the rate of new T1DM patients was significantly higher (P = 0.006) during the pandemic. Clearly, there were more cases of DKA during the pandemic (P = 0.007). The higher severity of DKA (0.026) and the need for higher doses of insulin (P = 0.005) were also observed. The hospitalization rate was higher during the corona peaks, particularly peaks 1 and 4, compared to the non-peak days of COVID-19.

The increase in the incidence of diabetes (new cases) in the pandemic can suggest the role of the COVID-19 virus as an igniter. Also, as a trigger for the higher incidence of DKA with higher severities, which is probably caused by more damage to the pancreatic beta cells and requires higher doses of insulin.

Background Some studies suggest that the SARS-CoV-2 pandemic has contributed to diverting attention from other community-acquired infections (CAIs), leading to an increase in their incidence and severity. Our study aimed to describe and compare clinical features of CAI before and during the pandemic as a factor precipitating diabetes ketoacidosis (DKA). Methodology We included 250 patients who presented with DKA due to CAIs, other than SARS-CoV-2, divided into two distinct groups: 100 patients (G1) who consulted two years before the pandemic, and 150 patients (G2) who consulted during the SARS-CoV-2 pandemic. Cases in both groups were matched for age and type and duration of diabetes. Primary outcomes were a longer diagnosis delay and more severe DKA in G2 during the pandemic. Secondary outcomes included blood test results, duration of ketosis, duration of antibiotic therapy, and diabetes treatment. Results The diagnosis and treatment delays were longer for patients seeking medical care during the pandemic (p < 0.001). The duration of DKA was also significantly longer in the G2 group (p = 0.007). During the pandemic, patients' blood tests showed more anomalies with higher glycated hemoglobin (p = 0.02), C-reactive protein (p = 0.001), and lymphocytosis (p = 0.016). The duration of antibiotic therapy was also significantly longer in G2 (p = 0.01). Conclusions This study showed the impact of the COVID-19 pandemic on the management of diseases other than SARS-CoV-2. Indeed, several factors played a part in the increased incidence of CAIs, which were more severe than in the pre-pandemic period. These included fear of contagion, confinement, and physicians' preoccupation with the pandemic.

COVID-19 and bacterial/fungal coinfections have posed significant challenges to human health. However, there is a lack of good tools for predicting coinfection risk to aid clinical work.

We aimed to investigate the risk factors for bacterial/fungal coinfection among COVID-19 patients and to develop machine learning models to estimate the risk of coinfection.

In this retrospective cohort study, we enrolled adult inpatients confirmed with COVID-19 in a tertiary hospital between January 1 and July 31, 2023, in China and collected baseline information at admission. All the data were randomly divided into a training set and a testing set at a ratio of 7:3. We developed the generalized linear and random forest models for coinfections in the training set and assessed the performance of the models in the testing set. Decision curve analysis was performed to evaluate the clinical applicability.

A total of 1244 patients were included in the training cohort with 62 healthcare-associated bacterial/fungal infections, while 534 were included in the testing cohort with 22 infections. We found that patients with comorbidities (diabetes, neurological disease) were at greater risk for coinfections than were those without comorbidities (OR = 2.78, 95%CI = 1.61-4.86; OR = 1.93, 95%CI = 1.11-3.35). An indwelling central venous catheter or urinary catheter was also associated with an increased risk (OR = 2.53, 95%CI = 1.39-4.64; OR = 2.28, 95%CI = 1.24-4.27) of coinfections. Patients with PCT > 0.5 ng/ml were 2.03 times (95%CI = 1.41-3.82) more likely to be infected. Interestingly, the risk of coinfection was also greater in patients with an IL-6 concentration < 10 pg/ml (OR = 1.69, 95%CI = 0.97-2.94). Patients with low baseline creatinine levels had a decreased risk of bacterial/fungal coinfections(OR = 0.40, 95%CI = 0.22-0.71). The generalized linear and random forest models demonstrated favorable receiver operating characteristic curves (ROC = 0.87, 95%CI = 0.80-0.94; ROC = 0.88, 95%CI = 0.82-0.93) with high accuracy, sensitivity and specificity of 0.86vs0.75, 0.82vs0.86, 0.87vs0.74, respectively. The corresponding calibration evaluation P statistics were 0.883 and 0.769.

Our machine learning models achieved strong predictive ability and may be effective clinical decision-support tools for identifying COVID-19 patients at risk for bacterial/fungal coinfection and guiding antibiotic administration. The levels of cytokines, such as IL-6, may affect the status of bacterial/fungal coinfection.

To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA).

This study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score.

911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11-16 % per morbidity in the three models.

Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by high blood glucose levels, impairing glucose production in the body. Its prevalence has steadily risen over the past decades, leading to compromised immunity and heightened susceptibility to microbial infections. Immune dysfunction associated with diabetes raises vulnerability, while neuropathy dulls sensation in the extremities, reducing injury awareness. Hence, the development of novel chemical compounds for anti-diabetic and anti-infective treatments is imperative to mitigate adverse effects. In this study, we designed and synthesized pyrimidine-based carbocyclic nucleoside derivatives with C-4 substitution to assess their potential in inhibiting α-glucosidase for managing diabetes mellitus (DM) and microbial infections. Compounds 8b and 10a displayed promising IC50 values against α-glucosidase (43.292 nmol and 48.638 nmol, respectively) and noteworthy docking energies (-9.4 kcal mol-1 and -10.3 kcal mol-1, respectively). Additionally, compounds 10a and 10b exhibited better antimicrobial activity against Bacillus cereus, with the zone of inhibition values of 2.2 ± 0.25 mm and 1.4 ± 0.1 mm at a 100 μl concentration, respectively. Compound 10a also exhibited a modest zone of inhibition of 1.2 ± 0.15 mm against Escherichia coli at 100 μl.

Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.

Diabetes is known to increase susceptibility to respiratory infections, but the underlying basis remains elusive. In a recent study in Nature, Nobs et al. showed that hyperglycemia impinges on the histone acetylation landscape to impair the ability of lung dendritic cells to prime adaptive immunity.

Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19.

The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China.

In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023.

There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94).

Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

The colorimetric detection of glucose typically involves a peroxidase reaction producing a color, which is then recorded and analyzed. However, enzyme detection has difficulties with purification and storage. In addition, replacing enzyme detection with chemical methods involves time-consuming steps such as centrifugation and purification and the optical instruments used for colorimetric detection are often bulky and not portable. In this study, ammonium metavanadate and sulfuric acid were used to prepare the detection solution instead of peroxidase to produce color. We also analyzed the effect of different concentrations of detection solution on absorbance sensitivity. Finally, a flip chip blue Mini-LEDs miniaturized optical instrument (FC blue Mini-LEDs MOI) was designed for glucose detection using optics fiber, collimating lenses, a miniaturized spectrometer, and an FC Blue Mini-LEDs with a center wavelength of 459 nm. While detecting glucose solutions in the concentration range of 0.1-10 mM by the developed MOI, the regression equation of y = 0.0941x + 0.1341, R2 of 0.9744, the limit of detection was 2.15 mM, and the limit of quantification was 7.163 mM. Furthermore, the preparation of the detection solution only takes 10 min, and the absorbance sensitivity of the optimized detection solution could be increased by 2.3 times. The detection solution remained stable with only a 0.6% decrease in absorbance compared to the original after storing it in a refrigerated environment at 3 °C for 14 days. The method proposed in this study for detecting glucose using FC blue light Mini-LEDs MOI reduces the use of peroxidase. In addition, it has a wide detection range that includes blood as well as non-invasive saliva and tear fluids, providing patients with a miniaturized, highly sensitive, and quantifiable glucose detection system.

The oral microbiome has long been considered a measure of overall systemic health. It is often significantly altered in case of chronic inflammation or any other systemic infection. Therefore, a shift in oral microbiota and oral health is bound to be observed in diabetics infected with the coronavirus. The prognosis of COVID-19 in a diabetic individual is often worse than that in a healthy individual. The increased pathogenicity of coronavirus in diabetics is due to the peculiar ways in which it interacts with specific physiological mechanisms in a diabetic patient and vice versa. Diabetes Mellitus Type-II (DM -II) is one of the most frequently associated co-morbidities in a COVID-19 patient, and therefore it is even more pertinent that their interrelationship is understood. It is essential to recognize the above-mentioned interactions and consider their implications while treating susceptible patients. This article attempts to review and summarize the said vital interactions. Additionally, it attempts to guide and prepare oral health professionals on what to expect and how to treat diabetic patients in a future where coronavirus is, as unfortunate as it is, a regularity and not a rarity.

The "diabetic lung" has been identified as a possible target organ in diabetes, with abnormalities in ventilation control, bronchomotor tone, lung volume, pulmonary diffusing capacity, and neuroadrenergic bronchial innervation.

This review summarizes studies related to diabetic pneumopathy, pathophysiology and a number of pulmonary disorders including type 1 and type 2 diabetes.

Electronic searches were conducted on databases such as Pub Med, Wiley Online Library (WOL), Scopus, Elsevier, ScienceDirect, and Google Scholar using standard keywords "diabetes," "diabetes Pneumopathy," "Pathophysiology," "Lung diseases," "lung infection" for review articles published between 1978 to 2023 very few previous review articles based their focus on diabetic pneumopathy and its pathophysiology.

Globally, the incidence of diabetes mellitus has been rising. It is a chronic, progressive metabolic disease. The "diabetic lung" may serve as a model of accelerated ageing since diabetics' rate of respiratory function deterioration is two to three-times higher than that of normal, non-smoking people.

Diabetes-induced pulmonary dysfunction has not gained the attention it deserves due to a lack of proven causality and changes in cellular properties. The mechanism underlying a particular lung illness can still only be partially activated by diabetes but there is evidence that hyperglycemia is linked to pulmonary fibrosis in diabetic people.

Patients with type 2 diabetes (T2D) are at an increased risk of morbidity and mortality of coronavirus disease 2019 (COVID-19). Data on the antibody response to COVID-19 vaccines in T2D patients are less studied. This study aimed to evaluate IgG antibody response to inactivated COVID-19 vaccines in hospitalized T2D patients. Hospitalized patients with no history of COVID-19 and received two doses of inactivated COVID-19 vaccines (Sinopharm or CoronaVac) were included in this study from March to October 2021. SARS-CoV-2 specific IgG antibodies were measured 14-60 days after the second vaccine dose. A total of 209 participants, 96 with T2D and 113 non-diabetes patients, were included. The positive rate and median titer of IgG antibody against receptor-binding domain (anti-RBD) of spike (S) protein of SARS-CoV-2 in T2D group were lower than in control group (67.7% vs 83.2%, p = .009; 12.93 vs 17.42 AU/ml, p = .014) respectively. Similarly, seropositivity and median titers of IgG antibody against the nucleocapsid (N) and S proteins of SARS-CoV-2 (anti-N/S) in T2D group were lower than in control group (68.8% vs 83.2%, p = .032; 18.81 vs 29.57 AU/mL, p = .012) respectively. After adjustment for age, sex, BMI, vaccine type, days after the second vaccine dose, hypertension, kidney disease, and heart disease, T2D was identified as an independent risk factor for negative anti-RBD and anti-N/S seropositivity, odd ratio 0.42 (95% confidence interval 0.19, 0.89) and 0.42 (95% CI 0.20, 0.91), respectively. T2D is associated with impaired antibody response to inactivated COVID-19 vaccine.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

This work provides an overview of young children's (aged 0-9) infectious diseases epidemiology, by exploring the link between various comorbid conditions, COVID-19, and death rate.

Public data on hospitalized young children was obtained from national databases of the Mexican health care system from 2020-2022. Data included age, year of entry, gender, the time between admission to death (hospitalization time), date of death, comorbidities, and admissions to the intensive care unit. Children were separated into age groups and frequencies were calculated. Binary regression models were developed to determine the correlation of comorbidities and COVID-19 to death as calculated by odds ratios (OR).

From 2020-2022, there were 11,815 hospitalizations among young children, of which 15.98% were due to COVID-19, 2.55% of hospitalizations resulted in fatalities from which 32.45% of deaths were COVID-19 related. The highest case-calculated fatality ratio of COVID-19 infected young children was estimated at 7.04% by early 2020, but dropped to 2.11% by the end of the second semester of 2022. The most frequent comorbidities associated with their hospitalization and death for the general population were intubation (OR: 17.967), pneumonia (OR: 2.263), diabetes (OR: 7.301), cardiovascular diseases (OR: 1.528) and COVID-19 (OR: 261). For the COVID-19-positive group, the most impactful comorbidities were intubation (OR: 20.232), pneumonia (OR: 3.057), and diabetes (OR: 12.824).

Children's hospitalizations and deaths were common during the pandemic; wherein major comorbidities played an important role. Therefore, effective comorbidity management and vaccination programs are essential to reduce hospitalizations and deaths among young children.

COVID-19 patients with comorbid DM face more severe outcomes, indicating that hyperglycemic conditions exacerbate SARS-CoV-2 infection. Negative side effects from existing hyperglycemia treatments have urged the need for safer compounds. Therefore, sourcing potential compounds from marine resources becomes a new potential approach. Algal lipids are known to possess beneficial activities for human health. However, due to limitations in analyzing large amounts of potential anti-hyperglycemic and anti-COVID-19-related marine metabolites, there is an increasing need for new approaches to reduce risks and costs. Therefore, the main aim of this study was to identify potential compounds in macroalgae Sargassum cristaefolium, Tricleocarpa cylindrica, and Ulva lactuca lipophilic extracts for treating DM and COVID-19 by an integrated approach utilizing in vitro anti-oxidant, in vivo anti-hyperglycemic, and metabolomic-integrated in silico approaches. Among them, S. cristaefolium and T. cylindrica showed potential anti-hyperglycemic activity, with S. cristaefolium showing the highest anti-oxidant activity. A GC-MS-based untargeted metabolomic analysis was used to profile the lipophilic compounds in the extracts followed by an in silico molecular docking analysis to examine the binding affinity of the compounds to anti-DM and anti-COVID-19 targets, e.g., α-amylase, α-glucosidase, ACE2, and TMPRSS2. Notably, this study reveals for the first time that steroid-derived compounds in the macroalgae T. cylindrica had higher binding activity than known ligands for all the targets mentioned. Studies on drug likeliness indicate that these compounds possess favorable drug properties. These findings suggest the potential for these compounds to be further developed to treat COVID-19 patients with comorbid DM. The information in this study would be a basis for further in vitro and in vivo analysis. It would also be useful for the development of these candidate compounds into drug formulations.

Diabetes mellitus (DM) is a chronic metabolic disorder that affects multiple organs and systems, including the pulmonary system. Pulmonary dysfunction in DM patients has been observed and studied for years, but the underlying mechanisms have not been fully understood. In addition to traditional mechanisms such as the production and accumulation of advanced glycation end products (AGEs), angiopathy, tissue glycation, oxidative stress, and systemic inflammation, recent studies have focused on programmed cell deaths (PCDs), especially the non-apoptotic ones, in diabetic pulmonary dysfunction. Non-apoptotic PCDs (NAPCDs) including autophagic cell death, necroptosis, pyroptosis, ferroptosis, and copper-induced cell death have been found to have certain correlations with diabetes and relevant complications. The AGE-AGE receptor (RAGE) axis not only plays an important role in the traditional pathogenesis of diabetes lung disease but also plays an important role in non-apoptotic cell death. In this review, we summarize novel studies about the roles of non-apoptotic PCDs in diabetic pulmonary dysfunction and focus on their interactions with the AGE-RAGE axis.

Diabetes mellitus (DM) is associated with severe forms of COVID-19 but little is known about the diabetes-related phenotype considering pre-admission, on-admission and data covering the entire hospitalization period.

We analyzed COVID-19 inpatients (n = 3327) aged 61.2(48.2-71.4) years attended from March to September 2020 in a public hospital.

DM group (n = 1218) differed from Non-DM group (n = 2109) by higher age, body mass index (BMI), systolic blood pressure and lower O2 saturation on admission. Gender, ethnicity and COVID-19-related symptoms were similar. Glucose and several markers of inflammation, tissue injury and organ dysfunction were higher among patients with diabetes: troponin, lactate dehydrogenase, creatine phosphokinase (CPK), C-reactive protein (CRP), lactate, brain natriuretic peptide, urea, creatinine, sodium, potassium but lower albumin levels. Hospital (12 × 11 days) and intensive care unit permanence (10 × 9 days) were similar but DM group needed more vasoactive, anticoagulant and anti-platelet drugs, oxygen therapy, endotracheal intubation and dialysis. Lethality was higher in patients with diabetes (39.3% × 30.7%) and increased with glucose levels and age, in male sex and with BMI < 30 kg/m2 in both groups (obesity paradox). It was lower with previous treatment with ACEi/BRA in both groups. Ethnicity and education level did not result in different outcomes between groups. Higher frequency of comorbidities (hypertension, cardiovascular/renal disease, stroke), of inflammatory (higher leucocyte number, RCP, LDH, troponin) and renal markers (urea, creatinine, potassium levels and lower sodium, magnesium) differentiated lethality risk between patients with and without diabetes.

Comorbidities, inflammatory markers and renal disfunction but not Covid-19-related symptoms, obesity, ethnicity and education level differentiated lethality risk between patients with and without diabetes.

The benefits of plant-based diets may depend on the type of plant. To determine the associations of healthy and unhealthy plant-based diet types on risk of hospitalization with respiratory infections or any infection, we used dietary intake data reported in a food frequency questionnaire from the Atherosclerosis Risk in Communities Study to calculate a plant-based diet index (PDI), a healthy PDI (HPDI), and an unhealthy PDI (UPDI). Cox regression was used to calculate hazard ratios for the associations of the three plant-based diet indices with the risk of hospitalization with respiratory infections and any infection-related hospitalization. Comparing the highest to lowest quintiles, HPDI was associated with a lower risk of hospitalization with respiratory infections (HR 0.86, 95% CI: 0.75, 0.99), and a lower risk of hospitalization with any infections (HR 0.87, 95% CI: 0.78, 0.97). The PDI was associated with a lower risk of hospitalization with any infections (HR 0.86, 95% CI: 0.76, 0.96). Significant associations were not observed with the UPDI. Adults with a high PDI and HPDI had a lower risk of hospitalization with any infections, whereas adults with a high HPDI had lower risk of hospitalizations with respiratory infections.

Pregestational diabetes increases the risk of group B streptococcus (GBS) colonization in pregnancy. Whether glycemic control is associated with differences in this risk is unknown. We examined the association between glycemic control and GBS colonization among pregnant individuals with pregestational diabetes.

A retrospective cohort of pregnant individuals with pregestational diabetes at a tertiary care center. The exposure was glycemic control, measured as hemoglobin A1c (A1c) at >20 weeks and assessed categorically at thresholds of <6.5% and <6.0%, and secondarily, as a continuous percentage. The outcome was maternal GBS colonization. Multivariable logistic regression was used and adjusted for age, parity, race, and ethnicity as a social determinant, body mass index, type of diabetes, and gestational age at A1c assessment.

Among 305 individuals (33% Type 1, 67% type 2), 45.0% (n = 140) were colonized with GBS. Individuals with an A1c < 6.5% were half as likely to be colonized with GBS compared with those with a A1c ≥ 6.5% (38.8% vs. 53.9%; adjusted odds ratio, AOR: 0.55; 95% CI: 0.33-0.91). Results were unchanged at an A1c threshold of <6.0% (35.7% vs. 48.5%; AOR: 0.60; 95% CI: 0.36-0.98). Individuals with a higher A1c as a continuous measure (%) were more likely to be colonized (AOR: 1.57 per 1%; 95% CI: 1.25-1.97).

Pregnant individuals with pregestational diabetes with worse glycemic control were at an increased risk of GBS colonization. Further study is needed to understand if improved glycemic control leads to lower risk of GBS colonization.

Diabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non-small cell lung cancer (NSCLC).

The authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5-million-member state health service was used.

Of the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression-free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11-2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09-2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients.

This study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.

Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and is related to serious health complications. It has been pointed out as a major risk factor for COVID-19. This study aimed to determine the impact of COVID-19 on the metabolomic profile, the correlation with the plasmatic levels of losartan and its active metabolite (EXP3174), biochemical markers, and blood pressure (BP) control in hypertensive patients. 1H NMR metabolomic profiles of hypertensive and normotensive patients with and without previous COVID-19 diagnosis were identified. Plasmatic levels of LOS and EXP3174 were correlated with BP, biochemical markers, and the metabolomic fingerprint of the groups. Biomarkers linked to important aspects of SAH and COVID-19 were identified, such as glucose, glutamine, arginine, creatinine, alanine, choline, erythritol, homogentisate, 0-tyrosine, and 2-hydroxybutyrate. Those metabolites are indicative of metabolic alterations, kidney damage, pulmonary dysfunction, and persistent inflammation, which can be found in both diseases. Some hypertensive patients did not reach the therapeutic levels of LOS and EXP3174, while the BP control was also limited among the normotensive patients with previous COVID-19 diagnoses. Metabolomics proved to be an important tool for assessing the effectiveness of losartan pharmacotherapy and the damage caused by SAH and COVID-19 in hypertensive patients.