Coronavirus Disease 2019 Disease Research Articles

Pulmonary Tuberculosis in Post COVID-19 Patients: Occurrence and Clinical Profile

Background: Tuberculosis continues to be a major public health disease to date. The mortality of this disease, which was reducing till 2019, was reversed in 2020 and 2021, as per the global tuberculosis report 2022. The novel coronavirus disease 2019(COVID-19) pandemic has af-fected tuberculosis management in various aspects. The transient immunosuppression associated with the disease and the treatment modality has been speculated to activate latent tuberculosis infec-tion as well as increase the infection risk with Mycobacterium Tuberculosis. Objective: The aim of this study was to analyze the clinical characteristics of post-COVID-19 pul-monary tuberculosis patients. Methods: We conducted a retrospective descriptive analysis of post-COVID-19 patients admitted from January 2021 to May 2022 with persistent or new-onset respiratory symptoms. The occurrence of pulmonary tuberculosis in these patients and their clinico- demographic details are summarized. Results: About 31(19.4%) of 160 post-COVID-19 patients with respiratory symptoms were diag-nosed to have pulmonary tuberculosis. About 21(67.7%) had comorbidities, of which the predomi-nant was diabetes mellitus in 14(45%) patients, and the majority (85%) had poorly controlled blood sugar levels. None of the patients had a history of contact with a pulmonary tuberculosis patient in the previous 2 years, but 4(13%) patients had a previous history of tuberculosis. Moreover,.66% of cases had a history of moderate and severe COVID-19 disease, and 70% had received systemic cor-ticosteroids and other immunosuppressive drugs like tocilizumab during the COVID-19 illness treatment. More than 50% of the patients had negative smears for acid-fast bacilli and were diag-nosed using rapid molecular methods like CBNAAT and LPA. Drug-resistant tuberculosis was seen in 6(19%) patients. 4(13%) patients died during the hospitalized course of treatment, and the re-maining 27(87%) were discharged with antituberculous treatment, but their final outcome is un-known. Conclusion: A high index of suspicion and use of rapid molecular diagnostic methods is indicated in post-COVID-19 patients with respiratory symptoms for early diagnosis of tuberculosis and pre-vention of community transmission. Identification of post-COVID-19 patients with latent tuberculo-sis infection and the feasibility of advocation of tuberculosis preventive therapy in such patients, es-pecially those with other risk factors like diabetes mellitus, need to be considered.

Epidemiological Characteristics of Generalized COVID-19 Deterministic Disease Model

Coronavirus disease 2019 (COVID-19) is an infection that can result in lung issues such as pneumonia and, in extreme situations, the most severe acute respiratory syndrome. COVID-19 is widely investigated by researchers through mathematical models from different aspects. Inspired from the literature, in the present paper, the generalized deterministic COVID-19 model is considered and examined. The basic reproduction number is obtained which is a key factor in defining the nonlinear dynamics of biological and physical obstacles in the study of mathematical models of COVID-19 disease. To better comprehend the dynamical behavior of the continuous model, two unconditionally stable schemes, i.e., mixed Euler and nonstandard finite difference (NSFD) schemes are developed for the continuous model. For the discrete NSFD scheme, the boundedness and positivity of solutions are discussed in detail. The local stability of disease-free and endemic equilibria is demonstrated by constructing Jacobian matrices for NSFD scheme; nevertheless, the global stability of aforementioned equilibria is verified by using Lyapunov functions. Numerical simulations are also presented that demonstrate how both the schemes are effective and suitable for solving the continuous model. Consequently, the outcomes obtained through these schemes are completely according to the solutions of the continuous model.

Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients?

From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it. In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were "Secondary Sclerosing Cholangiopathy", "SSC-CIP", "Secondary Sclerosing Cholangiopathy in critically ill patients", "Ketamine and cholangiopathy", "Ketamine abusers and liver disease", "Ketamine-related cholangiopathy", "SARS-CoV2 infection and liver disease", "post Covid-19 secondary sclerosing cholangitis", "Covid-19 cholangiopathy". Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out. Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.

Impaired systemic nucleocapsid antigen clearance in severe COVID-19.

The circulating nucleocapsid (NCP) antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detectable in coronavirus disease-2019 (COVID-19) patients. To better understand the biology of disease severity, we investigated NCP clearance kinetics in hospitalized COVID-19 patients. Serum NCP was quantified using a commercial NCP-specific enzyme-linked immunoassay in hospitalized COVID-19 patients (n = 63) during their hospital stay. Results were correlated to COVID-19 disease severity, inflammation parameters, antibody response, and results of SARS-CoV-2 PCR from nasopharyngeal swabs. We demonstrate that NCP antigen levels in serum remained elevated in 21/45 (46.7%) samples from patients in intensive care units (ICU) after >8 days postdiagnosis. The proportion of ICU patients with detectable antigenemia declined only gradually from 84.6% to 25.0% over several weeks. This was in contrast to complete NCP clearance in all non-ICU patients after 8 days, and also in contrast to mucosal clearance of the virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP. Clearance of NCP antigenemia is delayed in >40% of severely ill COVID-19 patients. Thus, NCP antigenemia detected after 8 days post COVID-19 diagnosis is a characteristic of patients requiring intensive care. Prospective trials should further investigate NCP antigen clearance kinetics as a mechanistic biomarker.

APRI has Utility as a Biomarker of COVID-19 Severity in Patients with Nonalcoholic Fatty Liver Disease.

Patients with NAFLD are reported to have greater coronavirus disease 19 (COVID-19) severity compared to patients without NAFLD. Previous studies have reported that noninvasive liver fibrosis scores, including the FIB-4 index, NAFLD fibrosis score (NFS), and AST to platelet ratio index (APRI), have utility in predicting COVID-19 mortality and disease severity in patients without NAFLD. However, the utility of liver fibrosis scores in predicting COVID-19 mortality and disease severity among patients with NAFLD infected with SARS-CoV-2 has yet to be evaluated. This retrospective observational study comprised 126 patients with NAFLD and active SARS-CoV-2 infection. Patients were classified into low COVID-19 severity (mild or moderate I disease) and high COVID-19 severity (moderate II or severe disease) groups based on the therapeutic guideline implemented by the Ministry of Health, Labour and Welfare of Japan. Of the 126 patients, only one had been diagnosed with NAFLD before admission. Age; levels of serum aspartate aminotransferase, γ-glutamyl transpeptidase, lactate dehydrogenase, blood urea nitrogen, serum CRP, FIB-4 index; NFS; and APRI levels on admission were higher in the high COVID-19 severity group compared to the low COVID-19 severity group. Serum albumin levels, platelet counts, and lymphocyte counts on admission were lower in the high COVID-19 severity group compared to the low COVID-19 severity group. Univariate and multivariate analysis revealed that APRI values were significantly associated with COVID-19 severity and hospitalization duration for COVID-19. APRI was independently associated with COVID-19 severity and hospitalization duration for COVID-19 in patients with NAFLD.

COVID-19 and Chronic Kidney Disease: A Narrative Review

The coronavirus disease-2019 (COVID-19) pandemic has had a profound impact on the world, causing loss of life, economic damage, and social disruption. Individuals with chronic kidney disease (CKD) are prone to complications and increased mortality related to COVID-19. Efforts have been made to increase understanding of the effects of COVID-19 in individuals with CKD. This paper aims to gather and discuss the state-of-the-art in the COVID-19 and CKD literature, involving the early history of COVID-19, the immunological aspects of CKD (such as abnormalities in neutrophilicand dendritic cells functions), the mechanisms of kidney injury by SARS-CoV-2 (for example, viral tropism to kidney tissue and direct cytotoxicity), the clinical course of the disease and consequences for CKD individuals (including kidney transplant recipients), and the emerging treatments (such as the use of Remdesivir, nirmatrelvir, and monoclonal neutralizing antibodies) and immunization for the CKD population.

CD147 rs8259T>A Variant Confers Susceptibility to COVID-19 Infection within the Mexican Population.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations of COVID-19 range from mild flu-like symptoms to severe respiratory failure. Nowadays, extracellular matrix metalloproteinase inducer (EMMPRIN), also known as cluster of differentiation 147 (CD147) or BASIGIN, has been studied as enabling viral entry and replication within host cells. However, the impact of the CD147 rs8259T>A single nucleotide variant (SNV) on SARS-CoV-2 susceptibility remains poorly investigated. To investigate the impact of rs8259T>A on the CD147 gene in individuals from Mexico with COVID-19 disease. We genotyped the CD147 rs8359T>A SNV in 195 patients with COVID-19 and 185 healthy controls from Mexico. In addition, we also measured the expression levels of CD147 and TNF mRNA and miR-492 from whole blood of patients with COVID-19 through RT-q-PCR. We observed a significant association between the CD147 rs8259T>A SNV and susceptibility to COVID-19: T vs. A; OR 1.36, 95% CI 1.02-1.81; p = 0.037; and TT vs. AA; OR 1.77, 95% CI 1.01-3.09; p = 0.046. On the other hand, we did not find differences in CD147, TNF or miR-492 expression levels when considering the genotypes of the CD147 rs8259T>A SNV. Our results suggest that the CD147 rs8259T>A variant is a risk factor for COVID-19.

SARS-CoV-2 infection alters mitochondrial and cytoskeletal function in human respiratory epithelial cells mediated by expression of spike protein.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, SCV2), which has resulted in higher morbidity and mortality rate than other respiratory viral infections, such as Influenza A virus (IAV) infection. Investigating the molecular mechanisms of SCV2-host infection vs IAV is vital in exploring antiviral drug targets against SCV2. We assessed differential gene expression in human nasal cells upon SCV2 or IAV infection using RNA sequencing. Compared to IAV, we observed alterations in both metabolic and cytoskeletal pathways suggestive of epithelial remodeling in the SCV2-infected cells, reminiscent of pathways activated as a response to chronic injury. We found that spike protein interaction with the epithelium was sufficient to instigate these epithelial responses using a SCV2 spike pseudovirus. Specifically, we found downregulation of the mitochondrial markers SIRT3 and TOMM22. Moreover, SCV2 spike infection increased extracellular acidification and decreased oxygen consumption rate in the epithelium. In addition, we observed cytoskeletal rearrangements with a reduction in the actin-severing protein cofilin-1 and an increase in polymerized actin, indicating epithelial cytoskeletal rearrangements. This study revealed distinct epithelial responses to SCV2 infection, with early mitochondrial dysfunction in the host cells and evidence of cytoskeletal remodeling that could contribute to the worsened outcome in COVID-19 patients compared to IAV patients. These changes in cell structure and energetics could contribute to cellular resilience early during infection, allowing for prolonged cell survival and potentially paving the way for more chronic symptoms. IMPORTANCE COVID-19 has caused a global pandemic affecting millions of people worldwide, resulting in a higher mortality rate and concerns of more persistent symptoms compared to influenza A. To study this, we compare lung epithelial responses to both viruses. Interestingly, we found that in response to SARS-CoV-2 infection, the cellular energetics changed and there were cell structural rearrangements. These changes in cell structure could lead to prolonged epithelial cell survival, even in the face of not working well, potentially contributing to the development of chronic symptoms. In summary, these findings represent strategies utilized by the cell to survive the infection but result in a fundamental shift in the epithelial phenotype, with potential long-term consequences, which could set the stage for the development of chronic lung disease or long COVID-19.

Demographics and outcomes of hemoglobin genotype in hospitalized patients with COVID-19 and sickle cell disease in the United States.

Coronavirus disease 2019 (COVID-19) is associated with poor outcomes in sickle cell disease (SCD) patients. However, there is a paucity of data comparing hemoglobin (Hb) genotypes in SCD and infection outcomes. The National Inpatient Sample was used to identify the record of hospitalizations with COVID-19 and SCD in 2020 using the International Classification of Disease, Tenth Revision codes. Study outcomes (invasive mechanical ventilation, extracorporeal membrane oxygenation, shock, vasopressor use, measures of resource utilization, and in-hospital mortality) were compared between hemoglobin SS, SC, and S-beta thalassemia (Sβ). Of the 102 975 COVID-19 hospitalizations with SCD, 87.26% had HbSS, 7.16% had HbSC, and 5.58% had HbSβ. Younger patients were more likely to have HbSS, while older patients were likely to have HbSC and HbSβ. HbSS was more frequent with Blacks, while HbSβ was more prevalent with Whites and Hispanics. Though measures of resource utilization were higher in HbSS, there was no significant difference in in-hospital outcomes between the three genotypes. There is no difference in COVID-19 outcomes among Hb genotypes in SCD. Further studies are needed to explore the reasons for this observation.

Severity of Prior Coronavirus Disease 2019 is Associated With Postoperative Outcomes After Major Inpatient Surgery.

To determine how the severity of prior history (Hx) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection influences postoperative outcomes after major elective inpatient surgery. Surgical guidelines instituted early in the coronavirus disease 2019 (COVID-19) pandemic recommended a delay in surgery of up to 8 weeks after an acute SARS-CoV-2 infection. This was based on the observation of elevated surgical risk after recovery from COVID-19 early in the pandemic. As the pandemic shifts to an endemic phase, it is unclear whether this association remains, especially for those recovering from asymptomatic or mildly symptomatic COVID-19. Utilizing the National COVID Cohort Collaborative, we assessed postoperative outcomes for adults with and without a Hx of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from infection to surgery were each used as independent variables in multivariable logistic regression models. This study included 387,030 patients, of whom 37,354 (9.7%) were diagnosed with preoperative COVID-19. Hx of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of respiratory failure. Impact of COVID-19 on postoperative outcomes is dependent on the severity of illness, with only moderate and severe disease leading to a higher risk of adverse outcomes. Existing perioperative policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Social Drivers of COVID-19 Disease Severity in Pregnant Patients.

While coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had global impact in all populations, certain groups of patients have experienced disproportionate rates of morbidity and mortality. The purpose of this study was to assess the relationship between COVID-19 disease severity, demographic variables, race and ethnicity, and social determinants of health among pregnant patients in a diverse urban population. A retrospective analysis was performed of all pregnant patients diagnosed with COVID-19 at two urban tertiary care centers in Houston, TX between March and August 2020. Maternal demographic, COVID-19 illness criteria, and delivery characteristics were collected. The Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and COVID-19 Community Vulnerability Index (CCVI) were obtained based on a patients' census tract of residence. Analyses compared persons with asymptomatic, mild, or severe-critical disease at diagnosis. A total of 317 persons tested positive for COVID-19 during this time period. Asymptomatic persons were more likely to be diagnosed at later gestational ages, but there were no other differences in baseline maternal characteristics. Persons with more severe disease had greater social vulnerability specifically for housing and transportation than those with mild disease (mean SVI [standard error]: 0.72 [0.06] vs. 0.58 [0.2], p = 0.03). Total SVI, total CCVI, and other themed SVI and CCVI indices were not significantly different between groups. In this cohort of pregnant persons infected with SARS-CoV-2, an association was shown between disease severity and increased vulnerability in living conditions and transportation. Drivers of the pandemic and COVID-19 outcomes are complex and multifactorial, and likely change over time. However, continued efforts to accurately identify and measure social determinants of health in medicine will likely help identify geographic areas and patient populations that are at risk of higher disease burden. This could facilitate preventative and mitigation measures in these areas in future disaster or pandemic situations. · SVI and CCVI estimate social determinants of health.. · COVID-19 is associated with housing and transportation vulnerability.. · Social determinants contribute to disease burden in pregnancy..

Immune biomarkers associated with COVID-19 disease severity in an urban, hospitalized population

ObjectivesWe sought to identify immune biomarkers associated with severe Coronavirus disease 2019 (COVID-19) in patients admitted to a large urban hospital during the early phase of the SARS-CoV-2 pandemic. DesignThe study population consisted of SARS-CoV-2 positive subjects admitted for COVID-19 (n = 58) or controls (n = 14) at the Los Angeles County University of Southern California Medical Center between April 2020 through December 2020. Immunologic markers including chemokine/cytokines (IL-6, IL-8, IL-10, IP-10, MCP-1, TNF-α) and serologic markers against SARS-CoV-2 antigens (including spike subunits S1 and S2, receptor binding domain, and nucleocapsid) were assessed in serum collected on the day of admission using bead-based multiplex immunoassay panels. ResultsWe observed that body mass index (BMI) and SARS-CoV-2 antibodies were significantly elevated in patients with the highest COVID-19 disease severity. IP-10 was significantly elevated in COVID-19 patients and was associated with increased SARS-CoV-2 antibodies. Interactions among all available variables on COVID-19 disease severity were explored using a linear support vector machine model which supported the importance of BMI and SARS-CoV-2 antibodies. ConclusionsOur results confirm the known adverse association of BMI on COVID-19 severity and suggest that IP-10 and SARS-CoV-2 antibodies could be useful to identify patients most likely to experience the most severe forms of the disease.

Serum amyloid A protein as a predictor of severity in coronavirus disease 2019-infected Egyptian patients

Background The coronavirus disease 2019 (COVID-19) pandemic is a worldwide pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus. Serum amyloid A (SAA) is an acute-phase protein secreted during the acute phase of inflammation and can be used to predict the severity of COVID-19 disease. When inflammatory stimuli occur, levels of SAA increase within hours and the magnitude of response becomes great and may be greater than that of C-reactive protein (CRP). Aim Assessment of the level of SAA in COVID-19 Egyptian patients to predict the severity of the disease. Patients and methods This was an observational case–control study conducted on 80 participants: 60 patients with RT-PCR positive and computed tomography chest for COVID-19 disease classified into three groups according to disease severity: group I (20 patients) mild cases, group II (20 patients) moderate cases, and group III (20 patients) severe cases, and 20 participants as a control group. All participants were investigated for complete blood count, Serum Glutamic Pyruvic Transaminase (SGPT), Serum Glutamic Oxaloacetic Transaminase (SGOT), blood urea, serum creatinine, CRP, D-dimer and SAA. Results There is no statistical significance among the comparison groups as regards SAA. There was a high statistically significant decrease in the number of lymphocytes in COVID-19 patient groups compared with the control group. There was a statistically significant difference as regards platelet count, CRP, D-dimer, serum urea, and creatinine among the groups (I, II, and III) compared with the control group. Conclusion Single use of SAA during the pandemic could not achieve prediction of severity or the prognosis of COVID-19.

A Multi-Study Synthesis of Facilitators and Barriers to SARS-CoV-2 Testing Enrollment in School Settings.

Understanding the motivators and barriers to testing enrollment from different stakeholder perspectives is essential to increasing participation in school-based testing programs, particularly among underserved populations. This multistudy analysis aimed to identify facilitators and barriers to enrollment in school-based testing for coronavirus disease 2019 (COVID-19). Four independent studies collected and analyzed qualitative data from study participants regarding: (1) motivators, benefits, and/or reasons for enrolling and/or participating in COVID-19 testing in schools; and/or (2) concerns, barriers, and/or negative outcomes related to COVID-19 testing in schools. Study authors conducted a retrospective review of findings from the independent studies to identify themes related to testing motivators and concerns that emerged across the studies. The analysis identified 10 distinct themes regarding the perceived motivators of COVID-19 testing in schools and 15 distinct themes regarding concerns and barriers to COVID-19 testing in schools. Common motivators across multiple studies included convenience of testing in school and the desire to keep self and others safe from COVID-19. Concerns about the implications of receiving a positive test result was a barrier identified by multiple studies. Themes from 4 independent studies revealed insights about the motivations and barriers to enrolling and participating in COVID-19 testing programs in kindergarten through 12th grade school settings. Study findings can be used to improve enrollment and participation in new and existing school-based testing programs to reduce transmission of COVID-19 and other infectious diseases in schools.

Predictors of disease severity in patients hospitalized with coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, manifests as a respiratory illness primarily and symptoms range from asymptomatic to severe respiratory syndrome and even death. During the pandemic, due to overcrowding of medical facilities, clinical assessment to triage patients for home care or in-hospital treatment was an essential element of management. Study the demographic features, comorbidities and bio-markers that predict severe illness and mortality from COVID-19 infection. Retrospective observational SETTING: Single tertiary care center PATIENTS AND METHODS: The study included all patients admitted with a positive PCR test for COVID-19 during the period from March 2020 to September 2020 (7 months). Data on demographics, clinical data and laboratory parameters was collected from medical records every 3 days during hospital stay or up until transfer to ICU. Demographic, comorbidities and biochemical features that might predict severe COVID-19 disease. 372 RESULTS: Of the 372 patients, 72 (19.4%) had severe disease requiring admission to intensive care unit (ICU); 6 (1.6%) died. Individuals over 62 years were more likely to be admitted to the ICU (P=.0001, while a BMI of 40 and higher increased the odds of severe disease (P=.032). Male gender (P=.042), hypertension (P=.006) and diabetes (P=.001) conferred a statistically significant increased risk of admission to ICU, while coexisting COPD, and ischemic heart disease did not. Laboratory features related to severe COVID-19 infection were: leukocytosis (P=.015), thrombocytopenia (P=.001), high levels of C-reactive protein (P=.0001), lactic dehydrogenase (P=.0001), D-dimer (P=.0001) and ferritin (P=.001). With the multivariate analysis, diabetes, high lac-tate dehydrogenase, C-reactive protein and thrombocytopenia were associated with severity of illness. Particular demographic and clinical parameters may predict severe illness and need for ICU care. Single referral center, several cases of severe COVID-19 could not be included due to lack of consent and or data. None.

Persistent immune and clotting dysfunction detected in saliva and blood plasma after COVID-19

A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal versus pathologic convalescence process have not been well-delineated. Here, we characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 20 and 90 days after initial clinical symptoms resolved. Convalescent subjects showed robust total IgA and IgG responses and positive antibody correlations in saliva and plasma samples. Shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells, such as neutrophil markers (e.g., myeloperoxidase), and clotting factors in plasma (e.g., fibrinogen), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered myeloid-derived pathways that correlated positively with SARS-CoV-2 IgA levels. Beyond plasma, our study positions saliva as a viable fluid to monitor normal and aberrant immune responses including vascular, inflammatory, and coagulation-related sequelae.

Role of Coagulation Parameters and Inflammatory Biomarkers in Coronavirus Disease 2019 Patients: A Demystifying Endeavor

BACKGROUND: Coronavirus disease 2019 (COVID-19) globally known as COVID-19 is a heterogeneous disease caused by the severe acute respiratory syndrome coronavirus 2. COVID-19 patients having severe disease and are critically ill are more prone to have abnormal coagulation prolife. It may lead to thromboinflammation in severe conditions. AIM: The aim is to evaluate the utility of coagulation parameters and inflammatory biomarkers in COVID-19 patients in the study conducted for 6 months duration. MATERIALS AND METHODS: It was a retrospective observational study conducted from April 2021 to September 2021 in a rural tertiary care referral Institute. Available data of the baseline values of coagulation parameters (platelet count [PLC], prothrombin time [PT], international normalized ratio [INR], partial thromboplastin time [PTT] and D-dimer) and inflammatory markers (C-reactive protein [CRP], serum lactate dehydrogenase [LDH], and serum ferritin) were evaluated with respect to the clinical severity of the disease and also the survival status of COVID-19 patients. RESULTS: One hundred and fifty-five cases of COVID-19-positive patients were analyzed. PT, INR, PTT, D-dimer, CRP, LDH, and ferritin had higher mean in severe cases than the nonsevere cases. PLC had higher mean in the severe cases than the nonsevere cases. PT, INR, PTT, D-dimer, CRP, LDH and ferritin had higher mean in nonsurvivors than the survivors. PLC had lower mean in nonsurvivors than the survivors. CONCLUSION: Baseline values of PT, INR, PTT, D-dimer, LDH, and ferritin may be considered reliable indicators of severity of COVID-19 disease. Baseline values of D-dimer, LDH, and ferritin may be considered a reliable indicator of survival of patients suffering from COVID-19 infection.

Implications of Inflammatory markers for disease management in patients with chronic kidney disease and COVID-19 infection: A cross-sectional study from North India

ABSTRACT Background: The world witnessed the emergence of a global pandemic. Individuals with chronic illnesses like chronic kidney disease (CKD), already known to be immunologically compromised, have the potential to develop a scenario of an acute-on-chronic condition on coronavirus disease 2019 (COVID-19) contraction. Measurement of serum inflammatory biomarkers like interleukin (IL-6), high-sensitivity C-reactive protein (hsCRP) and ferritin may foresee the prognosis despite the pre-existing low-grade inflammation in these patients. Aims: To determine the utility of serum IL-6, hsCRP and Ferritin levels to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19. Materials and Methods: A cross-sectional study was performed on 100 adult known cases of stage 5 of CKD, recently diagnosed as COVID-19 positive by real-time reverse transcription-polymerase chain reaction. The study population was divided into two groups according to COVID-19 severity: A non-severe and a severe group based on guidelines given in the Clinical Management Protocol: COVID-19. Their clinical and laboratory data obtained on the day of admission were analysed. Results: The severe group (n = 17) had 65% of males and 35% of females. A significant difference was found with respect to the age, body mass index and serum IL-6, hsCRP and ferritin levels between the two groups (P < 0.05). Among the three inflammatory biomarkers, hsCRP was found to have the maximum potential to categorise COVID-19 as severe or non-severe disease. Conclusion: Similar to patients with uncomplicated COVID-19 disease, higher serum levels of inflammatory biomarkers – IL-6, hsCRP and ferritin are seen in patients of CKD with severe COVID-19 illness in comparison to those with non-severe COVID-19, despite having a pre-existing background of low-grade chronic inflammation. The serum levels of IL-6, hsCRP and ferritin can be utilised to determine COVID-19 severity and probable prognosis in CKD patients with COVID-19.

REMOTE MONITORING FOR 5P (PREDICTIVE, PREVENTIVE, PARTICIPATORY, PERSONALIZED, AND PRECISION) CARDIOVASCULAR MEDICINE: PROGRESS AMIDST COVID-19 PANDEMIC

The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic that has affected the lives of billions of people. Clinical studies have reported an association between COVID-19 and cardiac diseases. Remote monitoring powered by wearable sensors impacts medical care by enabling health monitoring outside of the clinic. Wearable devices can provide a noninvasive and continuous multi-parameter assessment of ECG, Heart Rate Variability, arterial blood pressure, oxygen saturation and respiratory rate evaluation. Such monitoring may help predict and prevent cardiovascular events related to COVID-19 addresses the growing demand for a novel 5P (Predictive, Preventive, Participatory, Personalized, and Precision) medicine approach. This article aimed to review current and prospective advances in wearable devices for cardiac monitoring and their progress toward clinical application during the COVID-19 pandemic. We performed bibliometric analysis by Scopus, the largest and well organized bibliographic database and analyzed the top-cited articles in this field. Our analysis includes an overview of the most widespread practical implications of CVD-focused remote patient monitoring techniques based on wearable personalized devices. Assessment for both COVID-related conditions and general cases is included in the analysis. Recent studies have reported that cardiac abnormalities present in 19.7-27.8 % of hospitalized patients with COVID-19. COVID-19 associated myocarditis and heart rate abnormalities frequently occur. Additionally, patients with pre-existing CVD and hypertension are at high risk of worse outcomes. Data from several studies have identified atrial fibrillation as the most common form of arrhythmias in COVID-19 patients. Worsening of existing atrial fibrillation in COVID-19 patients is also a serious clinical concern. Implementation of wearable ECG devices for remote monitoring can improve the management of patients with atrial fibrillation and those at high risk for its development. Telecardiology based on wearable devices and remote monitoring allow out-of-hospital control of COVID-19 patients and patients suffering from chronic diseases at high risk of acute cardiovascular events, ensuring their early detection and tracking.

Multiscale Topological Indices for the Quantitative Prediction of SARS CoV-2 Binding Affinity Change upon Mutations.

The Coronavirus disease 2019 (COVID-19) has affected people's lives and the development of the global economy. Biologically, protein-protein interactions between SARS-CoV-2 surface spike (S) protein and human ACE2 protein are the key mechanism behind the COVID-19 disease. In this study, we provide insights into interactions between the SARS-CoV-2 S-protein and ACE2, and propose topological indices to quantitatively characterize the impact of mutations on binding affinity changes (ΔΔG). In our model, a series of nested simplicial complexes and their related adjacency matrices at various different scales are generated from a specially designed filtration process, based on the 3D structures of spike-ACE2 protein complexes. We develop a set of multiscale simplicial complexes-based topological indices, for the first time. Unlike previous graph network models, which give only a qualitative analysis, our topological indices can provide a quantitative prediction of the binding affinity change caused by mutations and achieve great accuracy. In particular, for mutations that happened at specifical amino acids, such as Polar amino acids or Arginine amino acids, the correlation between our topological gravity model index and binding affinity change, in terms of Pearson correlation coefficient, can be higher than 0.8. As far as we know, this is the first time multiscale topological indices have been used in the quantitative analysis of protein-protein interactions.