Severe Coronavirus Disease 2019 Disease Research Articles

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial.

To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19). Double-blind, randomized clinical trial. Two ICUs at an academic medical center. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support. SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days. We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial. The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial. Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis.

Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.

A-229 Immune Biomarkers Associated with COVID-19 Disease Severity in an Urban, Hospitalized Population

Abstract Background We sought to identify immune biomarkers associated with severe Coronavirus disease 2019 (COVID-19) in patients admitted to a large public county hospital during the early phase of the SARS-CoV-2 pandemic. We hypothesized that we could identify clinically relevant immune markers at the time of initial hospital admission that could be used to predict the course of COVID-19 illness. Methods The study population consisted of SARS-CoV-2 positive patients admitted for COVID-19 (n = 58) or controls (n = 14) at the Los Angeles County University of Southern California Medical Center between April-December 2020. Immunologic markers including chemokine/cytokines (IL-6, IL-8, IL-10, IP-10, MCP-1, TNFα) and serologic markers against SARS-CoV-2 antigens (including spike subunits S1 and S2, receptor binding domain (RBD), and nucleocapsid (N)) were assessed in serum collected on the day of admission using custom MILLIPLEX® immunoassay panels. Result values were computed using mean fluorescent intensity in individual samples fit to a standard curve using a 5PL logistic formula with power law variance. Comparison of patient demographic, clinical, cytokines and immunoglobulins characteristics between mild vs moderate/severe COVID-19 groups were conducted using Wilcoxon tests for continuous variables and Chi-square tests for categorical variables. Linear support vector machine models were fitted to perform the binary classification task of predicting mild vs moderate/severe COVID-19 using the python library scikit-learn. Results SARS-CoV-2 antibody levels were significantly elevated in patients with the highest COVID-19 disease severity, with IgM S1, IgG N, IgG RBD, IgG S1, and IgG S2 showing statistical significance between mild vs moderate/severe disease group medians (P = 0.037, 0.032, 0.007, 0.003, and 0.015, respectively). Of the chemokines/cytokines tested, only IP-10 showed significance across the disease groups (medians 640.8 pg/mL in mild, 493.3 pg/mL in moderate/severe, and 259.9 pg/mL in control, overall P = 0.005). The linear support vector machine model achieved an accuracy of 64% and an AUROC of 0.81 in predicting COVID-19 severity status. The most important clinical variables for predicting disease severity were white blood cell count, diastolic blood pressure, and platelet count, while the most important serologic markers were IgG anti-SARS-CoV-2 N, S1, S2, TNF-α, IP-10, and IL-10. Conclusion Our results suggest that IP-10 and anti-SARS-CoV-2 antibody measurements could be useful to identify patients most likely to experience the most severe forms of the disease. Strengths of this study include a focus on a racially and ethnically diverse patient population and a combined analysis of both cytokine/chemokine and immune response (antibody) biomarkers. However, we emphasize that our subjects were enrolled at a time before widespread vaccination against SARS-CoV-2.

Vitamin D status in hospitalized COVID‑19 patients is associated with disease severity and IL-5 production

BackgroundThere are many studies on the relationship between vitamin D and coronavirus disease 2019 (COVID-19), while the results are matters of debate and the mechanisms remain unknown. The present study was performed to assess the impact of serum 25-hydroxyvitamin D [25(OH)D] levels on the severity of disease in hospitalized COVID-19 patients and identify potential mechanisms of 25(OH)D alterations.MethodsA total of 399 hospitalized COVID-19 patients were recruited from three centers between December 19, 2022, and February 1, 2023. Medical history, laboratory examination, and radiologic data were retrospectively collected. The patients were divided into four groups based on disease severity. Serum 25(OH)D levels in the patients were determined by the electrochemiluminescence method and cytokines were detected by flow cytometry. The relationship between serum 25(OH)D status and the severity of COVID-19, and the correlation between 25(OH)D levels and cytokines in COVID-19 patients were assessed.ResultsLevels of 25(OH)D were significantly lower in the deceased group than in the other three groups (P < 0.05), and lower in the critical group than in the general group (P < 0.05). There were no significant differences in the 25(OH)D levels between the general and severe groups (P > 0.05). The levels of 25(OH)D (odds ratio = 0.986, 95% confidence interval: 0.973–0.998, P = 0.024) and IL-5 (odds ratio = 1.239, 95% confidence interval: 1.104–1.391, P = 0.04) were independent risk factors for the severity of COVID-19 disease upon admission. Serum 25(OH)D levels were able to predict the mortality of patients with COVID-19, and the predictive value was even higher when combined with IL-5 levels and eosinophil (Eos) count. Circulating 25(OH)D status correlated negatively with the expression of IL-5 (r=-0.262, P < 0.001) and was positively linked with CD8+ T cell counts (r=-0.121, P < 0.05) in patients with COVID-19.ConclusionsThis study found that the serum 25(OH)D status combined with IL-5 levels and Eos counts could be identified as a predictive factor for recognizing the risk of COVID-19 mortality. The serum 25(OH)D status in COVID-19 patients correlated negatively with the expression of IL-5. The potential mechanism for this relationship is worth further exploration.

COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor–associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.

Thyroid profile prognostic value on disease severity and mortality in COVID-19

Background: Precise accurate triage of Coronavirus disease 2019 (COVID-19) patients during hospitalization for early identification of individuals at risk of developing severe disease is essential as Intensive Care Units (ICUs) are overwhelmed by the pandemic burden. The aim of this study was to evaluate thyroid function in patients with COVID-19. Methods: 60 healthy controls and 180 patients were admitted to a cardiothoracic hospital, Minia University, Egypt, between March 2020 and September 2021 without a history of thyroid disease. Patients divided as 60 non-COVID pneumonia patients with a similar degree of severity were included as another control group to find any unique effects of COVID-19 on thyroid function, 120 positive COVID-19 divided according to clinical classifications into moderate (n = 58), severe (n = 21), and critical (n = 41), Critical group were admitted to ICU and classified to survivors (n = 33) and non-survivors (n = 8). COVID patients also were divided into tertiles according to their FT3 levels. Lowes tertile (n = 45), middle tertile (n = 37) and highest tertile (n = 38). All participants underwent routine physical checkups, acute physiology, and chronic health evaluation (APACHE-II) scores. The outcome measure was death during hospitalization; intensive care admission, mechanical ventilation, and length of hospitalization. We analyzed the ability of each parameter to predict mortality in participants. Further, we also evaluated whether the combination of free triiodothyronine (FT3) level with APACHE-II score could improve the mortality prediction. Results: Thyroid Stimulating Hormone (TSH) was lower than normal range in 56.7% (68/120) of patients with COVID-19. TSH and serum-free triiodothyronine (FT3) were significantly lower in COVID-19 patients than healthy control and non-COVID-19 pneumonia patients. TSH and FT3 were lower in severe COVID-19 with statistical significance (p &lt; 0.001) and both positively correlated with the severity. The free thyroxine (FT4) in COVID-19 patients was not significantly different from the control group. Patients in the lowest FT3 tertile had significantly higher rates of mortality (18/40), mechanical ventilation (24/53.3), and intensive care unit admission (20/44.4). In univariate analyses, FT3 remained the most significant independent predictor of death. Conclusion: The changes in serum TSH and FT3 levels may be important manifestations of COVID-19 courses.FT3 levels can serve as a prognostic tool for disease severity in early presentation of COVID-19.

A Study of the Role of Prognostic Laboratory Parameters among COVID-19 Patients: A Retrospective Cohort Study

Abstract Background: The emergence and spread of the coronavirus disease 2019 (COVID-19) pandemic presents an immense challenge to public health and has resulted in a dramatic loss of human life worldwide. Thus, diagnosis and identification of clinical laboratory parameters associated with the disease become crucial in critical cases, requiring intensive care management. Aim: To investigate clinical laboratory parameters that may be associated with severe or critical COVID-19 disease patients, particularly those requiring intensive care management. Materials and Methods: A retrospective cohort study was conducted at the U. N. Mehta Institute of Cardiology and Research Institute, Ahmedabad, Gujarat. A total of 1460 COVID-19-positive patients (aged 18 years and older) requiring admission to the intensive care unit were selected from April 3 to May 23, 2021, were enrolled, and were diagnostically monitored. Patients were evaluated based on their demographics. A Welsch t-test was used to calculate the progression in the mean difference among inflammatory and/or thromboembolic markers. Results: We analyzed and examined certain laboratory parameters across the timeline and compared survival (Group 1) and nonsurvival (Group 2). All the factors were higher in Group 2 compared to Group 1, except for C-reactive protein-Q (CRP-Q), which decreased in both groups, but in Group 1, there was a further decrease in CRP-Q value as compared to Group 2 on retest day. Conclusion: The results of the current study provide clinical value for prognostic factors associated with COVID-19 and establish the role of laboratory parameters in evaluating disease severity and complications.

Could ischemia-modified albumin levels predict the severity of disease in SARS-CoV-2 infection?

Ischemia-modified albumin (IMA) level increases in inflammatory conditions. We aimed to investigate the association between IMA levels and the severity of coronavirus disease 2019 (COVID-19) infection in adult patients. We grouped adult patients with COVID-19 infection: Group A - mild symptoms, but normal computed tomography (CT), Group B - mild/moderate illness, and Group C - severe or critical illness. We measured IMA levels at the time of diagnosis of COVID-19 infection. Mean age of the total number of patients (n = 90) was 54.43 (± 8.11) year, and 46.7% (n = 42) were female. IMA levels were highest in Group C and lowest in A (p < 0.001). The most important factor predicting COVID-19 disease severity was IMA. Type 2 diabetes was more frequent in Group C (n = 31) than in Group B (n = 30) (p = 0.042). Asthma was less frequent, and coronary artery disease was more frequent in Group C than in Group A (n = 29) and B (p = 0.009). Duration of hospitalization was highest in Group C (p < 0.001). We analyzed a sample of patients with COVID-19 infection and found that IMA predicted severe COVID-19 disease. Disease severity grouping was based on patients' clinical and radiological features. IMA level measured when SARS-CoV-2 infection is diagnosed may be a useful marker in predicting likely disease severity or intensive care need.

Prevalence, pathogenesis and spectrum of neurological symptoms in COVID-19 and post-COVID-19 syndrome: a narrative review.

Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware. The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID-19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID-19 disease. Neurological manifestations of acute COVID-19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain-Barré syndrome, and cerebrovascular disease. Commonly reported long term neurological sequelae of COVID-19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease. Assessment of cognitive dysfunction after COVID-19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID-19. The long term impact of COVID-19 on neurological diseases remains uncertain and requires ongoing vigilance.

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.

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.

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..

Aggregate Index of Systemic Inflammation (AISI), Disease Severity, and Mortality in COVID-19: A Systematic Review and Meta-Analysis.

Combined indices of different haematological cell types appear to be particularly promising for investigating the link between systemic inflammation and coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to assess the aggregate index of systemic inflammation (AISI), an emerging index derived from neutrophil, monocyte, platelet, and lymphocyte counts, in hospitalized COVID-19 patients with different disease severity and survival status. We searched electronic databases between the 1st of December 2019 and the 10th of June 2023 and assessed the risk of bias and the certainty of evidence. In 13 studies, severe disease/death was associated with significantly higher AISI values on admission vs. non-severe disease/survival (standard mean difference (SMD) = 0.68, 95% CI 0.38 to 0.97, p < 0.001). The AISI was also significantly associated with severe disease/death in five studies reporting odds ratios (4.39, 95% CI 2.12 to 9.06, p ˂ 0.001), but not in three studies reporting hazard ratios (HR = 1.000, 95% CI 0.999 to 1.002, p = 0.39). The pooled sensitivity, specificity, and area under the curve values for severe disease/death were 0.66 (95% CI 0.58 to 0.73), 0.78 (95% CI 0.73 to 0.83), and 0.79 (95% CI 0.76 to 0.83), respectively. Our study has shown that the AISI on admission can effectively discriminate between patients with different disease severity and survival outcome (PROSPERO registration number: CRD42023438025).

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.

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.

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.

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.

Decreased level of serum NT-proCNP associates with disease severity in COVID-19

BackgroundC-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the current study, we aimed to determine possible changes in the NT-proCNP levels of patients with coronavirus disease 2019 (COVID-19), with special regard to disease severity and outcome.MethodsIn this retrospective analysis, we determined the serum level of NT-proCNP in hospitalized patients with symptoms of upper respiratory tract infection, using their blood samples taken on admission, stored in a biobank. The NT-proCNP levels of 32 SARS-CoV-2 positive and 35 SARS-CoV-2 negative patients were measured to investigate possible correlation with disease outcome. SARS-CoV-2 positive patients were then divided into two groups based on their need for intensive care unit treatment (severe and mild COVID-19).ResultsThe NT-proCNP was significantly different in the study groups (e.g. severe and mild COVID-19 and non-COVID-19 patients), but showed inverse changes compared to previous observations in septic patients: lowest levels were detected in critically ill COVID-19 patients, while highest levels in the non-COVID-19 group. A low level of NT-proCNP on admission was significantly associated with severe disease outcome.ConclusionsLow-level NT-proCNP on hospital admission is associated with a severe COVID-19 disease course. The pathomechanism underlying this observation remains to be elucidated, while future studies in larger patient cohorts are necessary to confirm these observations and reveal therapeutic importance.Trial registration DRKS00026655 Registered 26. November 2021