Longitudinal analyses reveal immunological misfiring in severe COVID-19.

Comparison of D-Dimer Level on Mild, Moderate and Severe COVID-19 at Immanuel Hospital Bandung City October 1 st - December 31 st, 2020

TO THE EDITOR: We read with great interest the paper by Deng et al. ((1)). Obesity increases the risk of coronavirus disease 2019 (COVID-19) morbidity and mortality ((2, 3)). However, Deng et al. suggested that not simply obesity but also visceral adiposity is an independent risk factor for COVID-19 complications in young adults ((1)). Interestingly, visceral fat could serve as a reservoir for the virus and amplify the inflammatory response ((4, 5)). Deng et al. reported computed tomography (CT) data of ectopic fat depots, such as liver fat and epicardial adipose tissue (EAT), in young patients with COVID-19 ((1)). EAT, the visceral fat depot of the heart, has been suggested to play a role in COVID-19 myocardial inflammation ((6-8)). Hence, we retrospectively analyzed EAT from CT scans of patients who were admitted for COVID-19. We collected data from 41 patients with laboratory-confirmed COVID-19 infection who were admitted at the Policlinico San Donato, San Donato Milanese, Milan, University of Milan, Italy, between April 1 and April 9, 2020. A confirmed case of COVID-19 was defined by a positive result on a reverse transcriptase-polymerase chain reaction assay of a specimen collected on a nasopharyngeal swab. Chest CT scan was performed on admission day 1 in patients with suspected or confirmed COVID-19 infection to evaluate the presence of pulmonary embolism. EAT measurement was retrospectively obtained from each CT scan and analyzed according to the clinical and radiological criteria defining COVID-19 severity. EAT and subcutaneous adipose tissue (SAT) density was defined as mean attenuation expressed in Hounsfield units (HU). Patients' features on admission are reported in Table 1. More than half (54%) of the patients presented clinical and CT signs of pulmonary embolism. Almost two-thirds (26) of the patients had no coronary calcium content (CAC) score, and only two patients had a severe CAC score (> 400). Overall, EAT HU was significantly greater than SAT HU (−95 vs. −118 HU; P < 0.01); mean EAT thickness was 5.5 mm. We then compared EAT attenuation between the four different groups of patients according to COVID-19 severity. EAT attenuation significantly increased with increasing COVID-19 severity, whereas SAT attenuation did not substantially change, as depicted in Figure 1. Patients with severe and critical COVID-19 had significantly greater EAT attenuation than those presenting with mild and moderate COVID-19 (P ≤ 0.01 for all the comparisons; 95% CI: −99 to −69 HU). Results were substantially similar when EAT HU was calculated with or without contrast. CT-measured EAT thickness was similar among the groups of COVID-19 severity. EAT HU was significant correlated (r = −0.45; P < 0.05) with high-sensitivity troponin T levels, while there was no significant correlation with interleukin-6 levels (r = 0.05; P = 0.76). Moreover, EAT HU was significantly correlated with peripheral oxygen saturation (r = −054; P < 0.05) and body temperature (r = −0.43; P < 0.05). EAT attenuation reflects inflammatory changes within the fat depot ((9)). In our analysis, EAT showed imaging signs of increased inflammation in patients with severe and critical COVID-19. CT-measured EAT attenuation was consensually greater with higher degree of COVID-19 severity. Remarkably, EAT attenuation was similar to that observed in coronary artery disease despite most of these patients with COVID-19 having no history of coronary artery disease and no CAC. Deng et al. ((1)) found not quite statistically significant differences in CT-EAT attenuation between patients with moderate and severe COVID-19. However, in our study, patients were older and more critical than those evaluated by Deng et al. ((1)). Hence, the lower prevalence of patients with severe COVID-19 in the study by Deng et al. may explain the lack of statistically significant difference in CT-EAT attenuation. Also, elderly participants were more likely to have myocardial inflammation and injury ((1)). Notably, we found that SAT attenuation, unlike EAT, did not progress with the severity of COVID-19. This could be somehow consistent with Deng et al. who found no difference in SAT thickness between moderate and severe patients. Although our analysis presents with some limitations, cardiac imaging, particularly CT-measured EAT attenuation, could play a diagnostic and prognostic role in patients with COVID-19 with obesity ((10)). The authors declared no conflict of interest.

A high prevalence of antiphospholipid antibodies (aPL) has been reported in patients with coronavirus disease 2019 (COVID-19). Although some studies have demonstrated roles for aPL in thrombotic events in COVID-19, findings on their association with disease development and outcomes remain heterogeneous. Therefore, this study investigated whether aPL may serve as effective markers for determining the development and outcome of COVID-19. Serum samples were isolated from whole blood of 95 individuals with moderate and severe COVID-19. The prevalence of lupus anticoagulant (LA), IgM/IgG antiphospholipid (aPL), IgM/IgG anti-β2-glycoprotein I (aβ2GPI), and IgM/IgG anticardiolipin (aCL) antibodies was measured by enzyme-linked immunosorbent assay. A mixing test was performed in patients with unexplained prolongation of activated partial thromboplastin time (aPTT) to distinguish coagulation factor deficiencies from factor inhibitors. The percentage of selected immune cells and values of biochemical markers were also assessed. Patients with severe COVID-19 showed significant increases in IgG aβ2GPI and IgG aPL antibody levels compared with individuals with moderate COVID-19 (P < 0.05). The mixing test showed that LA had an increased prevalence in severe patients with unexplained prolongation of aPTT and prothrombin time (PT) (P < 0.01-0.05). No significant differences were observed in IgM/IgG aCL, IgM aPL, or IgM aβ2GPI antibody levels between severe and moderate cases. Additional findings revealed that severe COVID-19 patients who required intensive care unit (ICU) treatment had significant increases in IgM/IgG aPL, IgM/IgG aCL, and IgM/IgG aβ2GPI antibodies (P < 0.01-0.05). However, there was no significant change in the prevalence of LA or IgM aβ2GPI antibodies between severe patients who required ICU therapy and those who did not. IgM aCL and IgG aPL values were significantly higher in non-survivors compared with survivors (P < 0.001-0.05). A similar trend was observed for IgG aCL and IgM aPL levels in non-survivors, although these increases were not statistically significant. Changes in aPL levels may be considered effective markers for clarifying the severity and outcome of COVID-19. Not applicable.

Does MAFLD really increase the severity of COVID-19?

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.

Background: Limited clinical data are available regarding the impacts of coronavirus disease 2019 (COVID-19) on children. Objective: This study assessed the clinical characteristics, nutritional status, and disease severity in pediatric patients with COVID-19. Methods: A retrospective study examined medical records of children with COVID-19 admitted to Abuzar Hospital (Ahvaz, Iran) for nine months. Data related to their clinical, nutritional status and demographic characteristics were documented. Results: The present study included medical records of 500 patients. More than half of them were boys. Different levels of COVID-19 severity were observed in 202, 172, and 126 children as mild, moderate, and severe cases, respectively. Children with severe or moderate COVID-19 had substantially elevated levels of various inflammatory markers, blood urea nitrogen (BUN), gamma-glutamyl transferase (GGT), neutrophils, alanine transaminase (ALT), creatinine, bilirubin, and aspartate aminotransferase (AST) compared to those with mild COVID-19 (p &lt; 0.001). They had lower levels of lymphocytes and vitamin D, as well as longer hospital stays than children with mild COVID-19 (p &lt; 0.001). In addition, 52% and 40.2% of patients had malnutrition and anemia, respectively. The majority of underweight and stunted children had moderate or severe COVID-19. Conclusion: The current study revealed a high prevalence of malnutrition, anemia, insufficient levels of vitamin D, elevated levels of inflammatory markers, and abnormal liver and kidney function tests in children with severe or moderate cases of COVID-19 compared to those with mild COVID-19.

Presepsin, a cleaved peptide of soluble CD14, may become a promising biomarker for assessing disease severity and mortality in coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 frequently develop bacterial and fungal superinfections, as well as herpes simplex virus-1 (HSV-1) reactivation, which may exacerbate disease progression. This study aimed to evaluate the impact of concomitant infections on serum presepsin levels. Serum presepsin levels were measured using an enzyme-linked immunosorbent assay (ELISA) in 63 patients with moderate COVID-19, 60 patients with severe disease, and 49 healthy controls. Correlations with procalcitonin and the presence of superinfections or HSV-1 reactivation were assessed. Consistent with previous studies, serum presepsin levels were the highest in patients with severe COVID-19 (p = 0.002 compared to patients with moderate disease). Within this group, non-survivors exhibited significantly elevated presepsin levels (p = 0.027). A positive correlation between presepsin and procalcitonin was observed in both moderate and severe COVID-19 cases. Patients with bacterial or fungal superinfections showed presepsin levels comparable to those without secondary infections. However, presepsin levels were markedly elevated in patients with HSV-1 reactivation (p = 0.002). After excluding patients with HSV-1 reactivation, presepsin levels no longer differed between moderate and severe COVID-19 cases, though they remained higher than in healthy controls (p < 0.001 for both comparisons). In conclusion, these findings suggest that elevated serum presepsin levels in severe COVID-19 are primarily driven by HSV-1 reactivation rather than bacterial or fungal superinfections.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Knowing the severity of COVID-19 is important during a pandemic. Measurement of Lactate Dehydrogenase (LDH) levels is a simple, quick, and widely available laboratory test in most health facilities. Lactate dehydrogenase levels change significantly in patients with tissue damage including COVID-19 disease. The purpose of this study was to analyze the LDH levels as a marker of the severity of COVID-19. The research method used was a cross-sectional approach using primary data from 70 suspected COVID-19 patients from June to July 2021 at Labuang Baji Hospital, Hasanuddin University Hospital, and Makassar City Hospital. Samples were grouped into mild, moderate, and severe COVID-19. The LDH levels at the time of hospital admission were measured using an Architect device. Chi-Square, Kruskal-Wallis, and ROC curve statistical tests were used to obtain the LDH value with a significant value of p&lt;0.05. The sample consisted of 24 mild COVID-19, 23 moderate COVID-19, and 23 severe COVID-19. The LDH levels in mild COVID-19 were 101.00 U/L (74.00-156.00 U/L) significantly different from moderate COVID-19 was 143.00 U/L (126.00-253.00 U/L) and COVID-19 were 291.00 U/L (177.00-655.00 U/L) (p&lt;0.001) and had a very strong positive correlation (r=0.914). The ROC curve showed that LDH had a sensitivity of 91.3%, specificity of 94.7% with the cut-off &gt;250.5 U/L, NPV of 96.4%, PPV of 87.5%, and accuracy of 91.3%. LDH levels increase along with the increasing severity of COVID-19 caused by tissue damage due to increased inflammatory response. LDH can be used as a marker of COVID-19 severity.

In this secondary analysis, we aimed to characterize the lymphocytes population and placental inflammation in pregnant women with moderate and severe coronavirus disease 2019 (COVID-19) forms. In the analysis of this prospective evaluation, we included 26 pregnant women at term with moderate and severe COVID-19 forms that were evaluated in a tertiary maternity center in a one-year timeframe. Clinical data, along with blood immunophenotyping results and placental histopathological examinations were comparatively evaluated between two study groups depending on the COVID-19 severity: Group 1 (moderate COVID-19, n=14 patients) and Group 2 (severe COVID-19, n=12 patients). Pregnant patients with severe COVID-19 presented significantly lower total amount of lymphocytes (p<0.001), T-lymphocytes (p=0.009), cluster of differentiation (CD)4+ T-cells (p=0.002), B-lymphocytes (p=0.001). Also, the number of CD4+ T-cells (p=0.01), CD8+ T-cells (p=0.02) and B-lymphocytes (p=0.002) was lower enough for cases with severe COVID-19. Lymphocytopenia could be a useful hematological marker for risk stratification of COVID-19 in pregnant women at term. A vertical transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cannot be confirmed in this study, mainly because of the limited sample size and short timeframe between infection and birth.

Since the emergence of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) in Wuhan, China, it has been extensively studied by many scientists. Susceptibility to SARS-CoV-2 infection is shown by people of all ages, especially those with different comorbidities. Our goal was to describe the clinical characteristics, treatment, course, and outcome of COVID-19 in patients with pre-existing neurological disorders. We retrospectively studied 70 patients with COVID-19 and previous neurological diseases who were treated in the Central Clinical Hospital of the Ministry of the Interior and Administration from 16 March to 15 June 2020. Demographic data, symptoms, image data, laboratory results, treatment methods and results, clinical signs and symptoms of patients hospitalised due to CNS diseases with COVID-19 were collected. The average age of hospitalised patients was 72, and the majority (63%) were women (44/70). The most common neurological disease was dementia, which was present in almost a third of patients (30.76%), followed by ischaemic stroke (24.61%). Chest imaging showed the presence of interstitial changes in 47% (33) of patients. Laboratory tests revealed increased total blood cells, increased levels of C-reactive protein, procalcitonin, D-dimers, liver indicator markers and IL-6 in the most severely affected patients. The treatment of patients was focused on monitoring their clinical condition, and supporting respiratory inefficiency with passive oxygen therapy and mechanical ventilation. According to the guidelines of the Hospital Therapeutic Committee, pharmacological treatment (Arechin®, Kaletra®) was introduced in cases without contraindications. In patients with moderate COVID-19, antimalarial or antiviral agents were applied (78%). 30% of our observed patients died during the hospitalisation. We studied a select group of patients (elderly, with comorbidities, and moderate or severe COVID-19 course). Pre-existing neurological disorders were additionally associated with a poorer prognosis and a high fatality rate (30%). Dementia and CNS vascular disorder were the most frequent pre-existing neurological conditions. The neurological symptoms of COVID-19 were various. We observed impaired consciousness, dizziness, headache, nausea, myalgia, psychomotor agitation and slowness, delirium, and psychoses. Further analysis is needed to elucidate the incidence of COVID-19 neurological complications.

Metabolic biomarkers measured from single blood test can identify apparently healthy people at high susceptibility for developing severe pneumonia, and may also be useful for preventive COVID-19 screening.

Background: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that is produced at varying levels in patients with coronavirus disease 2019 (COVID-19). The neutrophil-lymphocyte ratio (NLR) is one of the new inflammatory markers of COVID-19. This study aimed to evaluate the differences in IL-6 level and the NLR in mild and severe COVID-19 and assess their correlation with COVID-19 severity and the correlation of IL-6 and NLR in COVID-19. Methods: A total of 91 patients with COVID-19 were divided into mild (n = 57) and severe (n = 34) COVID-19 groups. IL-6 levels were measured using the electrochemiluminescence immunoassay method on Roche Cobas e411. The NLR was the ratio of the total neutrophil and lymphocyte counts from complete haematology on the Sysmex XS-800i. Data were analysed using the Kolmogorov-Smirnov, Mann-Whitney, receiver operating characteristic curve, chi-square and Spearman correlation tests. The statistical test was significant at p <0.05. Results: Serum IL-6 levels and NLR significantly differed in mild and severe COVID-19. The median (min-max) IL-6 levels for mild and severe COVID-19 were 3.59 (1.50-638.30) pg/mL and 28.82 (5.52-926.30) pg/mL, respectively (p <0.001). The median (min-max) NLR in mild and moderate COVID-19 was 2.18 (0.69-15.58) and 8.13 (2.24-30.90), respectively (p <0.001). The obtained cut-off values for IL-6 and NLR were >6.99 pg/mL and >4.18, with odds ratios of 29.29 and 26.19, respectively. A positive correlation was found between IL-6 and NLR and COVID-19 severity (r = 0.612; p <0.001). Conclusions: The results indicated that serum IL-6 levels and NLR are higher in severe COVID-19 than in mild COVID-19. Patients with IL-6 levels >6.99 pg/mL and NLR >4.18 are 29 and 26 times more likely to suffer from severe COVID-19, respectively. Serum IL-6 levels and NLR are strongly correlated with COVID-19 severity. Serum IL-6 levels correlate with NLR in COVID-19.

Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic.

This study aimed to develop a prediction model that estimates the probability that a pregnant person who has had asymptomatic or mild coronavirus disease 2019 (COVID-19) prior to delivery admission will progress in severity to moderate, severe, or critical COVID-19. This was a secondary analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients who delivered from March through December 2020 at hospitals across the United States. Those eligible for this analysis presented for delivery with a current or previous asymptomatic or mild SARS-CoV-2 infection. The primary outcome was moderate, severe, or critical COVID-19 during the delivery admission through 42 days postpartum. The prediction model was developed and internally validated using stratified cross-validation with stepwise backward elimination, incorporating only variables that were known on the day of hospital admission. Of the 2,818 patients included, 26 (0.9%; 95% confidence interval [CI], 0.6-1.3%) developed moderate-severe-critical COVID-19 during the study period. Variables in the prediction model were gestational age at delivery admission (adjusted odds ratio [aOR], 1.15; 95% CI, 1.08-1.22 per 1-week decrease), a hypertensive disorder in a prior pregnancy (aOR 3.05; 95% CI, 1.25-7.46), and systolic blood pressure at admission (aOR, 1.04; 95% CI, 1.02-1.05 per mm Hg increase). This model yielded an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.72-0.91). Among individuals presenting for delivery who had asymptomatic-mild COVID-19, gestational age at delivery admission, a hypertensive disorder in a prior pregnancy, and systolic blood pressure at admission were predictive of delivering with moderate, severe, or critical COVID-19. This prediction model may be a useful tool to optimize resources for SARS-CoV-2-infected pregnant individuals admitted for delivery. · Three factors were associated with delivery with more severe COVID-19.. · The developed model yielded an area under the receiver operating characteristic curve of 0.82 and model fit was good.. · The model may be useful tool for SARS-CoV-2 infected pregnancies admitted for delivery..