Evaluation of IGFBP5 expression and plasma osteopontin level in COVID-19 patients

PurposeThe aim of this study is to investigate insulin-like growth factor binding protein 5 (IGFBP5) expression in coronavirus disease 2019 (COVID-19) patients and its relationships with COVID-19 laboratory findings and plasma osteopontin (OPN) levels.Materials and methodsWe enrolled 60 patients with COVID-19 and 30 healthy individuals in this study. mRNA expression of IGFBP5 was measured by RT-PCR. Plasma OPN levels were measured via the ELISA method.ResultsPlasma OPN levels were higher and IGFBP5 expression levels were lower in COVID-19 patients than in the healthy individuals (p ?= ?0.0057 and p ?= ?0.0142, respectively). Critically ill patients had higher OPN and lower IGFBP5 than non-critically ill patients. Patients with affected lungs demonstrated increased OPN and decreased IGFBP5 (p ?= ?0.00032 and p ?= ?0.044, respectively). Receiver operating characteristic (ROC) analysis indicated that IGFBP5 expression and OPN levels can be used discriminate non-critically from critically ill patients (p ?= ?0.049; p ?= ?0.0016, respectively).ConclusionThis study demonstrated that patients with a poor prognosis had increased OPN and decreased IGFBP5. High values of OPN and low values of IGFBP5 may be considered as signs of disease severity. Tissue-specific IGFBP5 expression may contribute to understanding the role of IGFBP5 in the lungs in COVID-19 cases.     

Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC)

PurposeThere is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE).Patients and methodsFifty-one participants (PBC group – 38 patients, all patients but one Child-Pugh A; control group – 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE.ResultsThe sGPV levels were higher in the PBC group compared to the controls: 36.07 ?± ?11.32 ?ng/mL vs 27.04 ?± ?11.72 ?ng/mL, p ?= ?0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83–58.83) sec. vs 45.90 (43.3–50.5) sec., p ?= ?0.0065. PPL levels were correlated with platelet count (rho ?= ??0.46, p ?= ?0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE.ConclusionsWe have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.     

Presence of diarrhea associated with better outcomes in patients with COVID-19 – A prospective evaluation

PurposeGastrointestinal (GI) manifestations have been well documented in patients with coronavirus disease 2019 (COVID-19), but its clinical impact on the course of the disease is debatable. Majority of the available data is retrospective, and hence this prospective study was planned to study the impact of GI symptoms on COVID-19 outcome.MethodsAll COVID-19 patients admitted in a tertiary care centre from August–October 2020 were screened and patients without pre-existing GI diseases were included. A detailed history of the various symptoms including duration was documented. Various baseline laboratory investigations and inflammatory markers were conducted as per the protocol. Patients with and without diarrhea were compared for the various disease outcome parameters.ResultsOf the 244 patients screened, 203 patients (128 males; 63.1%) were included. Respiratory symptoms alone were present in 49 (24.1%), GI symptoms alone in 20 (9.9%) and 117 (57.6%) had both. Overall GI symptoms was noted in 137 (67.5%) cases with the commonest being diarrhea (61; 30.0%). Patients with both respiratory and any GI symptoms showed a lower trend towards need for mechanical ventilation (12.2% vs 7.7%; p ?= ?0.35) and mortality (10.2% vs 4.3%; p ?= ?0.14) compared to respiratory symptoms alone, although not statistically significant. Patients with diarrhea (n ?= ?61) had no mortality (0% vs 7.7%; p ?= ?0.036) or need for mechanical ventilation and shorter hospital stay compared to those who did not have diarrhea.ConclusionGI symptoms are frequent in patients with SARS-CoV-2 infection and the commonest is diarrhea. Diarrhea is a harbinger of better outcome with lower mortality among COVID-19 positive patients.     

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study

ObjectivesIntravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients.MethodsThis retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors.ResultsThe study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI –0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = –0.022, 95% CI –0.041 to –0.002, p 0.028).DiscussionIVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.     

Eosinopenia <100/μL as a marker of active COVID-19: An observational prospective study

ObjectivesTo analyse the diagnostic performance of eosinopenia, alone or combined with polymorphonuclear neutrophils (PMN) and/or lymphocytes, as a marker of active COVID-19 in patients hospitalized for suspicion of SARS-CoV-2 infection.MethodsA prospective observational study including patients hospitalized for suspicion of COVID-19 in a COVID unit was performed from 20th March to 5th April 2020, in Perpignan, France. Patients for which there was a doubt upon diagnosis, who were recently under oral corticosteroids, had myeloid malignancy or human immunodeficient virus infection were excluded. SARS-CoV-2 detection was performed using an RT-PCR assay, from nasopharyngeal swab specimens. Complete blood count were performed for all patients.ResultsOne-hundred and twenty-one patient were included: 57 patients were diagnosed with COVID-19, 64 patients were not. Eosinophil count was lower in the COVID-19 group (median: 0/μL versus 70/μL, p < 0.0001). To diagnose COVID-19, eosinopenia had a sensitivity of 89.5% and a specificity of 78.1% while lymphopenia's were 73.7% and 62.5% respectively. Using area under curve (AUC) of receiving operating characteristics (ROC) curves, eosinophil's optimal cut-off level was 10/μL, sensitivity and specificity were 86%, and 79.7% respectively. Regarding the eosinophil/PMN ratio, the optimal cut-off level was 3.344, sensitivity and specificity were 87.7% and 73.4% respectively. The AUC of lymphocyte/PMN ratio was significantly lower than eosinophil/PMN ratio's (0.621 versus 0.846, p = 0.0003).ConclusionEosinopenia – <10/μL – and eosinophil/PMN ratio are useful, low-cost, reproducible tools to help diagnose COVID-19, during an epidemic period, in a population of hospitalized patients admitted for suspicion of COVID-19.     

The levels of IL-1β and soluble IL-1 receptors in patients with IgG4-related periaortitis/periarteritis

PurposeIgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory and an immune-mediated disease characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system, and its pathogenesis and characteristics remain unclear.The inflammatory cytokine IL-1β is involved in a variety of cellular activities including inflammation, fibrosis, and angiogenesis. The present study compared the levels of the inflammatory cytokine IL-1β and two soluble IL-1 receptors, IL-1R1 and IL-1R2, between IgG4-RD patients with and without IgG4-related periaortitis/periarteritis.MethodsThe patients with IgG4-related periaortitis/periarteritis (n ?= ?38), those without (n ?= ?66) and healthy (n ?= ?33) were recruited to measure cytokines of IL-1β and soluble receptors (sIL-1R1 and sIL-1R2) in sera by ELISA assay.ResultsSerum IgG4 was significantly higher in patients with periaortitis/periarteritis compared to non-periaortitis/periarteritis (p ?= ?0.0074), while serum IL-1β was significantly lower in patients with periaortitis/periarteritis (p ?= ?0.00037).The three groups did not show significant difference in sIL1-R1, while sIL-1R2 in the periaortitis/periarteritis and healthy group was higher than in the group without periaortitis/periarteritis (p ?= ?0.00001).ConclusionsThe characteristic changes in IL-1β, sIL-1R1, and sIL-1R2 levels in IgG4-RD patients with and without IgG4-related periaortitis/periarteritis may indicate an active phase of the inflammatory process in these diseases.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

COVID-19 and geographical area of origin

ObjectivesTo describe and compare the main clinical characteristics and outcome measures in hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) according to geographical area of origin.MethodsA retrospective analysis of patients hospitalized with confirmed COVID-19 at a referral centre in Madrid, Spain, during March–May 2020 was performed. Recorded variables (age, gender, intensive care unit (ICU) admission, outcome), and geographical area of origin were compared for Europeans and non-Europeans (Latin Americans, Asians and Africans).ResultsIn total, 2345 patients with confirmed COVID-19 hospitalized during the study period were included in the study. Of these, 1956 (83.4%) were European and 389 (16.6%) were non-European (of whom over 90%, 354/389, were Latin American). Non-Europeans were significantly younger than Europeans (mean 54 (SD 13.5) versus 70.4 (SD 15.1) years, p < 0.001); the majority were male (1420/2345, 60.6%), with no significant differences in gender between Europeans and non-Europeans (1197/1956 (61.2%) male in the European group versus 223/389 (57.3%) male in the non-European group, p 0.15). In-hospital mortality overall was higher in Europeans (443/1956, 22.7%) than in non-Europeans (40/389, 10.3%) (p < 0.001), but there were no significant differences when adjusted for age/gender (OR 1.27, 95% CI 0.86–1.88). Non-Europeans were more frequently admitted to ICU (71/389, 18.3%) compared with Europeans (187/1956, 9.6%) (p < 0.001) and a difference in ICU admission rate was also found when adjusted for age/gender (OR 1.43, 95% CI 1.03–1.98).ConclusionsNo significant differences in mortality were observed between Europeans and non-Europeans (mainly Latin Americans), but an increase in ICU admission rate was found in non-Europeans.     

Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

ObjectivesThe main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis.MethodsWe conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise.ResultsProbable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1–8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01).ConclusionIPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.     

Predictors of poor prognosis in healthy,young, individuals with SARS-CoV-2 infections

ObjectivesTo identify predictors of poor prognosis in previously healthy young individuals admitted to hospital with coronavirus disease 2019 (COVID-19).MethodsWe studied a cohort of patients hospitalized with COVID-19. All patients without co-morbidities, without usual treatments and ≤65 years old were selected from an international registry (HOPE-COVID-19, NCT04334291). We focused on baseline variables—symptoms and signs at admission—to analyse risk factors for poor prognosis. The primary end point was a composite of major adverse clinical events during hospitalization including mortality, mechanical ventilation, high-flow nasal oxygen therapy, prone, sepsis, systemic inflammatory response syndrome and embolic events.ResultsOverall, 773 healthy young patients were included. The primary composite end point was observed in 29% (225/773) and the overall mortality rate was 3.6% (28/773). In the combined event group, 75% (168/225) of patients were men and the mean age was 49 (±11) years, whereas in the non-combined event group, the prevalence of male gender was 43% (238/548) and the mean age was 42 (±13) years (p < 0.001 for both). On admission, respiratory insufficiency and cough were described in 51.4% (114/222) and 76% (170/223) of patients, respectively, in the combined event group, versus 7.9% (42/533) and 56% (302/543) of patients in the other group (p < 0.001 for both). The strongest independent predictor for the combined end point was desaturation (Spo₂ <92%) (OR 5.40; 95% CI 3.34–8.75; p < 0.001), followed by tachypnoea (OR 3.17; 95% CI 1.93–5.21; p < 0.001), male gender (OR 3.01; 95% CI 1.96–4.61; p < 0.001) and pulmonary infiltrates on chest X-ray at admission (OR 2.21; 95% CI 1.18–4.16; p 0.014).ConclusionsMajor adverse clinical events were unexpectedly high considering the baseline characteristics of the cohort. Signs of respiratory compromise at admission and male gender, were predictive for poor prognosis among young healthy patients hospitalized with COVID-19.     

N-antigenemia detection by a rapid lateral flow test predicts 90-day mortality in COVID-19: A prospective cohort study

ObjectivesTo evaluate if the detection of N antigen of SARS-CoV-2 in plasma by a rapid lateral flow test predicts 90-day mortality in COVID-19 patients hospitalized at the wards.MethodsThe presence of N-antigenemia was evaluated in the first 36 hours after hospitalization in 600 unvaccinated COVID-19 patients, by using the Panbio COVID-19 Ag Rapid Test Device from Abbott (Abbott Laboratories Inc., Chicago, IL, USA). The impact of N-antigenemia on 90-day mortality was assessed by multivariable Cox regression analysis.ResultsPrevalence of N-antigenemia at hospitalization was higher in nonsurvivors (69% (82/118) vs. 52% (250/482); p < 0.001). The patients with N-antigenemia showed more frequently RNAemia (45.7% (148/324) vs. 19.8% (51/257); p < 0.001), absence of anti-SARS-CoV-2 N antibodies (80.7% (264/327) vs. 26.6% (69/259); p < 0.001) and absence of S1 antibodies (73.4% (240/327) vs. 23.6% (61/259); p < 0.001). The patients with antigenemia showed more frequently acute respiratory distress syndrome (30.1% (100/332) vs. 18.7% (50/268); p = 0.001) and nosocomial infections (13.6% (45/331) vs. 7.9% (21/267); p = 0.026). N-antigenemia was a risk factor for increased 90-day mortality in the multivariable analysis (HR, 1.99 (95% CI,1.09–3.61), whereas the presence of anti-SARS-CoV-2 N-antibodies represented a protective factor (HR, 0.47 (95% CI, 0.26–0.85).DiscussionThe presence of N-antigenemia or the absence of anti-SARS-CoV-2 N-antibodies after hospitalization is associated to increased 90-day mortality in unvaccinated COVID-19 patients. Detection of N-antigenemia by using lateral flow tests is a quick, widely available tool that could contribute to early identify those COVID-19 patients at risk of deterioration.     

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression

ObjectivesD-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19.MethodsA literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468).ResultsThirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I² ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001).ConclusionsProlonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.     

Serum CK-MB,COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression

ObjectivesWe conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients.MethodsWe searched PubMed, Web of Science and Scopus, for studies published between January 2020 and January 2021 that reported CK-MB, COVID-19 severity and mortality (PROSPERO registration number: CRD42021239657).ResultsFifty-five studies in 11,791 COVID-19 patients were included in the meta-analysis. The pooled results showed that CK-MB concentrations were significantly higher in patients with high disease severity or non-survivor status than patients with low severity or survivor status (standardized mean difference, SMD, 0.81, 95% CI 0.61 to 1.01, p<0.001). The rate of patients with CK-MB values above the normal range was also significantly higher in the former than the latter (60/350 vs 98/1,780; RR ​= ​2.84, 95%CI 1.89 to 4.27, p<0.001; I² ​= ​19.9, p ​= ​0.254). Extreme between-study heterogeneity was observed (I² ​= ​93.4%, p<0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified (effect size range, 0.77 to 0.84). Begg's (p ​= ​0.50) and Egger's (p ​= ​0.86) t-tests did not show publication bias. In meta-regression analysis, the SMD was significantly and positively associated with the white blood count, aspartate aminotransferase, myoglobin, troponin, brain natriuretic peptide, lactate dehydrogenase, and D-dimer.ConclusionsHigher CK-MB concentrations were significantly associated with severe disease and mortality in COVID-19 patients. This biomarker of myocardial injury might be useful for risk stratification in this group.     

The caspase-8 and procaspase-3 expression in gastric cancer and non-cancer mucosa in relation to clinico-morphological factors and some apoptosis-associated proteins

PurposeThe aim of the study was to assess the expression of caspase-8 and procaspase-3 proteins in gastric cancer (GC) cells and non-cancerous mucosa in relation to clinical and morphological characteristics of the tumor, postoperative survival as well as other apoptosis-related proteins.Materials and methodsThe study included 91 ?GC patients. Expression of the proteins was assessed using immunohistochemical method.ResultsPositive expression of procaspase-3 was found in all GC cells. A significant difference was found between high expression of this protein in cancer cells (70.3%) and non-cancerous mucosa (1.25%) (p ?≤ ?0.05). Caspase-8 expression was observed in 50.7% of GC cells and 46.7% of mucosa. Caspase-8 was more common in Lauren type II compared to Lauren type I cancer (p ?= ?0.009), while a statistically significant difference was reported between positive procaspase-3 expression and differentiation of GC (p ?= ?0.043) and Lauren's classification (p ?= ?0.028). We observed a significant positive correlation between the expression of caspase-8 and bcl-xl (p ?= ?0.030) as well as between the procaspase-3 and BID (p ?= ?0.026). Positive caspase-8 expression was associated with longer survival of GC patients (p ?≤ ?0.01).ConclusionsOur findings indicate the potential role of the analyzed proteins in GC pathogenesis. Positive expression of caspase-8 is associated with longer survival and better patient prognosis.     

HLA B53 is associated with a poor outcome in black COVID-19 patients

A disproportionate incidence of death has occurred in African Americans (Blacks) in the United States due to COVID-19. The reason for this disparity is likely to be multi-factorial and may involve genetic predisposition. The association of human leukocyte antigens (HLA) with severe COVID-19 was examined in a hospitalized population (89% Black, n = 36) and compared to HLA typed non-hospitalized individuals (20% Black, n = 40) who had recovered from mild disease. For additional comparison, HLA typing data was available from kidney transplant recipients and deceased donors. Hospitalized patients were followed for 45 days after admission to our medical center with death as the primary end-point. One HLA allele, B53, appeared to be more prevalent in the hospitalized COVID-19 patients (percent of positive subjects, 30.5) compared to national data in US Black populations (percent of positive subjects, 24.5). The percent B53 positive in non-hospitalized COVID-19 patients was 2.6, significantly less than the percent positive in the hospitalized COVID-19 patients (p = 0.001, Fisher’s exact test) and less than the 8 percent positive listed in national data bases for US Caucasian populations. Significantly greater deaths (73 percent) were observed in HLA B53 positive hospitalized COVID-19 patients compared to hospitalized COVID-19 patients who were B53 negative (40 percent). Multi-variate analysis indicated that HLA B53 positive Black hospitalized COVID-19 patients were at a 7.4 fold greater risk of death than Black COVID-19 patients who were B53 negative. Consideration for accelerated vaccination and treatment should be given to HLA B53 positive Black COVID19 patients.     

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study)

PurposeThe aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement.Material and methodsThe study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants).ResultsSignificant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p ?< ?0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p ?< ?0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p ?< ?0.05).Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 ?pg/ml (OR-2.14), D-dimer concentration over 1000 ?ng/ml (OR-1.62) and PLT count below 150,000/μl (OR-1.57).ConclusionsSevere course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 ?pg/ml, D-dimer>1000 ?ng/ml and PLT<150,000/μl.     

National surveillance of bacterial and fungal coinfection and secondary infection in COVID-19 patients in England: lessons from the first wave

ObjectivesThe impact of bacterial/fungal infections on the morbidity and mortality of persons with coronavirus disease 2019 (COVID-19) remains unclear. We have investigated the incidence and impact of key bacterial/fungal infections in persons with COVID-19 in England.MethodsWe extracted laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (1st January 2020 to 2nd June 2020) and blood and lower-respiratory specimens positive for 24 genera/species of clinical relevance (1st January 2020 to 30th June 2020) from Public Health England's national laboratory surveillance system. We defined coinfection and secondary infection as a culture-positive key organism isolated within 1 day or 2–27 days, respectively, of the SARS-CoV-2-positive date. We described the incidence and timing of bacterial/fungal infections and compared characteristics of COVID-19 patients with and without bacterial/fungal infection.Results1% of persons with COVID-19 (2279/223413) in England had coinfection/secondary infection, of which >65% were bloodstream infections. The most common causative organisms were Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Cases with coinfection/secondary infections were older than those without (median 70 years (IQR 58–81) versus 55 years (IQR 38–77)), and a higher percentage of cases with secondary infection were of Black or Asian ethnicity than cases without (6.7% versus 4.1%, and 9.9% versus 8.2%, respectively, p < 0.001). Age-sex-adjusted case fatality rates were higher in COVID-19 cases with a coinfection (23.0% (95%CI 18.8–27.6%)) or secondary infection (26.5% (95%CI 14.5–39.4%)) than in those without (7.6% (95%CI 7.5–7.7%)) (p < 0.005).ConclusionsCoinfection/secondary bacterial/fungal infections were rare in non-hospitalized and hospitalized persons with COVID-19, varied by ethnicity and age, and were associated with higher mortality. However, the inclusion of non-hospitalized persons with asymptomatic/mild COVID-19 likely underestimated the rate of secondary bacterial/fungal infections. This should inform diagnostic testing and antibiotic prescribing strategy.     

Post–COVID-19 syndrome and humoral response association after 1 year in vaccinated and unvaccinated patients

ObjectivesThis study aimed to describe the impact of vaccination and the role of humoral responses on post–COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2).MethodsThis prospective study was conducted through interviews to investigate post–COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March–May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed.ResultsA total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post–COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post–COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post–COVID-19 syndrome (OR: 1.35; 95% CI, 1.11–1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7–37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4–31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post–COVID-19 syndrome (>2500 U/mL vs. 0.9–2500 U/mL; OR: 1.36; 95% CI, 0.62–3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451).DiscussionThe SARS-CoV-2 vaccination is not associated with the emergence of post–COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19.     

Application of a solid-phase microextraction-gas chromatography-mass spectrometry/metal oxide sensor system for detection of antibiotic susceptibility in urinary tract infection-causing Escherichia coli – A proof of principle study

PurposeAntibiotic resistance is widespread throughout the world and represents a serious health concern. There is an urgent need for the development of novel tools for rapidly distinguishing antibiotic resistant bacteria from susceptible strains. Previous work has demonstrated that differences in antimicrobial susceptibility can be reflected in differences in the profile of volatile organic compounds (VOCs) produced by dissimilar strains. The aim of this study was to investigate the effect of the presence of cephalosporin antibiotics on the VOC profile of extended spectrum beta-lactamase (ESBL) and non-ESBL producing strains of Escherichia coli.Material and methodsIn this study, VOCs from strains of Escherichia coli positive and negative for the most commonly encountered ESBL, CTX-M in the presence of cephalosporin antibiotics were assessed using solid-phase microextraction (SPME) coupled with a combined gas chromatography-mass spectrometry/metal oxide sensor (GC-MS/MOS) system.ResultsOur proof-of-concept study allowed for distinguishing CTX-M positive and negative bacteria within 2 ?h after the addition of antibiotics. One MOS signal (RT: 22.6) showed a statistically significant three-way interaction (p ?= ?0.033) in addition to significant two-way interactions for culture and additive (p ?= ?0.046) plus time and additive (p ?= ?0.020). There were also significant effects observed for time (p ?= ?0.009), culture (p ?= ?0.030) and additive (p ?= ?0.028). No effects were observed in the MS data.ConclusionsThe results of our study showed the potential of VOC analysis using SPME combined with a GC-MS/MOS system for the early detection of CTX-M-producing, antibiotic-resistant E. coli, responsible for urinary tract infections (UTIs).     

Reduced susceptibility to COVID-19 associated with ABO blood group and pre-existing anti-A and anti-B antibodies

BackgroundSusceptibility to severe acute respiratory syndrome coronavirus 2 shows individual variability in un-vaccinated and previously un-exposed individuals. We investigated the impact of ABO blood group, titers of anti-A and anti-B, other blood group antigens, and the extracellular deposition of ABH antigens as controlled by secretor fucosyltransferase 2 (FUT2) status.Study design and methodsWe studied incidents in three different hospitals between April to September 2020, where un-diagnosed coronavirus disease 2019 (COVID-19) patients were cared for by health care workers without use of personal protection and with close contact while delivering therapy. We recruited 108 exposed staff, of whom 34 were diagnosed with COVID-19. ABO blood type, titer of anti-A and -B, blood group specific alleles, and secretor status were determined.ResultsBlood group O was associated with lower risk of COVID-19 (OR 0.39, 95 %CI (0.16–0.92), p = 0.03) compared to non-O, i.e., blood groups A, B and AB. High titer anti-A immunoglobulin G (IgG) compared to low titer was associated with lower risk of COVID-19 (OR 0.24 95 %CI (0.07–0.78), p = 0.017). High titer of anti-B immunoglobulin M (IgM) compared to no anti-B (IgM) was associated with lower risk of COVID-19 (OR 0.16, 95 %CI (0.039–0.608), p = 0.006) and the same applies to low titer anti-B (IgM) compared to no titer (OR 0.23, 95 %CI (0.07–0.72), p = 0.012).The 33Pro variant in Integrin beta-3, that is part of human platelet antigen 1b (HPA-1b), was associated with lower risk of COVID-19 (OR 0.23, 95 %CI (0.034–0.86), p = 0.028).ConclusionOur data showed that blood group O, anti-A (IgG) titer, anti-B (IgM) titer as well as HPA-1b are associated with lower risk for COVID-19.