Background: During the COVID pandemic increased rates of intensive care unit (ICU) admission, mechanical ventilation, caesarean delivery, and preterm birth among women with SARS-CoV-2 infection in pregnancy were recorded. Purpose: This study describes the clinical course and perinatal outcomes of pregnant women with COVID-19 across pre- and post-vaccination periods. Methods: This study included all pregnant women with confirmed SARS-CoV-2 infection who subsequently delivered at the University General Hospital of Larissa between March 2020 and May 2023. Demographics, comorbidities, gestational age at infection and at delivery, COVID-19 symptoms, need for hospitalization, obstetric complications, mode of delivery, and neonatal outcomes were documented. An assessment of ischemia-modified albumin (IMA) was performed in a subset of women. Results: A total of 327 women (including 14 twin gestations) were recorded. Most women experienced mild disease while a minority required hospital admission, or intensive care (1.8 and 0.3% for the studied population, respectively). Fever and upper respiratory symptoms predominated, while radiologic evidence of pneumonia was rare. Overall preterm birth (<37 weeks) occurred in 13% of pregnancies and caesarean section in about two thirds of deliveries. Neonatal outcomes were favorable, with low rates of neonatal intensive care unit (NICU) admission and no early neonatal deaths. IMA values were higher during acute infection and declined towards recovery. Conclusion: Pregnant women with COVID-19 in Central Greece had predominantly mild clinical courses and excellent perinatal outcomes. IMA may represent a biologically plausible marker of disease activity, but further studies are needed.

BackgroundPatients with COVID-19 can rapidly deteriorate and develop acute hypoxic respiratory failure. Prominent features of the disease include severe inflammation, endotheliitis, and thrombosis.ObjectivesThe aim of the study was to evaluate the diagnostic and prognostic effectiveness of ischemia modified albumin (ΙΜΑ) in a cohort of COVID-19 patients.MethodsThis prospective observational study included adults with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction test, who were hospitalized specifically for COVID-19. The outcomes of interest were progression to severe acute respiratory failure during the index hospitalization defined as partial pressure of oxygen/fraction of inspired oxygen lower or equal to 150, admission to the intensive care unit (ICU) and in-hospital mortality. Admission IMA levels were determined using the commercially available “IMA Assay Kit” method (Abbexa LTD, Cambridge, UK). Adults without SARS-CoV-2 infection were used as controls.Results135 COVID-19 patients and 64 controls were included. Admission IMA levels were significantly higher in COVID-19 patients compared to controls [[24.38 (11.94) ng/ml vs. 14.69 (3.52) ng/ml, p < 0.01]. Receiver operating characteristic analysis of admission IMA showed an area under the curve (AUC) of 94% (p < 0.0001) for COVID-19 diagnosis (cut-off value: 17.5 ng/ml; sensitivity: 90.37%; specificity: 87.5%). Admission IMA was also associated with mortality (AUC: 68%, p = 0.01). However, it was not associated with severe acute respiratory failure (AUC: 47%, p = 0.53) or ICU admission (AUC: 58%, p = 0.41).ConclusionAdmission IMA was significantly increased in COVID-19 patients and was associated with in-hospital mortality.

Background: The clinical significance of combinations of inflammatory biomarkers in severe COVID-19 infection is yet to be proved. Although several studies have evaluated the prognostic value of biomarkers in patients with COVID-19, there are limited data regarding the value of the combination scores that could take full advantage of the prognostic value of several biomarkers and that could account for the heterogeneity of patients with severe COVID-19. We investigated the prognostic value of combination scores of admission values of inflammatory biomarkers in adults with severe COVID-19. Methods: Adults admitted to the Department of Respiratory Medicine of the UHL with severe COVID-19 (April-September 2021, NCT05145751) were included. Demographics, medical history, laboratory tests and outcome (high-flow nasal cannula (HFNC), admission to Intensive Care Unit (ICU) or death) were recorded. The optimal cut-off points of on admission values of C-reactive protein (CRP), CRP to lymphocyte ratio (CLR), lymphocyte to neutrophil ratio (LNR) and derived variation of neutrophil to lymphocyte ratio (dv-NLR (neutrophil/white blood count-lymphocyte)) for the predetermined outcome were defined. Based on the cut-off of CRP, LNR, dv-NLR and CLR, which were found to be predictors for HFNC, 3 scores were defined: CRP and LNR (C-CRP #1), CRP and dv-NLR (C-CRP #2), CRP and CLR (C-CRP #3). Likewise, based on the cut-off of CRP and CLR, which were found to be predictors for death, the score of CRP and CLR (C-CRP #3*) was defined. The combination scores were then classified as: 2 points (both biomarkers elevated); 1 point (one biomarker elevated) and 0 points (normal values). None of the biomarkers was predictive for the ICU admission, so no further analysis was performed. Binomial logistic regression analysis was used to establish the predictive role for each biomarker. Results: One hundred and fifteen patients (60% males, mean age 57.7 years) were included. Thirty-seven (32.2%) patients required HFNC, nine (7.8%) died and eight (7%) were admitted to ICU, respectively. As far as HFNC is concerned, the cut-off point was 3.2 for CRP, 0.231 for LNR, 0.90 for dv-NLR and 0.004 for CLR. Two points of C-CRP #1 and 2 points of C-CRP #3 predicted HFNC with a probability as high as 0.625 (p = 0.005) and 0.561 (p < 0.001), respectively. Moreover, 1 point of C-CRP #2 and 2 points of C-CRP #2 predicted HFNC with a probability of 0.333 and 0.562, respectively. For death, the optimal cut-off point for CRP was 1.11 and for CLR 3.2*1033. Two points of C-CRP #3* with an accuracy of 0.922 predicted mortality (p = 0.0038) in severe COVID-19. Conclusions: The combination scores of CRP and inflammatory biomarkers, based on admission values, are promising predictors for respiratory support using HFNC and for mortality in patients suffering from severe COVID-19 infection.

COVID-19 is a pandemic viral disease with a catastrophic global impact. The severity of COVID-19 symptoms ranges from very mild to severe and affects mainly the respiratory system. Spontaneous pneumothorax and pleural effusion are rarely seen in spontaneously breathing COVID-19 patients. We herein report a case of a patient with mild COVID-19 disease presenting to the emergency department with hydropneumothorax. Due to persistent air leak, the patient was managed with video-assisted thoracoscopic surgery (VATS) bullectomy and talc pleurodesis. Clinicians managing these patients should be alert to early diagnose this complication.

BACKGROUND:COVID-19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID-19.METHODS:The primary outcome measure in this international, multi-centre, prospective, observational study with adult patients hospitalized primarily for COVID-19 was the association of WHO Clinical Progression Scale (WHO-CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin-6. Admission plasma suPAR levels were determined using the suPARnostic® ELISA and suPARnostic® Turbilatex assays.RESULTS:Seven hundred and sixty-seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log-suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point (p < .001). All the other markers were also correlated with WHO-CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47-3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO-CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759-0.836).CONCLUSIONS:suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

BACKGROUND/AIM:The relationship between the kinetics of antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the severity of Coronavirus Disease 2019 (COVID-19) is poorly understood. The aim of the present study was to investigate whether serum SARS-CoV-2 antibody kinetics serve as an early predictor of clinical deterioration or recovery in hospitalized patients with COVID-19.PATIENTS AND METHODS:In this prospective observational study, 102 consecutive patients (median age: 60 years, 58% males) with symptomatic COVID-19 infection diagnosed by real-time polymerase chain reaction assay, hospitalized in two tertiary hospitals, were included. Rapid test for qualitative detection of immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies was performed at pre-defined time intervals during hospitalization (days: 0, 3, 7, 10, 14, 21 and 28).RESULTS:During a 3-month follow-up period after COVID-19 disease onset, a total of 87 patients were discharged, 12 patients were intubated and entered the Intensive Care Unit, and three patients died. The median time for seroconversion was 10 days for IgM and 12 days for IgG post onset of symptoms. Univariate logistic regression analysis found no associations between IgM or IgG positivity and clinical outcomes or complications during hospitalization for COVID-19 infection. Diabetes and dyslipidemia were the only clinical risk factors predictive of COVID-19-related complications during hospitalization.CONCLUSION:SARS-CoV-2 antibody responses do not predict clinical outcome in hospitalized patients with moderate-to-severe COVID-19 infection.

Background. The direct effect of SARS-CoV-2 on the lungs results in increased hospitalization rates of patients with pneumonia. Severe COVID-19 patients often develop ARDS which is associated with poor prognosis. Assessing risk factors for COVID-19 severity is indispensable for implementing and evaluating therapeutic interventions. We investigated the temporal associations between the SARS-CoV-2 antigen (Ag), total Immunoglobulin (Ig) levels, and several laboratory parameters in hospitalized patients with varying degrees of COVID-19 severity. Methods. The SARS-CoV-2 nucleocapsid protein (NP) and total Ig Spike (S) protein-specific antibodies were determined for each patient with lateral flow assays through repeated sampling every two days. Hematological and biochemical parameters were evaluated at the same time points. Results. 40 Greek COVID-19 patients (31 males, 9 females) with a median age of 59.50 ± 16.21 years were enrolled in the study. The median time from symptom onset to hospitalization was 8.0 ± 4.19 days. A significant negative correlation was observed between the SARS-CoV-2 Ag and total Ig levels. The temporal correlation patterns of the SARS-CoV-2 NP Ag and anti-S total Ig levels with laboratory markers varied among patients with differing degrees of COVID-19 severity. Severe-critical cases had lower SARS-CoV-2 Ag and increased total Ig levels as compared to mild-moderate cases. Conclusions. Distinct temporal profiles of the SARS-CoV-2 NP Ag and anti-S total Ig levels may distinguish different groups of COVID-19 severity.

The progress of COVID-19 from moderate to severe may be precipitous, while the characteristics of the disease are heterogenous. The aim of this study was to describe the development of sinus bradycardia in critically ill patients with COVID-19 and its association with outcome in outbreak due to the SARS-CoV-2 B.1.1.7 Lineage. We leveraged the multi-center SuPAR in Adult Patients With COVID-19 (SPARCOL) study and identified patients who required admission to intensive care unit (ICU). Inclusion criteria were: (a) adult (≥18 years old) patients hospitalized primarily for COVID-19; (b) a confirmed SARS-CoV-2 infection diagnosed through reverse transcriptase polymerase chain reaction test of nasopharyngeal or oropharyngeal samples; and (c) at least one blood sample collected at admission and stored for suPAR, hs-CRP, and ferritin testing. All patients had continuous heart rate monitoring during hospitalization. In total, 81 patients were included. Of them, 17 (21 %) and 64 (79 %) were intubated and admitted to the ICU during the first and second wave, respectively. Two (12 %) and 62 (97 %) developed bradycardia before ICU admission, respectively (p < 0.001). Patients with bradycardia had increased suPAR (p < 0.001) and hs-CRP level (p < 0.001). Infusion of isoprenaline and/or noradrenaline was necessary to maintain an adequate rate and peripheral perfusion in all patients. Mortality was significantly higher in patients with bradycardia (p < 0.001). In conclusion, bradycardia was associated with poor outcome. As B.1.1.7 variant strain is spreading more rapidly in many countries, our findings help in the identification of patients who may require early admission to ICU.

The interesting work by Goel et al. [1] supported that alanine aminotransferase (ALT) is negatively associated with mortality in coronavirus disease 2019 (COVID-19) patients. Reinforcing this finding, we confirm an association between ALT levels and severe acute respiratory syndrome coronavirus 2 antigen (SARS-CoV-2 Ag) kinetics that could reveal a mechanism underlying clinical disease course. In an interim analysis of an ongoing prospective study, we have established a relationship between SARS-CoV-2 Ag and ALT serum levels in immunocompetent patients hospitalized at the COVID-19 Department of the University Hospital of Larissa, Greece. Our study currently involved a cohort of 20 Greek RT-PCR confirmed COVID-19 patients (15 male and 5 female). Nasopharyngeal swabs and whole blood specimens were obtained every 2 days until hospital discharge or death. We quantitatively determined for every patient the SARS-CoV-2 nucleocapsid protein and the IgA, IgM, IgG spike protein-specific antibodies, respectively, using lateral flow immunochromatographic assays (Catalog numbers: V1310/30 and V1210/ V1230, Prognosis Biotech, Larissa, Greece). ALT levels were recorded on the same dates. Pooled values of serial measurements of ALT and SARS-CoV-2 Ag from each patient were correlated. The mean age of participants was 65.60 ± 17.84 years. The mean duration of hospitalization was 14 ± 3 days. ALT values (U/L) on admission and at peak ranged from 11.0 to 1102 and 17.7 to 1230.10, respectively. Mean values of ALT (75.34 ± 177.15 U/L) and mean values of SARSCoV-2 Ag were (81.91 ± 248.46 AU). SARS-CoV-2 Ag was negatively correlated with ALT (ρ = −0.355, P = 0.001) and Ig (ρ = −0.536, P < 0.001). These data strongly support the view of Goel et al. that the inability to raise ALT as COVID-19 progressed portended a worse outcome in infected patients. Higher SARS-CoV-2 Ag detection implies higher viral load which leads to a worse prognosis [2]. We suggest that the underlying pathophysiological mechanism of liver-associated mortality in COVID-19 patients should further be studied in the context of ALT and hepatocyte immune function [3,4].

Introduction: COVID-19 patients present with hematological changes. Data regarding the relation between SARS-CoV-2 Ag or Total Ig antibody levels and hematological profile in Greek COVID-19 patients are limited. Aims: To identify probable correlates between SARS-CoV-2 antibody titers and hematological parameters in a cohort of hospitalized patients in the COVID-19 Unit of the University of Thessaly in Greece from November to December 2020. Methods: Nasopharyngeal swabs and whole blood specimens were obtained every two days from admission to discharge or death. The SARS-CoV-2 nucleocapsid protein and the IgA, IgM, IgG spike protein-specific antibodies were quantitatively determined in each patient by lateral flow assays (Prognosis Biotech, Larissa, Greece). Hematological parameters were recorded at the same time points. Results: 40 Greek COVID-19 patients (31 male, 9 female) with a median age of 59.50±16.21 years were enrolled in the study. The median time from symptom onset to hospitalization was 8.0±4.19 days. All patients had pneumonia on chest computed tomography. A significant negative correlation was found between the SARS-CoV-2 Ag and Total Ig levels (ρ=-0.489/p<0.001). SARS-CoV-2 Ag levels were inversely correlated with white blood cell (WBC) (ρ=-0.227/p=0.002), platelet (ρ=-0.327/p<0.001) and lymphocyte counts (ρ=-0.216/p=0.004). Total Ig levels were positively correlated with WBC, neutrophils, platelets and lymphocytes (ρ=0.257/p=0.001; ρ=0.259/p=<0.001; r=0.262/p=<0.001 and r=0.161/p=0.031, respectively). Conclusions: Our results indicate an association between SARS-CoV-2 Ag or Total Ig antibody responses with altered blood parameters.

Rationale: The progress of COVID-19 from moderate to severe may be precipitous, while the heterogenous characteristics of the disease pose challenges to the management of these patients. Objectives: To characterize the clinical course and outcomes of critically ill patients with COVID-19 during two successive waves. Methods: We leveraged the multi-center SuPAR in Adult Patients With COVID-19 (SPARCOL) study and collected data from consecutive patients requiring admission to the intensive care unit from April 1st to November 30th, 2020. Measurements and Main Results: Of 252 patients, 81 (32%) required intubation and mechanical ventilation. Of them, 17 (20.9%) were intubated during the first wave, while 64 (79%) during the second wave. The most prominent difference between the two waves was the overall survival (first wave 58.9% vs. second wave 15.6%, adjusted p-value=0.006). This difference is reflected in the prolonged hospitalization during the first wave. The mean ICU length of stay (19.1 vs. 11.7 days, p=0.022), hospital length of stay (28.5 vs. 17.1 days, p=0.012), and days on ventilator (16.7 vs. 11.5, p=0.13) were higher during the first wave. A significant difference between the two waves was the development of bradycardia. In the first wave, 2 (11.7%) patients developed sinus bradycardia only after admission to the intensive care unit, while in the second wave, 63 (98.4%) patients developed sinus bradycardia during hospitalization. Conclusions: Survival of critically ill patients with COVID-19 was significantly lower during the second wave. The majority of these patients developed sinus bradycardia during hospitalization.