Unilateral Pleural Effusion after Third Dose of BNT162b2 mRNA Vaccination: Case Report.

Vaccination remains the best strategy against coronavirus disease 2019 (COVID-19) in terms of prevention. The efficacy and safety of COVID-19 vaccines is supported by well-designed clinical trials that recruited many participants. It is well-known that vaccination is associated with local side effects related to the injection site, and mild, systemic side effects. However, there has been an increase in the occurrence of what is known as infrequent adverse effects in the population of vaccinated individuals in real life. We present the case of a 46-year-old woman with no past medical history, who presented with a sharp chest pain with deep inspiration, a few days after receiving the third dose of the Pfizer-BioNTech COVID-19 mRNA vaccine (BNT162b2). There is an association between the BNT16b2 vaccination and myocarditis, pericarditis, and even bilateral pleural effusions. To the best of our knowledge, this is the first report featuring a unilateral pleural effusion in a patient with no known past medical history, who did not develop cardiac involvement nor have any viral infection. The aim of our report is to inform health professionals of the possibility of encountering this rare adverse event in their daily practice, as the population of individuals who are receiving additional vaccine doses is increasing steadily.

Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection.

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer-BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38-54) years and body mass index of 24·84 (22.6-28.51) kg/m2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6-7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = -0.178, p < 0.001), poor sleep quality (r = -0.094, p < 0.05), insomnia (r = -0.098, p < 0.05), and nap frequency per week (r = -0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.

C3a and C5b-9 Differentially Predict COVID-19 Progression and Outcome.

SARS-CoV-2 infection may result in severe pneumonia leading to mechanical ventilation and intensive care (ICU) treatment. Complement activation was verified in COVID-19 and implicated as a contributor to COVID-19 pathogenesis. This study assessed the predictive potential of complement factors C3a and C5b-9 for COVID-19 progression and outcome. We grouped 80 COVID-19 patients into severe COVID-19 patients (n = 38) and critically ill (n = 42) and subdivided into non-intubated (n = 48) and intubated (n = 32), survivors (n = 57) and non-survivors (n = 23). Results: A significant increase for C3a and C5b-9 levels was observed between: severely and critically ill patients (p < 0.001 and p < 0.0001), non-intubated vs intubated (p < 0.001 and p < 0.05), survivors vs non-survivors (p < 0.001 and p < 0.01). ROC analysis for the need for ICU treatment revealed a higher AUC for C5b-9 (0.764, p < 0.001) compared to C3a (AUC = 0.739, p < 0.01). A higher AUC was observed for C3a for the need for intubation (AUC = 0.722, p < 0.001) or mortality (AUC = 0.740, p < 0.0001) compared to C5b-9 (need for intubation AUC = 0.656, p < 0.05 and mortality AUC = 0.631, p = NS). Combining the two markers revealed a powerful prediction tool for ICU admission (AUC = 0.773, p < 0.0001), intubation (AUC = 0.756, p < 0.0001) and mortality (AUC = 0.753, p < 0.001). C3a and C5b-9 may be considered as prognostic tools separately or in combination for the progression and outcome of COVID-19.

Testosterone, free, bioavailable and total, in patients with COVID-19.

BACKGROUND: Low testosterone (mainly total testosterone [TTe]) has been noted in patients with COVID-19. Calculated free testosterone (FTe) and bioavailable testosterone (BavTe) may reflect more accurately this hormone's levels. In this study, we sought to assess TTe, FTe as well as BavTe in male patients with COVID-19. METHODS: Sera were collected upon admission from 65 men (10 in the intensive care units [ICU] and 55 in the wards) with polymerase chain reaction - proven COVID-19. A group of age-matched COVID-19-negative men (N.=29) hospitalized in general medical wards served as controls. Age, Body Mass Index (BMI) and 28-day mortality were noted. Measurements included TTe, sex-hormone binding globulin, albumin (the latter two for calculating FTe and BavTe) and laboratory markers of inflammation (white blood cell count [WBC], D-Dimers [D-D], lactate dehydrogenase [LDH], ferritin [Fer] and C-reactive protein [CRP]). RESULTS: Profoundly low TTe, FTe and BavTe were noted in most patients, and were associated with disease severity/outcome (being the lowest in COVID-19 patients in the ICU and overall being lower in non-survivors; analysis of covariance P<0.05). Pearson's correlations for logTe, logFTe or logBavTe versus WBC, D-D, LDH, Ferr or CRP were negative, ranging from -0.403 to -0.293 (P=0.009 to 0.014). CONCLUSIONS: TTe, FTe and BavTe are prone to be low in patients with COVID-19, are negatively associated with disease severity and may be considered to have prognostic value.

Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure.

Background: During COVID-19 pandemic, people who developed pneumonia and needed supplemental oxygen, where treated with low-flow oxygen therapy systems and non-invasive methods, including oxygen therapy using high flow nasal cannula (HFNC) and the application of bi-level or continuous positive airway pressure (BiPAP or CPAP). We aimed to investigate the outcomes of critical COVID-19 patients treated with HFNC and unveil predictors of HFNC failure. Methods: We retrospectively enrolled patients admitted to COVID-19 wards and treated with HFNC for COVID-19-related severe hypoxemic respiratory failure. The primary outcome of this study was treatment failure, such as the composite of intubation or death during hospital stay. The association between treatment failure and clinical features was evaluated using logistic regression models. Results: One hundred thirty-two patients with a median (IQR) PaO2/FiO2 ratio 96 (63-173) mmHg at HFNC initiation were studied. Overall, 45.4% of the patients were intubated. Hospital mortality was 31.8%. Treatment failure (intubation or death) occurred in 50.75% and after adjustment for age, gender, Charlson Comorbidity index (CCI) score and National Early Warning Score 2 (NEWS2) score on admission and PaO2/FiO2 ratio and acute respiratory distress syndrome (ARDS) severity at the time of HFNO initiation, it was significantly associated with the presence of dyspnea [adjusted OR 2.48 (95% CI: 1.01-6.12)], and higher Urea serum levels [adjusted OR 1.25 (95% CI: 1.03-1.51) mg/dL]. Conclusions: HFNC treatment was successful in almost half of the patients with severe COVID-19-related acute hypoxemic respiratory failure (AHRF). The presence of dyspnea and high serum Urea levels on admission are closely related to HFNC failure.

Depression, Insomnia and Post-Traumatic Stress Disorder in COVID-19 Survivors: Role of Gender and Impact on Quality of Life.

Evidence to date suggests that a significant proportion of COVID-19 patients experience adverse psychological outcomes and neuropsychiatric complications. The aim of this study was to evaluate the effect of SARS-CoV-2 infection and subsequent hospitalization on the mental health, sleep, and quality of life of COVID-19 survivors. Patients were assessed 1-2 months after hospital discharge using standardized screening tools for depression and anxiety (HADS), post-traumatic stress disorder (IES-R), insomnia (AIS), and quality of life (EQ-5D-5L). Sociodemographic factors, comorbidities, disease severity and type of hospitalization were also collected. Amongst the 143 patients included, mental health symptoms were common (depression-19%; anxiety-27%; traumatic stress-39%; insomnia-33%) and more frequently reported in female than in male patients. Age, smoking status, comorbidities and illness severity were not found to significantly correlate with the presence of mood, sleep, or stress disorders. Finally, quality of life was worse for patients requiring ICU (p = 0.0057) or a longer hospital stay (p < 0.001) but was unaffected by factors such as sex and other measured outcomes. These findings highlight the need for appropriate intervention to properly manage the immediate and enduring mental health complications of COVID-19.

Increased Glucocorticoid Receptor Alpha Expression and Signaling in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: Critical illness is characterized by increased serum cortisol concentrations and bioavailability resulting from the activation of the hypothalamic-pituitary-adrenal axis, which constitutes an essential part of the stress response. The actions of glucocorticoids are mediated by a ubiquitous intracellular receptor protein, the glucocorticoid receptor. So far, data on coronavirus disease 2019 and glucocorticoid receptor alpha expression are lacking. DESIGN: Prospective observational study. SETTING: One academic multidisciplinary ICU. SUBJECTS: Twenty-six adult coronavirus disease 2019 patients; 33 adult noncoronavirus disease 2019 patients, matched for age, sex, and disease severity, constituted the control group. All patients were steroid-free. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Glucocorticoid receptor alpha, glucocorticoid-inducible leucine zipper expression, and serum cortisol were measured on ICU admission. In coronavirus disease 2019 patients, glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper messenger RNA expression were upregulated (4.7-fold, p < 0.01 and 14-fold, p < 0.0001, respectively), and cortisol was higher (20.3 vs 14.3 µg/dL, p < 0.01) compared with the control group. CONCLUSIONS: ICU coronavirus disease 2019 patients showed upregulated glucocorticoid receptor alpha and glucocorticoid-inducible leucine zipper expression, along with cortisol levels, compared with ICU noncoronavirus disease 2019 patients. Thus, on ICU admission, critical coronavirus disease 2019 appears to be associated with hypercortisolemia, and increased synthesis of glucocorticoid receptor alpha and induced proteins.

Low Admission Immunoglobulin G Levels Predict Poor Outcome in Patients with Mild-to-Critical COVID-19: A Prospective, Single-Center Study.

INTRODUCTION: Immunoglobulins (Igs) comprise a critical part of the immune response. Little information exists on Ig serum levels in COVID-19 patients. We, therefore, investigated whether hospital admission Igs in patients with mild-to-critical disease are associated with clinical outcome. MATERIALS AND METHODS: This prospective, observational, single-center, cross-sectional study included 126 consecutive non-critically ill and critically ill and COVID-19 patients, in whom IgG, IgM, and IgA were measured on hospital admission. RESULTS: The cohort was divided in survivors and non-survivors, based on in-hospital mortality. Median IgG levels of survivors were significantly higher than non-survivors (p < 0.01). The cohort was subsequently divided in IgG deficient (< 690 mg/dl) and sufficient (≥ 690 mg/dl) patients. IgG-deficient patients had a higher mortality rate (p < 0.01). The multivariate logistic regression model showed that subnormal IgG was significantly associated with increased mortality risk (p < 0.01). CONCLUSION: In our COVID-19 cohort, admission subnormal IgG levels might be independently associated with reduced survival.

Covid-19 and Growth Hormone/Insulin-Like Growth Factor 1: Study in Critically and Non-Critically Ill Patients.

Objective: We aimed to measure insulin-like growth factor 1 (IGF1) and growth hormone (GH) in critically and non-critically ill patients with Covid-19 and assess them vis-a-vis clinical and laboratory parameters and prognostic tools. Subjects and Methods: We included patients who were admitted to the wards or the ICU of the largest Covid-19 referral hospital in Greece; patients with non-Covid-19 pneumonia served as controls. Apart from the routine laboratory work-up for Covid-19 we measured GH and IGF1 (and calculated normalized IGF-1 values as standard deviation scores; SDS), after blood sampling upon admission to the wards or the ICU. Results: We studied 209 critically and non-critically ill patients with Covid-19 and 39 control patients. Patients with Covid-19 who were ICU non-survivors were older and presented with a worse hematological/biochemical profile (including white blood cell count, troponin, glucose, aminotransferases and lactate dehydrogenase) compared to ICU survivors or Covid-19 survivors in the wards. Overall, IGF-1 SDS was higher in Covid-19 survivors compared to non-survivors (-0.96 ± 1.89 vs -2.05 ± 2.48, respectively, p=0.030). No significant differences were noted in GH between the groups. Nevertheless, in critically ill patients with Covid-19, the prognostic value of IGF-1 (raw data), IGF-1 (SDS) and GH for survival/non-survival was on a par with that of APACHE II and SOFA (with a marginal difference between GH and SOFA). Conclusion: In conclusion, our findings suggest that there might be an association between low IGF1 (and possibly GH) and poor outcome in patients with Covid-19.

Antibody Response Following a Two-Dose mRNA Vaccination Regimen, in Health Care Workers of a Tertiary Hospital in Athens, Greece.

We analyzed the antibody responses of 564 hospital workers in Athens, Greece, after vaccination with two doses of the BNT162b2 (Comirnaty®; BioNTech and Pfizer) mRNA COVID-19 vaccine. A greater antibody increase was observed in women, younger age groups, previously infected individuals and personnel working in COVID-19 clinics. Notably, individuals with a prior COVID-19 infection mounted a significantly higher antibody titer following the first dose than the rest of the population; the same was true for those working in COVID-19 clinics, even without history of previous infection.

Could Soluble Endothelial Protein C Receptor Levels Recognize SARS-CoV2-Positive Patients Requiring Hospitalization?

INTRODUCTION: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients' requirement for hospitalization. METHODS: Plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value. RESULTS: In our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers. CONCLUSIONS: In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.

From Recession to Depression? Prevalence and Correlates of Depression, Anxiety, Traumatic Stress and Burnout in Healthcare Workers during the COVID-19 Pandemic in Greece: A Multi-Center, Cross-Sectional Study.

The COVID-19 pandemic has the potential to adversely affect the mental health of healthcare workers (HCWs). The public healthcare system in Greece was already facing serious challenges at the outset of the outbreak following years of austerity and an escalating refugee crisis. This multi-center, cross-sectional study aims to assess the levels and associated risk factors of anxiety, depression, traumatic stress and burnout of frontline staff in Greece. A total of 464 self-selected HCWs in six reference hospitals completed a questionnaire comprising sociodemographic and work-related information and validated psychometric scales. The proportion of HCWs with symptoms of moderate/severe depression, anxiety and traumatic stress were 30%, 25% and 33%, respectively. Burnout levels were particularly high with 65% of respondents scoring moderate/severe in emotional exhaustion, 92% severe in depersonalization and 51% low/moderate in personal accomplishment. Predictive factors of adverse psychological outcomes included fear, perceived stress, risk of infection, lack of protective equipment and low social support. The psychological burden associated with COVID-19 in healthcare professionals in Greece is considerable, with more than half experiencing at least mild mental health difficulties. Findings signal the need for immediate organizational and individually tailored interventions to enhance resilience and support wellbeing under pandemic conditions.

Glycemia, Beta-Cell Function and Sensitivity to Insulin in Mildly to Critically Ill Covid-19 Patients.

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.