Bioavailability by design - Vitamin D3 liposomal delivery vehicles.

Vitamin D3 deficiency has serious health consequences, as demonstrated by its effect on severity and recovery after COVID-19 infection. Because of high hydrophobicity, its absorption and subsequent redistribution throughout the body are inherently dependent on the accompanying lipids and/or proteins. The effective oral vitamin D3 formulation should ensure penetration of the mucus layer followed by internalization by competent cells. Isothermal titration calorimetry and computer simulations show that vitamin D3 molecules cannot leave the hydrophobic environment, indicating that their absorption is predominantly driven by the digestion of the delivery vehicle. In the clinical experiment, liposomal vitamin D3 was compared to the oily formulation. The results obtained show that liposomal vitamin D3 causes a rapid increase in the plasma concentration of calcidiol. No such effect was observed when the oily formulation was used. The effect was especially pronounced for people with severe vitamin D3 deficiency.

The Clinical Significance of Urinary Retinol-Binding Protein 4: A Review.

Effective biomarkers for early diagnosis, prognostication, and monitoring in renal diseases (in general) comprise an unmet need. Urinary retinol-binding protein 4, which is the most sensitive indicator of renal tubular damage, holds great promise as a universal biomarker for renal pathologies, in which tubular injury is the driving force. Here, we summarize the most important existing data on the associations between urinary retinol-binding protein 4 and renal diseases and highlight the untapped potential of retinol-binding protein 4 in clinical use.

Correlation between COVID-19 severity and previous exposure of patients to Borrelia spp.

Predictors for the risk of severe COVID-19 are crucial for patient care and control of the disease. Other infectious diseases as potential comorbidities in SARS-CoV-2 infection are still poorly understood. Here we identify association between the course of COVID-19 and Lyme disease (borreliosis), caused by Borrelia burgdorferi transmitted to humans by ticks. Exposure to Borrelia was identified by multi-antigenic (19 antigens) serological testing of patients: severe COVID-19 (hospitalized), asymptomatic to mild COVID-19 (home treated or not aware of being infected), and not infected with SARS-CoV-2. Increased levels of Borrelia-specific IgGs strongly correlated with COVID-19 severity and risk of hospitalization. This suggests that a history of tick bites and related infections may contribute to the risks in COVID-19. Though mechanisms of this link is not clear yet, screening for antibodies targeting Borrelia may help accurately assess the odds of hospitalization for SARS-CoV-2 infected patients, supporting efforts for efficient control of COVID-19.

Dynamics of anti-SARS-CoV-2 seroconversion in individual patients and at the population level.

The immune response and specific antibody production in COVID-19 are among the key factors that determine both prognostics for individual patients and the global perspective for controlling the pandemics. So called "dark figure", that is, a part of population that has been infected but not registered by the health care system, make it difficult to estimate herd immunity and to predict pandemic trajectories. Here we present a follow up study of population screening for hidden herd immunity to SARS-CoV-2 in individuals who had never been positively diagnosed against SARS-CoV-2; the first screening was in May 2021, and the follow up in December 2021. We found that specific antibodies targeting SARS-CoV-2 detected in May as the "dark figure" cannot be considered important 7 months later due to their significant drop. On the other hand, among participants who at the first screening were negative for anti-SARS-CoV-2 IgG, and who have never been diagnosed for SARS-CoV-2 infection nor vaccinated, 26% were found positive for anti-SARS-CoV-2 IgG. This can be attributed to of the "dark figure" of the recent, fourth wave of the pandemic that occurred in Poland shortly before the study in December. Participants who were vaccinated between May and December demonstrated however higher levels of antibodies, than those who undergone mild or asymptomatic (thus unregistered) infection. Only 7% of these vaccinated participants demonstrated antibodies that resulted from infection (anti-NCP). The highest levels of protection were observed in the group that had been infected with SARS-CoV-2 before May 2021 and also fully vaccinated between May and December. These observations demonstrate that the hidden fraction of herd immunity is considerable, however its potential to suppress the pandemics is limited, highlighting the key role of vaccinations.

Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021.

Population immunity (herd immunity) to SARS-CoV-2 derives from two sources: vaccinations or cases of infection with the virus. Infections can be diagnosed as COVID-19 and registered, or they can be asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered when patients recovered at home. Estimation of population immunity to SARS-CoV-2 is difficult and remains a subject of speculations. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (N = 501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Serum samples were collected in Wroclaw (Lower Silesia) on 15th and 22nd May 2021. Sera from hospitalized COVID-19 patients (N = 22) or from vaccinated citizens (N = 14) served as positive controls. Sera were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, and antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy individuals who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.3% (262 out of 501) were positive for SARS-CoV-2-specific IgA; 21.2% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus vaccination against COVID-19 is still of the most importance for controlling the pandemic.

The Value of Clinical Frailty Scale (CFS) as a Prognostic Tool in Predicting Mortality in COVID-19-A Retrospective Cohort Study.

BACKGROUND: Due to the unpredictable nature of COVID-19, there is a need to identify patients at high risk of severe course of the disease and a higher mortality rate. OBJECTIVE: This study aims to find the correlation between frailty and mortality in adult, hospitalized patients with COVID-19. METHODS: Clinical records of 201 patients who suffered from COVID-19 and were hospitalized between October 2020 and February 2021 were retrospectively analyzed. Demographic, clinical, and biochemical data were collected. Patients were assessed using Clinical Frailty Scale (CFS) and were divided into three groups: CFS 1-3 fit; CFS 4-6 vulnerable and with mild to moderate frailty; CSF 7-9, severe frailty. The association between frailty and in-hospital mortality was the primary outcome. RESULTS: Severe frailty or terminal illness was observed in 26 patients (12.94%) from a cohort of 201 patients. Those patients were older (median age 80.73, p < 0.001) and had more comorbidities. Frailty was also associated with higher requirement for oxygen supplementation, greater risk of in-hospital complications and worse biochemical laboratory results. An increase in CFS score also correlated with higher mortality (OR = 1.89, p < 0.001). The Conclusions: Clinical Frailty Scale (CFS) can be used as a potentially useful tool in predicting mortality in patients with COVID-19.

Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients' medical, epidemiological and diagnostic data, virus-neutralizing capability and kinetics. N-specific IgG and IgA are the most reliable diagnostic targets for infection. Serum IgG levels correlate to IgA levels. Half a year after infection, anti-N and anti-S1 IgG decreased, but sera preserved virus-inhibitory potency; thus, testing for IgG may underestimate the protective potential of antibodies. Historical and pre-epidemic sera did not inhibit SARS-CoV-2, thus its circulation before the pandemic and a protective role from antibodies pre-induced by other coronaviruses cannot be confirmed by this study.

Pentoxifylline as a Potential Adjuvant Therapy for COVID-19: Impeding the Burden of the Cytokine Storm.

The outburst of inflammatory response and hypercoagulability are among the factors contributing to increased mortality in severe COVID-19 cases. Pentoxifylline (PTX), a xanthine-derived drug registered for the treatment of vascular claudication, has been reported to display broad-spectrum anti-inflammatory and immunomodulatory properties via adenosine A2A receptor (A2AR)-related mechanisms, in parallel to its rheological actions. Prior studies have indicated the efficacy of PTX in the treatment of various pulmonary diseases, including the management of acute respiratory distress syndrome of infectious causes. Therefore, PTX has been proposed to have potential benefits in the treatment of SARS-CoV-2 symptoms, as well as its complications. The aim of this review is to discuss available knowledge regarding the role of PTX as a complementary therapeutic in SARS-CoV-2.

Delirium Severely Worsens Outcome in Patients with COVID-19-A Retrospective Cohort Study from Temporary Critical Care Hospitals.

Delirium is a sign of deterioration of homeostasis and worse prognosis. The aim of this study was to investigate the frequency, risk factors and prognosis of delirium in patients with COVID-19 in a temporary acute setting hospital. A retrospective cohort analysis of data collected between October 2020 and February 2021 from two temporary acute care hospitals was performed. All consecutive hospitalized patients ≥18 years old with COVID-19 were included. An assessment of consciousness was carried out at least two times a day, including neurological examination. Delirium was identified through retrospective chart review according to DSM-5 criteria if present at least once during hospitalization. Analysis included 201 patients, 39 diagnosed with delirium (19.4%). Delirious patients were older (p < 0.001), frailer (p < 0.001) and the majority were male (p = 0.002). Respiratory parameters were worse in this group with higher oxygen flow (p = 0.013), lower PaO2 (p = 0.043) and higher FiO2 (p = 0.006). The mortality rate was significantly higher in patients with delirium (46.15% vs 3.70%, p < 0.001) with OR 17.212 (p < 0.001) corrected for age and gender. Delirious patients experienced significantly more complications: cardiovascular (OR 7.72, p < 0.001), pulmonary (OR 8.79, p < 0.001) or septic (OR 3.99, p = 0.029). The odds of mortality in patients with COVID-19 presenting with delirium at any point of hospitalization were seventeen times higher.

Spontaneous Pneumothorax in COVID-19 Patients Treated with High-Flow Nasal Cannula outside the ICU: A Case Series.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic and a burden to global health at the turn of 2019 and 2020. No targeted treatment for COVID-19 infection has been identified so far, thus supportive treatment, invasive and non-invasive oxygen support, and corticosteroids remain a common therapy. High-flow nasal cannula (HFNC), a non-invasive oxygen support method, has become a prominent treatment option for respiratory failure during the SARS-CoV-2 pandemic. HFNC reduces the anatomic dead space and increases positive end-expiratory pressure (PEEP), allowing higher concentrations and higher flow of oxygen. Some studies suggest positive effects of HFNC on mortality and avoidance of intubation. Spontaneous pneumothorax has been observed in patients suffering from SARS-CoV-2 pneumonia. Although the viral infection itself contributes to its development, higher PEEP generated by both HFNC and mechanical ventilation is another risk factor for increased alveoli damage and air-leak. Herein, we present three cases of patients with no previous history of lung diseases who were diagnosed with COVID-19 viral pneumonia. All of them were supported with HFNC, and all of them presented spontaneous pneumothorax.