COVID-19 Lung Ultrasound Scores and Lessons from the Pandemic: A Narrative Review.

The WHO recently declared that COVID-19 no longer constitutes a public health emergency of international concern; however, lessons learned through the pandemic should not be left behind. Lung ultrasound was largely utilized as a diagnostic tool thanks to its feasibility, easy application, and the possibility to reduce the source of infection for health personnel. Lung ultrasound scores consist of grading systems used to guide diagnosis and medical decisions, owning a good prognostic value. In the emergency context of the pandemic, several lung ultrasound scores emerged either as new scores or as modifications of pre-existing ones. Our aim is to clarify the key aspects of lung ultrasound and lung ultrasound scores to standardize their clinical use in a non-pandemic context. The authors searched on PubMed for articles related to "COVID-19", "ultrasound", and "Score" until 5 May 2023; other keywords were "thoracic", "lung", "echography", and "diaphragm". A narrative summary of the results was made. Lung ultrasound scores are demonstrated to be an important tool for triage, prediction of severity, and aid in medical decisions. Ultimately, the existence of numerous scores leads to a lack of clarity, confusion, and an absence of standardization.

Preoperative SARS-CoV-2 Infection Screening before Thoracic Surgery during COVID-19 Pandemic: A Multicenter Retrospective Study

Objectives During coronavirus disease (COVID-19) pandemic, preoperative screening before thoracic surgery is paramount in order to protect patients and staff from undetected infections. This study aimed to determine which preoperative COVID-19 screening tool was the most effective strategy before thoracic surgery. Methods This retrospective cohort multicenter study was performed at 3 Italian thoracic surgery centers. All adult patients scheduled for thoracic surgery procedures from 4th March until 24th April, 2020, and submitted to COVID-19 preoperative screenings were included. The primary outcome was the yield of screening of the different strategies. Results A total of 430 screenings were performed on 275 patients;275 anamnestic questionnaires were administered. 77 patients were screened by an anamnestic questionnaire and reverse transcriptase polymerase chain reaction (RT-PCR). 78 patients were selected to combine screening with anamnestic questionnaire and chest computed tomography (CT). The positive yield of screening using a combination of anamnestic questionnaire and RT-PCR was 7.8% (95% CI: 2.6–14.3), while using a combination of anamnestic questionnaire and chest CT was 3.8% (95% CI: 0–9). Individual yields were 1.1% (95% CI: 0–2.5) for anamnestic questionnaire, 5.2% (95% CI: 1.3–11.7) for RT-PCR, and 3.8% (95% CI: 0–9). Conclusions The association of anamnestic questionnaire and RT-PCR is able to detect around 8 positives in 100 asymptomatic patients. This combined strategy could be a valuable preoperative SARS-CoV-2 screening tool before thoracic surgery.

Preoperative SARS-CoV-2 Infection Screening before Thoracic Surgery during COVID-19 Pandemic: A Multicenter Retrospective Study.

Objectives: During coronavirus disease (COVID-19) pandemic, preoperative screening before thoracic surgery is paramount in order to protect patients and staff from undetected infections. This study aimed to determine which preoperative COVID-19 screening tool was the most effective strategy before thoracic surgery. Methods: This retrospective cohort multicenter study was performed at 3 Italian thoracic surgery centers. All adult patients scheduled for thoracic surgery procedures from 4th March until 24th April, 2020, and submitted to COVID-19 preoperative screenings were included. The primary outcome was the yield of screening of the different strategies. Results: A total of 430 screenings were performed on 275 patients; 275 anamnestic questionnaires were administered. 77 patients were screened by an anamnestic questionnaire and reverse transcriptase polymerase chain reaction (RT-PCR). 78 patients were selected to combine screening with anamnestic questionnaire and chest computed tomography (CT). The positive yield of screening using a combination of anamnestic questionnaire and RT-PCR was 7.8% (95% CI: 2.6-14.3), while using a combination of anamnestic questionnaire and chest CT was 3.8% (95% CI: 0-9). Individual yields were 1.1% (95% CI: 0-2.5) for anamnestic questionnaire, 5.2% (95% CI: 1.3-11.7) for RT-PCR, and 3.8% (95% CI: 0-9). Conclusions: The association of anamnestic questionnaire and RT-PCR is able to detect around 8 positives in 100 asymptomatic patients. This combined strategy could be a valuable preoperative SARS-CoV-2 screening tool before thoracic surgery.

Psychological Health in Intensive Care Unit Health Care Workers after the COVID-19 Pandemic.

BACKGROUND: Although the COVID-19 pandemic had an impact on the general population, health care workers (HCWs) constituted one of the groups that were most adversely affected by the associated risks, owing to the significant consequences on their mental health. This study examined these psychological effects on HCWs who cared for COVID-19 patients who were admitted to the intensive care unit in an Italian hospital. METHODS: Subjects were administered several self-reported questionnaires: Kessler 10 Psychological Distress Scale (K10), Perceived Stress Scale-10 (PSS), Impact of Event Scale Revised (IES-R), and Post-traumatic Growth Inventory (PTGI), as well as two open-ended questions oriented toward understanding their positive and negative emotional experience and differentiating between two phases of the emergency. RESULTS: Overall, 45% of HCWs showed medium-to-high anxiety/depressive symptoms, whereas 60% presented with medium-to-high levels of perceived stress. In addition, 37% of subjects developed symptoms of PTSD and 50% showed post-traumatic growth in the "appreciation of life" and "new possibilities" dimensions. With regard to the open-ended questions, three themes were identified: quality of workplace relationships, sense of emotional-relational competence, and sense of clinical-technical competence. In addition, two macrocategories of responses were identified in the answers: growth and block. CONCLUSIONS: The mental health of HCWs who are involved in the front line of COVID-19 was significantly impacted by this experience, showing high levels of post-traumatic stress and anxiety and depressive symptoms more than 1 year after the emergency began. A qualitative analysis of staff experiences can be a useful guide for structuring interventions and prevention.

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients.

BACKGROUND: Thyroid hormones (TH)s are master regulators of mitochondrial activity and biogenesis. Nonthyroidal illness syndrome (NTIS) is generally considered an adaptative response to reduced energy that is secondary to critical illness, including COVID-19. COVID-19 has been associated with profound changes in the cell energy metabolism, especially in the cells of the immune system, with a central role played by the mitochondria, considered the power units of every cell. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects and alters mitochondrial functions, both to influence its intracellular survival and to evade host immunity. AIM OF THE STUDY: This study was undertaken to analyze the oxidative balance and mitochondrial respiration in COVID-19 patients with and without NTIS to elucidate the role that thyroid hormones (TH)s play in this context. METHODS: In our cohort of 54 COVID-19 patients, admitted to our University Hospital during the COVID-19 pandemic, we evaluated the generation of reactive oxygen species (ROS) by measuring the serum levels of derivatives of reactive oxygen metabolites (dROMs), and we analyzed the antioxidant capacity by measuring the serum biological antioxidant potential (BAP). We then analyzed the mitochondrial respiration in peripheral blood mononuclear cells (PBMC)s of 28 of our COVID-19 patients, using the seahorse instrument (Agilent). Results were correlated with the serum levels of THs and, in particular, of FT3. In addition, the role of T3 on bioelectrical impedance analysis (BIA) and mitochondrial respiration parameters was directly evaluated in two COVID-19 patients with NTIS, in which treatment with synthetic liothyronine (LT3) was given both in vivo and in vitro. RESULTS: In our COVID-19 patients with NTIS, the dROMs values were significantly lower and the BAP values were significantly higher. Consequently, the oxidative stress index (OSi), measured as BAP/dROMs ratio was reduced compared to that observed in COVID-19 patients without NTIS, indicating a protective role exerted by NTIS on oxidative stress. In our COVID-19 patients, the mitochondrial respiration, measured in PBMCs, was reduced compared to healthy controls. Those with NTIS showed a reduced maximal respiratory capacity and a reduced proton leak, compared to those with normal FT3 serum values. Such lowered mitochondrial respiratory capacity makes the cells more vulnerable to bioenergetic exhaustion. In a pilot study involving two COVID-19 patients with NTIS, we could reinforce our previous observation regarding the role of T3 in the maintenance of adequate peripheral hydroelectrolytic balance. In addition, in these two patients, we demonstrated that by treating their PBMCs with LT3, both in vitro and in vivo, all mitochondrial respiration parameters significantly increased. CONCLUSIONS: Our results regarding the reduction in the serum levels of the reactive oxygen species (ROS) of COVID-19 patients with NTIS support the hypothesis that NTIS could represent an adaptative response to severe COVID-19. However, beside this beneficial effect, we demonstrate that, in the presence of an acute reduction of FT3 serum levels, the mitochondrial respiration is greatly impaired, with a consequent establishment of a hypoenergetic state of the immune cells that may hamper their capacity to react to massive viral infection.

Psychological health in COVID-19 patients after discharge from an intensive care unit.

Along with physical changes, psychological changes are detectable in patients with COVID-19. In these patients, the stressful experience of intensive care unit (ICU) hospitalization may aggravate psychological conditions. Our study examines the short- and long-term psychological consequences of COVID-19 in ICU patients. COVID-19 patients completed the self-rating questionnaires Kessler 10 Psychological Distress Scale (K10), Perceived Stress Scale-10 (PSS), Impact of Event Scale Revised (IES-R), and Post-traumatic Growth Inventory (PTGI) and were clinically interviewed 1 and 6 months after discharge. Altered behavioral-psychological symptoms and patients' strategies (adaptive vs. maladaptive) for coping with stress during and after hospitalization were coded during clinical interviews. Between 20 and 30% of patients showed moderate symptoms of depression or anxiety and perceived stress 1 and 6 months after discharge. Sleep problems, difficulty concentrating, confusion in placing events, and fear of reinfection were observed in many (6-17%) patients. At 6 months, only 7% of patients showed PTSD symptoms, and 50% showed post-traumatic growth in the "appreciation of life" sub-scale. Finally, 32% of subjects were classified as "maladaptive coping patients," and 68% as "adaptive coping patients." Patients who adopted "adaptive" coping strategies showed significantly lower levels of anxious-depressive symptoms and perceived stress when compared to subjects with "maladaptive" strategies at both time points. Coping strategy had no effect on PTSD symptoms or post-traumatic growth at 6 months. These findings clarify the short- and long-term psychological effects of intensive care due to COVID-19 infection and demonstrate that patient characteristics, particularly strategies for coping with stress, seem to play a critical role in psychological outcomes.

Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.

Background and Objective: Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs. Methods: We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results. Results: We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality. Conclusions: NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.

The lived experiences of family members who visit their relatives in Covid-19 intensive care unit for the first time: A phenomenological study.

BACKGROUND: COVID-19 patient experiences in the intensive care unit (ICU) are marked by family separation. Families understand the importance of isolation and hospital visiting policies, but they consider it necessary to visit their loved ones and use personal protective equipment. OBJECTIVE: To describe the lived experiences of family members in their first contact with a relative in a COVID-ICU. METHODS: A phenomenological study was conducted using Cohen's method. The subjects were interviewed using an open-question format to allow them full freedom of expression. Twelve family members were recruited between February and March 2021. RESULTS: Analysis of the qualitative data resulted in five major themes: (1) fear of contagion related to donning/doffing procedures, (2) positive emotions related to first contact with the hospitalized relative, (3) concern for the emotional state of the hospitalized relative, (4) impact of the COVID-ICU and comparisons between imagination and reality regarding the severity of the disease, and (5) recognition of and gratitude toward healthcare professionals. CONCLUSIONS: It has been confirmed that visits to the ICU reduce anxiety among family members. Our findings constitute an internationally relevant contribution to understanding of the needs of relatives who meet loved ones for the first time while wearing personal protective equipment.

Comparison of Thrombotic Events and Mortality in Patients with Community-Acquired Pneumonia and COVID-19: A Multicenter Observational Study.

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicenter observational cohort study, 1,138 patients, hospitalized for CAP (n = 559) or COVID-19 (n = 579) from seven clinical centers in Italy, were included in the study. Consecutive adult patients (age ≥ 18 years) with confirmed COVID-19-related pneumonia, with or without mechanical ventilation, hospitalized from March 1, 2020 to April 30, 2020, were enrolled. COVID-19 was diagnosed based on the World Health Organization interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p = 0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses.During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p < 0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6 vs. 13.4% in thrombotic-event-free patients; p < 0.001). In CAP, 13.8% of patients experiencing thrombotic events died versus 1.8% of thrombotic event-free ones (p < 0.001). A multivariable Cox-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (hazard ratio: 2.1; 95% confidence interval: 1.4-3.3; p < 0.001). CONCLUSION: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.

Lung Ultrasound: A Diagnostic Leading Tool for SARS-CoV-2 Pneumonia: A Narrative Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global pandemic. In this context, lung ultrasound (LUS) has played an important role due to its high diagnostic sensitivity, low costs, simplicity of execution and radiation safeness. Despite computed tomography (CT) being the imaging gold standard, lung ultrasound point of care exam is essential in every situation where CT is not readily available nor applicable. The aim of our review is to highlight the considerable versatility of LUS in diagnosis, framing the therapeutic route and follow-up for SARS-CoV-2 interstitial syndrome.

Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium.

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

The lived experiences of family members of Covid-19 patients admitted to intensive care unit: A phenomenological study.

INTRODUCTION: The family members of a patient admitted to a COVID Intensive Care Unit (COVID-ICU) could not communicate with and stay close to their loved one, which resulted in them becoming dependent on hospital staff for remote updates. OBJECTIVE: To describe the lived experiences of families with a member admitted to a COVID-ICU. METHODS: A phenomenological study was conducted. The subjects were interviewed with open-ended questions to allow them full freedom of expression. The researchers involved in the analysis immersed themselves in the data, independently reading and rereading the transcripts to gain a sense of the entire dataset. RESULTS: Fourteen first-degree family members were recruited. Five main themes emerged: fear, detachment, life on standby, family-related loneliness in the COVID-ICU, and an unexpected event. CONCLUSIONS: Knowing the experience of families who have a relative in the COVID-ICU is essential for recognizing and reducing the risk of developing symptoms of post-intensive care syndrome.

H-Ras gene takes part to the host immune response to COVID-19.

Ras gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

Arterial and venous thrombosis in coronavirus 2019 disease (Covid-19): relationship with mortality.

BACKGROUND: Patients with coronavirus disease 2019 (Covid-19) may experience venous thrombosis while data regarding arterial thrombosis are sparse. METHODS: Prospective multicenter study in 5 hospitals including 373 patients with Covid-19-related pneumonia. Demographic data, laboratory findings including coagulation tests and comorbidities were reported. During the follow-up any arterial or venous thrombotic events and death were registered. RESULTS: Among 373 patients, 75 (20%) had a thrombotic event and 75 (20%) died. Thrombotic events included 41 venous thromboembolism and 34 arterial thrombosis. Age, cardiovascular disease, intensive care unit treatment, white blood cells, D-dimer, albumin and troponin blood levels were associated with thrombotic events. In a multivariable regression logistic model, intensive care unit treatment (Odds Ratio [OR]: 6.0; 95% Confidence Interval [CI] 2.8-12.6; p < 0.001); coronary artery disease (OR: 2.4; 95% CI 1.4-5.0; p = 0.022); and albumin levels (OR: 0.49; 95% CI 0.28-0.87; p = 0.014) were associated with ischemic events. Age, sex, chronic obstructive pulmonary disease, diabetes, heart failure, coronary heart disease, intensive care unit treatment, in-hospital thrombotic events, D-dimer, C-reactive protein, troponin, and albumin levels were associated with mortality. A multivariable Cox regression analysis showed that in-hospital thrombotic events (hazard ratio [HR]: 2.72; 95% CI 1.59-4.65; p < 0.001), age (HR: 1.035; 95% CI 1.014-1.057; p = 0.001), and albumin (HR: 0.447; 95% CI 0.277-0.723; p = 0.001) predicted morality. CONCLUSIONS: Covid-19 patients experience an equipollent rate of venous and arterial thrombotic events, that are associated with poor survival. Early identification and appropriate treatment of Covid-19 patients at risk of thrombosis may improve prognosis.

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19.

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345.

The role of teicoplanin in the treatment of SARS-CoV-2 infection: A retrospective study in critically ill COVID-19 patients (Tei-COVID study).

Teicoplanin has a potential antiviral activity expressed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was suggested as a complementary option to treat coronavirus disease 2019 (COVID-19) patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID-19 in critically ill patients. Fifty-five patients with severe COVID-19, hospitalized in the intensive care units (ICUs) and treated with best available therapy were retrospectively analysed. Among them 34 patients were also treated with teicoplanin (Tei-COVID group), while 21 without teicoplanin (control group). Crude in-hospital Day-30 mortality was lower in Tei-COVID group (35.2%) than in control group (42.8%), however not reaching statistical significance (p = .654). No statistically significant differences in length of stay in the ICU were observed between Tei-COVID group and control group (p = .248). On Day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei-COVID group and 57.1% of control group, without statistical difference. Serum C-reactive protein level was significantly reduced in Tei-COVID group compared to control group, but not other biochemical parameters. Finally, Gram-positive were the causative pathogens for 25% of BSIs in Tei-COVID group and for 70.6% in controls. No side effects related to teicoplanin use were observed. Despite several limitations require further research, in this study the use of teicoplanin is not associated with a significant improvement in outcomes analysed. The antiviral activity of teicoplanin against SARS-CoV-2, previously documented, is probably more effective at early clinical stages.

Computational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2.

The rapidly developing pandemic, known as coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread across 213 countries and territories. This pandemic is a dire public health threat-particularly for those suffering from hypertension, cardiovascular diseases, pulmonary diseases, or diabetes; without approved treatments, it is likely to persist or recur. To facilitate the rapid discovery of inhibitors with clinical potential, we have applied ligand- and structure-based computational approaches to develop a virtual screening methodology that allows us to predict potential inhibitors. In this work, virtual screening was performed against two natural products databases, Super Natural II and Traditional Chinese Medicine. Additionally, we have used an integrated drug repurposing approach to computationally identify potential inhibitors of the main protease of SARS-CoV-2 in databases of drugs (both approved and withdrawn). Roughly 360,000 compounds were screened using various molecular fingerprints and molecular docking methods; of these, 80 docked compounds were evaluated in detail, and the 12 best hits from four datasets were further inspected via molecular dynamics simulations. Finally, toxicity and cytochrome inhibition profiles were computationally analyzed for the selected candidate compounds.

Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study.

Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.

Cardiometabolic multimorbidity is associated with a worse Covid-19 prognosis than individual cardiometabolic risk factors: a multicentre retrospective study (CoViDiab II).

BACKGROUND: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. METHODS: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. RESULTS: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). CONCLUSIONS: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.