Role of IgG and IgM and proinflammatory aspecific markers in the diagnosis and prognosis of COVID-19 patients stratified by number of positive SARS-CoV-2 genes.

BACKGROUND: A prompt set of suitable biomarkers is needed in suspected COVID-19 patients. This study aims to assess patients positive for one or more gene associated with the C reactive protein (CRP) and procalcitonin (PCT) as non-specific pro-inflammatory markers and IgG and IgM kinetic as specific diagnostic and prognostic tools in SARS-CoV-2 RT-PCR positive patients. METHODS: We enrolled 101 patients within a two month time span (March 26, 2020 to May 31, 2020). A reverse transcription-Real-Time PCR assay on nasopharyngeal/oropharyngeal swabs was used for SARS-CoV-2 identification. Serum anti-SARS-COV-2 IgM and IgG were measured by enzyme immunoassay , PCT levels by Enzyme linked fluorescent assay (ELFA)and CRP by nephelometry. RESULTS: We found that older patients were significantly associated with a worse prognosis. Serum IgM levels were significantly lower during the late stage of the disease, regardless of the presence of one or three genes and patients' outcome. On the contrary, IgG levels exhibited a higher concentration in the late phases of the illness, regardless of the gene found or patients' prognosis. With the exception of the very first sample tested, an increase in CRP in surviving patients (both one and three genes) and a time-dependent decrease of deceased patients CRP was found. PCT levels were always within the normal reference range. The difference between one gene and three genes patients was significant during late disease stages regarding IgG levels and also between three genes survivors vs. three genesdeceased , where the IgG levels were progressively increasing over time. CONCLUSIONS: The relevant finding of the present study is the significant and consistent increase of IgG and IgM in deceased patients. The associated evaluation of antibody kinetics and non specific inflammatory markers (CRP and PCT) in positive patients stratified according to the presence of one gene or three genes could help the clinician in both the diagnosis and prognosis of COVID-19 patients.

Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Changing patterns and clinical outcomes of hospitalized patients with COVID-19 severe pneumonia treated with remdesivir according to vaccination status: results from a real-world retrospective study.

Since the beginning of Coronavirus Disease 2019 (COVID-19) pandemic, many drugs have been purposed for the treatment of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Remdesivir emerged as an encouraging antiviral drug for patients with documented severe COVID-19-related pneumonia. Although several studies about remdesivir effectiveness exist, no study investigated the effect of the combination of remdesivir with the vaccination status. The aim of this study was to assess whether the administration of remdesivir could show some differences in terms of clinical outcomes in patients vaccinated against SARS-CoV-2 versus those who were not. The primary outcome was the in-hospital mortality. The secondary outcomes were 30-days mortality, the need for ICU admission and for oxygen supplementation. This is a retrospective cohort study including all consecutive adult patients hospitalized for severe COVID-19 at the Padua University Hospital (Italy), between September 1st, 2020, and January 31st, 2022, and who received a 5-days course of remdesivir. A total of 708 patients were included, 467 (66%) were male, and the median age was 67 (IQR: 56-79) years. To better estimate the outcomes of interest, a propensity score weighted approach was implemented for vaccination status. A total of 605/708 patients (85.4%) did not complete the vaccination schedule. In-hospital mortality rate was 5.1% (n = 36), with no statistically significant difference between the unvaccinated (n=29, 4.8%) and vaccinated (n=7, 6.8%; p=0.4) patients. After propensity score matching, mortality between the two groups remained similar. However, both the need for ICU and oxygen supplementation were significantly lower in the vaccinated group. Our finding suggests that a complete vaccination course could have an impact in reducing the need for transfer in ICU and for high-flow therapy in moderate-to-severe COVID-19 patients treated with remdesivir.

Risk of hospitalization and sequelae in patients with COVID-19 treated with 3-day early remdesivir vs. controls in the vaccine and Omicron era: A real-life cohort study.

Recently, a benefit from administration of a 3-day course of early remdesivir (ER) in the outpatients' setting was reported. However, real-life data on its use is scarce. Therefore, we explored the ER clinical outcome in our outpatients' s cohort, compared to untreated controls. We included all patients who were prescribed ER from February to May 2022 and followed them up for 3 months and compared patients who received treatment with untreated controls. In the two groups the following outcomes were investigated: hospitalization and mortality rate, time of negativization and symptom's resolution, and postacute coronavirus disease 19 (COVID-19) syndrome prevalence. Overall, 681 patients were analyzed, mostly females (53.6%), and with a median age of 66 years (interquartile range: 54-77), 316 (46.4%) patients received ER, and 365 (53.6%) did not receive antiviral treatment (control group). Overall, 8.5% patients eventually required oxygen support, 8.7% were hospitalized for COVID-19, and 1.5% died. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and ER (adjusted odds ratio [aOR]: 0.049 [0.015; 0.16], p < 0.001) independently reduced hospitalization risk. ER was significantly associated with a shorter duration of SARS-CoV-2 positivity at nasopharyngeal swabs (aß -8.15 [-9.21; -7.09], p < 0.001) and of symptoms (aß -5.11 [-5.82; -4.39], p < 0.001), and with lower rate of COVID-19 sequelae compared to control group (aOR: 0.18 [0.10; 0.31], p < 0.001). Even in the SARS-CoV-2 vaccination and Omicron era, in patients at high risk of developing severe disease, ER demonstrated to have a good safety profile and to significantly reduce the risk of disease progression and COVID-19 sequelae compared to untreated controls.

COVID-19 and myotonic dystrophy: Case reports and systematic review.

INTRODUCTION: Steinert's disease is a rare genetic disorder characterized by progressive myotonia and multi-organ damage. It is associated with respiratory and cardiological complications often leading patients to exitus. These conditions are also traditional risk factors for severe COVID-19. SARS-CoV-2 has affected people with chronic diseases, but the impact on people with Steinert's disease is poorly defined, with only a few reported and described. More data are needed to understand whether this genetic disease is a risk factor for more serious evolution or death in patients with COVID-19. METHODOLOGY: The study describes two cases of patients with SD and COVID-19 and summarizes available evidence of the clinical outcome of COVID-19 in patients with Steinert's disease, by performing a systematic review of the literature (following PRISMA statements and performing PROSPERO registration). RESULTS: Overall, 5 cases were retrieved from the literature review, with a median age of 47 years, of whom 4 had advanced SD and unfortunately died. By contrast, the 2 patients from our clinical practice and 1 from literature had a good clinical outcomes. Mortality ranged from 57% (all cases) to 80% (only literature review). CONCLUSIONS: There is a high mortality rate in patients with both Steinert's disease and COVID-19. It highlights the importance of strengthening prevention strategies, especially vaccination. All SD with SARS-CoV-2 infection/COVID-19 patients should be identified early and treated to avoid complications. It is still unknown which treatment regimen is best to use in those patients. Studies on a greater number of patients are necessary to provide clinicians with further evidence.

Molnupiravir and Nirmatrelvir/Ritonavir: Tolerability, Safety, and Adherence in a Retrospective Cohort Study.

BACKGROUND: Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce. METHODS: We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded. RESULTS: We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62-82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated. CONCLUSIONS: In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient's profile may benefit most from MOL and NIR.

The Role of the Microbiota Gut-Liver Axis during HCV Chronic Infection: A Schematic Overview.

Hepatitis C virus (HCV) still represents one of the most important worldwide health care problems. Since 2011, direct-acting antiviral (DAA) drugs have increased the number of people who have achieved a sustained virological response (SVR). Even if the program to eradicate HCV by 2030 is still ongoing, the SARS-CoV-2 pandemic has created a delay due to the reallocation of public health resources. HCV is characterized by high genetic variability and is responsible for hepatic and extra-hepatic diseases. Depending on the HCV genotype/subtype and comorbidities of patients, tailored treatment is necessary. Recently, it has been shown that liver damage impacts gut microbiota, altering the microbial community (dysbiosis) during persistent viral replication. An increasing number of studies are trying to clarify the role of the gut-liver axis during HCV chronic infection. DAA therapy, by restoring the gut microbiota equilibrium, seems to improve liver disease progression in both naïve and treated HCV-positive patients. In this review, we aim to discuss a snapshot of selected peer-reviewed papers concerning the interplay between HCV and the gut-liver axis.

Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring.

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration-time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Rapid Antigen Test LumiraDxTM vs. Real Time Polymerase Chain Reaction for the Diagnosis of SARS-CoV-2 Infection: A Retrospective Cohort Study

Background: Real time reverse transcription polymerase chain reaction (real time RT-PCR) testing is the gold standard for the diagnosis of SARS-CoV-2 infections. However, to expand the testing capacity, new SARS-CoV-2 rapid antigen tests (Ag-RDTs) have been implemented. Ag-RDTs are more rapid, but less reliable in terms of sensitivity, and real-life data on their performance in comparison with the real time RT-PCR test are lacking. Methods: We aimed at assessing the diagnostic performance of the third-generation antigenic swab LumiraDx™compared with real time RT-PCR in a retrospective cohort study at the Infectious Diseases Unit of Padua. All of the patients who were consecutively tested for SARS-CoV-2 in our centre (by both real time RT-PCR and Ag-RTD LumiraDxTM) from 19 January to 30 May 2021, were included. Cycle-threshold (Ct) values of positive real time RT-PCR were recorded as well as the number of days from symptoms' onset to testing. Results: Among the 282 patients included, 80.9% (N = 228) tested positive to real time RT-PCR, and among these, 174 tested positive also to LumiraDx™. Compared with real time RT-PCR, which is considered as the gold standard for the assessment of the presence/absence of SARS-CoV-2 infection, LumiraDx™showed an overall sensitivity of 76.3% and specificity of 94.4%. Sensitivity increased to 91% when testing was performed <10 days from symptoms' onset, and to 95% when considering Ct < 25. Multivariable binomial logistic regression showed that false negative LumiraDx™results were significantly associated with high Ct values, and with further testing from symptoms' onset. Conclusions: The results of our study suggested that the LumiraDx™SARS-CoV-2 antigen assay may be appropriate for the detection of SARS-CoV-2 infection, especially in its early phase when the test largely meets the performance requirements of the European Centre for Disease Prevention and Control (ECDC).

Factors Associated with Severe COVID-19 and Post-Acute COVID-19 Syndrome in a Cohort of People Living with HIV on Antiretroviral Treatment and with Undetectable HIV RNA.

SARS-CoV-2 can produce both severe clinical conditions and long-term sequelae, but data describing post-acute COVID-19 syndrome (PACS) are lacking for people living with HIV (PLWH). We aimed at assessing the prevalence and factors associated with severe COVID-19 and PACS in our cohort. We included all unvaccinated adult PLWH on antiretroviral treatment and plasma HIV-RNA < 40 cp/mL since at least six months before SARS-CoV-2 infection at the Infectious and Tropical Diseases Unit of Padua (Italy), from 20 February 2020 to 31 March 2021. COVID-19 severity was defined by WHO criteria; PACS was defined as the persistence of symptoms or development of sequelae beyond four weeks from SARS-CoV-2 infection. Demographic and clinical variables were collected, and data were analyzed by non-parametric tests. 123 subjects meeting the inclusion criteria among 1800 (6.8%) PLWH in care at the Infectious and Tropical diseases Unit in Padua were diagnosed with SARS-CoV-2 infection/COVID-19 during the study period. The median age was 51 years (40-58), 79.7% were males, and 77.2% of Caucasian ethnicity. The median CD4+ T-cell count and length of HIV infection were 560 cells/mmc (444-780) and 11 years, respectively. Of the patients, 35.0% had asymptomatic SARS-CoV-2 infection, 48% developed mild COVID-19, 17.1% presented moderate or severe COVID-19 requiring hospitalization and 4.1% died. Polypharmacy was the single independent factor associated with severe COVID-19. As for PACS, among 75 patients who survived SARS-CoV-2 symptomatic infection, 20 (26.7%) reported PACS at a median follow-up of six months: asthenia (80.0%), shortness of breath (50.0%) and recurrent headache (25.0%) were the three most common complaints. Only the severity of the COVID-19 episode predicted PACS after adjusting for relevant demographic and clinical variables. In our study, PLWH with sustained viral suppression and good immunological response showed that the risk of hospital admission for COVID-19 was low, even though the severity of the disease was associated with high mortality. In addition, the likelihood of developing severe COVID-19 and PACS was mainly driven by similar risk factors to those faced by the general population, such as polypharmacy and the severity of SARS-CoV-2 infection.

Whole-genome analysis of SARS-CoV-2 in a 2020 infection cluster in a nursing home of Southern Italy.

BACKGROUND: Nursing homes have represented important hotspots of viral spread during the initial wave of COVID-19 pandemics. The proximity of patients inside nursing homes allows investigate the dynamics of viral transmission, which may help understand SARS-Cov2 biology and spread. METHODS: SARS-CoV-2 viral genomes obtained from 46 patients infected in an outbreak inside a nursing home in Calabria region (South Italy) were analyzed by Next Generation Sequencing. We also investigated the evolution of viral genomes in 8 patients for which multiple swabs were available. Phylogenetic analysis and haplotype reconstruction were carried out with IQ-TREE software and RegressHaplo tool, respectively. RESULTS: All viral strains isolated from patients infected in the nursing home were classified as B.1 lineage, clade G. Overall, 14 major single nucleotide variations (SNVs) (frequency > 80%) and 12 minor SNVs (frequency comprised between 20% and 80%) were identified with reference to the Wuhan-H-1 sequence (NC_045512.2). All patients presented the same 6 major SNVs: D614G in the S gene; P4715L, ntC3037T (F924F) and S5398P in Orf1ab gene; ntC26681T (F53F) in the M gene; and ntC241T in the non-coding UTR region. However, haplotype reconstruction identified a founder haplotype (Hap A) in 36 patients carrying only the 6 common SNVs indicated above, and 10 other haplotypes (Hap BK) derived from Hap A in the remaining 10 patients. Notably, no significant association between a specific viral haplotype and clinical parameters was found. CONCLUSION: The predominant viral strain responsible for the infection in a nursing home in Calabria was the B.1 lineage (clade G). Viral genomes were classified into 11 haplotypes (Hap A in 36 patients, Hap BK in the remaining patients).

Histopathology and immunophenotyping of late onset cutaneous manifestations of COVID-19 in elderly patients: Three case reports.

BACKGROUND: Several cutaneous manifestations such as urticarial rash, erythematous patches and chilblain-like lesions have been described in young adults with coronavirus disease 2019 (COVID-19) and are present in up to 20% patients, but few reports exist describing histopathological and immunophenotypic characteristics of dermatological lesions in older patients. Our aim was to characterize skin lesions in elderly patients during late stages of COVID-19 from clinical, histological and immunophenotypic perspectives. CASE SUMMARY: Three patients, admitted for COVID-19, and who developed cutaneous manifestations underwent skin biopsies. Immunophenotypic analysis for CD20, CD3, CD4 and CD8 was performed on skin biopsies to assess immune cell infiltrates. CD1a was used as a marker of Langerhans cells, and CD31 as a marker of endothelial cells. In the three study patients, cutaneous manifestations were evident in the late-stage of COVID-19 (mean time from the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab to rash onset was 35 d). Skin biopsies showed a similar pattern of T lymphocyte infiltration in all patients. Indeed, a chronic dermatitis with perivascular lymphocytic infiltrate was observed with predominance of CD3+ T-cell (CD3+). CONCLUSION: Our study confirms previous reports. Histological and immunophenotypic patterns in our patients confirm results described in the two previous reported experiences. This pattern is similar to what is found in some lympho-proliferative disorders. Therefore, since these findings are non-specific, SARS-CoV-2 infection should be suspected.

SARS-CoV-2: Some Aspects of Molecular Evolution, Cellular Pathogenesis, and Immune System Mechanism Elusion

The purpose of this review is to address some of the latest aspects regarding molecular features, pathogenic mechanisms, and immune system response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on recent publications in this field from March 2020 to May 2021. Interpretation keys for periodic re-emergence of coronavirus infections and other lethal viral pandemics are suggested. Antibody-dependent enhancement (ADE) and other potential mechanisms of immune system deception are put forward. Therefore, vaccine development must take into account ADE and other unwanted side effects of immune-based medical intervention. Features reported in our review will allow both clinicians and basic science researchers to take home ideas to improve their knowledge about SARS-CoV-2.

Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience.

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

Multidisciplinary approach to a septic COVID-19 patient undergoing veno-venous extracorporeal membrane oxygenation and receiving thoracic surgery.

A multidisciplinary approach appears to be fundamental for the treatment of critically ill patients with COVID-19, improving clinical outcomes, even in the most severe cases. Such severe cases are advisable to be collegially discussed between intensivists, surgeons, infectious disease, and other physicians potentially involved.

A case report of pneumomediastinum in a COVID-19 patient treated with high-flow nasal cannula and review of the literature: Is this a "spontaneous" complication?

Oxygen support with high-flow nasal cannula (HFNC) is gentler than mechanical ventilation and may provide significant benefits, but more studies are needed to investigate the efficacy and safety of different respiratory supports in patients with COVID-19 pneumonia.

Characteristics, Management, and Outcomes of Elderly Patients with Diabetes in a Covid-19 Unit: Lessons Learned from a Pilot Study.

Background and objectives: Diabetes may affect in-hospital mortality of patients with Coronavirus disease 2019 (COVID-19). We have retrospectively evaluated clinical characteristics, diabetes management, and outcomes in a sample of COVID-19 patients with diabetes admitted to our hospital. Materials and Methods: All patients admitted to the Infectious Diseases Unit from 28 March 2020, to 16 June 2020, were enrolled. Clinical information and biochemical parameters were collected at the time of admission. Patients were ranked according to diabetes and death. Results: Sixty-one patients with COVID-19 were analyzed. Most of them were from a long-term health care facility. Mean age was 77 ± 16 years, and 19 had type 2 diabetes (T2D). Eighteen patients died, including 8 with T2D and 10 without T2D (p = 0.15). Patients with diabetes were significantly older, had a higher prevalence of cardiovascular diseases, and a significantly lower lymphocyte count. No significant relationship was found between diabetes and in-hospital mortality (Odds Ratio OR 2.3; Confidence Interval CI 0.73-7.38, p = 0.15). Patients with diabetes were treated with insulin titration algorithm. Severe hypoglycemic events, ketoacidosis and hyperosmolar hyperglycemias did not occur during hospitalization. Mean pre-meal capillary blood glucose was 157 ± 45 mg/dL, and the coefficient of variation of glycaemia was 29%. Conclusions: Our study, albeit limited by the small number of subjects, did not describe any significant association between T2D diabetes and mortality. Clinical characteristics of patients, and acceptable glucose control prior and during hospitalization may have influenced the result. The use of an insulin titration algorithm should be pursued during hospitalization.

Therapy with RAS inhibitors during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus first identified in Wuhan, China. The global number of confirmed cases of COVID-19 has surpassed 28,285,700 with mortality that appears higher than for seasonal influenza. About 20% of COVID-19 patients have experienced cardiac involvement and myocardial infarction in patients infected with SARS-CoV-2 had a worse prognosis. Furthermore, the widespread use of antiviral drugs can be linked to a worsening of heart function. Arrhythmias and hypertension have also been reported in patients with Covid-19. On the other hand, previous cardiac diseases are present in 30% of patients infected with SARS-CoV-2. There is uncertainty in the use of ace inhibitors and angiotensin II (Ang II) antagonists in the COVID-19 era. The mechanism of action of SARS-CoV-2 has been elucidated. It has been demonstrated that angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the new coronavirus SARS-CoV-2 and it is required for host cell entry and subsequent viral replication. The effect of the SARS-CoV-2 infection is the downregulation of ACE2 that may contribute to the severity of lung pathologies as well as the cardiac function. ACE2, a homolog of ACE, is a monocarboxypeptidase that converts Ang II into angiotensin 1-7 (Ang 1-7) that with its vasodilatory, antifibrotic, antihypertrophic effects counterbalances the negative effects of Ang II. On the other hand, angiotensin-converting enzyme inhibitors (ACEi) and AT1R blockers have been shown to upregulate the expression of ACE2. Based on the mechanism of action of SARS-CoV-2, the use of renin angiotensin system (RAS) inhibitors was questioned although all scientific societies did not recommend discontinuation when clinically recommended. The BRACE CORONA, a phase 4, randomized study tested two strategies: temporarily stopping the ACE inhibitor/angiotensin receptor blockers (ARB) for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalized with a confirmed diagnosis of COVID-19 was also discussed. Therefore, the goal of this review is to summarize recent laboratory and clinical investigations concerning the use of ACEi and ARBs during the COVID-19 pandemic. The available data, based also on a randomized trial, suggest that ACEIs or ARBs, when clinically indicated, should be regularly used in the COVID-19 era.