Elena Consolaro

Bio: Elena Consolaro is an academic researcher. The author has contributed to research in topics: Cohort & Observational study. The author has an hindex of 1, co-authored 3 publications receiving 9 citations.

A home-treatment algorithm based on anti-inflammatory drugs to prevent hospitalization of patients with early covid-19: a matched-cohort study (cover 2)

Abstract: AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackground and AimC_ST_ABSWhile considerable success has been achieved in the management of patients hospitalized with severe coronavirus disease 2019 (COVID-19), far less progress has been made with early outpatient treatment. We assessed whether the implementation of a home treatment algorithm - designed based upon on a pathophysiologic and pharmacologic rationale - during the initial, mild phase of COVID-19, could effectively reduce hospital admissions. MethodsThis fully academic, matched-cohort study evaluated outcomes in 108 consecutive consenting patients with mild COVID-19 managed at home by their family doctors from January 2021 to May 2021, according to the proposed treatment algorithm and in 108 age-, sex-, and comorbidities-matched patients who were given other therapeutic schedules (ClinicalTrials.gov: NCT04854824). The primary outcome was COVID-19-related hospitalization. Analyses were by intention-to-treat. ResultsOne (0.9%) patient in the recommended cohort and 12 (11.1%) in the control cohort were admitted to hospital (P=0.0136). The proposed algorithm reduced, by 85%, the cumulative length of hospital stays (from 141 to 19 days) and related costs (from {euro} 60.316 to {euro} 9.058). Only 9.8 patients needed to be treated with the recommended algorithm to prevent one hospitalization event. The rate of resolution of major symptoms was numerically, but not significantly, higher in the recommended compared to the control cohort (97.2% versus 93.5%, respectively; P=0.322). Other symptoms lingered in a lower proportion of patients in the recommended than in the control cohort (20.4% versus 63.9%, respectively; P<0.001), and for a shorter period. ConclusionThe adoption of the proposed outpatient treatment algorithm during the early, mild phase of COVID-19 reduced the incidence of subsequent hospitalization and related costs.

A simple, home-therapy algorythm to prevent hospitalization of covid-19 patients: a retrospective observational matched-cohort study

Abstract: Summary Background Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. Methods This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. Findings All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the ‘recommended’ schedule cohort and 14 [7-30] days in the matched ‘control’ cohort (p=0·033). Other symptoms persisted in a lower percentage of patients in the ‘recommended’ than in the ‘control’ cohort (23·3% versus 73·3%, respectively, p 90% (from 481 to 44 days and from €296.000 to €28.000, respectively. 1.2 patients had to be treated to prevent one hospitalisation event. Interpretation Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID 19, but almost eliminated the risk of hospitalisation and related treatment costs. Research in Context Evidence before this study We searched PubMed and the Cochrane Library for peer-reviewed articles published in any language up to March 19, 2021, using the search terms “2019-nCoV” or “SARS-CoV-2” or “COVID-19” and “early” or “outpatient” or “treatment” or “home”. Our search did not identify any randomised clinical trials or observational studies that assessed the effectiveness of treatment regimens targeting early, mild symptoms of COVID-19 in the outpatient setting. Added value of this study In this fully academic, observational matched-cohort study, we found that early home treatment of 90 consecutive patients with mild COVID-19 by their family physicians according to the proposed recommendation algorithm, designed based on a pathophysiologic and pharmacologic rationale, required few more days to achieve resolution of major symptoms including fever, dyspnea, musculoskeletal pain, headache and cough compared to 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens (primary outcome). Nonetheless, it is noteworthy that the home treatment of COVID-19 patients according to the proposed recommendation algorithm significantly reduced the risk of hospitalization compared to the other treatments in the ‘control’ cohort. Days of hospitalization and related treatment costs were reduced by over 90% in the ‘recommended’ cohort as compared to ‘control’ cohort. Just 1.2 patients needed to be treated according to the recommendation algorithm to prevent one hospitalization event. We also found that symptoms such as anosmia and ageusia/dysgeusia were less persistent and lasted a shorter time in the ‘recommendation’ than in the ‘control’ cohort. Implications of the available evidence The finding that the implementation of the proposed simple treatment algorithm during the initial, mild phase of COVID-19 has the potential to prevent disease progression, potentially limiting the need for hospital admission, may have major implications for patients and health care providers. Indeed, preventing hospitalisations due to the worsening of COVID-19 will not only save lives, but will also contribute to remarkably reduced treatment costs and to streamlining health care systems that are overburdened by the effects of the pandemic. However, time to hospitalization was a secondary outcome of the study and the possibility of a casual finding cannot be definitely excluded. Thus, the observed reduction in patients hospitalizations should be considered as an hypothesis generating finding that could provide a robust background for a prospective trial primarily aimed to test treatment effect on this outcome.

Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial

Abstract: Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing global pandemic known as COVID-19. Based on the potential antiviral role of quercetin, and on its described anti-blood clotting, anti-inflammatory and antioxidant properties, we hypothesize that subjects with mild COVID-19 treated with Quercetin Phytosome R (QP), a novel bioavailable form of quercetin, may have a shorter time to virus clearance, a milder symptomatology, and higher probabilities of a benign earlier resolution of the disease. Methods: In our 2-week, randomized, open-label, and controlled clinical study, we have enrolled 42 COVID-19 outpatients. Twenty-one have been treated with the standard of care (SC), and 21 with QP as add-on supplementation to the SC. Our main aims were to check virus clearance and symptoms. Results: The interim results reveal that after 1 week of treatment, 16 patients of the QP group were tested negative for SARS-CoV-2 and 12 patients had all their symptoms diminished;in the SC group, 2 patients were tested SARS-CoV-2 negative and 4 patients had their symptoms partially improved. By 2 weeks, the remaining 5 patients of the QP group tested negative for SARS-CoV-2, whereas in the SC group out of 19 remaining patients, 17 tested negatives by week 2, one tested negative by week 3 and one patient, still positive, expired by day 20. Concerning blood parameters, the add on therapy with QP, reduced LDH (-35.5%), Ferritin (-40%), CRP (-54.8%) and D-dimer (-11.9%). Conclusion: QP statistically shortens the timing of molecular test conversion from positive to negative, reducing at the same time symptoms severity and negative predictors of COVID-19.

A review of ischemic stroke in COVID-19: currently known pathophysiological mechanisms.

Abstract: Coronavirus disease 2019 (COVID-19), the third type of coronavirus pneumonia after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), is spreading widely worldwide now. This pneumonia causes not only respiratory symptoms but also multiple organ dysfunction, including thrombotic diseases such as ischemic stroke. The purpose of this review is to explore whether COVID-19 is a risk factor for ischemic stroke and its related pathophysiological mechanisms. Based on the high thrombosis rate and frequent strokes of COVID-19 patients, combined with related laboratory indicators and pathological results, the discussion is mainly from two aspects: nerve invasion and endothelial dysfunction. SARS-CoV-2 can directly invade the CNS through blood-borne and neuronal retrograde pathways, causing cerebrovascular diseases. In addition, the endothelial dysfunction in COVID-19 is almost certain. Cytokine storm causes thromboinflammation, and downregulation of ACE2 leads to RAS imbalance, which eventually lead to ischemic stroke.

Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?

Abstract: The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.

A Home-Treatment Algorithm Based on Anti-inflammatory Drugs to Prevent Hospitalization of Patients With Early COVID-19: A Matched-Cohort Study (COVER 2)

Abstract: Background and Aim While considerable success has been achieved in the management of patients hospitalized with severe coronavirus disease 2019 (COVID-19), far less progress has been made with early outpatient treatment. We assessed whether the implementation of a home treatment algorithm—designed based on a pathophysiologic and pharmacologic rationale—and including non-steroidal anti-inflammatory drugs, especially relatively selective cyclooxygenase-2 inhibitors and, when needed, corticosteroids, anticoagulants, oxygen therapy and antibiotics—at the very onset of mild COVID-19 symptoms could effectively reduce hospital admissions. Methods This fully academic, matched-cohort study evaluated outcomes in 108 consecutive consenting patients with mild COVID-19, managed at home by their family doctors between January 2021 and May 2021, according to the proposed treatment algorithm and in 108 age-, sex-, and comorbidities-matched patients on other therapeutic schedules (ClinicalTrials.gov: NCT04854824). The primary outcome was COVID-19-related hospitalization. Analyses were by intention-to-treat. Results One (0.9%) patient in the “recommended” cohort and 12 (11.1%) in the “control” cohort were admitted to hospital ( P = 0.0136). The proposed algorithm reduced the cumulative length of hospital stays by 85% (from 141 to 19 days) as well as related costs (from €60.316 to €9.058). Only 9.8 patients needed to be treated with the recommended algorithm to prevent one hospitalization event. The rate of resolution of major symptoms was numerically—but not significantly—higher in the “recommended” than in the “control” cohort (97.2 vs. 93.5%, respectively; P = 0.322). Other symptoms lingered in a smaller proportion of patients in the “recommended” than in the “control” cohort (20.4 vs. 63.9%, respectively; P &lt; 0.001), and for a shorter period. Conclusion The adoption of the proposed outpatient treatment algorithm during the early, mild phase of COVID-19 reduced the incidence of subsequent hospitalization and related costs.

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19.

Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.