Efficacy of Tocilizumab in Severely Ill COVID-19 Patients With Rapid Respiratory Deterioration: A Single Center Experience During the Third Pandemic Wave in Greece.

BACKGROUND/AIM: Immunomodulatory therapy with Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 receptor-alpha, has been endorsed by the World Health Organization and other major regulatory bodies, as part of the standard-of-care therapy for severe or critical COVID-19 cases despite discordant trial outcomes. The aim of the present study was to report the experience of our center regarding TCZ routine use in severely ill COVID-19 patients who were hospitalized during the third pandemic wave in Greece. PATIENTS AND METHODS: From March 2021 to December 2021, we retrospectively analyzed COVID-19 patients with radiological findings of pneumonia and signs of rapid respiratory deterioration that were treated with TCZ. The primary outcome included the risk of intubation or/and death in TCZ-treated patients compared to matched controls. RESULTS: TCZ administration was neither predictive of intubation and/or death [OR=17.5 (95% CI=0.47-652.2; p=0.12)] or associated with fewer events (p=0.92) in multivariate analysis. CONCLUSION: Our single-center real-life experience is in line with recently published research, revealing no benefit from TCZ routine use in severely or critically ill patients with COVID-19.

Prolonged SARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy.

BACKGROUND/AIM: Anti-CD20-depleting monoclonal antibodies predispose patients to the development of severe disease of SARS-CoV-2 infection. These antibodies are given as backbone or maintenance therapy in patients with hematological malignancies and rheumatology diseases, inducing effective B-cell depletion along with antibody-dependent cell-mediated cytotoxicity (ADCC) and disrupting infection-protective antibody responses. CASE REPORT: We describe two cases of prolonged SARS-CoV-2 infection with common features, in two patients receiving anti-CD20 therapies, the first for chronic lymphocytic leukemia (CLL) and the second for rheumatoid arthritis (RA). For CLL patient, despite administration of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 43 days, with resolution and lymphocyte recovery from day 33. For RA patient, despite administration of two courses of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 47 days, without resolution and lymphocyte recovery, leading to a fatal outcome due to acute respiratory distress syndrome (ARDS) and unspecified sepsis. CONCLUSION: These two cases highlight the risk for persistent SARS-CoV-2 infection in patients treated with anti-CD20 monoclonal antibodies and support a role for cellular immunity recovery for disease control.

Prone Positioning in Patients With COVID-19: Analysis of Multicenter Registry Data and Meta-analysis of Aggregate Data.

BACKGROUND/AIM: Evidence suggests a beneficial effect of prone positioning (PP) in COVID-19. MATERIALS AND METHODS: Meta-analysis of individual (7 investigators' groups) and aggregate data (PubMed/EMBASE) regarding the impact of PP on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PO2/FiO2) in patients with COVID-19. RESULTS: Among 121 patients (mean age±SD 59.1±10.7 years, 55% males, 57% intubated) the mean post-versus pre- PP PO2/FiO2 difference was: (i) 50.4±64.3 mmHg, p<0.01, (ii) similar in awake (58.7±72.1 mmHg) versus intubated patients (44.1±57.5 mmHg, p=NS), (iii) inversely correlated with body mass index (r=-0.43, p<0.01). Meta-analysis of 23 studies (n=547, weighted age 58.3±4.1, 73% males, 59% intubated) showed a pooled PO2/FiO2 difference of 61.8 [95% confidence intervals=49.9-73.6] mmHg. Meta-regression analysis revealed no associations with baseline demographics, the time in PP before assessment, and the risk of bias of the studies. CONCLUSION: PP seems to improve oxygenation of patients with COVID-19.

Early Occurrence of Adverse Events in Hospitalized Patients With COVID-19 and Beneficial Effect of Anticoagulation.

BACKGROUND/AIM: This study analyzed the characteristics of patients with COVID-19 with major events during the first days of hospitalization. PATIENTS AND METHODS: This is a retrospective analysis of prospectively collected data from consecutive patients admitted to two hospitals in Athens, Greece. The characteristics of patients with COVID-19 who suffered the primary endpoint (venous thromboembolic events, intubation, and death) during the first days of hospitalization were analyzed. RESULTS: Among 95 patients included in the analysis, 21 presented with major adverse events during a median follow-up of 13 days. More than 50% of these patients presented with a major event during the first 3 days. Anticoagulation treatment was inversely associated with the cumulative incidence of the primary endpoint [hazard ratio=0.16 (95% confidence interval=0.06-0.47)]. Patients with major events were older, with lower baseline SatO2, and higher number of Wells' criteria and Charlson comorbidity index. Among these patients, those with hypertension were at higher risk for early occurrence of events (≤ first three days of hospitalization). CONCLUSION: Major adverse events may occur early in hospitalized patients with COVID-19 with a high-risk profile. Anticoagulation treatment appears to reduce this risk and thus prompt thromboprophylaxis should be employed in these patients.

Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial.

INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.

Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis.

BACKGROUND AND AIMS: Statin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality. METHODS: A systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus non-users. RESULTS: 22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 ± 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58-100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Meta-analysis of 12 studies (n = 72,881, weighted age 65 ± 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities. CONCLUSIONS: This meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients.

Clinical examination practices and perceptions in the era of COVID-19.

Introduction The art of clinical examination has been the cornerstone of medical practices since ancient years. Recent technological achievements and their overuse have led falsely to underestimation of their significance, which has been further questioned during the coronavirus disease 2019 (COVID-19) pandemic, due to concerns regarding exposure risk and use of personal protective equipment.Areas covered The role of clinical examination (namely chest examination) during the pandemic is discussed. Emerging evidence is being accumulated concerning alternatives to traditional practices. Telemedicine stands out as a promising tool, allowing inspection and interaction between physicians and patients, proved to be useful for many medical specialties but not enough for some others. Medical practices cannot remain the same in the era of the COVID-19 pandemic, yet realistic strategies should be adopted for their optimal and safe implementation.Expert opinion The experiences of a dedicated Reference Center for COVID-19 along with a suggested algorithm for conducting clinical examinations are presented. According to our experience, an initial detailed clinical examination upon admission of each COVID-19 patient appears to be necessary. Then, vital signs and signs of respiratory distress using inspection should be checked frequently. A focused examination approach should be adopted, in case of new onset clinical problems.