Clinical Frailty Scale (CFS) indicated frailty is associated with increased in-hospital and 30-day mortality in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The concept of frailty provides an age-independent, easy-to-use tool for risk stratification. We aimed to summarize the evidence on the efficacy of frailty tools in risk assessment in COVID-19 patients. METHODS: The protocol was registered (CRD42021241544). Studies reporting on frailty in COVID-19 patients were eligible. The main outcomes were mortality, length of hospital stay (LOH) and intensive care unit (ICU) admission in frail and non-frail COVID-19 patients. Frailty was also compared in survivors and non-survivors. Five databases were searched up to 24th September 2021. The QUIPS tool was used for the risk of bias assessment. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using a random effect model. Heterogeneity was assessed using the I2 and χ2 tests. RESULTS: From 3640 records identified, 54 were included in the qualitative and 42 in the quantitative synthesis. Clinical Frailty Scale (CFS) was used in 46 studies, the Hospital Frailty Risk Score (HFRS) by 4, the Multidimensional Prognostic Index (MPI) by 3 and three studies used other scores. We found that patients with frailty (CFS 4-9 or HFRS ≥ 5) have a higher risk of mortality (CFS: OR: 3.12; CI 2.56-3.81; HFRS OR: 1.98; CI 1.89-2.07). Patients with frailty (CFS 4-9) were less likely to be admitted to ICU (OR 0.28, CI 0.12-0.64). Quantitative synthesis for LOH was not feasible. Most studies carried a high risk of bias. CONCLUSIONS: As determined by CFS, frailty is strongly associated with mortality; hence, frailty-based patient management should be included in international COVID-19 treatment guidelines. Future studies investigating the role of frailty assessment on deciding ICU admission are strongly warranted.

Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study.

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro^® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T₀) then after 24, 48 hours, then on day 5 and 7 (T_1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.

Effectiveness and safety of fibrinolytic therapy in critically ill patients with COVID-19 with ARDS: protocol for a prospective meta-analysis.

INTRODUCTION: The use of fibrinolytic therapy has been proposed in severe acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, anticoagulation has received special attention due to the frequent findings of microthrombi and fibrin deposits in the lungs and other organs. Therefore, the use of fibrinolysis has been regarded as a potential rescue therapy in these patients. In this prospective meta-analysis, we plan to synthesise evidence from ongoing clinical trials and thus assess whether fibrinolytic therapy can improve the ventilation/perfusion ratio in patients with severe COVID-19-caused ARDS as compared with standard of care. METHODS AND ANALYSIS: This protocol was registered in PROSPERO. All randomised controlled trials and prospective observational trials that compare fibrinolytic therapy with standard of care in adult patients with COVID-19 and define their primary or secondary outcome as improvement in oxygenation and/or gas exchange, or mortality will be considered eligible. Safety outcomes will include bleeding event rate and requirement for transfusion. Our search on 25 January 2022 identified five eligible ongoing clinical trials. A formal search of MEDLINE (via PubMed), Embase, CENTRAL will be performed every month to identify published results and to search for further trials that meet our eligibility criteria. DISSEMINATION: This could be the first qualitative and quantitative synthesis summarising evidence of the efficacy and safety of fibrinolytic therapy in critically ill patients with COVID-19. We plan to publish our results in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021285281.

Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54-1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44-0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25-2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67-2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31-1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63-1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.

Extracorporeal Cytokine Removal in Critically Ill COVID-19 Patients: A Case Series.

Introduction: Extracorporeal hemoadsorption (HA) is a potential adjunctive therapy in severe cases of COVID-19 associated pneumonia. In this retrospective study we report data from critically ill patients treated with HA during the first and second wave of the pandemic. Patients and Methods: All patients, who received HA therapy with CytoSorb within the first 96 h of intensive care unit (ICU) admission without hospital-acquired bacterial superinfection, were included. Clinical and laboratory data were collected: on admission, before (TB) and after (TA) HA therapy. Results: Out of the 367 COVID-19 cases, 13 patients were treated with CytoSorb, also requiring mechanical ventilation and renal replacement therapy. All patients were alive at the end of HA, but only 3 survived hospital stay. From TB-TA there was a tendency of decreasing norepinephrine requirement: 193.7 [IQR: 34.8-270.4] to 50.2 [6.5-243.5] ug/kg/day and increasing PaO2/FiO2 ratio 127.8 (95% CI: 96.0-159.6) to 155.0 (115.3-194.6) mmHg but they did not reach statistical significance (p = 0.14 and 0.58, respectively). Treatment related adverse events were not reported. Conclusion: The treatment was well-tolerated, and there was a tendency toward an improvement in vasopressor need and oxygenation during the course of HA. These observations render the need for prospective randomized trials.

Metabolic Associated Fatty Liver Disease Is Associated With an Increased Risk of Severe COVID-19: A Systematic Review With Meta-Analysis.

Background: The most common pre-existing liver disease, the metabolic dysfunction-associated fatty liver disease (MAFLD) formerly named as non-alcoholic fatty liver disease (NAFLD), may have a negative impact on the severity of COVID-19. This meta-analysis aimed to evaluate if MAFLD or NAFLD are associated with a more severe disease course of COVID-19. Methods: A systematic search was performed in five databases for studies comparing severity, the rate of intensive care unit (ICU) admission, and mortality of COVID-19 patients with and without MAFLD or NAFLD. In meta-analysis, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Altogether, we included nine studies in our quantitative and qualitative synthesis. MAFLD was associated with an increased risk of severe COVID-19 compared to the non-MAFLD group (28 vs. 13%, respectively; OR = 2.61, CI: 1.75-3.91). Similarly, in the NAFLD vs. non-NAFLD comparison, NAFLD proved to be a risk factor as well (36 vs. 12%, respectively; OR = 5.22, CI: 1.94-14.03). On the other hand, NAFLD was not associated with an increased risk of ICU admission (24 vs. 7%, respectively; OR = 2.29, CI: 0.79-6.63). We were unable to perform meta-analysis to investigate the association of MAFLD with the rate of ICU admission and with mortality. Conclusion: In conclusion, patients with MAFLD and NAFLD showed a more severe clinical picture in COVID-19. Our results support the importance of close monitoring of COVID-19 patients with MAFLD. Further research is needed to explore the cause of increased severity of COVID-19 in MAFLD.

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.

Insufficient etiological workup of COVID-19-associated acute pancreatitis: A systematic review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mostly causing respiratory symptoms, is also known to affect the gastrointestinal tract. Several case reports hypothesize that SARS-CoV-2 could be an etiological factor in acute pancreatitis (AP). AIM: To assess all the available evidence in the literature relating to coronavirus disease 2019 (COVID-19) and AP. METHODS: We performed a systematic review of the available literature on the topic. The systematic search was conducted on 15 May 2020 on MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus with a search key using the terms "amylase," "lipase," "pancr*," "COVID-19" and synonyms. Due to the low quality and poor comparability of the studies, a meta-analysis was not performed. RESULTS: Six case reports and two retrospective cohorts were included, containing data on eleven COVID-19 patients with AP. Five patients had AP according to the Atlanta classification. Other publications did not provide sufficient information on the diagnostic criteria. Most cases were considered SARS-CoV-2-induced, while several established etiological factors were not investigated. We were able to identify other possible causes in most of them. CONCLUSION: We strongly highlight the need for adherence to the guidelines during a diagnostic and etiological workup, which could alter therapy.

Personalised health education against health damage of COVID-19 epidemic in the elderly Hungarian population (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial.

BACKGROUND: Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5-26% and overall mortality can rise to 11% of the recognised cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for its prevention and treatment. We aim to compare the effects of a World Health Organization recommendation-based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19. METHODS: PROACTIVE-19 is a pragmatic, randomised controlled clinical trial with adaptive "sample size re-estimation" design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomised into two groups: (A) general health education and (B) personalised health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, and (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer than 48 h), and mortality in COVID-19-positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of 1 year. DISCUSSION: These interventions may boost the body's cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. TRIAL REGISTRATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov ( NCT04321928 ) on 25 March 2020.