Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review
Translational oncology. 2022;21:101443
PURPOSE Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility. METHODS A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated. RESULTS A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were included. Seven up-regulated markers, including CRP, d-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Moreover, we observed that the SARS-CoV-2 infected cancer patients with lower CRP, ferritin, and LDH levels successfully survived from COVID-19 treatments. CONCLUSION Several important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients.
Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19: A Meta-analysis
JAMA network open. 2022;5(1):e2147331
IMPORTANCE COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. OBJECTIVE To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. DATA SOURCES From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. STUDY SELECTION Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. DATA EXTRACTION AND SYNTHESIS A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. MAIN OUTCOMES AND MEASURES Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. RESULTS Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. CONCLUSIONS AND RELEVANCE This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.
Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis
PURPOSE As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES PROSPERO (registration number: CRD42021245308, 05/21/2021).
Convalescent Plasma Treatment in Patients with Covid-19: A Systematic Review and Meta-Analysis
Frontiers in immunology. 2022;13:817829
Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17(th), 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).
The impact of anti-tumor approaches on the outcomes of cancer patients with COVID-19: a meta-analysis based on 52 cohorts incorporating 9231 participants
BMC cancer. 2022;22(1):241
BACKGROUND This study was designed to investigate the impact of anti-tumor approaches (including chemotherapy, targeted therapy, endocrine therapy, immunotherapy, surgery and radiotherapy) on the outcomes of cancer patients with COVID-19. METHODS Electronic databases were searched to identify relevant trials. The primary endpoints were severe disease and death of cancer patients treated with anti-tumor therapy before COVID-19 diagnosis. In addition, stratified analyses were implemented towards various types of anti-tumor therapy and other prognostic factors. Furthermore, odds ratios (ORs) were hereby adopted to measure the outcomes with the corresponding 95% confidence intervals (CIs). RESULTS As indicated in the study consisting of 9231 individuals from 52 cohorts in total, anti-tumor therapy before COVID-19 diagnosis could elevate the risk of death in cancer patients (OR: 1.21, 95%CI: 1.07-1.36, P = 0.0026) and the incidence of severe COVID-19 (OR: 1.19, 95%CI: 1.01-1.40, P = 0.0412). Among various anti-tumor approaches, chemotherapy distinguished to increase the incidence of death (OR = 1.22, 95%CI: 1.08-1.38, P = 0.0013) and severe COVID-19 (OR = 1.10, 95%CI: 1.02-1.18, P = 0.0165) as to cancer patients with COVID-19. Moreover, for cancer patients with COVID-19, surgery and targeted therapy could add to the risk of death (OR = 1.27, 95%CI: 1.00-1.61, P = 0.0472), and the incidence of severe COVID-19 (OR = 1.14, 95%CI: 1.01-1.30, P = 0.0357) respectively. In the subgroup analysis, the incidence of death (OR = 1.17, 95%CI: 1.03-1.34, P = 0.0158) raised in case of chemotherapy adopted for solid tumor with COVID-19. Besides, age, gender, hypertension, COPD, smoking and lung cancer all served as potential prognostic factors for both death and severe disease of cancer patients with COVID-19. CONCLUSIONS Anti-tumor therapy, especially chemotherapy, augmented the risk of severe disease and death for cancer patients with COVID-19, so did surgery for the risk of death and targeted therapy for the incidence of severe COVID-19.
Comorbidities and mortality rate in COVID-19 patients with hematological malignancies: A systematic review and meta-analysis
Journal of clinical laboratory analysis. 2022;:e24387
INTRODUCTION The global pandemic of coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It seems that there is an association between blood cancer and an increased risk of severe COVID-19. This study aimed to review the literature reporting the COVID-19 outcomes in patients with hematological malignancies. MATERIAL AND METHODS In this systematic review and meta-analysis, Pubmed, Embase, and Web of Science databases were searched using the following keywords: COVID-19, SARS-CoV-2, blood cancer, myeloma, lymphoma, and leukemia. All the published articles in English from January 1, 2019, until March 10, 2021 were collected and evaluated. RESULTS In total, 53 studies with 2395 patients were included based on inclusion criteria. Most of these studies took place in Spain (14.81%), followed by the USA (11.11%), China (9.26%), and the UK (9.26%). More than half of COVID-19 patients with hematological malignancy were male (56.73%). Oxygen therapy played an important role in COVID-19 treatment. Moreover, anticoagulant therapies such as enoxaparin and heparin were two great assists for these patients. Fever (74.24%), cough (67.64%), and fatigue (53.19%) were the most reported clinical manifestations. In addition, hypertension and dyslipidemia were the most common comorbidities. The mortality rate due to COVID-19 in patients with hematological malignancies was 21.34%. CONCLUSION This study demonstrated that hematologic cancer patients were more susceptible to a severe COVID-19 than patients without blood cancer. Thus, the management of COVID-19 in these patients requires much more attention, and their screening should perform regularly.
High-Dose Convalescent Plasma for Treatment of Severe COVID-19
Emerging infectious diseases. 2022;28(3)
To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.
COVID-19 mortality and its predictors in the elderly: A systematic review
Health science reports. 2022;5(3):e657
BACKGROUND AND AIMS Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to systematically review the mortality in coronavirus disease 2019 (COVID-19) patients and its predictors in this age group. METHODS We searched PubMed, Web of Science, and Science Direct using relevant keywords. Retrieved records underwent a two-step screening process consisting of title/abstract and full-text screenings to identify the eligible studies. RESULTS Summarizing findings of 35 studies demonstrated that older patients have higher mortality rates compared to the younger population. A review of articles revealed that increasing age, body mass index, a male gender, dementia, impairment or dependency in daily activities, presence of consolidations on chest X-ray, hypoxemic respiratory failure, and lower oxygen saturation at admission were risk factors for death. High d-dimer levels, 25-hydroxy vitamin D serum deficiencies, high C-reactive protein (≥5 mg/L) levels plus any other abnormalities of lymphocyte, higher blood urea nitrogen or lactate dehydrogenase, and higher platelet count were predictors of poor prognosis and mortality in the elderly. Studies have also shown that previous treatment with renin-angiotensin-aldosterone system inhibitors, pharmacological treatments of respiratory disorders, antibiotics, corticosteroids, vitamin K antagonist, antihistamines, azithromycin, Itolizumab (an anti-CD6 monoclonal antibody) in combination with other antivirals reduces COVID-19 worsening and mortality. Vaccination against seasonal influenza might also reduce COVID-19 mortality. CONCLUSION Overall, a critical consideration is necessary for the care and management of COVID-19 in the aged population considering the drastic contrasts in manifestation and prognosis compared to other age groups. Mortality from COVID-19 is independently associated with the patient's age. Elderly patients with COVID-19 are more vulnerable to poor outcomes. Thus, strict preventive measures, timely diagnosis, and aggressive therapeutic/nontherapeutic care are of great importance to reduce acute respiratory distress syndrome and severe complications in older people.
Subclinical myocardial injury, coagulopathy, and inflammation in COVID-19: A meta-analysis of 41,013 hospitalized patients
International journal of cardiology. Heart & vasculature. 2022;:100950
BACKGROUND Infection with the SARS-CoV-2 virus can lead to myocardial injury, evidenced by increases in specific biomarkers and imaging. OBJECTIVE To quantify the association between biomarkers of myocardial injury, coagulation, and severe COVID-19 and death in hospitalized patients. METHODS Studies were identified through a systematic search of indexed articles in PubMed, Embase, CINAHL, Cochrane, Web of Science, and Scopus, published between December 2019 to August 2021. Effect estimates from individual studies for association between markers of myocardial injury (Troponin), myocardial stretch (N-terminal-pro hormone BNP, NT-proBNP), and coagulopathy (D-Dimer) and death or severe/critical COVID-19 were pooled using inverse variance weighted random-effects model. Odds Ratios (OR), Hazard Ratios (HR), and 95% Confidence Intervals (CI) were pooled separately and reported by outcomes of critical/severe COVID-19 and death. A meta-analysis of proportions was also performed to summarize the pooled prevalence of co-morbidities in patients hospitalized with COVID-19. RESULTS We included 62 articles, with a total of 41,013 patients. The pooled proportion of patients with history of hypertension was 39% (95% CI: 34-44%); diabetes, 21% (95% CI: 18%-24%); coronary artery disease, 13% (95% CI: 10-16%); chronic obstructive pulmonary disease, 7% (95% CI: 5-8%), and history of cancer, 5% (95% CI: 4-7%). Elevated troponin was associated with higher pooled odds of critical/severe COVID-19 and death [Odds Ratio (OR: 1.76, 95% CI: 1.42-2.16)]; and also separately for death (OR: 1.72, 95% CI: 1.32-2.25), and critical/severe COVID-1919 (OR: 1.93, 95% CI: 1.45-2.40). Elevations in NT-proBNP were also associated with higher severe COVID-19 and death (OR: 3.00, 95% CI: 1.58-5.70). Increases in D-dimer levels was also significantly associated with critical/severe COVID-19 and death (pooled OR: 1.38, 95% CI: 1.07-1.79). CONCLUSIONS This meta-analysis synthesizes existing evidence showing that myocardial injury, and coagulopathy are complications of COVID-19. The durability of these complications and their contributions to long-term cardiac implications of the disease is still being investigated. Patients who have recovered from COVID-19 may benefit from minimally invasive assessment for markers of myocardial injury, stretch and coagulopathy for early risk stratification purposes.
Convalescent plasma may not be an effective treatment for severe and critically ill covid-19 patients: A Systematic Review & Meta-Analysis of Randomized Controlled Trials
Heart & lung : the journal of critical care. 2022;53:51-60
BACKGROUND Convalescent plasma treatment for severe and critically ill Corona Virus Disease 2019 (COVID-19) patients remains controversial. OBJECTIVE To evaluate the clinical improvement and mortality risk of convalescent plasma treatment in patients with severe and critically ill COVID-19 patients. METHODS A literature search was conducted in the electronic databases for the randomized controlled studies about convalescent plasma therapy in severe and critically ill COVID-19 patients. Two reviewers independently extracted relevant data. The primary outcomes were clinical improvement and mortality risk of severe and critically ill COVID-19 patients that were therapied by convalescent plasma. RESULTS A total of 14 randomized controlled trials with 4543 patients were included in this meta-analysis. Compared to control, no significant difference was observed for either clinical improvement (6 studies, RR 1.07, 95% CI 0.97 to 1.17, p = 0.16, moderate certainty) or mortality risk (14 studies, RR 0.94, 95% CI 0.85 to 1.03, p= 0.18, low certainty) in patients of convalescent plasma therapy group. CONCLUSION Convalescent plasma did not increase the clinical improvement or reduce the mortality risk in the severe and critically ill COVID-19 patients.