COVID-19: Main findings after a year and half of unease and the proper scientific progress (Review)
Experimental and therapeutic medicine. 2022;23(6):424
Since the emergence of the disease in late December 2019, numerous studies have been published to date regarding clinical, laboratory and treatment aspects associated with COVID-19. The present study attempts to compare and unify the clinical, para-clinical and therapeutic aspects that have come to light regarding coronavirus disease-19 (COVID 19), mainly in adults. Between April 2020 and September 2021, a comprehensive systematic literature review was performed, which we added to from our own medical experiences. The search was performed on the PubMed, Scopus and Google Scholar databases, comprising studies with analyzable data that were identified alongside studies and documents containing general scientific data. All published studies were written in English, and were from different countries. A 95% confidence interval (CI95) was also calculated for almost each study using the Wilson formula. When compared with preliminary reports between December 2019 and January 2020, the most frequent symptoms were still identified as being fever (68.6%; CI95: 67.5-69.7) and cough (72.7%; CI95: 71.7-73.8). Nevertheless, asymptomatic cases also increased (by 21.4%; CI95: 16.6-27.1). Severe and critical cases accounted for 10.4% (CI95: 9.6-11.1) of all cases. The mean fatality rate was found to be 4% (CI95: 3.6-4.5). The primary co-morbidity found was hypertension (28.9%; CI95: 27-30.8), followed by other underlying cardiovascular diseases (15.4%; CI95: 13.9-16.9) and diabetes (14.5%; CI95: 13.1-16.1). The majority of studies showed lower white blood cell numbers with neutropenia and lymphopenia, and lower platelet levels. The levels of the biomarkers C-reaction protein and erythrocyte sedimentation rate were positive in all studied cases alongside other lab tests, such as examining the D-dimer levels and those of other hepatic, cardiac and renal injury markers. The procalcitonin level was also found to be elevated in many cases, resulting in high usage of antibiotics (83.7%; CI95: 81.2-85.9). Approximately 31.6% (CI95: 29.1-34.1) of the patients required non-invasive ventilation, whereas 9.9% (CI95: 8.1-12.1) of the patients were intubated or placed on extracorporeal membrane oxygenation. The most used antivirals were ribavirin (67.3%; CI95: 63.4-70.9), oseltamivir (52.5%; CI95: 49.4-55.5) and Arbidol™ (34.5%; CI95: 32-37.1). General admittance to the intensive care unit was ~7.2% (CI95: 6.5-7.9) of patients.
Low molecular weight heparin is associated with better outcomes than unfractionated heparin for thromboprophylaxis in hospitalized COVID-19 patients: a meta-analysis
European heart journal. Quality of care & clinical outcomes. 2022
AIMS: This study aimed to compare the outcomes of administration of LMWH and UFH in hospitalized COVID-19 patients. METHODS AND RESULTS We systematically searched several databases and included observational studies or clinical trials that compared the outcomes of administration of LMWH and UFH in hospitalized COVID-19 patients. A total of nine studies comprising 9637 patients were included. Metanalysis showed that LMWH administration was associated with a lower in-hospital mortality, and 28/30-day mortality compared with UFH administration ([RR 0.44; 95%CI 0.32-0.61; I2:87.9%] and [RR 0.45; 95%CI 0.24-0.86; I2:78.4%], respectively). Patient with LMWH had shorter duration of hospital and ICU length of stay compared with UFH ([WMD -2.20; 95%CI -3.01 to -1.40; I2:0%] and [WMD -1.41; 95%CI -2.20 to -0.63; I2:0%], respectively). The risk of ICU admission or mechanical ventilation was lower in patients who received LMWH than those who received UFH (RR 0.67; 95%CI 0.55-0.81; I2:67.3%). However, there was no difference in the incidence of bleeding with LMWH compared with UFH (RR 0.27; 95%CI 0.07-1.01; I2:64.6%). CONCLUSION Our meta-analysis showed that administration of LMWH was associated with better outcomes compared with UFH in hospitalized COVID-19 patients. Prospective cohorts and RCTs are urgently needed in exploring the definitive effect of LMWH to provide direct high-certainty evidence. PROSPERO registration number: CRD42021271977.
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.
Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics
BACKGROUND Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. METHODS We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis. FINDINGS Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 - 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43-18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55-95% CI 0.31-0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry. INTERPRETATION In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events. FUNDING DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).
Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials
Journal of thrombosis and thrombolysis. 2022
Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I(2) = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I(2) = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.
Multisystem inflammatory syndrome and COVID-19: a scoping review
Boletin medico del Hospital Infantil de Mexico. 2022
BACKGROUND Multisystem inflammatory syndrome temporally associated with COVID-19 presents with similar symptomatology and therapeutic approach to Kawasaki disease in the pediatric population. Given the novelty of the disease and the growing scientific literature on the subject, it is relevant to collect and report available scientific information. This review aimed to explore the medical evidence on multisystem inflammatory syndrome temporally associated with COVID-19 in a population under 18 years of age. METHODS We conducted a scoping review using Scopus and PubMed, including observational (cohort, case-control, and cross-sectional) studies and case series. RESULTS Of the total articles reviewed as of April 10, 2021, 45 articles met eligibility criteria: case series (n = 32), retrospective cohort studies (n = 6), prospective cohort studies (n = 4), case-control studies (n = 2), and cross-sectional studies (n = 1). Gastrointestinal and respiratory symptoms and myocardial dysfunction are the most commonly reported. The most relevant paraclinical markers were lymphopenia, thrombocytopenia, and elevated D-dimer levels. CONCLUSIONS The multisystem inflammatory syndrome temporally associated with COVID-19 presents a broad spectrum of signs and symptoms. Aneurysms of the coronary arteries and myocarditis are usually present in the acute phases of the disease. The early diagnosis led by a multidisciplinary group of pediatric intensivists, infectious disease specialists, cardiologists, and rheumatologists allows adequate and effective medical management.
High-dose versus low-dose venous thromboprophylaxis in hospitalized patients with COVID-19: a systematic review and meta-analysis
Internal and emergency medicine. 2022;:1-9
BACKGROUND Hospitalized COVID-19 patients are at high risk of venous thromboembolism (VTE). Standard doses of anticoagulant prophylaxis may not be sufficiently effective for the prevention of VTE. The objective of this systematic-review and meta-analysis was to compare the efficacy and safety of high-dose versus low-dose thromboprophylaxis in hospitalized patients with COVID-19. MATERIAL AND METHODS MEDLINE and EMBASE were searched up to October 2021 for randomized clinical trials (RCTs) comparing high-dose with low-dose thromboprophylaxis in hospitalized adult patients with COVID-19. The primary efficacy outcome was the occurrence of VTE and the primary safety outcome was major bleeding. RESULTS A total of 5470 patients from 9 RCTs were included. Four trials included critically ill patients, four non-critically ill patients, and one included both. VTE occurred in 2.9% of patients on high-dose and in 5.7% of patients on low-dose thromboprophylaxis (relative risk [RR] 0.53; 95% confidence intervals [CIs], 0.41-0.69; I(2) = 0%; number needed to treat for an additional beneficial outcome, 22). Major bleeding occurred in 2.5% and 1.4% of patients, respectively (RR 1.78; 95% CI, 1.20-2.66; I(2) = 0%; number needed to treat for an additional harmful outcome, 100). All-cause mortality did not differ between groups (RR 0.97; 95% CI, 0.75-1.26; I(2) = 47%). The risk of VTE was significantly reduced by high-dose thromboprophylaxis in non-critically ill (RR 0.54; 95% CI, 0.35-0.86; I(2) = 0%), but not in critically ill patients (RR 0.69; 95% CI, 0.39-1.21; I(2) = 36%). DISCUSSION In hospitalized patients with COVID-19, high-dose thromboprophylaxis is more effective than low-dose for the prevention of VTE but increases the risk of major bleeding.
Seroprevalence of SARS-CoV-2 Antibodies in Africa: A Systematic Review and Meta-Analysis
International journal of environmental research and public health. 2022;19(12)
A reliable estimate of SARS-CoV-2-specific antibodies is increasingly important to track the spread of infection and define the true burden of the ongoing COVID-19 pandemic. A systematic review and a meta-analysis were conducted with the objective of estimating the seroprevalence of SARS-CoV-2 infection in Africa. A systematic search of the PubMed, Scopus, Web of Science and Google Scholar electronic databases was conducted. Thirty-five eligible studies were included. Using meta-analysis of proportions, the overall seroprevalence of anti-SARS-CoV-2 antibodies was calculated as 16% (95% CI 13.1-18.9%). Based on antibody isotypes, 14.6% (95% CI 12.2-17.1%) and 11.5% (95% CI 8.7-14.2%) were seropositive for SARS-CoV-2 IgG and IgM, respectively, while 6.6% (95% CI 4.9-8.3%) were tested positive for both IgM and IgG. Healthcare workers (16.3%) had higher seroprevalence than the general population (11.7%), blood donors (7.5%) and pregnant women (5.7%). The finding of this systematic review and meta-analysis (SRMA) may not accurately reflect the true seroprevalence status of SARS-CoV-2 infection in Africa, hence, further seroprevalence studies across Africa are required to assess and monitor the growing COVID-19 burden.
The effect of previous oral anticoagulant use on clinical outcomes in COVID-19: A systematic review and meta-analysis
The American journal of emergency medicine. 2022;54:107-110
Data on the prognosis of patients treated with oral anticoagulation (OAC) prior to hospital admission for COVID-19 remains controversial and insufficient. Therefore, we endeavored to perform a systematic review and meta-analysis to evaluate the effect of chronic use of OAC prior to the diagnosis of COVID-19 on intensive care unit (ICU) admission and mortality. An electronic search of the Pubmed, Embase, Cochrane library databases was conducted. Meta-analysis and statistical analyses were completed with using the RevMan 5.3 and Stata 12.0. A total of 13 articles representing data from 1,266,231 participants were included in this study. The meta-analysis of unadjusted results showed no decrease in mortality (OR = 1.31, 95% CI: 0.99 to 1.73, P = 0.059) or ICU admission rate (OR = 0.71, 95% CI: 0.29 to 1.77, P = 0.46) in COVID-19 patients with prior OAC therapy at hospital admission compared to patients without prior use of OAC. Moreover, the meta-analysis of adjusted results showed no lower risk of mortality (OR = 1.08, 95% CI: 0.90 to 1.30, P = 0.415) or ICU admission (OR = 1.50, 95% CI: 0.72 to 3.12, P = 0.284) in patients with prior OAC use compared to patients without previous OAC use. In conclusion, the results of this study revealed that the use of OAC prior to hospital admission appeared to be ineffective in reducing the risk of intensive care need and mortality in COVID-19 patients. Randomized controlled trials are needed to evaluate and optimize the use of OAC in COVID-19 infection.
Meta-Analysis Addressing the Efficacy and Safety of Antiplatelet Agents in Patients With COVID-19
The American journal of cardiology. 2022