The World Heart Federation Global Study on COVID-19 and Cardiovascular Disease.

Background: The emergence of novel coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase, and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions facilitated by international travel, leading to a pandemic. To guide effective control and interventions, primary data is required urgently, globally, including from low- and middle-income countries where documentation of cardiovascular manifestations and risk factors in people hospitalized with COVID-19 is limited. Objectives: This study aims to describe the cardiovascular manifestations and cardiovascular risk factors in patients hospitalized with COVID-19. Methods: We propose to conduct an observational cohort study involving 5000 patients recruited from hospitals in low-, middle- and high-income countries. Eligible adult COVID-19 patients will be recruited from the participating hospitals and followed-up until 30 days post admission. The outcomes will be reported at discharge and includes the need of ICU admission, need of ventilator, death (with cause), major adverse cardiovascular events, neurological outcomes, acute renal failure, and pulmonary outcomes. Conclusion: Given the enormous burden posed by COVID-19 and the associated severe prognostic implication of CVD involvement, this study will provide useful insights on the risk factors for severe disease, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients particularly from low and middle income countries from where the data remain scant.

EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis.

BACKGROUND: Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA). METHODS: An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1-10) for each PTC. RESULTS: Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants' knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach. CONCLUSION: These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

Acute disseminated encephalomyelitis and COVID-19: A systematic synthesis of worldwide cases.

Acute disseminated encephalomyelitis (ADEM) has been reported after coronavirus disease 2019 (COVID-19). In this review, we systematically included worldwide reported cases on this association. We included 30 case reports (pediatric and adults) and explored epidemiological and clinical evidence. We described time to diagnosis, clinical, imaging, and laboratory features, response to treatment regimens, and differences regarding severity. Also, an original case report was presented. Neurologists must be alert to the occurrence of multifocal neurological symptoms with or without encephalopathy in patients recovered from COVID-19. Timely MRI studies should be performed to establish the diagnosis and to consider early corticosteroid-based treatment.

Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies.

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.

Real-world effectiveness of BNT162b2 mRNA vaccine: a meta-analysis of large observational studies.

This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies which reported the adjusted effectiveness of the BNT162b2 mRNA vaccine to prevent RT-PCR confirmed COVID-19. Meta-analyses with the random-effects model were used to calculate the pooled hazard ratio (HR) and pooled incidence rate ratio (IRR) at 95% confidence intervals, and the vaccine effectiveness was indicated as (pooled HR - 1)/HR or (pooled IRR - 1)/IRR. Nineteen studies were included for this meta-analysis. The meta-analysis revealed significant protective effect against RT-PCR confirmed COVID-19 ≥ 14 days after the first dose, with vaccine effectiveness of 53% (95% confidence interval 32-68%), and ≥ 7 days after the second dose, with vaccine effectiveness of 95% (95% confidence interval: 96-97%). Despite its effectiveness, reporting vaccine safety data by relevant stakeholders should be encouraged as BNT162b2 mRNA is a new vaccine that has not gained full approval. There have been limited data about vaccine effectiveness among immunocompromised patients; thus, the vaccine should be used cautiously in this patient population.

Using observational epidemiology to evaluate COVID-19 vaccines: integrating traditional methods with new data sources and tools.

Although clinical trials are necessary for vaccine approval, observational epidemiology will be required to evaluate the long-term effectiveness, safety, and population impacts of newly approved COVID-19 vaccines under real-world field conditions. In this commentary, I argue that a hybrid approach that combines new data sources and tools, including COVID-19 vaccine registries, with traditional epidemiological methods will be needed to evaluate COVID-19 vaccines using observational epidemiology. Wherever possible, primary data collection, active surveillance, and linkage with existing population-based cohorts should be leveraged to supplement secondary data sources and passive surveillance systems. Evidence-informed public health decision making around provincial COVID-19 immunization programs will need to account for potential biases, incomplete or conflicting information, and heterogeneity across subpopulations.

RéSUMé: Des essais cliniques sont nécessaires à l'approbation des vaccins, mais il faudra recourir à l'épidémiologie d'observation pour évaluer en conditions réelles de terrain l'efficacité à long terme, l'innocuité et les effets sur les populations des vaccins contre la COVID-19 nouvellement approuvés. Dans ce commentaire, je fais valoir qu'il faudra adopter une démarche hybride combinant de nouvelles sources de données et de nouveaux outils, dont les registres de vaccins anti-COVID-19, et des méthodes épidémiologiques classiques pour évaluer les vaccins anti-COVID-19 à l'aide de l'épidémiologie d'observation. Dans la mesure du possible, il faudra utiliser la collecte de données primaires, la surveillance active et les maillages avec les cohortes populationnelles existantes pour compléter les sources de données secondaires et les systèmes de surveillance passive. Les décisions de santé publique éclairées par les données probantes sur les programmes d'immunisation provinciaux contre la COVID-19 devront tenir compte des biais possibles, des informations incomplètes ou contradictoires et de l'hétérogénéité des sous-populations.

Neurological Associations of SARS-CoV-2 Infection: A Systematic Review.

BACKGROUND: The current ongoing COVID-19 pandemic has compelled us to scrutinize major outbreaks in the past two decades, Severe Acute Respiratory Syndrome (SARS), in 2002, and Middle East Respiratory Syndrome (MERS), in 2012. We aimed to assess the associated neurological manifestations with SARS CoV-2 infection. METHODS: In this systematic review, a search was carried out by key-electronic databases, controlled vocabulary, and indexing of trials to evaluate the available pertinent studies which included both medical subject headings (MeSH) and advanced electronic databases comprising PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL). Peer-reviewed studies published in English and Spanish were considered, which reported data on the neurological associations of individuals with suspected or laboratory-confirmed SARS-CoV-2 infection. Outcomes were nervous signs or symptoms, symptom severity, and diagnoses. RESULTS: Our search identified 45 relevant studies, with 21 case reports, 3 case series, 9 observational studies, 1 retrospective study, 9 retrospective reviews, and 2 prospective reviews. This systematic review revealed that most commonly reported neuronal presentations involved headache, nausea, vomiting and muscular symptoms like fibromyalgia. Anosmia and ageusia, defects in clarity or sharpness of vision (error in visual acuity), and pain may occur in parallel. Notable afflictions in the form of anxiety, anger, confusion, post-traumatic stress symptoms, and post-intensive care syndrome were observed in individuals who were kept in quarantine and those with long-stay admissions in healthcare settings. SARS CoV-2 infection may result in cognitive impairment. Patients with more severe infection exhibited uncommon manifestations, such as acute cerebrovascular diseases (intracerebral haemorrhage, stroke), rhabdomyolysis, encephalopathy, and Guillain-Barré syndrome. CONCLUSION: SARS-CoV-2 patients experience neuronal presentations varying with the progression of the infection. Healthcare professionals should be acquainted with the divergent neurological symptoms to curb misdiagnosis and limit long-term sequelae. Health-care planners and policymakers must prepare for this eventuality, while the ongoing studies increase our knowledge base on acute and chronic neurological associations of this pathogen.

Stroke in COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear. AIMS: We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke. METHODS: Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020). The review protocol was previously registered (PROSPERO ID = CRD42020185476). Data were extracted from articles reporting ≥5 stroke cases in COVID-19. We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality. Data were pooled using a random-effect model. SUMMARY OF REVIEW: Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis. Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9). The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%). Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54). Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = -6.0 years; 95%CI: -12.3 to -1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90). CONCLUSIONS: Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors. The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

The Involvement of Chronic Kidney Disease and Acute Kidney Injury in Disease Severity and Mortality in Patients with COVID-19: A Meta-Analysis.

BACKGROUND: A meta-analysis was performed to evaluate the association of chronic kidney disease (CKD) and acute kidney injury (AKI) with the clinical prognosis of patients with coronavirus disease 2019 (COVID-19). METHODS: The PubMed, EMBASE, Cochrane Library, medRxiv, Social Science Research Network, and Research Square databases (from December 1, 2019 to May 15, 2020) were searched to identify studies that reported the associations of CKD/AKI and disease severity/mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and meta-regression was performed. RESULTS: In total, 42 studies enrolling 8,932 participants were included in this meta-analysis. The quality of most included studies was moderate to high. Compared with patients without previously diagnosed CKD, those with CKD had a significantly increased risk of progressing to a severe condition (OR 2.31, 95% CI 1.64-3.24) or death (OR 5.11, 95% CI 3.36-7.77). Similarly, compared with patients without AKI, those with AKI had a significantly increased risk of progressing to a severe condition (OR 11.88, 95% CI 9.29-15.19) or death (OR 30.46, 95% CI 18.33-50.59). Compared with patients with previously diagnosed CKD, those with AKI were more likely to progress to a severe condition (pgroup < 0.001, I2 = 98.3%) and even to death (pgroup < 0.001, I2 = 96.5%). Age had a significant impact on the association between CKD and disease severity (p = 0.001) but had no impact on the associations between AKI and disease severity (p = 0.80), between CKD and mortality (p = 0.51), or between AKI and mortality (p = 0.86). Four important complications (cardiac injury, shock, acute respiratory distress syndrome, and liver injury) did not significantly affect the associations between CKD/AKI and disease severity/mortality, indicating that CKD/AKI may be independent clinical prognostic indicators for patients with COVID-19. CONCLUSIONS: In COVID-19 patients, CKD/AKI was associated with worse outcomes compared with those without CKD/AKI. AKI was associated with higher risks of severity and mortality than CKD.

Probiotics Against Viruses; COVID-19 is a Paper Tiger: A Systematic Review.

BACKGROUND: Probiotics can improve immune function leading to the prevention and management of viral infections like SARS-CoV-2 infection (COVID-19 disease). METHODS: We searched PubMed, EMBASE, Google Scholar, Science Direct, Scopus, and Web of Science up to May 2020 to identify interventional & observational studies documenting the effects of probiotics on incidence, severity, duration, and other clinical manifestations of viral infections, especially SARS-CoV-2-induced. RESULTS: From a total of 91 records, 24 studies were obtained and classified into three domains based on the efficacy of probiotics on 1) shortening the period and severity of infections (n=9), 2) incidence (n=6), and 3) other clinical complications that may be followed by viral disorders (n=9). Identified probiotics have positive effects on the mentioned domains. CONCLUSION: Based on the evidence, some probiotic strains may be useful in SARS-CoV-2 infection; randomized trials are needed to show the facts.

Antithrombotic Therapies in COVID-19 Disease: a Systematic Review.

BACKGROUND: Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state. OBJECTIVE: This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19. DATA SOURCES: We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking. RESULTS: Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes. CONCLUSIONS: New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.