Diabetes and Mortality among Patients with Chronic Kidney Disease and COVID-19: A Systematic Review, Meta-analysis, and Meta-regression.

Introduction: Patients with kidney disease and COVID-19, whether on hemodialysis (HD) or not, have a higher risk of contracting COVID-19 accompanied by a higher mortality rate due to suppressed immune functions. Diabetes, one of the ubiquitous etiology of kidney disease, is also associated with a composite of poor outcomes. Methods: Meta-analysis and meta-regression of 13 articles on COVID-19 patients with chronic kidney disease, with information on diabetes and mortality were performed using Review Manager 5.4 and OpenMetaAnalyst. Results: The meta-analysis of a pooled subject of 18,822 patients showed that the presence of diabetes in CKD patients with COVID-19 was associated with an increased risk of mortality (RR 1.41 (1.15, 1.72); P < 0.001; I2 70%, P < 0.001). Subgroup analysis showed that diabetes was not associated with mortality in the HD group (RR 1.27 (1.06, 1.54); P = 0.01; I2 0%, P = 0.70) but showed a significant association in the non-HD group (RR 1.66 (1.59, 1.73); P < 0.001; I2 85%, P < 0.001). Male gender (P = 0.070) contributed to the effect size differences (age: P < 0.001; hypertension: P = 0.007; CVD: P < 0.001; lung disease: P < 0.001). Conclusions: Diabetes was associated with higher mortality risk among CKD patients, primarily those who did not need RRT.

Antibody response following SARS-CoV-2 vaccination among patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND AND AIM: DM patients' antibody response after the COVID-19 vaccine is still unknown amid the COVID-19 vaccination rollout. This study aimed to explore the SARS-CoV-2 antibody response or seropositivity among DM patients following the COVID-19 vaccine administration. METHODS: We performed a systematic review of the literature consisting of observational or cross-sectional studies, which reported the antibody serology or seropositivity among DM patients by following the PRISMA 2020 guidelines. RESULTS: Eight studies with a total of 64468 patients were identified, and 5156 (7.9%) of them had diabetes. Most studies showed that antibody response and seropositivity in DM patients were lower than healthy population after one until four weeks following full COVID-19 vaccination dose. CONCLUSION: The antibody response and seropositivity after the COVID-19 vaccine in DM patients were lower than in healthy subjects. Therefore, DM patients are expected to receive vaccines according to the dose and schedule appropriately and might be prioritized to receive vaccine boosters.

Multisystem inflammatory syndrome in adults: a systematic review and meta-analysis of the rheumatological spectrum of complications post COVID-19 infection

Multisystem inflammatory syndrome in adults (MIS-A) is a rare but severe complication in adults infected with SARS-CoV-2. However, the pathophysiology remains elusive, as the limited number of reports preclude a broader understanding of this syndrome. We conducted this systematic review to explore the clinical spectrum of MIS-A, in particular its rheumatological manifestations. Meta-analyses of case-series were also performed. We identified 28 patients from 14 case reports and two case series of MIS-A. This disease occurred equally in both genders, with a mean age of 33+10 years old, and predominantly in those of African descent (40%). Rheumatological manifestations consisted of Kawasaki Disease (KD)-like symptoms. Ninety percent of patients had positive COVID-19 serology tests, while 48% of patients were negative for COVID-19 RT-PCR test. Twelve patients were admitted to ICU and unfortunately two died. Although the signs and symptoms of MIS mimicked KD, the gastro-intestinal findings were more prominent in the former group. The demographic make-up was also different, with MIS-A occurring mostly in those of African descent. Importantly, unlike their paediatric counterparts, the adult group did not have coronary artery abnormalities. Long-term monitoring is needed as safety data is scarce. Of note, although the prognosis of MIS-A is excellent, the life-threatening nature of this syndrome demands intensive care unit level of care and mechanical support. During the COVID-19 pandemic, a constellation of KD symptoms in an adult patient should alert the clinician to the possibility of MIS-A. Resumen El espectro clínico del síndrome inflamatorio multisistémico en adultos (MIS-A) es una complicación rara pero grave en adultos infectados con SARS- CoV-2. Realizamos una búsqueda bibliográfica en varias bases de datos, también se hicieron metanálisis. Identificamos 28 pacientes de 14 informes de casos y dos series de casos de MIS-A. Esta enfermedad se presentó por igual en ambos sexos, con una edad media de 33 + 10 años, y se presentó predominantemente en afrodescendientes (40%). Las manifestaciones reumatológicas consistieron en síntomas similares a la enfermedad de Kawasaki (KD). El 90% de los pacientes tuvo pruebas positivas de serología de COVID-19, mientras que el 48% dio negativo para la prueba de RT-PCR de COVID-19. Doce pacientes ingresaron en UCI y, lamentablemente, dos fallecieron. Encontramos que, si bien, los signos y los síntomas de MIS imitaban a KD, los hallazgos gastrointestinales eran más prominentes en el primer grupo. Además, la composición demográfica fue asimismo diferente, con MIS-A que se presentó principalmente en afrodescendientes. Es importante destacar que, a diferencia de sus homólogos pediátricos, el grupo de los adultos no experimentó anomalías en las arterias coronarias. Se necesita un seguimiento a largo plazo, ya que los datos de seguridad son escasos. Es de destacar que, aun cuando el pronóstico de MIS-A es excelente, la naturaleza potencialmente mortal de este síndrome exige el nivel de atención y el soporte mecánico de la unidad de cuidados intensivos. Durante la pandemia de COVID-19, una constelación de síntomas de EK en un paciente adulto debe alertar al médico sobre la posibilidad de MIS-A.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: a New Challenge amid the Pandemic.

Initially, SARS-CoV-2 infection had been reported as a relatively mild case in children than in adults. Nevertheless, recent evidence found that a subset of children then developed a significant systemic inflammatory response that resembles atypical/typical Kawasaki's disease (KD) and toxic shock syndrome. This novel clinical syndrome later identified as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). In contrast with KD, PIMS-TS appears to occur in children at an older age with a predominance of gastrointestinal symptoms, hemodynamic instability, and myocardial dysfunction. However, the exact pathomechanism remains to be understood. Nevertheless, the post-viral immunological reaction is postulated to be the underlying mechanistic underpinnings. The multifaceted nature of the PIMS-TS' course underlines the need for early recognition and multispecialty care and management.

Diabetes and COVID-19: The past, the present, and the future.

Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis.

BACKGROUND: The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. METHODS: We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. RESULTS: There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I2 99.7%). CONCLUSION: This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility. PROSPERO ID: CRD42020224286.

Cardiac manifestations, treatment characteristics, and outcomes of paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2: A systematic review.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) temporally associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (PIMS-TS) is a rare clinical syndrome associated with a multiorgan system dysfunction, especially acute cardiac injury, and mandates a higher level of care. AIM OF REVIEW: To investigate cardiac manifestations, treatment characteristics, and outcomes of PIMS-TS. KEY SCIENTIFIC CONCEPTS OF REVIEW: Twenty-six studies were included with 1228 pooled subjects, with a mean age of 8.6 years, which were dominated by male gender (53%), and African ethnicity (31%). 732 (38%) patients were reactive on a serological test, and 457 patients (45%) were positive on SARS-CoV-2 RT-PCR. ST-segment abnormalities were the most common ECG findings (16%, n/N: 34/212). Various markers of troponin and the pooled mean of BNP and NT-pro-BNP levels were elevated. Cardiomegaly and pericardial effusion (21.8%, n/N: 164/751) were the most common chest X-ray findings. In echocardiography, the majority of patients' left ventricular ejection fraction was reduced (59.0%, n/N: 180/305), with pericardial effusion/ pericarditis seen the most (17.44%, n/N: 221/1267), and Z score ≥ 2 in 28% (n/N: 42/139). Cardiac MRI findings were consistent with acute myocarditis. Intravenous immunoglobulin, corticosteroids, and vasoactive drugs were frequently utilized. The mean length of stay was 6 days, with most patients (71%, n/N: 834/1163) were admitted to the ICU. However, the overall prognosis was favorable, with 98% alive (n/N: 1235/1260), and more than 50% of patients experienced recovery of left ventricular systolic functions at discharge (116 out of 206 patients).

Clinical Characteristics and Outcomes of Venous Thromboembolism in Patients Hospitalized for COVID-19: Systematic Review and Meta-Analysis

Venous thromboembolism is prevalent in hospitalized COVID-19 patients. Through systematic review and meta-analysis, we have investigated the differences in clinical characteristics and outcome of hospitalized COVID-19 patients with (+) and without (-) venous thromboembolism (VTE). 45 studies with a total of 8859 patients were included in the qualitative synthesis. Subsequently, 38 studies with a total of 7847 patients, were quantitatively analysed. There was no mortality difference between the VTE (-) and VTE (+) hospitalized COVID-19 patients (RR1.32 (0.97, 1.79);0.07;I2 64%, p<0.001). Patients with VTE (+) were more likely to get admitted to the intensive care unit (RR1.77 (1.26, 2.50);p<0.001;I2 63%, p= 0.03) and mechanically ventilated (RR 2.35 (1.22, 4.53);p=0.01;I2 88%, p<0.001). Moreover, male gender (RR 1.19 (1.14,1.24), p<0.001;I2 0%, p=0.68), increased the risk of VTE. Regarding patients lab values’, VTE (+) was significantly associated with higher white blood cell, neutrophil count, D-Dimer, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and C-reactive protein (CRP), along with prolonged prothrombin time. On the contrary, VTE (+) was associated with lower albumin and neutrophil-lymphocyte ratio (NLR). This findings provide the initial framework for risk stratification of hospitalized COVID-19 patients with VTE.

Clinical frailty scale and mortality in COVID-19: A systematic review and dose-response meta-analysis.

INTRODUCTION: National Institute for Health and Care Excellence (NICE) endorsed clinical frailty scale (CFS) to help with decision-making. However, this recommendation lacks an evidence basis and is controversial. This meta-analysis aims to quantify the dose-response relationship between CFS and mortality in COVID-19 patients, with a goal of supplementing the evidence of its use. METHODS: We performed a systematic literature search from several electronic databases up until 8 September 2020. We searched for studies investigating COVID-19 patients and reported both (1) CFS and its distribution (2) CFS and its association with mortality. The outcome of interest was mortality, defined as clinically validated death or non-survivor. The odds ratio (ORs) will be reported per 1% increase in CFS. The potential for a non-linear relationship based on ORs of each quantitative CFS was examined using restricted cubic splines with a three-knots model. RESULTS: There were a total of 3817 patients from seven studies. Mean age was 80.3 (SD 8.2), and 53% (48-58%) were males. The pooled prevalence for CFS 1-3 was 34% (32-36%), CFS 4-6 was 42% (40-45%), and CFS 7-9 was 23% (21-25%). Each 1-point increase in CFS was associated with 12% increase in mortality (OR 1.12 (1.04, 1.20), p = 0.003; I2: 77.3%). The dose-response relationship was linear (Pnon-linearity=0.116). The funnel-plot analysis was asymmetrical; Trim-and-fill analysis by the imputation of two studies on the left side resulted in OR of 1.10 [1.03, 1.19]. CONCLUSION: This meta-analysis showed that increase in CFS was associated with increase in mortality in a linear fashion.

The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Diabetes is one of the most common comorbidities, and it is associated with poorer outcomes in patients with coronavirus disease 2019 (COVID-19). Preliminary findings showed that mortality was reduced in those who consume metformin compared to those who did not, and given its low cost and widespread availability; metformin is an attractive and potential agent to mitigate excessive risk in diabetic populations. METHODS: Several medical databases (Pubmed, EuropePMC, EBSCOhost, Proquest, Cochrane library) and two health-science preprint servers (preprint.org and Medrxiv) were systematically searched for relevant literature. RESULTS: Nine studies with 10,233 subjects were included in the qualitative and quantitative synthesis. Meta-analysis showed that metformin is associated with lower mortality in pooled non-adjusted model (OR 0.45 [0.25, 0.81], p = 0.008; I2: 63.9%, p = 0.026) and pooled adjusted model (OR 0.64 [0.43, 0.97], p = 0.035; I2: 52.1%, p = 0.064). CONCLUSION: The analysis showed that metformin consumption was associated with lower mortality. Randomized controlled trials are needed to confirm this finding.

Charlson comorbidity index and a composite of poor outcomes in COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The ongoing COVID-19 pandemic is disproportionately affecting patients with comorbidities. Therefore, thorough comorbidities assessment can help establish risk stratification of patients with COVID-19, upon hospital admission. Charlson Comorbidity Index (CCI) is a validated, simple, and readily applicable method of estimating the risk of death from comorbid disease and has been widely used as a predictor of long-term prognosis and survival. METHODS: We performed a systematic review and meta-analysis of CCI score and a composite of poor outcomes through several databases. RESULTS: Compared to a CCI score of 0, a CCI score of 1-2 and CCI score of ≥3 was prognostically associated with mortality and associated with a composite of poor outcomes. Per point increase of CCI score also increased mortality risk by 16%. Moreover, a higher mean CCI score also significantly associated with mortality and disease severity. CONCLUSION: CCI score should be utilized for risk stratifications of hospitalized COVID-19 patients.

Coronavirus Disease of 2019: a Mimicker of Dengue Infection?

At the beginning of 2020, the national health system and medical communities are faced with unprecedented public health challenges. A novel strain of coronavirus, later identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, marking another pandemic of coronaviruses. This viral disease is responsible for devastating pneumonia, named coronavirus disease of 2019 (COVID-19), and projected to persist until the end of the year. In tropical countries, however, concerns arise regarding the similarities of COVID-19 with other infectious diseases due to the same chief complaint, which is fever. One of the infectious disease of a primary concern is dengue infection, which its peak season is approaching. Others report that there are cases of serological cross-reaction of COVID-19 and dengue infection. In this comprehensive review, we underscore the importance of knowing similar clinical presentations of both diseases and emphasize why excluding COVID-19 in the differentials in the setting of a pandemic is imprudent.