Long-Term Neurological Sequelae Among Severe COVID-19 Patients: A Systematic Review and Meta-Analysis.

Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models.  We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years; 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR: 4.53; 95% CI: 2.37-8.65; p<0.00001; I2: 0%) and myalgia (pooled OR: 3.36; 95% CI: 2.71-4.17; p<0.00001; I2: 0%). Anosmia, fatigue, and dysgeusia had higher but non-significant odds following COVID-19. Although we had sufficient data for headache and fatigue to identify higher rates and associations following COVID-19, we could not establish relationships with other post-COVID-19 neurocognitive séqueles. Long-term follow-up may mitigate the neurocognitive effects among COVID-19 patients as these symptoms are also associated with a poor quality of life.

Using Ethereum Smart Contracts to Store and Share COVID-19 Patient Data.

Introduction The emergence and rapid spread of the coronavirus disease 2019 (COVID-19) pandemic have revealed the limitations in current healthcare systems to handle patient records securely and transparently, and novel protocols are required to address these shortcomings. An attractive option is the use of Ethereum smart contracts to secure the storage of medical records and concomitant data logs. Ethereum is an open-source platform that can be used to construct smart contracts, which are collections of code that allow transactions under certain parameters and are self-executable. Methods The present study developed a proof-of-concept smart contract that stores COVID-19 patient data such as the patient identifier (ID), variant, chest CT grade, and significant comorbidities. A sample, fictitious patient data for the purpose of testing was configured to a private network. A smart contract was created in the Ethereum state and tested by measuring the time to insert and query patient data. Results Testing with a private, Proof of Authority (PoA) network required only 191 milliseconds and 890 MB of memory per insertion to insert 50 records while inserting 350 records required 674 milliseconds and similar memory per insertion, as memory per insertion was nearly constant with the increasing number of records inserted. Retrieving required 912 MB for a query involving all three fields and no wildcards in a 350-record database. Only 883 MB was needed to procure a similar observation from a 50-record database. Conclusion This study exemplifies the use of smart contracts for efficient retrieval/insertion of COVID-19 patient data and provides a case use of secure and efficient data logging for sensitive COVID-19 data.

Posterior Reversible Encephalopathy Syndrome (PRES) Associated With COVID-19 Infection—A Case Report and Review

Coronavirus disease 2019 (COVID-19) has caused a large number of systemic complications including a variety of neurological complications. Some of the neurological complications are not known. Posterior reversible encephalopathy syndrome (PRES) is a known acute neurotoxic syndrome causing a wide range of neurological symptoms. If remains untreated, it can potentially become a life-threatening condition. However, it is not a known neurological complication of COVID-19. We describe a presentation of PRES in a patient with positive COVID-19 and presented with altered mental status. A 78-year-old male with history of idiopathic epilepsy was initially admitted with respiratory illness with negative COVID-19 test. Later during his hospitalization, his respiratory condition got worse and his repeat COVID-19 test came back positive. He had continued encephalopathy and was found to have status epilepticus afterward. Magnetic Resonance Imaging brain showed extensive PRES-related changes. His blood pressure remained overall within control without significant fluctuations. No other apparent etiology was identified for PRES except for possible correlation with COVID-19. Clinicians should consider PRES early in their differential diagnoses in patients with severe COVID-19 with continued encephalopathy.

COVID-19: a Disease with a Potpourri of Histopathologic Findings-a Literature Review and Comparison to the Closely Related SARS and MERS.

Since the coronavirus disease 2019 (COVID-19) pandemic has hit the entire world, there is ample knowledge regarding its clinical course and prognostic biomarkers. Still, the pathophysiology of COVID-19 is poorly understood. Since the first guidelines published in February 2020 for autopsy of both confirmed and suspected COVID-19 cases, there has been an increasing number of autopsies and literature reporting histopathological findings. However, our knowledge about the immunological response of various organ systems to the virus, as well as response patterns, is inadequate but is essential to understand and initiate timely and targeted antiviral, anti-inflammatory, or anticoagulative therapy. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily considered a respiratory virus, current evidence shows that it causes life-threatening complications in almost all organ systems including the heart, brain, kidney, spleen, liver, and eyes. Hence, in this article, we reviewed the published case reports and case series in order to increase our understanding of COVID-19 pathophysiology. The main histopathological findings of the lungs include diffuse alveolar damage with activated type II pneumocytes, fibroblasts, protein-rich exudate, and hyaline membranes. Other significant histopathological findings include cardiomegaly, right ventricular dilation, splenic pulp atrophy, kidneys with severe podocytopathy, and collapsing glomerulopathy, and the brain showed hypoxic changes in the cerebellum and cerebrum. Furthermore, in this review, we also explained different pathological findings of SARS-CoV and MERS and compared them to SARS-CoV-2. This comprehensive review will improve our understanding of COVID-19 pathophysiology and various disease stages, hence promoting the application of targeted therapy.

Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.

There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

Emerging Needs and Viability of Telepsychiatry During and Post COVID-19 Era: A Literature Review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in nationwide stay-at-home orders in an effort to slow the spread severely impacting the healthcare sector. Telepsychiatry provides a platform bridging the gap through advanced technologies connecting mental health providers and patients who need their services, overcoming previous barriers of great distances, lack of transportation, and even time constraints. The most obvious benefit is increased accessibility to mental healthcare, especially in underserved and remote areas where there is no easy access for in-person care. It is important to note that benefits are not limited to patients, but also allow clinicians greater flexibility in scheduling and reduced practice overhead costs, both of which aid with physician burnout and burden. Telepsychiatry during COVID-19 provides its own unique advantages over in-person visits. The risk of exposure to healthcare workers and patients receiving care is reduced, allowing immunocompromised patients to receive much-needed psychiatric care. Without the need to meet in person, self-isolating psychiatrists can still provide care, decreasing strain on their co-workers. Although telepsychiatry is relatively new, it has already exhibited considerable success in its effectiveness at treating psychiatric conditions and widespread corollary benefits. Telepsychiatric consults may be carried out synchronously and asynchronously, each having benefits and setbacks. Different mobile application interventions have been explored, which are available for the purpose of both monitoring/assessing patients and/or providing treatment. The scope of conditions these applications address is broad, from anxiety disorders to schizophrenia to depression. As promising and beneficial telepsychiatry may seem, it is necessary to recognize that building the program can be challenging. It involves adapting to new methods in medicine. We highlighted barriers to general telepsychiatry, the most prominent being technological literacy of both physician and patient, and possible negative effects of eliminating the in-person patient-doctor interaction.

Kidney disease and COVID-19 disease severity-systematic review and meta-analysis.

We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.

Obesity a predictor of outcomes of COVID-19 hospitalized patients-A systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) pandemic is a global health crisis. Very few studies have reported association between obesity and severity of COVID-19. In this meta-analysis, we assessed the association of obesity and outcomes in COVID-19 hospitalized patients. Data from observational studies describing the obesity or body mass index and outcomes of COVID-19 hospitalized patients from December 1, 2019, to August 15, 2020, was extracted following PRISMA guidelines with a consensus of two independent reviewers. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio (OR) and 95% confidence interval (95% CI) were obtained and forest plots were created using random-effects models. A total of 10 studies with 10,233 confirmed COVID-19 patients were included. The overall prevalence of obesity in our study was 33.9% (3473/10,233). In meta-analysis, COVID-19 patient with obesity had higher odds of poor outcomes compared with better outcomes with a pooled OR of 1.88 (95% CI: 1.25-2.80; p = 0.002), with 86% heterogeneity between studies (p < 0.00001). Our study suggests a significant association between obesity and COVID-19 severity and poor outcomes. Our results findings may have important suggestions for the clinical management and future research of obesity and COVID-19.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.

Early epidemiological indicators, outcomes, and interventions of COVID-19 pandemic: A systematic review.

BACKGROUND: Coronavirus disease-2019 (COVID-19), a pandemic that brought the whole world to a standstill, has led to financial and health care burden. We aimed to evaluate epidemiological characteristics, needs of resources, outcomes, and global burden of the disease. METHODS: Systematic review was performed searching PubMed from December 1, 2019, to March 25, 2020, for full-text observational studies that described epidemiological characteristics, following MOOSE protocol. Global data were collected from the JHU-Corona Virus Resource Center, WHO-COVID-2019 situation reports, KFF.org, and Worldometers.info until March 31, 2020. The prevalence percentages were calculated. The global data were plotted in excel to calculate case fatality rate (CFR), predicted CFR, COVID-19 specific mortality rate, and doubling time for cases and deaths. CFR was predicted using Pearson correlation, regression models, and coefficient of determination. RESULTS: From 21 studies of 2747 patients, 8.4% of patients died, 20.4% recovered, 15.4% were admitted to ICU and 14.9% required ventilation. COVID-19 was more prevalent in patients with hypertension (19.3%), smoking (11.3%), diabetes mellitus (10%), and cardiovascular diseases (7.4%). Common complications were pneumonia (82%), cardiac complications (26.4%), acute respiratory distress syndrome (15.7%), secondary infection (11.2%), and septic shock (4.3%). Though CFR and COVID-19 specific death rates are dynamic, they were consistently high for Italy, Spain, and Iran. Polynomial growth models were best fit for all countries for predicting CFR. Though many interventions have been implemented, stern measures like nationwide lockdown and school closure occurred after very high infection rates (>10cases per 100 000population) prevailed. Given the trend of government measures and decline of new cases in China and South Korea, most countries will reach the peak between April 1-20, if interventions are followed. CONCLUSIONS: A collective approach undertaken by a responsible government, wise strategy implementation and a receptive population may help contain the spread of COVID-19 outbreak. Close monitoring of predictive models of such indicators in the highly affected countries would help to evaluate the potential fatality if the second wave of pandemic occurs. The future studies should be focused on identifying accurate indicators to mitigate the effect of underestimation or overestimation of COVID-19 burden.

COVID-19 Outcomes Amongst Patients With Pre-existing Cardiovascular Disease and Hypertension.

INTRODUCTION:  Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. METHODS: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. RESULTS: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). CONCLUSION: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Elevated cardiac troponin I as a predictor of outcomes in COVID-19 hospitalizations: a meta-analysis.

Globally, coronavirus is causing more social, economic and healthcare disruption than expected. The emerging literature has reported the complications of coronavirus, and the mortality and risk factors involved, including cardiac injury and multisystem organ failure. In this meta-analysis, we aim to evaluate the association of elevated troponin I levels with outcomes in COVID-19 hospitalized patients. Observational studies describing troponin I levels and outcomes of COVID-19 hospitalized patients from 1 December 2019 to 15 August 2020 were identified. Data were extracted following PRISMA guidelines with a consensus of two independent reviewers. Adverse outcomes were defined as admission to intensive care units (ICUs), oxygen saturation <90%, invasive mechanical ventilation (IMV), and in-hospital mortality. The odds ratio (OR) and 95% confidence interval (95% CI) were obtained and forest plots were created using random-effects models. Ten studies with 3982 confirmed COVID-19 patients were included. In patients with poor outcomes, the prevalence of elevated troponin I levels was 51% (690/1341). In meta-analysis, patients with elevated troponin I levels had higher odds of poor outcomes compared to better outcomes with pooled OR of 7.92 (95% CI: 3.70-16.97; p<0.00001) with 70% heterogeneity (p=0.0005). Our meta-analysis suggests that COVID-19 patients with elevated troponin I levels had a higher risk of poor outcomes. Hence, evaluating the troponin I levels might be helpful in preventing risk of cardiac complications and other organ dysfunction.

Liver disease and outcomes among COVID-19 hospitalized patients - A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has been a challenge globally. In severe acute respiratory syndrome (SARS) epidemic 60% of patients had hepatic injury, due to phylogenetic similarities of the viruses it is assumed that COVID-19 is associated with acute liver injury. In this meta-analysis, we aim to study the occurrence and association of liver injury, comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations with outcomes. MATERIALS AND METHODS: Data from observational studies describing comorbid chronic liver disease, acute liver injury, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and outcomes of COVID-19 hospitalized patients from December 1, 2019, to June 30, 2020 was extracted following PRISMA guidelines. Adverse outcomes were defined as admission to intensive care unit (ICU), oxygen saturation <90%, invasive mechanical ventilation (IMV), severe disease and in-hospital mortality. Odds ratio (OR) and 95% confidence interval (95% CI) were obtained. RESULTS: 24 studies with 12,882 confirmed COVID-19 patients were included. Overall prevalence of CM-CLD was 2.6%, COVID-19-ALI was 26.5%, elevated AST was 41.1% and elevated ALT was 29.1%. CM-CLD had no significant association with poor outcomes (pooled OR: 0.96; 95% CI: 0.71-1.29; p=0.78). COVID-19-ALI (1.68;1.04-2.70; p=0.03), elevated AST (2.98; 2.35-3.77; p<0.00001) and elevated ALT (1.85;1.49-2.29; p<0.00001) were significantly associated with higher odds of poor outcomes. CONCLUSION: Our meta-analysis suggests that acute liver injury and elevated liver enzymes were significantly associated with COVID-19 severity. Future studies should evaluate changing levels of biomarkers amongst liver disease patients to predict poor outcomes of COVID-19 and causes of liver injury during COVID-19 infection.

Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis.

OBJECTIVE: To evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources. DESIGN AND SETTING: Systematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. PARTICIPANTS: Studies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers. MAIN OUTCOME MEASURES: Composite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis. RESULTS: 32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51-4.41); p<0.00001), thrombocytopenia (2.36 (1.64-3.40); p<0.00001), elevated D-dimer (3.39 (2.66-4.33); p<0.00001), elevated CRP (4.37 (3.37-5.68); p<0.00001), elevated PCT (6.33 (4.24-9.45); p<0.00001), elevated CK (2.42 (1.35-4.32); p=0.003), elevated AST (2.75 (2.30-3.29); p<0.00001), elevated ALT (1.71 (1.32-2.20); p<0.00001), elevated creatinine (2.84 (1.80-4.46); p<0.00001) and LDH (5.48 (3.89-7.71); p<0.00001) were independently associated with higher risk of poor outcomes. CONCLUSION: Our study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.

Age-Adjusted Risk Factors Associated with Mortality and Mechanical Ventilation Utilization Amongst COVID-19 Hospitalizations-a Systematic Review and Meta-Analysis.

The increasing COVID-19 cases in the USA have led to overburdening of healthcare in regard to invasive mechanical ventilation (IMV) utilization as well as mortality. We aim to identify risk factors associated with poor outcomes (IMV and mortality) of COVID-19 hospitalized patients. A meta-analysis of observational studies with epidemiological characteristics of COVID-19 in PubMed, Web of Science, Scopus, and medRxiv from December 1, 2019 to May 31, 2020 following MOOSE guidelines was conducted. Twenty-nine full-text studies detailing epidemiological characteristics, symptoms, comorbidities, complications, and outcomes were included. Meta-regression was performed to evaluate effects of comorbidities, and complications on outcomes using a random-effects model. The pooled correlation coefficient (r), 95% CI, and OR were calculated. Of 29 studies (12,258 confirmed cases), 17 reported IMV and 21 reported deaths. The pooled prevalence of IMV was 23.3% (95% CI: 17.1-30.9%), and mortality was 13% (9.3-18%). The age-adjusted meta-regression models showed significant association of mortality with male (r: 0.14; OR: 1.15; 95% CI: 1.07-1.23; I 2: 95.2%), comorbidities including pre-existing cerebrovascular disease (r: 0.35; 1.42 (1.14-1.77); I 2: 96.1%), and chronic liver disease (r: 0.08; 1.08 (1.01-1.17); I 2: 96.23%), complications like septic shock (r: 0.099; 1.10 (1.02-1.2); I 2: 78.12%) and ARDS (r: 0.04; 1.04 (1.02-1.06); I 2: 90.3%), ICU admissions (r: 0.03; 1.03 (1.03-1.05); I 2: 95.21%), and IMV utilization (r: 0.05; 1.05 (1.03-1.07); I 2: 89.80%). Similarly, male (r: 0.08; 1.08 (1.02-1.15); I 2: 95%), comorbidities like pre-existing cerebrovascular disease (r: 0.29; 1.34 (1.09-1.63); I 2:93.4%), and cardiovascular disease (r: 0.28; 1.32 (1.1-1.58); I 2: 89.7%) had higher odds of IMV utilization. COVID-19 patients with comorbidities including cardiovascular disease, cerebrovascular disease, and chronic liver disease had poor outcomes. Diabetes and hypertension had higher prevalence but no association with mortality and IMV. Our study results will be helpful in right allocation of resources towards patients who need them the most.

Is there a smoker's paradox in COVID-19?

Although it is well established that cigarette smoking is associated with morbidity and mortality in several respiratory infections, data from recent studies suggest that active smokers are underrepresented among patients with COVID-19. This has led to claims that a 'smoker's paradox' may exist in COVID-19, wherein smokers are protected from infection and severe complications of COVID-19. We aimed to review and summarise existing literature in this context. Electronic databases were searched for articles that reported prevalence of smokers among patients with COVID-19 or studied any association of smoking with outcomes among patients with COVID-19. We identified several biases and knowledge gaps which may give the false impression that smoking is protective in COVID-19. As of now, the data supporting smoker's paradox claims are limited and questionable. Plausible biologic mechanisms by which smoking might be protective in COVID-19 include an anti-inflammatory effect of nicotine, a blunted immune response in smokers (reducing the risk of a cytokine storm in COVID-19) and increased nitric oxide in the respiratory tract (which may inhibit replication of SARS-CoV-2 and its entry into cells). On the other hand, smoking may worsen susceptibility and prognosis in COVID-19, in a manner similar to other respiratory infections. The claims of a protective effect must be viewed with extreme caution by both the general population as well as clinicians. Further investigations into the interaction between smoking and COVID-19 are warranted to accurately assess the risk of contracting COVID-19 among smokers, and progression to mechanical ventilation or death in patients suffering from it.

Pre-existing cerebrovascular disease and poor outcomes of COVID-19 hospitalized patients: a meta-analysis.

BACKGROUND: Due to pro-inflammatory and hypercoagulation states, COVID-19 infection is believed to increase the risk of stroke and worsen the outcomes of the patients having pre-existing cerebrovascular diseases (CeVD). There is limited literature on prevalence of pre-existing CeVD in COVID-19 patients, and outcomes are unknown. The objective of this meta-analysis is to evaluate the outcomes of COVID-19 patients with pre-existing CeVD. METHODS: English full-text-observational studies having data on epidemiological characteristics of COVID-19 patients were identified searching PubMed, Web of Science, and Scopus using MeSH-terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from December 1, 2019 to April 30, 2020. Studies having CeVD or stroke as one of the pre-existing comorbidities and described outcomes including intensive care unit (ICU) admission, mechanical ventilation utilization, and mortality were selected with consensus of three reviewers. Following MOOSE protocol, 11 studies were included. The pooled prevalence of CeVD and outcomes were calculated. Meta-regression was performed, and correlation coefficient (r) and odds ratio (OR) were estimated to evaluate the effects of pre-existing CeVD on outcomes of COVID-19 patients. Meta-analysis with random-effects model was used to calculate OR along with its 95% CI from the studies containing data on composite poor outcome. RESULTS: Out of 8/11 studies showing data on mortality and mechanical ventilation, and 7/11 on ICU admission, pooled prevalence of pre-existing CeVD was 4.4% (244/4987). In age-adjusted meta-regression analysis, pre-existing CeVD was associated with ICU admission [r: 0.60; OR: 1.82 (1.25-2.69)], mechanical ventilation [r: 0.29; OR: 1.33 (1.09-1.63)], and mortality [r: 0.35; OR: 1.42 (1.14-1.77)] amongst COVID-19 hospitalizations. 9/11 studies reported data on binary composite outcomes, the pooled prevalence of pre-existing CeVD was 4.3% (155/3603) and 7.46% (83/1113) amongst COVID-19 hospitalizations and COVID-19 hospitalization-related poor outcomes, respectively. In meta-analysis, COVID-19 patient with pre-existing CeVD had 2.67-fold (1.75-4.06) higher odds of poor outcomes. CONCLUSION: COVID-19 patients with pre-existing cerebrovascular disease have poor outcomes and extra precautions should be taken in managing such patients during the ongoing pandemic.