COVID-19 and Cerebrovascular Disease.

COVID-19 has been associated with numerous neurological complications, with acute cerebrovascular disease being one of the most devastating complications. Ischemic stroke is the most common cerebrovascular complication of COVID-19, affecting between 1 and 6% of all patients. Underlying mechanisms for COVID-related ischemic strokes are thought to be due to vasculopathy, endotheliopathy, direct invasion of the arterial wall, and platelet activation. Other COVID-19-associated cerebrovascular complications include hemorrhagic stroke, cerebral microbleeds, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, and subarachnoid hemorrhage. This article discusses the incidence of these cerebrovascular complications, risk factors, management strategies, prognosis and future research directions, as well as considerations in pregnancy-related cerebrovascular events in the setting of COVID-19.

History of cerebrovascular disease but not dementia increases the risk for secondary vascular events during SARS-CoV-2 infection with presumed Omicron variant: a retrospective observational study.

BACKGROUND AND PURPOSE: This study aimed to investigate if pre-existing neurological conditions, such as dementia and a history of cerebrovascular disease, increase the risk of severe outcomes including death, intensive care unit (ICU) admission and vascular events in patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2022, when Omicron was the predominant variant. METHODS: A retrospective analysis was conducted of all patients with SARS-CoV-2 infection, confirmed by polymerase chain reaction test, admitted to the University Medical Center Hamburg-Eppendorf from 20 December 2021 until 15 August 2022. In all, 1249 patients were included in the study. In-hospital mortality was 3.8% and the ICU admission rate was 9.9%. Ninety-three patients with chronic cerebrovascular disease and 36 patients with pre-existing all-cause dementia were identified and propensity score matching by age, sex, comorbidities, vaccination status and dexamethasone treatment was performed in a 1:4 ratio with patients without the respective precondition using nearest neighbor matching. RESULTS: Analysis revealed that neither pre-existing cerebrovascular disease nor all-cause dementia increased mortality or the risk for ICU admission. All-cause dementia in the medical history also had no effect on vascular complications under investigation. In contrast, an increased odds ratio for both pulmonary artery embolism and secondary cerebrovascular events was observed in patients with pre-existing chronic cerebrovascular disease and myocardial infarction in the medical history. CONCLUSION: These findings suggest that patients with pre-existing cerebrovascular disease and myocardial infarction in their medical history may be particularly susceptible to vascular complications following SARS-CoV-2 infection with presumed Omicron variant.

Significant Mortality Associated With COVID-19 and Comorbid Cerebrovascular Disease: A Quantitative Systematic Review.

We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.

Impact of the COVID-19 pandemic lockdown on hospitalizations for cerebrovascular disease and related in-hospital mortality in China: A nationwide observational study.

BACKGROUND AND PURPOSE: The aim of this nationwide study was to assess the impact of the COVID-19 pandemic on cerebrovascular disease hospitalization rates, out-of-pocket rates, and in-hospital case fatality rates. METHODS: All hospitalizations for cerebrovascular disease from 1599 hospitals from 2019 to 2020 were selected using the International Classification of Diseases, 10th revision, in the Hospital Quality Monitoring System (HQMS). We defined 2019 as the pre-pandemic group and 2020 as the post-pandemic group. Multivariate analyses were done to assess the association between the pandemic and patient outcomes and out-of-pocket rate with odds ratios (OR) and 95% CIs presented. RESULTS: In total, 9 640 788 patients with the cerebrovascular disease were recruited (mean age was 65.7[SE.0.004] years, and 55.7% were male), and data is available for 5145358 patients in 2019 (pre-epidemic) and 4495430 patients in 2020(post-pandemic), indicating a 12.6% decrease. Out-of-pocket rate increase of 9.3% (2020 vs 2019: 34.1%% vs 31.2% [absolute difference, 2.9% {95% CI, 1.3% to 4.5%}, odd ratio {OR}, 1.1{95% CI, 1.0 to 1.1}]. The epidemic has led to an 18.0% increase in in-hospital mortality (2020 vs 2019: 1.1%% vs 0.9% [absolute difference, 0.2% {95% CI, 0.1% to 0.2%}, odd ratio {OR}, 1.1{95% CI, 1.1 to 1.2}]. The epidemic has led to significantly increased in-hospital mortality for patients with stroke but had no significant impact on other cerebrovascular diseases. CONCLUSIONS: During the COVID-19 pandemic lockdown, patients hospitalized for stroke fell by 12.6%, and there were substantial increases in out-of-pocket rates (9.3%) and in-hospital case fatality rates (18.0%).

Cerebrovascular radiological features of COVID-19 positive patients.

OBJECTIVE: To investigate acute cerebrovascular diseases (stroke and intracranial hemorrhage) by cranial radiologic examinations of patients infected with coronavirus disease 2019 (COVID-19) and with neurological signs. PATIENTS AND METHODS: Between March 2020 and May 2021, patients who were admitted to the Emergency Department and had a positive reverse transcription-polymerase chain reaction (RT-PCR) test and underwent Multidetector Computed Tomography (MDCT) and/or Magnetic Resonance Images (MRI), and/or diffusion MRI due to neurological findings were included in the study. RESULTS: The study reviewed a total of 925 patients, including 404 (43.67%) female and 521 (56.32%) male patients. The distribution of imaging methods was as follows: 805 (71%) patients had cranial MDCT, 71 (6.35%) patients had MRI, and 241 (21.57%) patients had diffusion MRI. Of the total 925 patients, 128 (13.8%) patients were detected with cerebrovascular diseases, 92 (9.9%) patients were detected with ischemic or hemorrhagic stroke, 37 (4%) patients were detected with intraparenchymal hemorrhage, 10 (1.1%) patients were detected with subarachnoid hemorrhage, and four (0.43%) patients were detected with subdural hemorrhage. There was no statistically significant difference in the incidence of subdural, subarachnoid, parenchymal hemorrhage, and stroke in terms of gender. While there was a significant difference in stroke according to age, there was no statistically significant difference in subdural, subarachnoid, and parenchymal hemorrhagic. Three (0.32%) patients were diagnosed with acute disseminated encephalomyelitis (ADEM)'s-like demyelinating lesions. CONCLUSIONS: Cerebrovascular diseases, which may cause severe disability and even threaten the patient's life, should be kept in mind, especially in COVID-19 patients who present with neurological symptoms.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries.

Importance: Vaccinations are paramount to halt the COVID-19 pandemic, and safety data are essential to determine the risk-benefit ratio of each COVID-19 vaccine. Objective: To evaluate the association between the AZD1222, BNT162b2, and mRNA-1273 vaccines and subsequent thromboembolic and thrombocytopenic events. Design, Setting, and Participants: This self-controlled case series used individual-level data from national registries in Norway, Finland, and Denmark. Participants included individuals with hospital contacts because of coronary artery disease, coagulation disorders, or cerebrovascular disease between January 1, 2020, and May 16, 2021. Exposures: AZD1222, BNT162b2, or mRNA-1273 vaccine. Main Outcomes and Measure: Relative rate (RR) of hospital contacts for coronary artery disease, coagulation disorders, or cerebrovascular disease in a 28-day period following vaccination compared with the control period prior to vaccination. Results: We found 265 339 hospital contacts, of whom 112 984 [43%] were for female patients, 246 092 [93%] were for patients born in 1971 or earlier, 116 931 [44%] were for coronary artery disease, 55 445 [21%] were for coagulation disorders, and 92 963 [35%] were for cerebrovascular disease. In the 28-day period following vaccination, there was an increased rate of coronary artery disease following mRNA-1273 vaccination (RR, 1.13 [95% CI, 1.02-1.25]), but not following AZD1222 vaccination (RR, 0.92 [95% CI, 0.82-1.03]) or BNT162b2 vaccination (RR, 0.96 [95% CI, 0.92-0.99]). There was an observed increased rate of coagulation disorders following all 3 vaccines (AZD1222: RR, 2.01 [95% CI, 1.75-2.31]; BNT162b2: RR, 1.12 [95% CI, 1.07-1.19]; and mRNA-1273: RR, 1.26 [95% CI, 1.07-1.47]). There was also an observed increased rate of cerebrovascular disease following all 3 vaccines (AZD1222: RR, 1.32 [95% CI, 1.16-1.52]; BNT162b2: RR, 1.09 [95% CI, 1.05-1.13]; and mRNA-1273: RR, 1.21 [95% CI, 1.09-1.35]). For individual diseases within the main outcomes, 2 notably high rates were observed: 12.04 (95% CI, 5.37-26.99) for cerebral venous thrombosis and 4.29 (95% CI, 2.96-6.20) for thrombocytopenia, corresponding to 1.6 (95% CI, 0.6-2.6) and 4.9 (95% CI, 2.9-6.9) excess events per 100 000 doses, respectively, following AZD1222 vaccination. Conclusions and Relevance: In this self-controlled case series, there was an increased rate of hospital contacts because of coagulation disorders and cerebrovascular disease, especially for thrombocytopenia and cerebral venous thrombosis, following vaccination with AZD1222. Although increased rates of several thromboembolic and thrombocytopenic outcomes following BNT162b2 and mRNA-1273 vaccination were observed, these increases were less than the rates observed after AZD1222, and sensitivity analyses were not consistent. Confirmatory analysis on the 2 mRNA vaccines by other methods are warranted.

Impact of COVID-19 pandemic on patients with cardio/cerebrovascular disease who visit the emergency department.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic situation is a state that has had a great impact on the medical system and society. To respond to the pandemic situation, various methods, such as a pre-triage system, are being implemented in the emergency medical field. However, there are insufficient studies on the effects of this pandemic situation on patients visiting the emergency department (ED), especially those with cardio/cerebrovascular diseases (CVD)1 classified as time-dependent emergencies. METHODS: We performed a retrospective analysis of a cohort of patients from April 2020 to December 2020 (April 2020 was when the pre-triage system was established) compared to a parallel comparison patient cohort from 2019. The primary outcome was in-hospital mortality. CVD was defined by the patient's final diagnosis. RESULTS: During the same period, the number of patients who had visited the ED after COVID-19 had decreased to 79.1% of the number of patients who had visited the ED before COVID-19. The overall patient mortality and the mortality in the patients cardiovascular disease had both increased, while the mortality from cerebrovascular disease did not increase. Meanwhile, the ED length of stay had increased in all patients but did not increase in the patients with cardiovascular disease. CONCLUSION: As with prior studies conducted in other regions, in our study, the total number of ED visits were decreased compared to before COVID-19. The overall mortality had increased, particularly in the patients with cardiovascular disease.

[The open observational study of aceclofenac and vinpocetine effectiveness and tolerability in treatment of patients with chronic cerebrovascular disease after COVID-19 (AQUA study)]. / Otkrytoe nablyudatel'noe issledovanie effektivnosti i perenosimosti vinpotsetina i atseklofenaka pri lechenii patsientov s khronicheskoi ishemiei golovnogo mozga posle COVID-19 (issledovanie AKVA).

OBJECTIVE: To estimate the frequency of long-COVID in patients with chronic cerebrovascular disease, to identify the risk factors for the development of this condition and to analyze effectiveness and tolerability of Vinpocetine and Aertal in treatment of this disease. MATERIAL AND METHODS: The study included 97 patients (64.5±5.2 years), among which 42 were diagnosed with long-COVID. The effectiveness of treatment was analyzed with NRS-P, Post-COVID-19 Functional Status (PCFS), Global Rating of Change Scale (GROC). RESULTS: Predictors of long-COVID was female gender (p=0.022), severe COVID-19 (p=0.035), comorbidities: cardiovascular diseases (p=0.032), endocrinopathies (p=0.041), affective disorders (p=0.021). Significant changes in the functional status of patients were recorded after 20 days of treatment (PCFS), in pain after 10 days (NRS-P). The most pronounced clinical effect (PCFS) was obtained after 1 mth of therapy with vinpocetine and 20 days with aceclofenac (NRS-P). After 30 days 25/59.5% of patients noted a «pronounced¼ improvement in their own well-being (GROC) without the development of significant side effects. CONCLUSIONS: 43.3% of patients with chronic cerebrovascular disease and certain predictors develop long-COVID. Aceclofenac and vinpocetine are effective in relieving a number of symptoms of long-COVID, which requires further study.

[Cerebral circulation disorders in COVID-19]. / Narusheniya mozgovogo krovoobrashcheniya pri COVID-19.

Present two clinical cases of cerebral circulation disorders in COVID-19. Cerebrovascular disorders in patients have been associated with COVID-19. Despite the similarity of symptoms, the pathogenesis of neurological damage in these patients was different due to damage to the arterial system in the first case and the venous system in the second case. It is concluded that during the COVID-19 pandemic, doctors need to be alert to all patients with new-onset neurological symptoms.

Cerebrovascular Involvement in Mucormycosis in COVID-19 Pandemic.

BACKGROUND: Many countries have seen an unprecedented rise of cases of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM). Cerebrovascular involvement in CAM has not been studied so far. We describe clinico-radiological manifestations of cerebrovascular complications observed in CAM. METHODS: In this multicentric retrospective observational study from India, patients with CAM who developed cerebrovascular involvement were studied. Their demographics, risk factors, clinical manifestations, imaging, laboratory profile and outcomes were noted. RESULTS: Out of 49 subjects with cerebrovascular involvement, 71.4% were males while average age was 52.9 years. Ischemic stroke was commonest (91.8%) followed by intracranial haemorrhage (6.1%) and subarachnoid haemorrhage (2%). The incidence of cerebrovascular complications in CAM was found to be 11.8% in one center. Cerebrovascular symptoms appeared a median of 8.3 days from the onset of mucormycosis. Commonest presentation of mucormycosis was rhino-orbito-cerebral syndrome in 98%. Diabetes mellitus was present in 81.7%. Forty percent developed stroke despite being on antiplatelet agent and/or heparin. Amongst subjects with ischemic strokes, location of stroke was unilateral anterior circulation (62.2%); bilateral anterior circulation (17.8%); posterior circulation (11.1%) and combined anterior and posterior circulation (8.9%). Vascular imaging revealed intracranial occlusion in 62.1%; extracranial occlusion in 3.4% and normal vessels in 34.5%. Mortality was 51% during hospital stay. CONCLUSIONS: Cerebrovascular involvement was seen in 11.8% patients of CAM. Angio-invasive nature of the fungus, prothrombotic state created by COVID-19, and diabetes were important causative factors. Subjects with CAM should be screened for involvement of the brain as well as its vessel. Antiplatelet agents/heparin did not seem to provide complete protection from this type of stroke.

A History of Cerebrovascular Disease Is Independently Associated with Increased Morbidity and Mortality in Patients with COVID-19: A Cohort Study of 369,563 COVID-19 Cases in the USA.

OBJECTIVES: We set out to evaluate the risk for severe coronavirus disease 2019 (COVID-19) infection and subsequent cerebrovascular disease (CVD) in the population with a prior diagnosis of CVD within the past 10 years. METHODS: We utilized the TriNetX Analytics Network to query 369,563 CO-VID-19 cases up to December 30, 2020. We created 8 cohorts of patients with COVID-19 diagnosis based on a previous diagnosis of CVD. We measured the odds ratios, relative risks, risk differences for hospitalizations, ICU/critical care services, intubation, mortality, and CVD recurrence within 90 days of COVID-19 diagnosis, compared to a propensity-matched cohort with no prior history of CVD within 90 days of COVID-19 diagnosis. RESULTS: 369,563 patients had a confirmed diagnosis of COVID-19 with a subset of 22,497 (6.09%) patients with a prior diagnosis of CVD within 10 years. All cohorts with a CVD diagnosis had an increased risk of hospitalization, critical care services, and mortality within 90 days of COVID-19 diagnosis. Additionally, the data demonstrate that any history of CVD is associated with significantly increased odds of subsequent CVD post-COVID-19 compared to a matched control. CONCLUSIONS: CVD, a known complication of CO-VID-19, is more frequent in patients with a prior history of CVD. Patients with any previous diagnosis of CVD are at higher risks of morbidity and mortality from COVID-19 infection. In patients admitted to the ED due to COVID-19 symptoms, these risk factors should be promptly identified as delayed or missed risk stratification and could lead to an ineffective and untimely diagnosis of subsequent CVD, which would lead to protracted hospitalization and poor prognosis.

Predicted and Observed Incidence of Thromboembolic Events among Koreans Vaccinated with ChAdOx1 nCoV-19 Vaccine.

We used the nationwide claims database to calculate the incidence of thrombotic events and predict their overall 2-week incidence. From 2006 to 2020, the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC) tended to increase. Unlike intracranial venous thrombosis (ICVT) and intracranial thrombophlebitis (ICTP), which showed no age difference, other venous embolism, and thrombosis (OVET), DIC, DVT, and PE were significantly more common in over 65 years. The overall 2-week incidence of ICVT was 0.21/1,000,000 (95% confidence interval [CI], 0.11-0.32). ICTP, OVET, DIC, DVT and PE were expected to occur in 0.08 (95% CI, 0.02-0.14), 7.66 (95% CI, 6.08-9.23), 5.95 (95% CI, 4.88-7.03), 13.28 (95% CI, 11.92-14.64), 14.09 (95% CI, 12.80-15.37) per 1,000,000, respectively. To date, of 8,548,231 patients vaccinated with ChAdOx1 nCoV-19 in Korea, two had confirmed thrombosis with thrombocytopenia syndrome within 2 weeks. The observed incidence of ICVT after vaccination was 0.23/1,000,000.

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies.

BACKGROUND: Recently, it has been shown that coronavirus disease 2019 (COVID-19), which has caused a pandemic since December 2019, can be accompanied by some neurological disorders. This study aimed to assess the prevalence of the most common neurological symptoms and comorbidities and systematically review the literature regarding the most prevalent neurological complications of COVID-19 infection. METHODS: All relevant studies had been collected from PubMed, Scopus, Embase, and Web of Science databases. All extracted data were analyzed using Stata version 11.2. The I2 index was applied, and a random-effects model or a fixed-effects model was used for pooled estimation to assess the heterogeneity of studies. Furthermore, Egger and Beeg's tests were used to evaluate the publication bias. RESULTS: Fifty-seven studies (26 observational and 31 case reports) were included (including 6,597 COVID-19 patients). The most prevalent general symptoms were fever, cough, and dyspnea with 84.6% (95% CI: 75.3-92.1; I2 = 98.7%), 61.3% (95% CI: 55.3-67.0; I2 = 94.6%), and 34.2% (95% CI: 25.6-43.4; I2 = 97.7%), respectively. Neurological symptoms observed among COVID-19 patients were fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea with 42.9% (95% CI: 36.7-49.3; I2 = 92.8%), 35.4% (95% CI: 11.2-64.4; I2 = 99.2%), 28.9% (95% CI: 19.9-38.8; I2 = 96.3%), 25.3% (95% CI: 1.6-63.4; I2 = 99.6%), 10.1% (95% CI: 2.7-21.0; I2 = 99.1%), 6.7% (95% CI: 3.7-10.5; I2 = 87.5%), and 5.9% (95% CI: 3.1-9.5; I2 = 94.5%). The most prevalent neurological comorbidity in COVID-19 was cerebrovascular disease with 4.3% (95% CI: 2.7-6.3; I2 = 78.7%). CONCLUSION: The most prevalent neurological manifestations of COVID-19 include fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea. Cerebrovascular disorders can either act as a risk factor for poorer prognosis in COVID-19 patients or occur as a critical complication in these patients. Guillain-Barre syndrome, encephalitis, and meningitis have also been reported as complications of COVID-19.

The impact of the COVID-19 pandemic on cerebrovascular disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a systemic disease that affects nearly all organ systems through infection and subsequent dysregulation of the vascular endothelium. One of the most striking phenomena has been a coronavirus disease 2019 (COVID-19)-associated coagulopathy. Given these findings, questions naturally emerged about the prothrombotic impact of COVID-19 on cerebrovascular disease and whether ischemic stroke is a clinical feature specific to COVID-19 pathophysiology. Early reports from China and several sites in the northeastern United States seemed to confirm these suspicions. Since these initial reports, many cohort studies worldwide observed decreased rates of stroke since the start of the pandemic, raising concerns for a broader impact of the pandemic on stroke treatment. In this review, we provide a comprehensive assessment of how the pandemic has affected stroke presentation, epidemiology, treatment, and outcomes to better understand the impact of COVID-19 on cerebrovascular disease. Much evidence suggests that this decline in stroke admissions stems from the global response to the virus, which has made it more difficult for patients to get to the hospital once symptoms start. However, there does not appear to be a demonstrable impact on quality metrics once patients arrive at the hospital. Despite initial concerns, there is insufficient evidence to ascribe a causal relationship specific to the pathogenicity of SARS-CoV-2 on the cerebral vasculature. Nevertheless, when patients infected with SARS-CoV-2 present with stroke, their presentation is likely to be more severe, and they have a markedly higher rate of in-hospital mortality than patients with either acute ischemic stroke or COVID-19 alone.

Clinical determinants of the severity of COVID-19: A systematic review and meta-analysis.

OBJECTIVE: We aimed to systematically identify the possible risk factors responsible for severe cases. METHODS: We searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients' disease. We analyzed the potential associations between clinical characteristics and severe cases. RESULTS: We identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34-2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33-1.71), obesity (OR = 1.89, 95% CI: 1.44-2.46), history of smoking (OR = 1.40, 95% CI:1.06-1.85), hypertension (OR = 2.42, 95% CI: 2.03-2.88), diabetes (OR = 2.40, 95% CI: 1.98-2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22-3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63-5.41), cerebrovascular disease (OR = 2.47, 95% CI: 1.54-3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89-4.38), malignancy (OR = 2.60, 95% CI: 2.00-3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06-2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99-78.41), shock (OR = 21.50, 95% CI: 10.49-44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34-18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions. CONCLUSION: Patients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

Comparison of the clinical features and therapeutics of COVID-19 in cardio-cerebrovascular disease (CCVD) and non-CCVD patients.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO2 were lower in the CCVD group. Although no statistical difference was observed in the outcomes between groups, CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients. Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19. In addition, given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk, the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.

Comorbidities' potential impacts on severe and non-severe patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus (SARS-CoV-2) emerged in December 2019 in Wuhan, China. Epidemiologic evidence suggests that patients with comorbidities and novel coronavirus disease 2019 (COVID-19) infection may have poor survival outcomes. However, the risk of these coexisting medical conditions in severe and non-severe cases has not been systematically reported. PURPOSE: The present study aimed to estimate the association of chronic comorbidities in severe and non-severe cases. METHODS: A literature search was conducted using the databases PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang Database, Chinese Scientific Journals Full-text Database (CQVIP) from the inception dates to April 1, 2020, to identify cohort studies assessing comorbidity and risk of adverse outcome. Either a fixed- or random-effects model was used to calculate the overall combined risk estimates. RESULTS: A total of 22 studies involving 3286 patients with laboratory-confirmed COVID-19 were included in the analysis. Overall, compared with the patients with non-severe cases, the pooled odds ratios (ORs) of hypertension, diabetes mellitus, and cardiovascular, cerebrovascular, and respiratory diseases in patients with severe cases were 2.79 (95% confidence intervals [95% CI]: 1.66-4.69), 1.64 (95% CI: 2.30-1.08), 1.79 (95% CI: 1.08-2.96), 3.92 (95% CI: 2.45-6.28), and 1.98 (95% CI: 1.26-3.12), respectively. CONCLUSIONS: This meta-analysis supports the finding that chronic comorbidities may contribute to severe outcome in patients with COVID-19. According to the findings of the present study, old age and 2 or more comorbidities are significantly impactful to COVID-19 outcomes in hospitalized patients in China.

Nervous system diseases are associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Previous studies showed that comorbidities in patients with COVID-19 are risk factors for adverse outcomes. This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. We performed a systematic literature search of four electronic databases and included studies reporting the prevalence of nervous system diseases in COVID-19 patients with severe and non-severe disease or among survivors and non-survivors. The included studies were pooled into a meta-analysis to calculate the odds ratio (OR) with 95% confidence intervals (95%CI). We included 69 studies involving 17 879 patients. The nervous system diseases were associated with COVID-19 severity (OR = 3.19, 95%CI: 2.37 to 4.30, P < 0.001) and mortality (OR = 3.75, 95%CI: 2.68 to 5.25, P < 0.001). Specifically, compared with the patients without cerebrovascular disease, patients with cerebrovascular disease infected with COVID-19 had a higher risk of severity (OR = 3.10, 95%CI: 2.21 to 4.36, P < 0.001) and mortality (OR = 3.45, 95% CI: 2.46 to 4.84, P < 0.001). Stroke was associated with severe COVID-19 disease (OR = 1.95, 95%CI: 1.11 to 3.42, P = 0.020). No significant differences were found for the prevalence of epilepsy (OR = 1.00, 95%CI: 0.42 to 2.35, P = 0.994) and dementia (OR = 2.39, 95%CI: 0.55 to 10.48, P = 0.247) between non-severe and severe COVID-19 patients. There was no significant association between stroke (OR = 1.79, 95%CI: 0.76 to 4.23, P = 0.185), epilepsy (OR = 2.08, 95%CI: 0.08 to 50.91, P = 0.654) and COVID-19 mortality. In conclusion, nervous system diseases and cerebrovascular disease were associated with severity and mortality of patients with COVID-19. There might be confounding factors that influence the relationship between nervous system diseases and COVID-19 severity as well as mortality.