Neurological Manifestations in COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence showed that coronavirus disease 2019 (COVID-19) infection may present with neurological manifestations. This review aimed to determine the neurological manifestations and complications in COVID-19. METHODS: We conducted a systematic review and meta-analysis that included cohort and case series/reports involving a population of patients confirmed with COVID-19 infection and their neurologic manifestations. We searched the following electronic databases until April 18, 2020: PubMed, Embase, Scopus, and World Health Organization database (PROSPERO registration number: CRD42020180658). RESULTS: From 403 articles identified, 49 studies involving a total of 6,335 confirmed COVID-19 cases were included. The random-effects modeling analysis for each neurological symptom showed the following proportional point estimates with 95% confidence intervals: "headache" (0.12; 0.10-0.14; I2 = 77%), "dizziness" (0.08; 0.05-0.12; I2 = 82%), "headache and dizziness" (0.09; 0.06-0.13; I2 = 0%), "nausea" (0.07; 0.04-0.11; I2 = 79%), "vomiting" (0.05; 0.03-0.08; I2 = 74%), "nausea and vomiting" (0.06; 0.03-0.11; I2 = 83%), "confusion" (0.05; 0.02-0.14; I2 = 86%), and "myalgia" (0.21; 0.18-0.25; I2 = 85%). The most common neurological complication associated with COVID-19 infection was vascular disorders (n = 23); other associated conditions were encephalopathy (n = 3), encephalitis (n = 1), oculomotor nerve palsy (n = 1), isolated sudden-onset anosmia (n = 1), Guillain-Barré syndrome (n = 1), and Miller-Fisher syndrome (n = 2). Most patients with neurological complications survived (n = 14); a considerable number of patients died (n = 7); and the rest had unclear outcomes (n = 12). CONCLUSION: This review revealed that neurologic involvement may manifest in COVID-19 infection. What has initially been thought of as a primarily respiratory illness has evolved into a wide-ranging multi-organ disease.

Clinical Outcomes of Older Persons and Persons with Dementia Admitted for Coronavirus Disease 2019: Findings from the Philippine CORONA Study.

INTRODUCTION: The Philippine CORONA Study was a multicenter, retrospective, cohort study of 10,881 coronavirus disease 2019 (COVID-19) admissions between February and December 2020. METHODS: Subgroup analysis was done on clinical outcomes of mortality, respiratory failure, duration of ventilator dependence, intensive care unit (ICU) admission, length of ICU stay, and length of hospital stay among older persons and persons with dementia. RESULTS: The adjusted hazard ratios for mortality among the mild and severe cases were significantly higher by 3.93, 95% CI [2.81, 5.50] and by 1.81, 95% CI [1.43, 2.93], respectively, in older persons compared to younger adults. The adjusted hazard ratios for respiratory failure in older persons were increased by 2.65, 95% CI [1.92, 3.68] and by 1.27, 95% CI [1.01, 1.59] among the mild and severe cases, respectively. The adjusted hazard ratio for ICU admission in older persons was higher by 1.95, 95% CI [1.47, 2.59] among the mild cases. The adjusted hazard ratios for mortality and ICU admission in persons with dementia were higher by 7.25, 95% CI [2.67, 19.68] and by 4.37, 95% CI [1.08, 17.63], respectively, compared to those without dementia. CONCLUSION: Older age and dementia significantly increased the risk of mortality, respiratory failure, and ICU admission among COVID-19 patients.

Clinical outcomes of older persons and persons with dementia admitted for COVID‐19: findings from the Philippine CORONA Study

Background The coronavirus disease 2019 (COVID‐19) pandemic substantially threatens the health of all populations worldwide, but even more so of vulnerable groups. In our subanalysis of The Philippine CORONA Study, we aimed to determine the impact of older age and dementia on clinically relevant outcomes in COVID‐19 patients. Method We included data that were collected in The Philippine CORONA Study, a multicenter, comparative, retrospective, cohort study of 10,881 adult COVID‐19 patients who were admitted between February 2020 and December 2020. Clinical outcomes analyzed were mortality, respiratory failure, duration of ventilator dependence (DVD), intensive care unit (ICU) admission, length of ICU stay (LICUS), and length of hospital stay (LHS) among older persons (individuals ≥ 60 years old) and persons with dementia admitted for COVID‐19 infection. Result The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 3.93, 95% CI [2.81, 5.50] and by 1.81, 95% CI [1.43, 2.93], respectively, in older patients compared to younger adults. The aHRs for respiratory failure in the elderly were significantly increased by 2.65, 95% CI [1.92, 3.68] and by 1.27, 95% CI [1.01, 1.59] among the mild and severe cases, respectively. The aHR for ICU admission in the older group was significantly higher by 1.95, 95% CI [1.47, 2.59] among the mild cases. Older COVID‐19 patients had significantly shorter median DVD and LHS than younger patients. The aHRs for mortality and ICU admission in persons with dementia were significantly higher by 7.25, 95% CI [2.67, 19.68] and by 4.37, 95% CI [1.08, 17.63], respectively, compared to those without dementia. The group with dementia had a significantly longer median LHS than the group without dementia. Conclusion Older age and dementia significantly increased the risk of mortality, respiratory failure, and ICU admission among COVID‐19 patients.

Clinical outcomes in COVID-19 among patients with hypertension in the Philippine CORONA Study.

OBJECTIVE: To describe the association between hypertension and clinical outcomes in a cohort of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Thirty-seven (37) hospitals in the Philippines. PATIENTS: 10,881 patients admitted for COVID-19 from February to December 2020. MEASUREMENTS AND MAIN RESULTS: Among the 10,881 patients included in the Philippine CORONA Study, 3647 (33.5%) had hypertension. On regression analysis adjusted for confounders (age group, sex, smoking history, diabetes, chronic cardiac disease, chronic kidney disease, chronic respiratory disease, chronic neurologic disease, chronic liver disease, HIV/AIDS, and malignancy), patients with hypertension had significantly greater odds of in-hospital mortality (OR 1.33, 95% CI 1.17-1.52), respiratory failure (OR 1.99, 95% CI 1.75-2.28), ICU admission (OR 2.16, 95% CI 1.90-2.45) and severe/critical disease (OR 1.57, 95% CI 1.41-1.75), compared to patients without hypertension. The time-to-event analysis with confounder adjustment also showed that hypertension was significantly associated with shorter time-to-event outcomes of in-hospital mortality (HR 1.13, 95% CI 1.01-1.26), respiratory failure (HR 1.86, 95% CI 1.65-2.10), and ICU admission (HR 1.99, 95% CI 1.76-2.23). CONCLUSIONS: Our analysis of nationwide data confirmed previous findings that hypertension is an independent risk factor for worse clinical outcomes among patients hospitalized for COVID-19, with increased odds of in-hospital mortality, respiratory failure, ICU admission, and severe/critical COVID-19. More specific studies should be done to elucidate the impact of hypertension characteristics, such as chronicity, severity, drug therapy, and level of control on these clinical outcomes.

Clinical Outcomes of COVID-19 Infection in Pregnant and Nonpregnant Women: Results from The Philippine CORONA Study.

OBJECTIVE: Our study determined the association of pregnancy with various clinical outcomes among women with COVID-19 infection. METHODS: We conducted a retrospective, cohort, subgroup analysis of the Philippine CORONA Study datasets comparing the clinical/neurological manifestations and outcomes of pregnant and nonpregnant women admitted in 37 Philippine hospitals for COVID-19 infection. RESULTS: We included 2448 women in the analyses (322 pregnant and 2.126 nonpregnant). Logistic regression models showed that crude odds ratio (OR) for mortality (OR 0.26 [95% CI 0.11, 0.66]), respiratory failure [OR 0.37 [95% CI 0.17, 0.80]), need for intensive care (OR 0.39 [95% CI 0.19, 0.80]), and prolonged length of hospital stay (OR 1.73 [95% CI 1.36, 2.19]) among pregnant women were significant. After adjusting for age, disease severity, and new-onset neurological symptoms, only the length of hospital stay remained significant (adjusted OR 1.99 [95% CI 1.56,2.54]). Cox regression models revealed that the unadjusted hazard ratio (HR) for mortality (HR 0.22 [95% CI 0.09, 0.55]) among pregnant women was statistically significant; however, after adjustment, the HR for mortality became nonsignificant. CONCLUSION: We did not find a significantly increased risk of mortality, respiratory failure, and need for ICU admission in pregnant women compared with nonpregnant women with COVID-19. However, the likelihood of hospital confinement beyond 14 days was twice more likely among pregnant women than nonpregnant women with COVID-19.

Incidence and risk factors for stroke in patients with COVID-19 in the Philippines: An analysis of 10,881 cases.

BACKGROUND: While most large studies on the possible association of COVID-19 and stroke were done in high-income countries, only a few studies consisting of small sample populations have been done in low- to middle-income countries like the Philippines. OBJECTIVES: To determine the risk factors of stroke among hospitalized COVID19 patients in the Philippines; to determine the possible association between these risk factors and stroke among the same cohort; and to determine if there is an association between mortality and stroke in this same group. METHODOLOGY: We obtained relevant clinical and neurological, including stroke data from the Philippine CORONA study, an observational study involving 10,881 patients with COVID-19 admitted in 37 referral hospitals from all over the Philippines. RESULTS: The incidence of stroke among patients with COVID-19 was 3.4% (n = 367). There were more deaths among patients with stroke and COVID-19 than those without stroke and COVID-19 (42.2% vs 14.7%, p < 0.01). In addition, more patients with stroke were admitted in the ICU (43.3% vs 15.0%, p < 0.01) regardless of cause. Smoking (OR: 1.5, 95% CI: 1.3 to 1.7, p < 0.0001), hypertension (OR:1.75, 95% CI:1.53 to 1.97, p < 0.0001), presence of heart failure (OR: 1.4, 95% CI: 1.07 to 1.86, p = 0.01), presence of any neurologic co-morbidities (OR: 1.4, 95% CI:1.11 to 1.46, p = 0.004), and history of stroke (OR:2.3, 95% CI:1.82 to 2.97, p < 0.0001) had direct significant correlation with stroke; while being a health care worker (OR: 0.5, 95% CI: 0.33 to 0.70, p < 0.0004) had an inverse significant association with stroke. CONCLUSION: COVID-19 stroke patients in the Philippines have a higher mortality and ICU admission rates than patients with COVID-19 alone or COVID-19 stroke patients from developed countries. Our cohort has similar cardiovascular and metabolic risk factors to western patients with stroke, highlighting that COVID-19 may only have a small contribution to stroke incidence.

Googling Alzheimer Disease: An Infodemiological and Ecological Study.

INTRODUCTION: Understanding the emergent role of the internet on the health-seeking behavior of people is critical not only in the areas of medicine and public health but also in the field of infodemiology. METHODS: Using Google Trends, data on global search queries for Alzheimer disease (AD) between January 2004 and April 2021 were analyzed. The relationship between online interest, as reflected by search volume index (SVI), and measures of disease burden, namely prevalence, deaths, and disability-adjusted life years, was evaluated. RESULTS: There was a reduction in the tendency to search for AD during the past two decades. SVI peaks corresponded to news of famous people with AD and awareness months. Symptoms, causes, and differences with the term dementia were central queries for persons interested in AD. No notable overall correlation between SVI and measures of disease burden was found due to competing results. Sub-group analyses, however, showed that these correlations may be influenced by socioeconomic development, with strong negative significant associations observed in lower middle-income countries. CONCLUSION: Online interest in AD may represent a more complex metric influenced by socioeconomic factors. Awareness of the impact of celebrity diagnosis and awareness months on online search behavior may prove useful in the planning of public health campaigns for AD.

Outcomes and Risk Factors of Patients With COVID-19 and Cancer (ONCORONA): Findings from The Philippine CORONA Study.

Background: A study conducted in China on patients with coronavirus disease 2019 (COVID-19) showed that cancer conferred a five times increased risk for needing intensive care admission and mortality; No data has yet been collected and published from the Philippines. Thus, the investigators conducted this substudy to determine the association of having a history of cancer with clinical outcomes among patients included in the Philippine CORONA Study. Methodology: Multi-center, retrospective cohort design. Results: A total of 244 patients had a history of cancer, out of 10,881 COVID-19 hospital admissions. After adjusting for different confounding variables of interest, having cancer was significantly associated with a 75% increased odds of having severe/critical COVID-19 at nadir (CI 95% 1.32, 2.33; p < 0.001). After adjusting for different confounding variables of interest, having cancer was significantly associated with the following time-to-event outcomes: 72% increase in hazard of in-hospital mortality (CI 95% 1.37, 2.16; p < 0.001), 65% increase in hazard of respiratory failure (CI 95% 1.31, 2.08; p < 0.001), and 57% increase in hazard of being admitted to ICU (CI 95% 1.24, 1.97; p < 0.001). Conclusion: A history of cancer conferred poorer clinical outcomes on adult, hospitalized COVID-19 patients.

Body mass index and its association with COVID-19 clinical outcomes: Findings from the Philippine CORONA study.

BACKGROUND AND AIMS: To explore the association between body mass index (BMI) and adverse outcomes in a large cohort of patients with coronavirus disease 2019 (COVID-19). METHODS: This is a secondary analysis of a 37-site, nationwide, multicenter, retrospective cohort study that investigated the clinical and neurological outcomes of adult patients with confirmed COVID-19 admitted from February to December 15, 2020. RESULTS: We analyzed 4,463 patients with BMI and outcome data. A total of 790 (17.7%) and 710 (15.9%) had the primary outcome of in-hospital mortality and need for invasive mechanical ventilation (IMV), respectively. There was no significant association between WHO BMI groups and these outcomes. Using Asia-Pacific cutoffs showed a significant association between obesity and in-hospital mortality risk (P = 0.012). Being underweight was an independent predictor of prolonged IMV requirement regardless of BMI criteria used (P < 0.01). Obesity correlated with the need for intensive care unit admission using Asia-Pacific cutoffs (P = 0.029). There was a significant association between any BMI abnormality and odds of severe/critical COVID-19 (P < 0.05). Obese patients with concomitant acute neurological presentation/diagnosis during their COVID-19 admission were shown to have lower odds of neurologic recovery (P < 0.05). CONCLUSIONS: We found BMI abnormalities to be associated with several adverse clinical and neurologic outcomes, although such associations may be more evident with the use of race-specific BMI criteria.

The outcomes of patients with diabetes mellitus in The Philippine CORONA Study.

Patients diagnosed with diabetes mellitus (DM) who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) belong to the most vulnerable patient subgroups. Emerging data has shown increased risks of severe infections, increased in ICU admissions, longer durations of admission, and increased mortality among coronavirus disease 2019 (COVID-19) patients with diabetes. We performed a subgroup analysis comparing the outcomes of patients diagnosed with DM (n = 2191) versus patients without DM (n = 8690) on our data from our study based on a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from around the Philippines. We determined distribution differences between two independent samples using Mann-Whitney U and t tests. Data on the time to onset of mortality, respiratory failure, intensive care unit (ICU) admission were used to build Kaplan-Meier curves and to compute for hazard ratios (HR). The odds ratios (OR) for longer ventilator dependence, longer ICU stay, and longer hospital stays were computed via multivariate logistic regression. Adjusted hazard ratios (aHR) and ORs (aOR) with 95% CI were calculated. We included a total of 10,881 patients with confirmed COVID-19 infection (2191 have DM while 8690 did not have DM). The median age of the DM cohort was 61, with a female to male ratio of 1:1.25 and more than 50% of the DM population were above 60 years old. The aOR for mortality was significantly higher among those in the DM group by 1.46 (95% CI 1.28-1.68; p < 0.001) as compared to the non-DM group. Similarly, the aOR for respiratory failure was also significantly higher among those in the DM group by 1.67 (95% CI 1.46-1.90). The aOR for developing severe COVID-19 at nadir was significantly higher among those in the DM group by 1.85 (95% CI 1.65-2.07; p < 0.001). The aOR for ICU admission was significantly higher among those in the DM group by 1.80 (95% CI 1.59-2.05) than those in the non-DM group. DM patients had significantly longer duration of ventilator dependence (aOR 1.33, 95% CI 1.08-1.64; p = 0.008) and longer hospital admission (aOR 1.13, 95% CI 1.01-1.26; p = 0.027). The presence of DM among COVID-19 patients significantly increased the risk of mortality, respiratory failure, duration of ventilator dependence, severe/critical COVID-19, ICU admission, and length of hospital stay.

Cerebral Vasculitis in a COVID-19 Confirmed Postpartum Patient: A Case Report.

COVID-19 has primarily been reported as a respiratory illness, but involvement of other organ systems has been reported. We describe a case of a postpartum with COVID-19 who had cerebral vasculitis. The patient presented with headache, blurring of vision, right-sided body weakness, and incoordination. Cranial magnetic resonance imaging (MRI) and angiography (MRA) showed a small acute hemorrhage on the left occipital lobe with associated acute subarachnoid hemorrhage along the parietal and occipital convexities and bilateral moderate to severe narrowing of the cerebral vessels. The patient was discharged asymptomatic. On follow-up, patient had no residual neurologic deficits, and repeat cranial MRI/MRA showed complete resolution of the vasculitis. This report was compatible with the pattern of viral-induced vasculitis and provides support to the mechanism of COVID-19-associated neurologic manifestation.

The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study.

INTRODUCTION: The SARS-CoV-2, virus that caused the COVID-19 global pandemic, possesses a neuroinvasive potential. Patients with COVID-19 infection present with neurological signs and symptoms aside from the usual respiratory affectation. Moreover, COVID-19 is associated with several neurological diseases and complications, which may eventually affect clinical outcomes. OBJECTIVES: The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA) study investigators will conduct a nationwide, multicentre study involving 37 institutions that aims to determine the neurological manifestations and factors associated with clinical outcomes in COVID-19 infection. METHODOLOGY AND ANALYSIS: This is a retrospective cohort study (comparative between patients with and without neurological manifestations) via medical chart review involving adult patients with COVID-19 infection. Sample size was determined at 1342 patients. Demographic, clinical and neurological profiles will be obtained and summarised using descriptive statistics. Student's t-test for two independent samples and χ2 test will be used to determine differences between distributions. HRs and 95% CI will be used as an outcome measure. Kaplan-Meier curves will be constructed to plot the time to onset of mortality (survival), respiratory failure, intensive care unit (ICU) admission, duration of ventilator dependence, length of ICU stay and length of hospital stay. The log-rank test will be employed to compare the Kaplan-Meier curves. Stratified analysis will be performed to identify confounders and effects modifiers. To compute for adjusted HR with 95% CI, crude HR of outcomes will be adjusted according to the prespecified possible confounders. Cox proportional regression models will be used to determine significant factors of outcomes. Testing for goodness of fit will also be done using Hosmer-Lemeshow test. Subgroup analysis will be performed for proven prespecified effect modifiers. The effects of missing data and outliers will also be evaluated in this study. ETHICS AND DISSEMINATION: This protocol was approved by the Single Joint Research Ethics Board of the Philippine Department of Health (SJREB-2020-24) and the institutional review board of the different study sites. The dissemination of results will be conducted through scientific/medical conferences and through journal publication. The lay versions of the results may be provided on request. TRIAL REGISTRATION NUMBER: NCT04386083.