Outcomes of Extracorporeal Life Support in Children with Meningococcal Septicemia: A Retrospective Cohort Study.

Meningococcal disease is associated with high mortality despite aggressive antibiotic therapy and intensive care support. Patients may develop refractory hypotension and acute respiratory distress syndrome in which extracorporeal membrane oxygenation (ECMO) could serve as a life-saving rescue therapy. However, there is limited data regarding the outcomes of ECMO support in the setting of meningococcal disease. This retrospective analysis of prospectively collected data from Extracorporeal Life Support Organization registry (1989-2019) enrolled children (29 days-18 years old) with Neisseria meningitidis infection receiving ECMO for any support type and mode. A total of 122 patients underwent a single course of ECMO support, equating to 122 ECMO runs. The overall survival-to-discharge rate was 46.7%. Patients receiving pulmonary venovenous (VV) ECMO had the highest survival-to-discharge of 85.7%, while those receiving venoarterial (VA) ECMO for pulmonary indications had a survival of 32.4%. Patients receiving VA ECMO support for cardiac indications had a survival-to-discharge rate of 60.9%. Those needing extracorporeal cardiopulmonary resuscitation (ECPR) had a poor survival (14.3%). Hemorrhagic complications were common, occurring in 43.4% of patients, but not found to be associated with mortality (complication was present in 47.7% of deceased and 38.6% of survivors, p = 0.31). Multivariable logistic regression analysis revealed that neurologic complications were associated with increased odds of mortality (odds ratio: 44.11; 95% confidence interval: 4.95-393.08). ECMO can be utilized as rescue therapy in children with refractory cardiopulmonary failure in setting of meningococcemia. Patients who require pulmonary VV or cardiac ECMO have the best ECMO outcomes. However, the use of ECMO in those suffering cardiac arrest (ECPR) should be undertaken with caution.

Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting.

This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen's kappa value of 0.8. Youden's index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.

Outcomes of extracorporeal life support for respiratory failure in children with primary immunodeficiencies.

OBJECTIVE: Extracorporeal Membrane Oxygenation (ECMO) may serve as a life-saving rescue therapy in critically ill children with respiratory failure. While survival rates of ECMO in children with secondary immunodeficiency is considered relatively poor, survival rates in children with primary immunodeficiencies (PID) has yet to be thoroughly investigated. DESIGN: Retrospective analysis of prospectively collected data from children (29 days-18 years old). PID patients were identified by using International Classification of Diseases (ICD) codes. SETTING: Data were retrieved from Extracorporeal Life Support Organization Registry (1989-2018). INTERVENTIONS: ECMO for a pulmonary support indication. The survival-to-discharge rate was calculated and factors influencing outcomes were compared between survivors and non-survivors. MEASUREMENTS AND MAIN RESULTS: A total of 73 eligible ECMO runs were included. The survival-to-discharge rate in pediatric PID patients was 45.2%. No differences were noted in survival based on type of immunodeficiency (p = 0.42) or decade of support (p = 0.98). There was no difference in the rate of pre-ECMO infection in survivors versus non-survivors (p = 0.69). The survival-to-discharge rate in patients with a culture positive infection during the ECMO run was 45.0% versus 45.3% in those with no infection (p = 0.98). In multivariate analysis, only cardiac complications (OR 5.09, 95% CI: 1.15-22.53), pulmonary complications (OR: 13.00, 95% CI: 1.20-141.25), and neurologic complications (OR: 9.86, 95% CI: 1.64-59.21) were independently associated with increased mortality. CONCLUSION: Children with a PID who require extracorporeal life support due to respiratory failure have a reasonable chance of survival and should be considered candidates for ECMO. The presence of a pre-ECMO infection should not be considered an ECMO contraindication.

Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis.

Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.

Complement Levels at Admission Reflecting Progression to Severe Acute Kidney Injury (AKI) in Coronavirus Disease 2019 (COVID-19): A Multicenter Prospective Cohort Study.

Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients. Materials and Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers. The primary endpoint was development of severe AKI defined by KDIGO stage 2+3 criteria, while the secondary endpoint was need for renal replacement therapy (RRT). Complement markers with significant associations with endpoints were then correlated with a panel of inflammatory and thrombotic biomarkers and assessed for independent association with outcome measures using logistic regression. Results: A total of 131 hospitalized COVID-19 patients (median age 66 [IQR, 54-75] years; 54.2% males) were enrolled, 33 from the US, and 98 from Hungary. There was a greater prevalence of complement over-activation and consumption in those who developed severe AKI and need for RRT during hospitalization. C3a/C3 ratio was increased in groups developing severe AKI (3.29 vs. 1.71; p < 0.001) and requiring RRT (3.42 vs. 1.79; p < 0.001) in each cohort. Decrease in alternative and classical pathway activity, and consumption of C4 below reference range, as well as elevation of complement activation marker C3a above the normal was more common in patients progressing to severe AKI. In the Hungarian cohort, each standard deviation increase in C3a (SD = 210.1) was independently associated with 89.7% increased odds of developing severe AKI (95% CI, 7.6-234.5%). Complement was extensively correlated with an array of inflammatory biomarkers and a prothrombotic state. Conclusion: Consumption and dysregulation of complement system is associated with development of severe AKI in COVID-19 patients and could represent a promising therapeutic target for reducing thrombotic microangiopathy in SARS-CoV-2 infection.

Cell-Free DNA, Neutrophil extracellular traps (NETs), and Endothelial Injury in Coronavirus Disease 2019- (COVID-19-) Associated Acute Kidney Injury.

Introduction: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of cell-free DNA (cfDNA), a surrogate for NETosis, may be associated with the development of acute kidney injury (AKI), a major contributor to poor outcomes and mortality in COVID-19. Methods: Blood samples were collected prospectively from adult patients infected with SARS-CoV-2 presenting to the emergency department (ED). Circulating levels of cfDNA were quantified from patients' serum. Further assessment of correlations between cfDNA levels and markers of AKI (i.e., serum creatinine (SCr), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)), biomarkers of thrombotic microangiopathy and of inflammation in patients' serum was performed. Results: Fifty-one COVID-19 patients were enrolled. cfDNA levels were found to be significantly higher in those who developed severe AKI (p < 0.001) and those needing renal replacement therapy (p = 0.020). cfDNA positively correlated with ED SCr, NGAL, cystatin C, neutrophil count, neutrophil-to-lymphocyte ratio, C3a, C5a, Scb5-9, IL-6, IL-8, IL-10, TNF-α, LDH, CRP, ferritin, and fibrinogen and negatively correlated with ADAMTS13/von-Willebrand factor ratio and lymphocyte count. In a multivariate logistic regression, a one-unit increase in cfDNA value was associated with 4.6% increased odds of severe AKI (OR = 1.046; p = 0.040). Finally, cfDNA significantly correlated with established NETs components, myeloperoxidase, and neutrophil elastase. Conclusion: Intravascular NETosis could be an important contributing factor in the development of microthrombosis and COVID-19-associated AKI. Further research is urgently needed to understand the role of NETosis in COVID-19 and evaluate therapeutic avenues for targeting this process.

The Predictive Value of Serum ACE2 and TMPRSS2 Concentrations in Patients with COVID-19-A Prospective Pilot Study.

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review.

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

Early prediction of COVID-19-associated acute kidney injury: Are serum NGAL and serum Cystatin C levels better than serum creatinine?

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with a high risk of acute kidney injury (AKI), often requiring renal replacement therapy (RRT). Serum Cystatin C (sCysC) and serum Neutrophil Gelatinase-Associated Lipocalin (sNGAL) are emerging biomarkers for kidney injury, and were suggested to be superior to serum creatinine (sCr) in several clinical settings. Moreover, elevated sCysC is associated with disease severity and mortality in COVID-19. We aimed to assess the utility of sCysC and sNGAL for predicting COVID-19-associated AKI, need for RRT, and need for intensive care unit (ICU) admission, when measured at presentation to the emergency department (ED). METHODS: Patients presenting to the ED with laboratory-confirmed COVID-19 were included. The primary outcome was development of COVID-19-associated AKI, while the secondary outcomes were need for RRT and ICU admission. RESULTS: Among 52 COVID-19 patients, 22 (42.3%) developed AKI with 8/22 (36.4%) requiring RRT. Both sCr and sCysC demonstrated excellent performance for predicting AKI (AUC, 0.86 and 0.87, respectively) and need for RRT (AUC, 0.94 and 0.95, respectively). sNGAL displayed acceptable performance for predicting AKI (AUC, 0.81) and need for RRT (AUC, 0.87). CONCLUSIONS: SCr and sCysC measured at ED presentation are both highly accurate predictors of AKI and need for RRT, whereas sNGAL demonstrated adequate diagnostic performance. While sCyC was previously shown to be superior to sCr as a diagnostic biomarker of kidney injury in certain etiologies, our findings demonstrate that sCr is comparable to sCyC in the context of predicting COVID-19-associated AKI. Given the high sensitivity of these biomarkers for predicting the need for RRT, and as sCysC is associated with mortality in COVID-19 patients, we recommend their measurement for enabling risk stratification and early intervention.

The role of lipoprotein(a) in coronavirus disease 2019 (COVID-19) with relation to development of severe acute kidney injury.

Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for correlation with a wide panel of biomarkers. Serum Lp(a) did not significantly differ between COVID-19 patients and sick controls, though its concentration was found to be significantly associated with severity of COVID-19 illness, including acute kidney failure stage (r = 0.380, p = 0.007), admission disease severity (r = 0.355, p = 0.013), and peak severity (r = 0.314; p = 0.03). Lp(a) was also positively correlated with interleukin (IL)-8 (r = 0.308; p = 0.037), fibrinogen (r = 0.344; p = 0.032) and creatinine (r = 0.327; p = 0.027), and negatively correlated with ADAMTS13 activity/VWF:Ag (r = - 0.335; p = 0.021); but not with IL-6 (r = 0.241; p = 0.106). These results would hence suggest that adverse outcomes in patients with COVID-19 may be aggravated by a genetically determined hyper-Lp(a) state rather than any inflammation induced elevations.

Serum ACE activity and plasma ACE concentration in patients with SARS-CoV-2 infection.

Significant controversy has arisen over the role of the renin-angiotensin-aldosterone system (RAAS) in COVID-19 pathophysiology. In this prospective, observational study, we evaluated plasma angiotensin converting enzyme (ACE) concentration and serum ACE activity in 52 adults with laboratory-confirmed SARS-CoV-2 infection and 27 non-COVID-19 sick controls. No significant differences were observed in ACE activity in COVID-19 patients versus non-COVID-19 sick controls (41.1 [interquartile range (IQR): 23.0-55.2] vs. 42.9 [IQR 13.6-74.2] U/L, p = .649, respectively). Similarly, no differences were observed in ACE concentration in COVID-19 patients versus non-COVID-19 sick controls (108.4 [IQR: 95.8-142.2] vs. 133.8 [IQR: 100.2-173.7] µg/L, p = .059, respectively). Neither ACE activity (p = .751), nor ACE concentration (p = .283) was associated with COVID-19 severity. Moreover, neither ACE activity, nor ACE concentration was correlated with any inflammatory biomarkers.

Complement levels at admission as a reflection of coronavirus disease 2019 (COVID-19) severity state.

Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.

Alterations in the lipid profile associate with a dysregulated inflammatory, prothrombotic, anti-fibrinolytic state and development of severe acute kidney injury in coronavirus disease 2019 (COVID-19): A study from Cincinnati, USA.

BACKGROUND AND AIMS: Reduction of atherogenic lipoproteins is often the ultimate goal of nutritional interventions, however this is complicated given that hypolipidemia is frequently observed in coronavirus disease 2019 (COVID-19) patients. We aimed to explore the association of hypolipidemia with patient outcomes in terms of immunothrombosis and multiorgan injury, focusing on specialized apolipoproteins apo A1 and apo B. METHODS: Lipid profiles of 50 COVID-19 patients and 30 sick controls presenting to the Emergency Department (ED) were measured in this prospective observational study. The primary outcome was development of severe acute kidney injury (AKI). Need for hospitalization and ICU admission were secondary outcomes. Lipoproteins were analyzed for independent association with serum creatinine (SCr) increase ratio and correlated with a wide panel of biomarkers. RESULTS: COVID-19 cohort had significantly lower apo A1 (p = 0.006), and higher apo B/apo A1 ratio (p = 0.041). Patients developing severe AKI had significantly lower LDL-C (p = 0.021). Apo B/apo A1 was associated with 2.25-fold decrease in serum SCr increase ratio, while LDL-C with a 1.5% decrease. Hypolipidemia correlated with low plasminogen, ADAMTS13 activity/VWF:Ag, and high inflammatory biomarkers (CRP, IL-6, IL-8, IL-10), plasminogen activator inhibitor-1 (PAI-1), ED creatinine, and SCr increase ratio. CONCLUSION: Although favored in dietetics, findings of a low LDL-C in COVID-19 patients should be alarming in light of our observations. Low apo B/apo A1 ratio and LDL-C are predictive of renal deterioration in COVID-19 patients, and low LDL-C in particular may potentially serve to indicate COVID-19 related AKI driven by disrupted fibrinolysis and a secondary thrombotic microangiopathy-like process.

Clinical Predictors of SARS-CoV-2 Testing Pressure on Clinical Laboratories: A Multinational Study Analyzing Google Trends and Over 100 Million Diagnostic Tests.

OBJECTIVE: Evidence has shown that Google searches for clinical symptom keywords correlates with the number of new weekly patients with COVID-19. This multinational study assessed whether demand for SARS-CoV-2 tests could also be predicted by Google searches for key COVID-19 symptoms. METHODS: The weekly number of SARS-CoV-2 tests performed in Italy and the United States was retrieved from official sources. A concomitant electronic search was performed in Google Trends, using terms for key COVID-19 symptoms. RESULTS: The model that provided the highest coefficient of determination for the United States (R2 = 82.8%) included a combination of searching for cough (with a time lag of 2 weeks), fever (with a time lag of 2 weeks), and headache (with a time lag of 3 weeks; the time lag refers to the amount of time between when a search was conducted and when a test was administered). In Italy, headache provided the model with the highest adjusted R2 (86.8%), with time lags of both 1 and 2 weeks. CONCLUSION: Weekly monitoring of Google Trends scores for nonspecific COVID-19 symptoms is a reliable approach for anticipating SARS-CoV-2 testing demands ~2 weeks in the future.

The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).

OBJECTIVES: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes. METHODS: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit. RESULTS: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8. CONCLUSIONS: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.

Ups and Downs of COVID-19: Can We Predict the Future? Local Analysis with Google Trends for Forecasting the Burden of COVID-19 in Pakistan.

BACKGROUND: We aim to study the utility of Google Trends search history data for demonstrating if a correlation may exist between web-based information and actual coronavirus disease 2019 (COVID-19) cases, as well as if such data can be used to forecast patterns of disease spikes. PATIENTS & METHODS: Weekly data of COVID-19 cases in Pakistan was retrieved from online COVID-19 data banks for a period of 60 weeks. Search history related to COVID-19, coronavirus and the most common symptoms of disease was retrieved from Google Trends during the same period. Statistical analysis was performed to analyze the correlation between the two data sets. Search terms were adjusted for time-lag over weeks, to find the highest cross-correlation for each of the search terms. RESULTS: Search terms of 'fever' and 'cough' were the most commonly searched online, followed by coronavirus and COVID. The highest peak correlations with the weekly case series, with a 1-week backlog, was noted for loss of smell and loss of taste. The combined model yielded a modest performance for forecasting positive cases. The linear regression model revealed loss of smell (adjusted R2 of 0.7) with significant 1-week, 2-week and 3-week lagged time series, as the best predictor of weekly positive case counts. CONCLUSIONS: Our local analysis of Pakistan-based data seemingly confirms that Google trends can be used as an important tool for anticipating and predicting pandemic patterns and pre-hand preparedness in such unprecedented pandemic crisis.

Congenital Anomalies of the Tracheobronchial Tree: A Meta-Analysis and Clinical Considerations.

BACKGROUND: The aim of this study was to determine the prevalence and anatomic features of major tracheobronchial anomalies. METHODS: Major electronic databases were systematically searched to identify eligible studies. Data were extracted and pooled into a meta-analysis. The primary outcome was the prevalence of major tracheobronchial anomalies, specifically tracheal bronchus (TB) and accessory cardiac bronchus (ACB). Secondary outcomes included the origin and types of TB and ACB. RESULTS: A total of 27 studies (n = 119,695 patients) were included. A TB was present in 0.99% (95% confidence interval, 0.67 to 1.37) of patients, and an ACB was present in 0.14% (95% confidence interval, 0.09 to 0.20). The overall prevalence of TB was higher in imaging than in operative studies (1.81% vs 0.82%). It was also higher in pediatric (2.55%) than in adult studies (0.50%). Patients with other congenital anomalies were 15 times more likely to have a TB (odds ratio 14.89; 95% confidence interval, 7.09 to 31.22). The most common origin of TBs was from the trachea (81.42%), primarily from the right side (96.43%). The most common origin of ACBs was from the intermediate bronchus (74.32%). The ACBs terminated as blind-ending diverticulum in two thirds of cases. CONCLUSIONS: Major tracheobronchial anomalies are present in approximately 1% of the population, although the prevalence is higher among pediatric patients and patients with accompanying congenital anomalies. Although rare, major tracheobronchial anomalies can be associated with significant respiratory morbidities and present challenges during airway management in surgical and critical care patients. Establishing a preoperative diagnosis of these variations is essential for planning and implementing an appropriate airway management strategy to minimize attendant complications.