Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies.

OBJECTIVES: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. DESIGN: Prospective cohort study. SETTING: A tertiary care ICU in Riyadh, Saudi Arabia. PATIENTS: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1ß, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1ß, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). CONCLUSIONS: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

Assessing Pediatric Inter-Hospital Transfer: A single-center, Retrospective, Observational Study of Saudi Arabia's National Life-Saving Protocol.

Objective: To examine the accuracy of our national Life-Saving Protocol (LSP). To the best of our knowledge, this is the first study addressing this issue in Saudi Arabia. Background: LSP was created to facilitate triaging patients with LIFE or LIMB threatening conditions in peripheral hospitals with limited services to large regional hospitals to receive definitive care. Method: This is a retrospective single-center observational study over 12 months studying the patients who arrived via LSP to our Emergency room (ED), at the only regional pediatric hospital. For the subgroup of patients who were admitted to PICU through LSP, we further assessed their outcomes like mortality and length of stay (LOS) through a matched case-control study of 1:1 with similar patients who were admitted to our PICU via other routes rather than LSP. The primary outcome is to assess the accuracy of the LSP in triaging pediatric patients with LIFE of LIMB conditions. Secondary outcomes include assessing the association between LSP and (mortality, LOS) for those who were admitted to the regional PICU via LSP compared to patients admitted to PICU via other sources of admission. Results: During the study period, 118 patients arrived at our ED via LSP. Only 43 patients (36 %) were admitted to the PICU with LIFE or LIMB conditions. A total of 64 patients (54%) of the patients were admitted directly to the general pediatric ward from ED level due to absence of LIFE of LIMB threatening condition and 8% (n=9) were discharged immediately home from the ED level due to lack of any significant illness. One patient died at ED level, and one was referred to another hospital with a minor orthopedic injury. For those who were admitted to the PICU via LSP, the mortality rate was (13.9%) (6/43), and the control group was (4.6%) (2/43) with a p-value of 0.08. Conclusion: LSP is an excellent initiative and essential tool in our healthcare system; however, our study showed huge variation in the ability of the system to recognize true pediatric patients with LIFE or LIMB conditions. Our study might form a stepping-stone in future studies assessing the LSP at the national level.

Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) manifested by a broad spectrum of symptoms, ranging from asymptomatic manifestations to severe illness and death. The purpose of the study was to extensively describe the clinical features and outcomes in critically ill patients with COVID-19 in Saudi Arabia. METHOD: This was a multicenter, non-interventional cohort study for all critically ill patients aged 18 years or older, admitted to intensive care units (ICUs) between March 1 to August 31, 2020, with an objectively confirmed diagnosis of COVID-19. The diagnosis of COVID-19 was confirmed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasopharyngeal and/or throat swabs. Multivariate logistic regression and generalized linear regression were used. We considered a P value of <0.05 statistically significant. RESULTS: A total of 560 patients met the inclusion criteria. An extensive list of clinical features was associated with higher 30-day ICU mortality rates, such as requiring mechanical ventilation (MV) or developing acute kidney injury within 24 hours of ICU admission, higher body temperature, white blood cells, blood glucose level, serum creatinine, fibrinogen, procalcitonin, creatine phosphokinase, aspartate aminotransferase, and total iron-binding capacity. During ICU stay, the most common complication was respiratory failure that required MV (71.4%), followed by acute kidney injury (AKI) and thrombosis with a proportion of 46.8% and 11.4%, respectively. CONCLUSION: Among patients with COVID-19 who were admitted to the ICU, several variables were associated with an increased risk of ICU mortality at 30 days. Respiratory failure that required MV, AKI, and thrombosis were the most common complications during ICU stay.

Time-to-Death approach in revealing Chronicity and Severity of COVID-19 across the World.

BACKGROUND: The outbreak of coronavirus disease, 2019 (COVID-19), which started from Wuhan, China, in late 2019, have spread worldwide. A total of 5,91,971 cases and 2,70,90 deaths were registered till 28th March, 2020. We aimed to predict the impact of duration of exposure to COVID-19 on the mortality rates increment. METHODS: In the present study, data on COVID-19 infected top seven countries viz., Germany, China, France, United Kingdom, Iran, Italy and Spain, and World as a whole, were used for modeling. The analytical procedure of generalized linear model followed by Gompertz link function was used to predict the impact lethal duration of exposure on the mortality rates. FINDINGS: Of the selected countries and World as whole, the projection based on 21st March, 2020 cases, suggest that a total (95% Cl) of 76 (65-151) days of exposure in Germany, mortality rate will increase by 5 times to 1%. In countries like France and United Kingdom, our projection suggests that additional exposure of 48 days and 7 days, respectively, will raise the mortality rates to10%. Regarding Iran, Italy and Spain, mortality rate will rise to 10% with an additional 3-10 days of exposure. World's mortality rates will continue increase by 1% in every three weeks. The predicted interval of lethal duration corresponding to each country has found to be consistent with the mortality rates observed on 28th March, 2020. CONCLUSION: The prediction of lethal duration was found to have apparently effective in predicting mortality, and shows concordance with prevailing rates. In absence of any vaccine against COVID-19 infection, the present study adds information about the quantum of the severity and time elapsed to death will help the Government to take necessary and appropriate steps to control this pandemic.

Association of Antibiotics Administration Timing With Mortality in Children With Sepsis in a Tertiary Care Hospital of a Developing Country.

Objective: To investigate the association between antibiotics administration timing with morbidity and mortality in children with severe sepsis and septic shock, presenting to a tertiary care center in a developing country. Methods: This is a retrospective study of children aged 14 years or younger diagnosed with severe sepsis or septic shock at a free-standing tertiary children's hospital in Saudi Arabia between April 2015 and February 2018. We investigated the association between antibiotic administration timing and pediatric intensive care unit (PICU) mortality, PICU length of stay (LOS), hospital LOS, and ventilation-free days after adjusting for confounders. Results: Among the 189 admissions, 77 patients were admitted with septic shock and 112 with severe sepsis. Overall, the mortality rate was 16.9%. The overall median time from sepsis recognition to antibiotic administration was 105 min (IQR: 65-185.5 min); for septic shock patients, it was 85 min (IQR: 55-148 min), and for severe sepsis, 130 min (IQR: 75.5-199 min). Delayed antibiotic administration (> 3 h) was associated with 3.85 times higher PICU mortality (95% confidence intervals 1.032-14.374) in children with septic shock than in children who receive antibiotics within 3 h, after controlling for severity of illness, age, comorbidities, and volume resuscitation. However, delayed antibiotics administration was not significantly associated with higher PICU mortality in children diagnosed with severe sepsis. Conclusions: Delayed antibiotics administration in children with septic shock admitted to a free-standing children's hospital in a developing country was associated with PICU mortality.

Prevalence and determinants of caesarean section in South and South-East Asian women.

BACKGROUND: Caesarean section is considered a relatively preferable and safe method of delivery as compared to normal delivery. Since the last decade, its prevalence has increased in both developed and developing countries. In the context of developing countries viz., South Asia (the highest populated region) and South-East Asia (the third-highest populated region), where a significant proportion of home deliveries were reported,however, the preference for, caesarean delivery and its associated factors are not well understood. OBJECTIVE: To study the caesarean delivery in the South and South-East Asian countries and to determine the factors associated with the preference for caesarean delivery. METHODOLOGY: Demographic and Health Survey Data on from ever-married women of nine developing countries of South and South-East Asia viz., Vietnam, India, Maldives, Timor-Leste, Nepal, Indonesia, Pakistan, Bangladesh, and Cambodia have been considered. Both bivariate and binary logistic regression models were used to estimate the propensity of a woman undergoing for caesarean delivery and to assess the influence of maternal socioeconomic characteristics towards the preference for caesarean delivery. RESULTS: Obtained results have shown an inclination of caesarean delivery among urban than rural women and are quite conspicuous, but is found to be underestimated mostly among rural women. Caesarean delivery in general is mostly predisposed among women whose baby sizes are either very large or smaller than average, have a higher level of education and place of delivery is private medical institutions. The logistic regression also revealed the influence of maternal socioeconomic characteristics towards the preference for caesarean delivery. Based on nine South and South-East Asian countries an overall C-section prevalence of 13%, but based on institutional births its increase to 19%. The forest plot demonstrated that a significant inclination of C-section among urban than rural regions. In Meta-Analysis, very high and significant heterogeneity among countries is observed, but confirms that in terms of prevalence of C-section all of the countries follow independent pattern. CONCLUSION: Study of seven urban and four rural regions of nine South and South- East Asian countries showed, a significant inclination towards the caesarean delivery above the more recent outdated WHO recommended an optimal range of 10-15%and are associated maternal socioeconomic characteristics. In order to control unwanted caesarean delivery, the government needs to develop better healthcare infrastructure and along with more antenatal care related schemes to reduce the risks associated with increased caesarean delivery.

Global impact of environmental temperature and BCG vaccination coverage on the transmissibility and fatality rate of COVID-19.

The 2019-Coronavirus (COVID-19) pandemic has had a global impact. The effect of environmental temperature on transmissibility and fatality rate of COVID-19 and protective efficacy of Bacillus Calmette-Guérin (BCG) vaccination towards COVID-19 remains ambiguous. Therefore, we explored the global impact of environmental temperature and neonatal BCG vaccination coverage on transmissibility and fatality rate of COVID-19. The COVID-19 data for reported cases, deaths and global temperature were collected from 31st December 2020 to 3rd April 2020 for 67 countries. Temperature data were split into quartiles for all three categories (minimum temperature, maximum temperature and mean temperature). The impact of three types of temperature data and policy of BCG vaccination on COVID-19 infection was determined by applying the multivariable two-level negative binomial regression analysis keeping daily new cases and daily mortality as outcome. The highest number of cases fell in the temperature categories as following: mean temperature in the second quartile (6°C to 10.5°C), median 26, interquartile range (IQR) 237; minimum temperature in the first quartile (-26°C to 1°C), median 23, IQR 173; maximum temperature in the second quartile (10°C to 16°C), median 27.5, IQR 219. For the minimum temperature category, 28% statistically significant lower incidence was noted for new cases from the countries falling in the second quartile (2°C to 6°C) compared with countries falling in the first quartile (-26°C to 1°C) (incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.57 to 0.93). However, no statistically significant difference in incidence rate was observed for mean temperature categories in comparison to the first quartile. Countries with BCG vaccination policy had 58% less mortality as compared with countries without BCG coverage (IRR 0.42; 95% CI 0.18 to 0.95). Our exploratory study provides evidence that high temperature might not be associated with low transmissibility and countries having neonatal BCG vaccination policy had a low fatality rate of COVID-19.

Global lockdown: An effective safeguard in responding to the threat of COVID-19.

RATIONALE, AIMS, AND OBJECTIVES: The recent outbreak of coronavirus (COVID-19) has infected around 1 560 000 individuals till 10 April 2020, which has resulted in 95 000 deaths globally. While no vaccine or anti-viral drugs for COVID-19 are available, lockdown acts as a protective public health measures to reduce human interaction and lower transmission. The study aims to explore the impact of delayed planning or lack of planning for the lockdown and inadequate implementation of the lockdown, on the transmission rate of COVID-19. METHOD: Epidemiological data on the incidence and mortality of COVID-19 cases as reported by public health authorities were accessed from six countries based on total number of infected cases, namely, United States and Italy (more than 100 000 cases); United Kingdom, and France (50 000-100 000 cases), and India and Russia (6000-10 000 cases). The Bayesian inferential technique was used to observe the changes (three points) in pattern of number of cases on different duration of exposure (in days) in these selected countries 1 month after World Health Organization (WHO) declaration about COVID-19 as a global pandemic. RESULTS: On comparing the pattern of transmission rates observed in these six countries at posterior estimated change points, it is found that partial implementation of lockdown (in the United States), delayed planning in lockdown (Russia, United Kingdom, and France), and inadequate implementation of the lockdown (in India and Italy) were responsible to the spread of infections. CONCLUSIONS: In order to control the spreading of COVID-19, like other national and international laws, lockdown must be implemented and enforced. It is suggested that on-time or adequate implementation of lockdown is a step towards social distancing and to control the spread of this pandemic.