Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer–BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine;nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.

The Impact of Strict Public Health Measures on COVID-19 Transmission in Developing Countries: The Case of Kuwait.

Background: Many countries have succeeded in curbing the initial outbreak of COVID-19 by imposing strict public health control measures. However, little is known about the effectiveness of such control measures in curbing the outbreak in developing countries. In this study, we seek to assess the impact of various outbreak control measures in Kuwait to gain more insight into the outbreak progression and the associated healthcare burden. Methods: We use a SEIR mathematical model to simulate the first wave of the epidemic outbreak of COVID-19 in Kuwait with additional testing and hospitalization compartments. We calibrate our model by using a NBD observational framework for confirmed case and death counts. We simulate trajectories of model forecasts and assess the effectiveness of public health interventions by using maximum likelihood to estimate both the basic and effective reproduction numbers. Results: Our results indicate that the early strict control measures had the effect of delaying the intensity of the outbreak but were unsuccessful in reducing the effective reproduction number below 1. Forecasted model trajectories suggest a need to expand the healthcare system capacity to cope with the associated epidemic burden of such ineffectiveness. Conclusion: Strict public health interventions may not always lead to the same desired outcomes, particularly when population and demographic factors are not accounted for as in the case in some developing countries. Real-time dynamic modeling can provide an early assessment of the impact of such control measures as well as a forecasting tool to support outbreak surveillance and the associated healthcare expansion planning.

Effect of sleeve gastrectomy on the expression of meteorin-like (METRNL) and Irisin (FNDC5) in muscle and brown adipose tissue and its impact on uncoupling proteins in diet-induced obesity rats.

BACKGROUND: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). OBJECTIVES: To study the effect of SG on the levels of proteins involved in thermogenesis process. SETTING: Laboratory rats at Kuwait University. METHODS: Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. RESULTS: The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. CONCLUSIONS: Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.

Prevalence, predictors and outcomes of bleeding events in patients with COVID-19 infection on anticoagulation: Retrospective cohort study.

BACKGROUND: This study aims to examine risk factors and complications associated with bleeding events in patients with COVID-19 who are on anticoagulation. MATERIAL AND METHODS: We conducted retrospective review of all patients who were admitted with COVID-19 and developed bleeding events between March and June 2020. Data were analyzed in accordance with three major outcomes. Mortality within 30 days of bleeding episode, resolution of the bleeding event, and the type of bleeding event. RESULTS: Of 122 bleeds, there was 55 (28 %) gastrointestinal (GI) bleeds. Overall mortality was 59 % (n = 72). The prevalence of therapeutic invasive interventions was 11.5 % (n = 14) all were successful in resolving the bleeding event. We found that having a GI bleeds was associated with higher risk of mortality compared to non-GI bleeds (p = 0.04) and having occult bleeds to be associated with 15 times increased risk of mortality (OR 15, 95%CI 1.97-29.1, p = 0.01). Furthermore, patients who were on no anticoagulation (none) (OR 0.1, 95%CI 0.01-0.86, p < 0.00), on prophylactic dose anticoagulation (OR 0.07, 95%CI 0.02-0.28, p = 0.03) or intermediate dose anticoagulation (OR 0.36, 95%CI 0.09-1.34, p = 0.13) were less likely to die than patients on therapeutic dose. CONCLUSIONS: The best approach to manage COVID-19 bleeding patients is to prioritize therapies that manage sepsis induce coagulopathy and shock over other approaches. In COVID-19 patients' routine prescription of supra-prophylactic dose anticoagulation should be revisited and more individualized approach to prescription should be the norm. Regardless of the cause of bleeding event it appears that the majority of bleeding events resolve with noninvasive interventions and when invasive interventions were necessary, they were associated with high success rate despite the delay.

Probabilities of ICU admission and hospital discharge according to patient characteristics in the designated COVID-19 hospital of Kuwait.

BACKGROUND: Subsequent epidemic waves have already emerged in many countries and in the absence of highly effective preventive and curative options, the role of patient characteristics on the development of outcomes needs to be thoroughly examined, especially in middle-east countries where such epidemiological studies are lacking. There is a huge pressure on the hospital services and in particular, on the Intensive Care Units (ICU). Describing the need for critical care as well as the chance of being discharged from hospital according to patient characteristics, is essential for a more efficient hospital management. The objective of this study is to describe the probabilities of admission to the ICU and the probabilities of hospital discharge among positive COVID-19 patients according to demographics and comorbidities recorded at hospital admission. METHODS: A prospective cohort study of all patients with COVID-19 found in the Electronic Medical Records of Jaber Al-Ahmad Al-Sabah Hospital in Kuwait was conducted. The study included 3995 individuals (symptomatic and asymptomatic) of all ages who tested positive from February 24th to May 27th, 2020, out of which 315 were treated in the ICU and 3619 were discharged including those who were transferred to a different healthcare unit without having previously entered the ICU. A competing risk analysis considering two events, namely, ICU admission and hospital discharge using flexible hazard models was performed to describe the association between event-specific probabilities and patient characteristics. RESULTS: Results showed that being male, increasing age and comorbidities such as chronic kidney disease (CKD), asthma or chronic obstructive pulmonary disease and weakened immune system increased the risk of ICU admission within 10 days of entering the hospital. CKD and weakened immune system decreased the probabilities of discharge in both females and males however, the age-related pattern differed by gender. Diabetes, which was the most prevalent comorbid condition, had only a moderate impact on both probabilities (18% overall) in contrast to CKD which had the largest effect, but presented only in 7% of those admitted to ICU and in 1% of those who got discharged. For instance, within 5 days a 50-year-old male had 19% (95% C.I.: [15,23]) probability of entering the ICU if he had none of these comorbidities, yet this risk jumped to 31% (95% C.I.: [20,46]) if he had also CKD, and to 27% in the presence of asthma/COPD (95% C.I.: [19,36]) or of weakened immune system (95% C.I.: [16,42]). CONCLUSIONS: This study provides useful insight in describing the probabilities of ICU admission and hospital discharge according to age, gender, and comorbidities among confirmed COVID-19 cases in Kuwait. A web-tool is also provided to allow the user to estimate these probabilities for any combination of these covariates. These probabilities enable deeper understanding of the hospital demand according to patient characteristics which is essential to hospital management and useful for developing a vaccination strategy.

The impact of ABO blood groups on clinical outcomes and susceptibility to COVID-19: A retrospective study in an unselected population.

BACKGROUND: ABO blood groups have been linked to susceptibility to infection with certain microorganisms, including coronaviruses. We examined the relationship between blood group and clinical outcomes in individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and compared their blood group distribution with the general population. METHODS: At the inception of the pandemic, all individuals testing positive for SARS-CoV-2 in Kuwait were admitted to one designated coronavirus disease 2019 (COVID-19) hospital and enrolled in a prospective registry. Patients admitted from February 24 to May 27, 2020, were stratified according to blood group. As a control, blood groups of 3,730,027 anonymized individuals representing almost Kuwait's entire population were obtained from a national database. RESULTS: Of 3305 SARS-CoV-2-positive patients, 37.1%, 25.5%, 28.9%, and 8.5% were groups O, A, B, and AB, respectively. Univariate analysis revealed no significant differences in severe clinical outcomes or death among the blood groups. However, multivariable analysis demonstrated that group A individuals had higher odds of developing pneumonia compared with non-group A (adjusted odds ratio 1.32, 95% confidence interval 1.02-1.72, p < .036). Compared with the general population, the COVID-19 cohort had a lower frequency of group O, equivalent frequency of A, and higher frequency of B and AB. No significant difference in the RhD group was found. CONCLUSION: This study supports potential involvement of the ABO blood group system in predisposing to infection with SARS-CoV-2 in an unselected population. Examination of the mechanistic link between blood group and COVID-19 and its implications on controlling the current pandemic is warranted.

Prevalence and risk factors of barotrauma in Covid-19 patients admitted to an intensive care unit in Kuwait; a retrospective cohort study.

BACKGROUND: The development of barotrauma has been suggested to complicate the management of mechanically ventilated COVID-19 patients admitted to the intensive care unit (ICU). This study aims to identify potential risk factors associated with the development of barotrauma related complications in COVID-19 patients receiving mechanical ventilation. METHODS: A retrospective cohort study was carried out in a single COVID-19 designated center in Kuwait. Three hundred and forty-three confirmed COVID-19 patients transferred and/or admitted to our institution between February 26, 2020 and June 20, 2020 were included in the study. All patients were admitted into the ICU with the majority being mechanically ventilated (81.3%). RESULTS: Fifty-four (15.4%) patients developed barotrauma, of which 49 (90.7%) presented with pneumothorax, and 14.8% and 3.7% due to pneumomediastinum and pneumopericardium respectively. Of those that developed barotrauma, 52 (96.3%) patients were in acute respiratory distress syndrome (ARDS). Biochemically, the white blood cells (p = 0.001), neutrophil percentage (p = 0.012), lymphocyte percentage (p = 0.014), neutrophil: lymphocyte ratio (NLR) (p=<0.001) and lactate dehydrogenase (LDH) (p = 0.002) were found to be significantly different in patients that developed barotrauma. Intubation due to low level of consciousness (p = 0.007), a high admission COVID-GRAM score (p = 0.042), and a positive-end expiratory pressure (PEEP) higher than the control group (p = 0.016) were identified as potential risk factors for the development of barotrauma. CONCLUSION: Patients infected with COVID-19 have a significant risk of developing barotrauma when receiving invasive mechanical ventilation. This poses a substantial impact on the hospital course of the patients and clinical outcome, correlating to a higher mortality rate in this cohort of patients.

A biomarker based severity progression indicator for COVID-19: the Kuwait prognosis indicator score.

BACKGROUND: COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. METHODS: We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. RESULTS: There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. CONCLUSION: We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at covidkscore.com.

Perceptions, Knowledge, and Behaviors Related to COVID-19 Among Social Media Users: Cross-Sectional Study.

BACKGROUND: Social media is one of the most rapid and impactful ways of obtaining and delivering information in the modern era. OBJECTIVE: The aim of this study was to rapidly obtain information on public perceptions, knowledge, and behaviors related to COVID-19 in order to identify deficiencies in key areas of public education. METHODS: Using a cross-sectional study design, a survey web link was posted on the social media and messaging platforms Instagram, Twitter, and WhatsApp by the study investigators. Participants, aged ≥18 years, filled out the survey on a voluntary basis. The main outcomes measured were knowledge of COVID-19 symptoms, protective measures against COVID-19, and source(s) of information about COVID-19. Subgroup analyses were conducted to determine the effects of age, gender, underlying illness, and working or studying in the health care industry on the perceived likelihood of acquiring COVID-19 and getting vaccinated. RESULTS: A total of 5677 subjects completed the survey over the course of 1 week. "Fever or chills" (n=4973, 87.6%) and "shortness of breath" (n=4695, 82.7%) were identified as the main symptoms of COVID-19. Washing and sanitizing hands (n=4990, 87.9%) and avoiding public places and crowds (n=4865, 85.7%) were identified as the protective measures most frequently used against COVID-19. Social media was the most utilized source for information on the disease (n=4740, 83.5%), followed by the World Health Organization (n=2844, 50.1%). Subgroup analysis revealed that younger subjects (<35 years), males, and those working or studying in health care reported a higher perceived likelihood of acquiring COVID-19, whereas older subjects, females, and those working or studying in non-health care areas reported a lower perceived likelihood of acquiring COVID-19. Similar trends were observed for vaccination against COVID-19, with older subjects, females, and those working or studying in non-health care sectors reporting a lower likelihood of vaccinating against COVID-19. CONCLUSIONS: Our results are indicative of a relatively well-informed cohort implementing appropriate protective measures. However, key knowledge deficiencies exist with regards to vaccination against COVID-19, which future efforts should aim at correcting.

COVID-19 clinical outcomes and nationality: results from a Nationwide registry in Kuwait.

BACKGROUND: In light of the COVID-19 pandemic, many have flagged racial and ethnic differences in health outcomes in western countries as an urgent global public health priority. Kuwait has a unique demographic profile with two-thirds of the population consisting of non-nationals, most of which are migrant workers. We aimed to explore whether there is a significant difference in health outcomes between non-Kuwaiti and Kuwaiti patients diagnosed with COVID-19. METHODS: We used a prospective COVID-19 registry of all patients (symptomatic and asymptomatic) in Kuwait who tested positive from February 24th to April 20th, 2020, collected from Jaber Al-Ahmad Al-Sabah Hospital, the officially-designated COVID-19 healthcare facility in the country. We ran separate logistic regression models comparing non-Kuwaitis to Kuwaitis for death, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS) and pneumonia. RESULTS: The first 1123 COVID-19 positive patients in Kuwait were all recruited in the study. About 26% were Kuwaitis and 73% were non-Kuwaiti. With adjustments made to age, gender, smoking and selected co-morbidities, non-Kuwaitis had two-fold increase in the odds of death or being admitted to the intensive care unit compared to Kuwaitis (OR: 2.14, 95% CI 1.12-4.32). Non-Kuwaitis had also higher odds of ARDS (OR:2.44, 95% CI 1.23-5.09) and pneumonia (OR: 2.24, 95% CI 1.27-4.12). CONCLUSION: This is the first study to report on COVID-19 outcomes between Kuwaiti and non-Kuwaiti patients. The current pandemic may have amplified the differences of health outcomes among marginalized subpopulations. A number of socioeconomic and environmental factors could explain this health disparity. More research is needed to advance the understanding of policymakers in Kuwait in order to make urgent public health interventions.

Characteristics, risk factors and outcomes among the first consecutive 1096 patients diagnosed with COVID-19 in Kuwait.

BACKGROUND: In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations, and outcomes in this unique patient population. METHODS: This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were included. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes (admission to intensive care and/or mortality). FINDINGS: Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (46.3%), of whom 35 later developed symptoms, and 59.7% had no signs of infection. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study's cutoff date. On multivariable analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort.