Effect of non-pharmaceutical interventions in the early phase of the COVID-19 epidemic in Saudi Arabia

Non-pharmaceutical interventions have been widely employed to control the COVID-19 pandemic. Their associated effect on SARS-CoV-2 transmission have however been unequally studied across regions. Few studies have focused on the Gulf states despite their potential role for global pandemic spread, in particular in the Kingdom of Saudi Arabia through religious pilgrimages. We study the association between NPIs and SARS-CoV-2 transmission in the Kingdom of Saudi Arabia during the first pandemic wave between March and October 2020. We infer associations between NPIs introduction and lifting through a spatial SEIR-type model that allows for inferences of region-specific changes in transmission intensity. We find that reductions in transmission were associated with NPIs implemented shortly after the first reported case including Isolate and Test with School Closure (region-level mean estimates of the reduction in R0 ranged from 25–41%), Curfew (20–70% reduction), and Lockdown (50–60% reduction), although uncertainty in the estimates was high, particularly for the Isolate and Test with School Closure NPI (95% Credible Intervals from 1% to 73% across regions). Transmission was found to increase progressively in most regions during the last part of NPI relaxation phases. These results can help informing the policy makers in the planning of NPI scenarios as the pandemic evolves with the emergence of SARS-CoV-2 variants and the availability of vaccination.

A scoping review on the impact of the COVID-19 pandemic on physical activity and sedentary behavior in Saudi Arabia.

BACKGROUND: In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. METHODS: We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. RESULTS: Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2-18 years), and 16 studies included adults (age: 15-99 years). Data collection periods were < = 5 months, with 17 studies collecting data in 2020 only, one study in 2020-2021, and one study in 2021. The median analytic sample size was 363 (interquartile range 262-640). Three studies of children/adolescents collected behaviors online at one time using parental reporting, with one also allowing self-reporting. All three studies found that physical activity was lower during and/or following the lockdown than before the lockdown. Two studies found screen time, television watching, and playing video games were higher during or following the lockdown than before the lockdown. Sixteen adult studies assessed physical activity, with 15 utilizing self-reporting and one using accelerometry. Physical activity, exercise, walking, and park visits were all lower during or following the lockdown than before the lockdown. Six adult studies assessed sedentary behavior using self-report. Sitting time (4 studies) and screen time (2 studies) were higher during or following the lockdown than before the lockdown. CONCLUSIONS: Among children, adolescents, and adults, studies consistently indicated that in the short-term, physical activity decreased and sedentary behavior increased in conjunction with the movement restrictions. Given the widespread impact of the pandemic on other health behaviors, it would be important to continue tracking behaviors post-lockdown and identify subpopulations that may not have returned to their physical activity and sedentary behavior to pre-pandemic levels to focus on intervention efforts.

Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion.

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform's true impact on human health.

Effect of non-pharmaceutical interventions in the early phase of the COVID-19 epidemic in Saudi Arabia.

Non-pharmaceutical interventions have been widely employed to control the COVID-19 pandemic. Their associated effect on SARS-CoV-2 transmission have however been unequally studied across regions. Few studies have focused on the Gulf states despite their potential role for global pandemic spread, in particular in the Kingdom of Saudi Arabia through religious pilgrimages. We study the association between NPIs and SARS-CoV-2 transmission in the Kingdom of Saudi Arabia during the first pandemic wave between March and October 2020. We infer associations between NPIs introduction and lifting through a spatial SEIR-type model that allows for inferences of region-specific changes in transmission intensity. We find that reductions in transmission were associated with NPIs implemented shortly after the first reported case including Isolate and Test with School Closure (region-level mean estimates of the reduction in R0 ranged from 25-41%), Curfew (20-70% reduction), and Lockdown (50-60% reduction), although uncertainty in the estimates was high, particularly for the Isolate and Test with School Closure NPI (95% Credible Intervals from 1% to 73% across regions). Transmission was found to increase progressively in most regions during the last part of NPI relaxation phases. These results can help informing the policy makers in the planning of NPI scenarios as the pandemic evolves with the emergence of SARS-CoV-2 variants and the availability of vaccination.

The economic burden of overweight and obesity in Saudi Arabia.

CONTEXT: The prevalence of overweight and obesity in Saudi Arabia has been rising. Although the health burden of excess weight is well established, little is known about the economic burden. AIMS: To assess the economic burden-both direct medical costs and the value of absenteeism and presenteeism-resulting from overweight and obesity in Saudi Arabia. SETTINGS AND DESIGN: The cost of overweight and obesity in Saudi Arabia was estimated from a societal perspective using an epidemiologic approach. METHODS AND MATERIALS: Data were obtained from previously published studies and secondary databases. STATISTICAL ANALYSIS USED: Overweight/obesity-attributable costs were calculated for six major noncommunicable diseases; sensitivity analyses were conducted for key model parameters. RESULTS: The impact of overweight and obesity for these diseases is found to directly cost a total of $3.8 billion, equal to 4.3 percent of total health expenditures in Saudi Arabia in 2019. Estimated overweight and obesity-attributable absenteeism and presenteeism costs a total of $15.5 billion, equal to 0.9 percent of GDP in 2019. CONCLUSIONS: Even when limited to six diseases and a subset of total indirect costs, results indicate that overweight and obesity are a significant economic burden in Saudi Arabia. Future studies should identify strategies to reduce the health and economic burden resulting from excess weight in Saudi Arabia.

Estimating the effect of non-pharmaceutical interventions to mitigate COVID-19 spread in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) quickly controlled the spread of SARS-CoV-2 by implementing several non-pharmaceutical interventions (NPIs), including suspension of international and national travel, local curfews, closing public spaces (i.e., schools and universities, malls and shops), and limiting religious gatherings. The KSA also mandated all citizens to respect physical distancing and to wear face masks. However, after relaxing some restrictions during June 2020, the KSA is now planning a strategy that could allow resuming in-person education and international travel. The aim of our study was to evaluate the effect of NPIs on the spread of the COVID-19 and test strategies to open schools and resume international travel. METHODS: We built a spatial-explicit individual-based model to represent the whole KSA population (IBM-KSA). The IBM-KSA was parameterized using country demographic, remote sensing, and epidemiological data. A social network was created to represent contact heterogeneity and interaction among age groups of the population. The IBM-KSA also simulated the movement of people across the country based on a gravity model. We used the IBM-KSA to evaluate the effect of different NPIs adopted by the KSA (physical distancing, mask-wearing, and contact tracing) and to forecast the impact of strategies to open schools and resume international travels. RESULTS: The IBM-KSA results scenarios showed the high effectiveness of mask-wearing, physical distancing, and contact tracing in controlling the spread of the disease. Without NPIs, the KSA could have reported 4,824,065 (95% CI: 3,673,775-6,335,423) cases by June 2021. The IBM-KSA showed that mandatory mask-wearing and physical distancing saved 39,452 lives (95% CI: 26,641-44,494). In-person education without personal protection during teaching would have resulted in a high surge of COVID-19 cases. Compared to scenarios with no personal protection, enforcing mask-wearing and physical distancing in schools reduced cases, hospitalizations, and deaths by 25% and 50%, when adherence to these NPIs was set to 50% and 70%, respectively. The IBM-KSA also showed that a quarantine imposed on international travelers reduced the probability of outbreaks in the country. CONCLUSIONS: This study showed that the interventions adopted by the KSA were able to control the spread of SARS-CoV-2 in the absence of a vaccine. In-person education should be resumed only if NPIs could be applied in schools and universities. International travel can be resumed but with strict quarantine rules. The KSA needs to keep strict NPIs in place until a high fraction of the population is vaccinated in order to reduce hospitalizations and deaths.

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses.

Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs' ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.

Effective COVID-19 Control: A Comparative Analysis of the Stringency and Timeliness of Government Responses in Asia.

AIM: Many governments in East and Southeast Asia responded promptly and effectively at the onset of the COVID-19 pandemic. Synthesizing and analyzing these responses is vital for disease control evidence-based policymaking. METHODS: An extensive review of COVID-19 control measures was conducted in selected Asian countries and subregions, including Mainland China, Hong Kong, Taiwan, South Korea, Singapore, Japan, and Vietnam from 1 January to 30 May 2020. Control measures were categorized into administrative, public health, and health system measures. To evaluate the stringency and timeliness of responses, we developed two indices: the Initial Response Index (IRI) and the Modified Stringency Index (MSI), which builds on the Oxford COVID-19 Government Response Tracker (OxCGRT). RESULTS: Comprehensive administrative, public health, and health system control measures were implemented at the onset of the outbreak. Despite variations in package components, the stringency of control measures across the study sites increased with the acceleration of the outbreak, with public health control measures implemented the most stringently. Variations in daily average MSI scores are observed, with Mainland China scoring the highest (74.2), followed by Singapore (67.4), Vietnam (66.8), Hong Kong (66.2), South Korea (62.3), Taiwan (52.1), and Japan (50.3). Variations in IRI scores depicting timeliness were higher: Hong Kong, Taiwan, Vietnam, and Singapore acted faster (IRI > 50.0), while Japan (42.4) and Mainland China (4.2) followed. CONCLUSIONS: Timely setting of stringency of the control measures, especially public health measures, at dynamically high levels is key to optimally controlling outbreaks.

Covid-19 and non-communicable diseases: evidence from a systematic literature review.

BACKGROUND: Since early 2020, the Covid-19 pandemic has engulfed the world. Amidst the growing number of infections and deaths, there has been an emphasis of patients with non-communicable diseases as they are particularly susceptible to the virus. The objective of this literature review is to systematize the available evidence on the link between non-communicable diseases and Covid-19. METHODS: We have conducted a systematic review of the literature on Covid-19 and non-communicable diseases from December, 2019 until 15th of November, 2020. The search was done in PubMed and in doing so we used a variety of searching terms in order to isolate the final set of papers. At the end of the selection process, 45 papers were selected for inclusion in the literature review. RESULTS: The results from the review indicate that patients with certain chronic illnesses such as diabetes, hypertension (and other cardiovascular diseases), chronic respiratory illnesses, chronic kidney and liver conditions are more likely to be affected by Covid-19. More importantly, once they do get infected by the virus, patients with chronic illnesses have a much higher likelihood of having worse clinical outcomes (developing a more severe form of the disease or dying) than an average patient. There are two hypothesized channels that explain this strong link between the chronic illnesses enumerated above and Covid 19: (i) increased ACE2 (angiotensin-converting enzyme 2) receptor expressions, which facilitates the entry of the virus into the host body; and (ii) hyperinflammatory response, referred to as "cytokine storm". Finally, the literature review does not find any evidence that diabetes or hypertension related medications exacerbate the overall Covid-19 condition in chronic illness patients. CONCLUSIONS: Thus, the evidence points out to 'business as usual' disease management model, although with greater supervision. However, given the ongoing Covid-19 vulnerabilities among people with NCDs, prioritizing them for the vaccination process should also figure high on the agenda on health authorities.

Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships.

The linkage of individuals with obesity and COVID-19 is controversial and lacks systematic reviews. After a systematic search of the Chinese and English language literature on COVID-19, 75 studies were used to conduct a series of meta-analyses on the relationship of individuals with obesity-COVID-19 over the full spectrum from risk to mortality. A systematic review of the mechanistic pathways for COVID-19 and individuals with obesity is presented. Pooled analysis show individuals with obesity were more at risk for COVID-19 positive, >46.0% higher (OR = 1.46; 95% CI, 1.30-1.65; p < 0.0001); for hospitalization, 113% higher (OR = 2.13; 95% CI, 1.74-2.60; p < 0.0001); for ICU admission, 74% higher (OR = 1.74; 95% CI, 1.46-2.08); and for mortality, 48% increase in deaths (OR = 1.48; 95% CI, 1.22-1.80; p < 0.001). Mechanistic pathways for individuals with obesity are presented in depth for factors linked with COVID-19 risk, severity and their potential for diminished therapeutic and prophylactic treatments among these individuals. Individuals with obesity are linked with large significant increases in morbidity and mortality from COVID-19. There are many mechanisms that jointly explain this impact. A major concern is that vaccines will be less effective for the individuals with obesity.