Influenza prevalence and vaccine efficacy among diabetic patients in Qatar.

Seasonal influenza viruses may lead to severe illness and mortality in patients with comorbidities, including Diabetes Mellitus (DM). Vaccination against influenza in DM patients may reduce influenza incidence and severity. Before the emergence of the COVID-19 pandemic, influenza infections were the most prevalent respiratory infections in Qatar. Still, reports about influenza prevalence and vaccine efficacy in DM patients have not been reported. This study aimed to analyze influenza prevalence among other respiratory infections and assess influenza vaccine efficacy in DM patients in Qatar. Statistical analysis was performed on data obtained from Hamad Medical Corporation (HMC) database for patients that visited the emergency department (ED) with respiratory-like illnesses. The analysis was done for the period between January 2016 to December 2018. Among 17,525 patients who visited HMC-ED with clinical symptoms of respiratory infections, 2611(14.9%) were reported to have DM. Among DM patients, influenza was the most prevalent respiratory pathogen at 48.9%. Influenza virus A (IVA) was the most circulating type, contributing to 38.4%, followed by IVB contributing to 10.4% of total respiratory infections. Among the typed IVA-positive cases, 33.4% were H1N1, and 7.7% were H3N2. A significant decrease in influenza infections was reported in vaccinated DM patients (14.5%) when compared to non-vaccinated patients (18.9%) (p-value = 0.006). However, there was no significant relaxation in the clinical symptoms among vaccinated DM patients compared to their non-vaccinated counterparts. In conclusion, influenza was the most common etiology for respiratory viral infection among diabetic patients at the leading healthcare provider in Qatar. Although vaccination reduced the incidence rate among DM patients, it was less effective in preventing symptoms. Further studies on a larger cohort and for a more extended period are required to investigate influenza prevalence and vaccine efficacy among DM patients.

Antibody Response to SARS-CoV-2: A Cohort Study in Qatar's Primary Care Settings.

BACKGROUND: Globally, countries are rolling out Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quarantine policies and vaccination programs. Research studies are needed in helping understand the likelihood of acquired immunity to reinfection and identify priority groups for vaccination to inform them. This study aimed to assess period prevalence and longitudinal changes in antibody levels after SARS-CoV-2 infection in Qatari primary care settings. METHODS: A cohort study design with 2 data collection phases was undertaken-Phase 1 (conducted in July 2020) and Phase 2 (conducted in October 2020). A stratified random sampling technique by age, gender and nationality was utilized to identify the study sample. The total sample size required for the study was estimated to be 2102. Participants were invited to an appointment where they were administered a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin G immunoassay tests. RESULTS: A total of 943 individuals participated in both Phase 1 and Phase 2. In this cohort, seroprevalence of SARS-CoV-2 was found to be 12% (N = 113) in Phase 1 and 17.2% (N = 162) in Phase 2. Of the 113 participants who were seropositive in Phase 1, 38.1% (CI 29.5-47.2%, N = 43) had a reduction, 54.9% (CI 45.7-63.8%, N = 62) had no change, and 7.1% (CI 3.4-12.9%, N = 8) had an increase in IgG titer in Phase 2. All (N = 18) participants aged 10 to 17 years retained their antibodies. The proportion of men who retained their antibodies was slightly higher compared to women-92.5% (N = 74) and 87.9% (N = 29) respectively. Similarly, symptomatic individuals (97.8%; N = 45) had a higher antibody retention compared with asymptomatic individuals (86.4%; N = 57). CONCLUSIONS: This study provides preliminary information on the longitudinal changes in antibody levels after SARS-CoV-2 infection. These findings will help inform quarantine policies and vaccination programs.

Identification of potential natural inhibitors of the receptor-binding domain of the SARS-CoV-2 spike protein using a computational docking approach.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only zoonotic-origin CoV to reach the pandemic stage, to which neither an effective vaccine nor a specific therapy is available. The spike glycoprotein harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. This study aimed to identify novel inhibitors that target the spike protein's RBD domain through computational screening of chemical and natural compounds. Method: The spike protein was modeled from the recently reported electron microscopy protein structure (PDB ID: 6VSB) and the previously described SARS-CoV protein structure (PDB ID: 6ACD and 6ACJ). Virtual lab bench CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n = 22), natural antiviral drugs (n = 100), and natural compounds (n = 35032). Quantitative Structure-Activity Relationship (QSAR) studies were also performed to determine the leading binders known for their antiviral activity. Results: Among the drugs currently used to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of four H-bonds, with a binding affinity of - 36.66 kcal/mol and a minimum interaction energy of - 6.63 kcal/mol. In an evaluation of antiviral compounds, fosamprenavir and abacavir showed effective binding of five H-bonds, with an average binding affinity of - 18.75 kcal.mol- 1 and minimum interaction energy of - 3.57 kcal/mol. Furthermore, screening of 100 natural antiviral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, epigallocatechin gallate, and theaflavin (average binding affinity of - 49.88 kcal/mol and minimum interaction energy of - 4.35 kcal/mol). Additionally, the study reports a list of 25 natural compounds that showed effective binding with an improved average binding affinity of - 51.46 kcal/mol. Conclusions: Using computational screening, we identified potential SARS-CoV-2 S glycoprotein inhibitors that bind to the RBD region. Using structure-based design and combination-based drug therapy, the identified molecules could be used to generate anti-SARS-CoV-2 drug candidates.

Pandemic COVID-19 caused by SARS-CoV-2: genetic structure, vaccination, and therapeutic approaches.

We give a summary of SARS-genetic CoV-2's structure and evolution, as well as current attempts to develop efficient vaccine and treatment methods for SARS-CoV-2 infection, in this article. Most therapeutic strategies are based on repurposing of existing therapeutic agents used against various virus infections and focused mainly on inhibition of the virus replication cycle, enhancement of innate immunity, and alleviation of CRS caused by COVID-19. Currently, more than 100 clinical trials on COVID-19 aim to provide robust evidence on the efficacy of the currently available anti-SARS-CoV-2 antiviral substances, such as the nucleotide analogue remdesivir, the antimalarial drug chloroquine, and drugs directed against docking of SARS-CoV-2 to the membrane-associated angiotensin-converting enzyme 2 (ACE2) such as transmembrane protease serine 2 (TMPRSS2). The current vaccination campaign is ongoing worldwide using different types of vaccines such as Pfizer-BioNTech and Moderna, Johnson & Johnson, Oxford-AstraZeneca, Novavax, and others with efficacy ranging from 72-95%. In March 2021 Germany limited the use of the Oxford-AstraZeneca COVID-19 vaccine to people 60 years of age and older due to concerns that it may be causing blood clots. Further study and more data are needed to confirm the safety of different available vaccines.

Epidemiology of SARS-CoV2 in Qatar's primary care population aged 10 years and above.

BACKGROUND: There is an urgent need to elucidate the epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and characterize its potential impact. Investing in characterising the SARS-CoV2 will help plan and improve the response to the pandemic. Furthermore, it will help identify the most efficient ways of managing the pandemic, avoiding public health policies and interventions that may be unduly restrictive of normal activity or unnecessarily costly. This paper describes the design and reports findings of a population based epidemiological study undertaken to characterise SARS-CoV2 in Qatar using limited resources in a timely manner. METHODS: Asymptomatic individuals ≥10 years registered with Qatar's publicly funded primary health provider were eligible. A stratified random sampling technique was utilized to identify the study sample. Participants were invited to an appointment where they completed a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin M and G immunoassay tests. Data collected were analyzed to calculate point and period prevalence by sociodemographic, lifestyle and clinical characteristics. RESULTS: Of 18,918 individuals invited for the study, 2084 participated (response rate 10.8%). The overall point prevalence and period prevalence were estimated to be 1.6% (95% CI 1.1-2.2) and 14.6% (95% CI 13.1-16.2) respectively. Period prevalence of SARS-CoV2 infection was not considerably different across age groups (9.7-19.8%). It was higher in males compared to females (16.2 and 12.7% respectively). A significant variation was observed by nationality (7.1 to 22.2%) and municipalities (6.9-35.3%). CONCLUSIONS: The study provides an example of a methodologically robust approach that can be undertaken in a timely manner with limited resources. It reports much-needed epidemiological data about the spread of SARS-CoV2. Given the low prevalence rates, majority of the population in Qatar remains susceptible. Enhanced surveillance must continue to be in place, particularly due to the large number of asymptomatic cases observed. Robust contact tracing and social distancing measures are key to prevent future outbreaks.

Analytic comparison between three high-throughput commercial SARS-CoV-2 antibody assays reveals minor discrepancies in a high-incidence population.

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 "ever" (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1-47.8%), 40.6% (95% CI 35.9-45.5%), and 42.4% (95% CI 37.6-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2-95.7%, 89.3-92.8%, and 93.8-97.8%, respectively; Cohen's kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

SARS-CoV-2 (COVID-19) PCR cycle threshold: can it help in the timing of urgent cardiac surgery?

BACKGROUND: The COVID-19 pandemic has resulted in a significant reduction in urgent cardiac surgery due to concerns about safety for both patients and care givers. The timing of safe cardiac surgery is yet to be clarified in the setting of COVID-19 diagnosis. METHODS: Due to the urgency of the cardiac conditions on presentation, we have operated on four patients who exhibited the spectrum of COVID-19 disease from asymptomatic to severe COVID-19 pneumonia. With the evolving knowledge about SARS-CoV-2 and its genetic determinants as well as the cycle threshold levels obtained from real-time reverse transcription polymerase chain reaction, we have attempted to develop a strategy to deal with these patients. RESULTS: All four patients underwent urgent cardiac surgery following a thorough evaluation and multidisciplinary team approach with guidance based on the virus cycle threshold values obtained by reverse transcription polymerase chain reaction. CONCLUSION: We have shown that, with thorough preparations, consideration of the significance of the cycle threshold obtained on reverse transcription polymerase chain reaction and meticulous timing, COVID-19 diagnosed patients may undergo open heart surgery safely.

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies.

OBJECTIVES: To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. METHODS: Seventy negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptom onset: ≤7, 8-14 and >14 days) were used to compare the sensitivity, specificity, agreement, and positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. RESULTS: Lionex showed the highest specificity (98.6%; 95% CI 92.3-99.8), followed by EDI and Dia.Pro (97.1%; 95% CI 90.2-99.2), NovaTec (85.7%; 95% CI 75.7-92.1), then AnshLabs (75.7%; 95% CI 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG-positive sample, except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptom onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95% CI 72.7-95.2) and 86.4% (95% CI 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen's kappa was as follows: Lionex (0.89) > NovaTec (0.70) > Dia.Pro (0.69) > AnshLabs (0.63) > EDI (0.55). CONCLUSION: The Lionex and NovaLisa IgG ELISA kits, demonstrated the best overall performance.

Immune Modulatory Effects of Vitamin D on Viral Infections

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D"s antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.