Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: A randomized, double-blind, placebo-controlled phase 1/2 clinical trial.

BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 µg, 40 µg or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 µg and 40 µg SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study.

Clinical and Laboratory Profile of Hospitalized Symptomatic COVID-19 Patients: Case Series Study From the First COVID-19 Center in the UAE.

Introduction: COVID-19 is raising with a second wave threatening many countries. Therefore, it is important to understand COVID-19 characteristics across different countries. Methods: This is a cross-sectional descriptive study of 525 hospitalized symptomatic COVID-19 patients, from the central federal hospital in Dubai-UAE during period of March to August 2020. Results: UAE's COVID-19 patients were relatively young; mean (SD) of the age 49(15) years, 130 (25%) were older than 60 and 4 (<1%) were younger than 18 years old. Majority were male(47; 78%). The mean (SD) BMI was 29 (6) kg/m2. While the source of contracting COVID-19 was not known in 369 (70%) of patients, 29 (6%) reported travel to overseas-country and 127 (24%) reported contact with another COVID-19 case/s. At least one comorbidity was present in 284 (54%) of patients and 241 (46%) had none. The most common comorbidities were diabetes (177; 34%) and hypertension (166; 32%). The mean (SD) of symptoms duration was 6 (3) days. The most common symptoms at hospitalization were fever (340; 65%), cough (296; 56%), and shortness of breath (SOB) (243; 46%). Most of the laboratory values were within normal range, but (184; 35%) of patients had lymphopenia, 43 (8%) had neutrophilia, and 116 (22%) had prolong international normalized ratio (INR), and 317 (60%) had high D-dimer. Chest x ray findings of consolidation was present in 334 (64%) of patients and CT scan ground glass appearance was present in 354 (68%). Acute cardiac injury occurred in 124 (24%), acute kidney injury in 111 (21%), liver injury in 101 (19%), ARDS in 155 (30%), acidosis in 118 (22%), and septic shock in 93 (18%). Consequently, 150 (29%) required ICU admission with 103 (20%) needed mechanical ventilation. Conclusions: The study demonstrated the special profile of COVID-19 in UAE. Patients were young with diabetes and/or hypertension and associated with severe infection as shown by various clinical and laboratory data necessitating ICU admission.

D-dimer, Troponin, and Urea Level at Presentation With COVID-19 can Predict ICU Admission: A Single Centered Study.

Background: Identifying clinical-features or a scoring-system to predict a benefit from hospital admission for patients with COVID-19 can be of great value for the decision-makers in the health sector. We aimed to identify differences in patients' demographic, clinical, laboratory, and radiological findings of COVID-19 positive cases to develop and validate a diagnostic-model predicting who will develop severe-form and who will need critical-care in the future. Methods: In this observational retrospective study, COVID-19 positive cases (total 417) diagnosed in Al Kuwait Hospital, Dubai, UAE were recruited, and their prognosis in terms of admission to the hospital and the need for intensive care was reviewed until their tests turned negative. Patients were classified according to their clinical state into mild, moderate, severe, and critical. We retrieved all the baseline clinical data, laboratory, and radiological results and used them to identify parameters that can predict admission to the intensive care unit (ICU). Results: Patients with ICU admission showed a distinct clinical, demographic as well as laboratory features when compared to patients who did not need ICU admission. This includes the elder age group, male gender, and presence of comorbidities like diabetes and history of hypertension. ROC and Precision-Recall curves showed that among all variables, D dimers (>1.5 mg/dl), Urea (>6.5 mmol/L), and Troponin (>13.5 ng/ml) could positively predict the admission to ICU in patients with COVID-19. On the other hand, decreased Lymphocyte count and albumin can predict admission to ICU in patients with COVID-19 with acceptable sensitivity (59.32, 95% CI [49.89-68.27]) and specificity (79.31, 95% CI [72.53-85.07]). Conclusion: Using these three predictors with their cut of values can identify patients who are at risk of developing critical COVID-19 and might need aggressive intervention earlier in the course of the disease.

The inflammatory biomarkers profile of hospitalized patients with COVID-19 and its association with patient's outcome: A single centered study.

Several reports highlighted the central role of inflammation in the pathogenesis of corona virus disease-19 (COVID-19) disease. Also, the hyper-inflammatory response that is triggered by severe acute respiratory syndrom-Covid-2 (SARS-CoV-2) infection was believed to play an essential role in disease severity and adverse clinical course. For that reason, the classical inflammatory markers were proposed as a possible indicator for COVID-19 severity. However, an extensive analysis of the predictive value of inflammatory biomarkers in large patients' cohorts is still limited and critically needed. In this study we investigated the predictive value of the classical inflammatory biomarkers in a patient cohort consists of 541 COVID-19 patients admitted to Al Kuwait Hospital, Dubai, UAE. A detailed analysis of the association between the essential inflammatory markers and clinical characteristics as well as clinical outcome of the patients were made. In addition, the correlation between those markers and a wide range of laboratory biomarkers and incidence of acute organs injury were investigated. Our results showed a significant elevation of many inflammatory markers including white cell count (WBC) count, neutrophils count, C-reactive protein (CRP), D-Dimer, ferritin, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels in patients with more severe illness. Also, our results highlighted that higher levels of those markers can predict worse patient outcome including the need of ventilation, intensive care unit (ICU) admission, multiple organs dysfunction as well as death. In addition, Our results showed that the presence of lymphopenia and lower absolute lymphocyte count (ALC) at the time of admission were associated with severe to critical COVID-19 illness (P<0.0001), presence of acute respiratory distress syndrome (ARDS) (P<0.0001) and the need for ventilation and ICU admission., Moreover, our results showed a strong association between lower ALC count and multiple organs dysfunction and patient's death (P<0.0001). In conclusion, our results highlighted the possible use of classical inflammatory biomarkers at time of admission as a potential predictive marker for more severe clinical course in COVID-19 patients that might need more aggressive therapeutic approach including the need of ventilators and ICU admission. The presence of such predictive markers might improve patient's stratification and help in the direction of the available resources to patients in need, which in turn help in improving our response to the disease pandemic.

COVID-19 Infection Associated with Psychosis in Hemodialysis Patient.

Hemodialysis is a medical procedure to correct electrolyte imbalance and remove fluids and waste products from the blood of patients with end-stage renal disease. Dialysis patients are immunosuppressed and hence at risk of complications of coronavirus infection. In addition, dialysis for most patients is performed in-center, with therapy offered three times per week for 3.5 hours per session in sites highly exposed to virus contamination. A weak immune system and low cytokine storm explain why COVID-19 may be less severe in dialysis patients as death due to COVID-19 or effects on comorbidities in COVID-19 patients is due to overresponse against the virus by the immune system and cytokine storm. However, during the frequent trips between the dialysis center and home, the risk of coronavirus infection could be high. Moreover, hemodialysis patients constitute a distinct and high-risk group that is often associated with low immunity, decline or loss of the ability to work, substantial economic burden, the inability to fulfill family responsibilities and participate in an active social life, and suffer from various complications such as muscle weakness, pruritus, fatigue, diabetes, hypertension, and restless legs. These factors are associated with lower quality of life and poor clinical outcomes, leading to a higher risk of psychological problems than in the general population. We report a rare case of new-onset psychosis (mostly delirium) following COVID-19 infection in a middle-aged hemodialysis patient with rapid recovery.

Enhanced Expression of Autoantigens During SARS-CoV-2 Viral Infection.

Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset. To validate our in-silico analysis, we measured plasma protein levels of two autoantigens, MPO and PRTN3, in severe and asymptomatic COVID-19. The protein levels of these two autoantigens were significantly upregulated in more severe COVID-19 infections. In conclusion, the immunopathology and severity of COVID-19 could result in transient autoimmune activation. Longitudinal follow-up studies of confirmed cases of COVID-19 could determine the enduring effects of viral infection including development of autoimmune disease.

A single centered study reveals association between liver injury and COVID-19 infection.

BACKGROUND AND AIM: Despite the fact that it has been over a year with the pandemic COVID-19 infection, ongoing research and analysis reveal many complications and comorbidities associated with COVID-19. In this study, we aimed at investigating the clinical and laboratory assessments in COVID-19 patients with and without liver injury. METHODS: Symptomatic 541 COVID-19 positive patients, who were admitted to Al Kuwait Hospital, Dubai, United Arab Emirates (UAE), were recruited in this study. Their data was collected retrospectively, including demographic data, blood tests, symptoms, radiographical assessments, and clinical outcomes of COVID-19. RESULTS: Around 19% of the recruited COVID-19 patients displayed signs of acute liver injury. Also, there was an increase in the percentage of critical, ICU-admitted and mortality rates in COVID-19 cases with liver injury, as well as a higher percentage of septic shock and acute respiratory distress syndrome (ARDS). COVID-19 patients with liver injury had more pronounced bilateral consolidation, lymphopenia and neutrophilia. Additionally, these patients had higher levels of CRP, LDH, procalcitonin, ferritin and D dimer levels. Finally, there was a higher percentage of patients taking various COVID-19 therapies in the COVID-19 patients with liver injury group. CONCLUSION: COVID-19 patients with acute liver injury are at a higher risk for serious outcomes including death.

Higher Temperatures, Higher Solar Radiation, and Less Humidity Is Associated With Poor Clinical and Laboratory Outcomes in COVID-19 Patients.

Background: The COVID-19 pandemic varies between countries, with suggestions that weather might contribute to the transmission mode, disease presentation, severity, and clinical outcomes. Yet the exact link between climate and COVID-19 is still not well-explored. Objectives: This study aimed to evaluate the effect of hot geographical region weather [like United Arab Emirates (UAE)] on COVID-19 clinical profile and outcomes. Temperature, wind speed, cloud cover, precipitation, and other weather-related variables were studied concerning COVID-19 patients outcomes and laboratory results. Methodology: A total of 434 COVID-19 positive patients admitted between January and June 2020, were recruited from Al Kuwait Hospital, Dubai, UAE. Temperature, wind speed, cloud cover, and precipitation rate were retrieved from history+ for the day when COVID-19 patients presented to the hospital. These weather parameters were correlated with COVID-19 clinical and laboratory parameters. Results: Our results showed that patients needed admission in days with higher temperatures, higher solar radiation, and less humidity were associated with higher deaths. This association can be linked to the association of these weather parameters with age at diagnosis; higher C-reactive protein (CRP), neutrophil count, white cell count (WCC), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and lower lymphocyte count, estimated glomerular filtration rate (eGFR), hemoglobin (Hb), Na, and albumin, all of which are considered poor prognostic factors for COVID-19. Conclusion: Our study highlighted the importance of weather-related variables on the dynamics of mortality and clinical outcomes of COVID-19. The hot weather might makes some people, especially those with comorbidities or older ages, develop aggressive inflammation that ends up with complications and mortality.

COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies.

In March 2020, COVID-19 infection caused by SARS-CoV-2 has been declared to be a global pandemic, where its complications, severity and mortality are reported to be due to the released inflammatory cytokines or the so-called cytokine storm. This is quite similar to that observed in the autoimmune and chronic inflammatory rheumatic disease, rheumatoid arthritis (RA). It was hypothesized that RA patients are at a higher risk of acquiring COVID-19; however, recent studies reported that they are not when compared to the rest of the population. In this review, we aim to highlight the mutual pathological features, cytokine profiles and risk factors between COVID-19 and RA. Also, many researchers are currently working to explore therapeutic agents that could aid in the eradication of COVID-19 infection. Due to the similarity between the inflammation status in COVID-19 and RA, many anti-rheumatic drugs such as hydroxychloroquine, tocilizumab, baricitinib and anakinra were proposed to be therapeutic modalities for COVID-19 infection.

Acute cardiac injury is associated with adverse outcomes, including mortality in COVID-19 patients. A single-center experience.

OBJECTIVES: To evaluate acute cardiac injury in COVID-19 patients and its association with adverse outcomes including mortality in the United Arab Emirates (UAE) population. METHODS: A retrospective study conducted between February and June 2020 in Dubai, UAE, for all laboratory-confirmed Coronavirus disease-19 patients. Demographic, clinical, laboratory, radiological, and clinical outcomes were compared between patients with and without acute cardiac injury. RESULTS: During the study period, 203 patients were included, of which, 44 (21.7%) had evidence of acute cardiac injury. Compared with patients without acute cardiac injury, patients with acute cardiac injury were: older, had more shortness of breath, diabetes, hypertension, and more bilateral airspace shadowing on admission chest radiography. These patients also had a higher neutrophil count, C-reactive protein, procalcitonin, ferritin, D-dimers and lactate dehydrogenase but lower lymphocyte count. Regarding outcomes, these patients had higher intensive care admissions; a higher rate of complications including acute kidney and liver injury, acidosis, septic shock, acute respiratory distress syndrome, needed more mechanical ventilation, and had a significantly higher risk of death. CONCLUSION: Acute cardiac injury is common among Coronavirus disease-19 patients. These patients present with higher comorbidities, have high inflammatory markers and have greater risk for in-hospital multi-organ damage, need for mechanical ventilation, and death. Prompt full assessment and intervention are recommended.

Kidney Dysfunction among COVID-19 Patients in the United Arab Emirates.

OBJECTIVES: We sought to determine the estimated glomerular filtration rate (eGFR) among patients with COVID-19 and to examine its correlation with different demographic, clinical, and laboratory characteristics. METHODS: This study examined patients diagnosed with COVID-19 and enrolled at Al Kuwait Hospital, Dubai, UAE. eGFR was calculated using the Modification of Diet in Renal Disease equation, 186 × (SCr mg/dL)-1.154 × (age)-0203 × 0.742 [if female] × 1.212 [if black], and compared for 250 COVID-19 cases and 153 non-COVID-19 controls. Analysis were performed using univariate statistics. RESULTS: The overall mean age of the cohort was 47.2±14.0 years, and 54.6% (n = 220) were males. The results showed that 45.3% of COVID-19 patients had mild-severe renal impairment, as reflected in the eGFR. When compared to patients with normal eGFR, those with severe renal impairment were older (62.5 vs. 40.2 years; p < 0.001), more likely to be male (100% vs. 71.1%; p = 0.016), and have comorbidities (90.9% vs. 40.0%; p < 0.001) including diabetes mellitus (72.7% vs. 21.5%; p < 0.001) and hypertension (72.7% vs. 25.2%; p = 0.003). They were also more likely to be associated with those that had severe (36.4% vs. 25.9%; p < 0.001) and critical (63.6% vs. 16.3%; p < 0.001) COVID-19 infection as well as intensive care unit admission (72.7% vs. 16.3%; p < 0.001). Correlational analysis showed a significant association between renal function indicators and different laboratory markers, including hematological indices and different liver enzymes. CONCLUSIONS: This is the first study to examine the renal function among COVID-19 cases in the Middle East. Nearly half of COVID-19 patients had moderate to severe renal impairment. Diabetes mellitus and hypertension were the most common underlying comorbidities associated with moderate-severe renal function impairment among COVID-19 patients.

Diabetes mellitus as a comorbidity in COVID-19 infection in the United Arab Emirates.

OBJECTIVES: To compare risk factors and clinical outcomes among COVID-19 patients with or without diabetes in the United Arab Emirates (UAE). METHODS: Data of 350 COVID-19 positive patients, admitted to Al Kuwait Hospital in Dubai, UAE, from February to May 2020 was collected retrospectively, including demographic data, clinical symptoms, blood tests, as well as radiographical assessments, and clinical outcomes of COVID-19. The design of the study is a retrospective cohort study. RESULTS: COVID-19 patients with diabetes belong to an older age group, had a higher percentage of male patients, exhibited more lymphopenia and neutrophilia, and higher ferritin levels. Additionally, patients with diabetes presented fever and shortness of breath (SOB), displayed more bilateral airspace consolidation and opacities in their chest x-ray and CT scans, compared to non-diabetics. A higher percentage of critical, ICU-admitted, and death of COVID-19 cases in the diabetic group was also reported. This was along with a concomitant increase in C-reactive protein, procalcitonin, and lactate dehydrogenase levels. CONCLUSIONS: Diabetes is considered a comorbidity as diabetic patients showed more severe COVID-19 symptoms that led to critical clinical outcomes such as ICU admission and death.

Combination of obesity and co-morbidities leads to unfavorable outcomes in COVID-19 patients.

OBJECTIVE: Obesity has been described as a significant independent risk factors of COVID-19. We aimed to study the association between obesity, co-morbidities and clinical outcomes of COVID-19. METHODS: Clinical data from 417 patients were collected retrospectively from the Al Kuwait Hospital, Ministry of Health and Prevention (MOHAP), Dubai, United Arab Emirates, who were admitted between March and June 2020. Patients were divided according to their body mass index (BMI). Various clinical outcomes were examined: presenting symptoms, severity, major co-morbidities, ICU admission, death, ventilation, ARDS, septic shock and laboratory parameters. RESULTS: The average BMI was 29 ± 6.2 kg/m2. BMI alone was not associated with the outcomes examined. However, class II obese patients had more co-morbidities compared to other groups. Hypertension was the most significant co-morbidity associated with obesity. Patients with BMI above the average BMI (29 kg/m2) and presence of underlying co-morbidities showed significant increase in admission to ICU compared to patients below 29 kg/m2 and underlying co-morbidities (21.7% Vs. 9.2%), ARDS development (21.7% Vs. 10.53%), need for ventilation (8.3% Vs. 1.3%), and mortality (10% Vs. 1.3%). CONCLUSIONS: Our data suggests that presence of underlying co-morbidities and high BMI work synergistically to affect the clinical outcomes of COVID-19.

C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis.

Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease - 19 (COVID-19). On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.