Efficacy and Safety of Sinopharm Vaccine for SARS-CoV-2 and breakthrough infections in Iranian Patients with Hemoglobinopathies: A Preliminary Report.

Background: The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to high morbidity and mortality worldwide. Vaccination against SARS-CoV-2 is a leading strategy to change the course of the COVID-19 pandemic. Aims of the study: Our aim was to investigate the efficacy and side effects of the Sinopharm vaccine in patients with hemoglobinopathies in Iran and the frequency of breakthrough infection after a full course of vaccination. Methods: A multicenter cross-sectional study of 434 patients with hemoglobinopathies (303 ß-thalassemia major, 118 ß-thalassemia intermedia, and 13 sickle-thalassemia) were conducted from March to July 2021 in IRAN. All patients have received the first dose of the China Sinopharm vaccine and received the second dose of the vaccine 28 days apar. Antibody testing: Detection of immunity after vaccination was evaluated by commercial enzyme-linked immunosorbent assay (Pishtazteb ELISA commercial kit), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total neutralizing antibody (NAb). Results: The mean age of patients was 35.0 ± 8.5 (from 18 to 70) years, and 55.6% were positive for the antibody. Overall, 48.2% of the studied population had at least one side effect after vaccination. The most frequent side effects were fever and chills, dizziness, and body pain. A total of 90 (20.7%) vaccinated patients developed breakthrough infections after two doses of Sinopharm vaccination. Disease severity was recorded, and it was classified as mild in 77.8%, moderate in 13.6%, and severe in 7.4% of patients. One 28-year-old woman with ß-thalassemia major died eight days after diagnosing a breakthrough SARS-CoV-2 infection. Conclusion: No safety concerns were identified in patients who received two doses of the Sinopharm vaccine. Its efficacy was not optimal due to the lack of effect on new variations of the virus. However, our data show that it seems to be protective against the severity of COVID-19 infection in patients with hemoglobinopathies. The frequency of breakthrough infections after two doses of Sinopharm vaccination supports the evolving dynamic of SARS-CoV-2 variants requiring special challenge since such infection may represent a risk for vulnerable patients.

mRNA-based COVID-19 Vaccines Booster Dose: Benefits, Risks and Coverage.

The number of COVID-19 vaccine-rich countries that have started COVID-19 third-dose booster programs is growing dramatically despite the lack of robust evidence on the effectiveness, safety, and frequency of the required booster doses that makes the individuals/populations immune to COVID -19 infection. Beyond the ethical dilemma, the scarcity of studies on the optimal timing for offering booster doses, eligibility criteria, and if there is any association between premature or delayed administration and the degree of protection against infection. The aim of this mini- review was to collect and analyze published data on this topic in a trial to answer some questions related to the benefits versus the risks of offering frequent boosters of mRNA vaccines for increasing the population immunity against COVID-19 infection considering the current policy of providing SARS-CoV-2 vaccine booster doses in rich countries versus those in relatively poor countries with limited access to vaccination. (www.actabiomedica.it).

Preliminary Data on COVID-19 in Patients with Hemoglobinopathies: A Multicentre ICET-A Study.

OBJECTIVES: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent ß thalassemia major (TM), ß-thalassemia intermedia (TI) and sickle cell disease (SCD). DESIGN: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. MAIN OUTCOME DATA: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. RESULTS: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). CONCLUSIONS: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID- 19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age.

Multisystem inflammatory syndrome in children (MIS-C) related to COVID-19 infection in the state of Qatar: Association with Kawasaki-like Illness.

INTRODUCTION: World Health Organization (WHO) is encouraging reporting of children with Multisystem Inflammatory Syndrome (MIS-C) associated with SARS-CoV-2 infection for better understanding and management of the disease. METHODOLOGY: This retrospective study included the first 15 pediatrics patient with a confirmed diagnosis of MIS-C associated with SARS-CoV-2 infection in the state of Qatar. We studied and analyzed their demographic data, clinical manifestations, laboratory tests, treatment, and outcome. RESULTS: A total of 15 children were studied (mean age 3.5 ± 2.7year). Recent severe acute respiratory syndrome coronavirus 2 infection was identified in all of them (100%). The majority of these patients had 4 or more systems involvement. Nine of the 15 presented with Kawasaki disease - picture and all had gastrointestinal symptoms (vomiting and diarrhea). Five required Pediatrics Intensive Care Unit (PICU) admission. Lab investigations revealed high D-Dimer, hyponatremia, and hypoalbuminemia in all. Low hemoglobin (Hb) , thrombocytopenia, and sterile pyuria occurred in 86.6%, 60% and 75% of them, respectively. Treatment with combined anti-inflammatory medications (intravenous immunoglobulin, corticosteroids) was used in along with immunomodulatory agents (Anakinra) in a selected group of refractory patients. No mortality happened. CONCLUSION: Our young children who presented with MIS-C related to SARS-CoV-2 infection had significantly higher Kawasaki-disease picture compared to other reports. One third of them required PICU admission but no mortality occurred.

Antithrombotic prophylaxis in children and adolescents' patients with SARS-CoV-2 (COVID-19) infection: A practical guidance for clinicians.

Severe coronavirus disease 2019 (COVID-19) is often associated with features of hypercoagulable state which can manifest as venous thromboembolism (VTE) and/or microthrombosis. Given the high risk of VTE in critically ill COVID-19 patients, appropriate VTE prophylaxis seems to be an important part of managing these patients. Although many protocols regarding venous thromboembolism (VTE) prophylaxis or therapeutic (full-dose) anticoagulation have been conducted worldwide, primarily in hospitalised adult patients, details on paediatric patients, if included, are limited or incomplete. The current evidences suggest that anticoagulation therapy with low molecular weight heparins (LMWH) appears to be associated with better prognosis in patients with moderate to severe COVID-19 induced coagulopathies or elevated D-dimer levels.  Our recommendations are intended to offer guidance for anticoagulation prophylaxis and treatment in COVID-19 children and adolescent patients and not intend to supersede the clinician judgement. We are also conscious that several clinical questions deserve further studies and clarifications because this area is rapidly evolving.

The Multifacets of COVID-19 in Adult Patients: A Concise Clinical Review on Pulmonary and Extrapulmonary Manifestations for Healthcare Physicians.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Most people with COVID-19 have a mild to moderate respiratory illness; others experience severe illness, such as COVID-19 pneumonia. The first and most accessible diagnostic information is from symptoms and signs from clinical examination. Infected patients present with a variety of manifestations. Formal diagnosis requires laboratory analysis of nose and throat samples, or imaging tests like CT scans. Emerging data suggest that coronavirus disease 2019 (COVID-19) has extrapulmonary manifestations. Sometimes these extra-respiratory manifestations may be the initial or only symptom of COVID-19, prior to fever or respiratory manifestations. In summary, our concise review shows that there is a wide range of symptoms that can be presented by COVID-19 patients. Extra-respiratory manifestations of SARS-CoV-2 infection have recently been observed in the rapidly increasing number of COVID-19 cases. Considering the broad spectrum of clinical manifestations and the increasing worldwide burden of the disease, there is an urgent need to rapidly scale up the diagnostic capacity to detect COVID-19 and its complications.

Prevalence, Clinical Manifestations, and Biochemical Data of Hypertensive versus Normotensive Symptomatic Patients with COVID-19: A Comparative Study.

BACKGROUND: There is a scarcity of data regarding the effect of hypertension on the clinical presentation and outcome of symptomatic patients with COVID-19 infection in comparison with non-hypertensive patients. AIM OF THE STUDY: To describe the clinical presentation, radiological and hematological data of a cohort of symptomatic COVID-19 positive hypertensive patients (n=50) in comparison with another cohort of normotensive symptomatic COVID-19 positive patients (n=250) diagnosed at the same time and managed in the same health facilities (from Jan 2020 to May 2020). Associated comorbidities were assessed, and the Charlson Comorbidity Index was calculated. The outcomes, including duration of hospitalization, length of ICU stay, duration of mechanical ventilation, and duration of O2 supplementation, were also assessed. RESULTS: The prevalence of hypertension in symptomatic COVID-19 positive patients was 50/300 (16%; the prevalence of hypertension in Qatari adults is ~30%). Hypertensive patients had a higher prevalence of DM, CKD, and cardiac dysfunction compared to normotensive patients (p<0.01).They had a higher Charlson Co-morbidity score (2.3±1.8) compared to the normotensive patients (0.4±0.9) (p<0.01). Clinically and radiologically, hypertensive patients had significantly higher percentage of pneumonia, severe pneumonia, and ARDS versus normotensive patients (p<0.01). CBC and differential WBC did not differ between hypertensive and normotensive patients. Hypertensive patients had significantly higher CRP(58.5±84), compared to normotensive patients (28±59) (p<0.01). Furthermore, a longer duration of hospitalization, intensive care unit (ICU) stay, mechanical ventilation and oxygen therapy versus normotensive patients was also observed. CRP was correlated significantly with the duration of stay in the ICU and the duration for oxygen supplementation (r=0.56 and 0.61, respectively; p<0.01). CONCLUSIONS: Hypertensive patients with COVID-19 had a higher inflammatory response (higher CRP levels), a significant increase of comorbidities, and a more aggressive course of the disease necessitating a higher rate of ICU admission, longer requirement for hospitalization and oxygen use compared to normotensive patients.

Proposed Scoring System for Evaluating Clinico-radiological Severity of COVID- 19 using Plain Chest X- ray (CXR) changes (CO X-RADS): Preliminary results.

BACKGROUND: Plain chest radiograph (CXR), although less sensitive than chest CT, is usually the first-line imaging modality used for patients with symptomatic SARS-CoV-2 infection. The relation between radiological changes in CXR and clinical severity of the disease in symptomatic patients with COVID 19 has not been fully studied and there is no scoring system for the severity of the lung involvement, using the plain CXR. AIM OF THE STUDY: Current COVID-19 radiological literature is dominated by CT and a detailed description CXR appearances in relation to the disease time course is lacking. We propose an easy scoring system (CO X-RADS) to describe the severity of chest involvement in symptomatic COVID 19 patients using CXR and to correlate the radiological changes with the clinical severity of the disease. PATIENTS AND METHODS: The clinical manifestations and CXR findings were recorded in 500 symptomatic COVID-19 positive patients who were admitted to Hamad Medical Corporation (HMC) COVID-19 designated facility Center from January to June 2020. The severity and outcome of the disease included: intensive care unit admission, need for oxygen therapy, mechanical ventilation. and mortality rate. RESULTS: Most of our symptomatic patients (86.8%) had mild and moderate clinical manifestations. The remaining 13.2% had severe manifestations, including: fever, persistent dry cough, shortness of breath, dyspnea, abdominal and generalized body pains. Based on our radiological scoring system (0 to 10) patients were distributed according to their CXR findings into different categories and according to our suggested (CO X-RADS) severity system into five categories (0 to IV). Patients with mild clinical manifestations showed low scoring in CXR (score 0 up to 4) and they represented 72% of our patients. Patients with moderately severe clinical manifestations showed mainly GGO (scoring 5 and 6) and represented about 14.8% of patients. Patients presented with severe clinical manifestations had obvious lung consolidations at the time of presentation with CXR scoring system ≥ 7 and represented about 13.2% of patients. CONCLUSION: We proposed a simple CXR reporting scoring system (CO X-RADS) to categorize COVID-19 patients according to their radiological severity. This radiological score was correlated well with the clinical severity score of patients. We encourage other centers to test this scoring system in correlation with the clinical status of patients.

Clinical Outcome of Eosinophilia in Patients with COVID-19: A Controlled Study.

BACKGROUND: Eosinophils can be considered as multifunctional leukocytes that contribute to various physiological and pathological processes depending on their location and activation status. There are emerging eosinophil-related considerations concerning COVID-19. Variable eosinophil counts have been reported during COVID-19. Whether these changes are related to the primary disease process or due to immunomodulation induced by the treatment has not yet been elucidated. AIM OF THE STUDY: To describe changes in the differential leukocyte counts including eosinophils, in a cohort of symptomatic patients with confirmed COVID-19 and to correlate these changes, if any, with the severity of the disease. PATIENTS AND METHODS: We recorded the clinical data, lab findings, including inflammatory markers and leukocyte and differential count, course of the disease and severity score in 314 confirmed symptomatic cases of COVID-19. RESULTS: Laboratory tests revealed that 28.7 % (n =86) had mild eosinophilia (eosinophil count > 500 <1,500/µL). Thirty-four patients (11.3%) had elevated absolute neutrophil count (ANC) (>8,000/µL), and 7 (2.3%) had decreased ANC (< 1,500/µl). Seven patients (2.3%) had lymphopenia (<1,000/µL) and 4 (4.67%) had lymphocytosis (> 4,000/µL). C-reactive protein (CRP) was elevated in 83 patients (27.6%). Chest X-Ray changes included: increased broncho vascular markings (38%), ground-glass opacity (GGO) pneumonitis (19.3%), lobar consolidation (5%), bronchopneumonia (8.3%), nodular opacity (1%), acute respiratory distress syndrome (ARDS) (2.3%), pleural effusion (1.0%) and other atypical findings (6.6%). Patients with eosinophilia had significantly lower CRP, and lower % of GGO, lobar and bronchopneumonia and ARDS in their chest images compared to patients without eosinophilia (p: <0.05). They also had a lower requirement for a hospital stay, ICU admission, mechanical ventilation, and oxygen supplementation versus patients without eosinophilia (p: <0.05). The eosinophils count was correlated negatively with the duration of ICU admission, mechanical ventilation, and oxygen supplementation and with CRP level (r: - 0.34, -0.32, -0.61 and - 0.39, respectively) (p: < 0.01). CONCLUSIONS: Our study reports a relatively high prevalence of eosinophilia in symptomatic COVID-19 positive patients. Patients with eosinophilia had a lower level of CRP, milder clinical course and better disease outcomes compared to those without eosinophilia. Our findings indicated a protective role of eosinophils in mitigating the severity of inflammatory diseases through an inhibitory mechanism, as evidenced by lower CRP. This protective role of eosinophils needs to be validated by further prospective studies.

Prevalence, clinical manifestations, and biochemical data of type 2 diabetes mellitus versus nondiabetic symptomatic patients with COVID-19: A comparative study.

BACKGROUND: There is a scarcity of data regarding the effect of Type 2 diabetes mellitus (T2DM) and associated comorbidities on the clinical presentation and outcome of symptomatic patients with -COVID-19 infection in comparison with non-diabetic patients. AIM OF THE STUDY: We described and compared the clinical presentation and radiological and hematological data of a cohort of symptomatic COVID19 positive T2DM diabetic patients (n = 59) versus another cohort of non-diabetic symptomatic COVID19 positive patients (n =244) diagnosed at the same time from January 2020 to May 2020. Associated comorbidities were -assessed, and the Charlson Comorbidity Index was calculated. The outcomes including duration of hospitalization, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation, and duration of O2 -supplementation were assessed. RESULTS: Prevalence of T2DM in symptomatic COVID19 positive patients was 59/303 (=19.5%).  Diabetic patients had higher prevalence of hypertension, chronic kidney disease (CKD) and cardiac dysfunction [coronary heart disease (CHD)], and congestive heart failure (CHF). Charlson Comorbidity score was significantly higher in the T2DM patients (2.4± 1.6) versus the non-diabetic -patients (0.28 ± 0.8; p: < 0.001). Clinically and radiologically, T2DM patients had significantly higher percentage of pneumonia, severe pneumonia and ARDS versus the non-diabetic patients. Hematologically, diabetic patients had significantly higher C-reactive protein (CRP), higher absolute neutrophilic count (ANC) and lower counts of lymphocytes and eosinophils compared to non-diabetic patients. They had significantly higher systolic and diastolic blood pressures, longer duration of hospitalization, ICU stay, mechanical ventilation and oxygen therapy. CRP was correlated significantly with the duration of stay in the ICU and the duration for oxygen supplementation (r = 0.37 and 0.42 respectively; p: <0.01). CONCLUSIONS: T2DM patients showed higher inflammatory response to COVID 19 with higher absolute neutrophilic count (ANC) and CRP with lower lymphocytic and eosinophilic counts. Diabetic patients had more comorbidities and more aggressive course of the disease with higher rate of ICU admission and longer need for hospitalization and oxygen use.

Congenital Bleeding Disorders amid the COVID-19 pandemic: Open questions and recommendations.

This article reviews the current knowledges of congenital bleeding disorders (CBD) amid the COVID-19 pandemic. It appears that CBD is not associated with higher risk of getting COVID-19 and so the prevalence of COVID-19 among them seems not higher compared to the general population. In absence of specific therapeutic recommendations, it is essential to make a correct assessment of the risk of haemorrhage/thrombosis. Based on expert opinion, strategies for outpatient management include adherence to prescribed regimens, telemedicine, and communication about COVID-19 in patients with CBD. More data should be also collected to better characterize the impact of COVID-19 on patients with CBD. The current findings encourage further studies to determine the prevalence of SARS-CoV2 infection in CBD patients to understand more fully the burden of this novel pathogen and to develop adequate preventive measures against this infection.

Prevalence and severity of Coronavirus disease 2019 (COVID-19) in Transfusion Dependent and Non-Transfusion Dependent ß-thalassemia patients and effects of associated comorbidities: an Iranian nationwide study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreak is a global and challenging disease that is accompany with mortality and morbidity. AIM OF STUDY: We evaluated the prevalence and the impact of comorbidities in thalassemia Iranian patients affected by COVID-19.  Methods: A multicenter, retrospective, cross-sectional study was conducted across all comprehensive thalassemia centers in Iran, from January to June 15th, 2020. RESULTS: Forty-three confirmed COVID-19 thalassemia patients (32 TDT, and 11 NTDT) were detected. The mean age of patients was 35.3 ± 11.5 years (range 9 - 67); 21 females and 22 males. Overall, 78.1% of TDT and 90.9% of NTDT patients were complicated with at least one comorbidity (P: 0.656). The overall mortality rate of thalassemia patients with COVID-19 was 18.6% while 27.3% was in NTDT patients compared to 15.6% in TDT patients (P:0.401). The dead group had a non-significant higher frequency of endocrinopathies compared to the recovered group (62.5% versus 45.7% P:0.457). Ten female thalassemia patients with positive COVID-19 had hypogonadism, six patients were receiving hormone replacement therapy and all of them recovered (zero death) compared to two deaths from 4 patients who were not receiving hormone replacement therapy (P:0.133). Furthermore, the prevalence of COVID-19 in NTDT patients was significantly higher than the general population (45 per 10,000 versus 22.29 per 10,000 respectively, P:0.018) while the prevalence of TDT was almost similar to the normal population (P:0.539). The mortality rate of COVID-19 was 4.71% in the normal Iranian population compared to 18.6% in ß-thalassemias (P: <0.001) at the same date. CONCLUSIONS: It is important to acknowledge that ß-thalassemia patients, especially young adults/adults, have a chronic condition which may contribute to increase susceptibility to SARS-CoV-2 infection. A higher susceptibility to the infection was observed in patients with NTDT and in untreated hypogonadal female thalassemic patients. However, to confirm these data, more accurate designed studies are needed.

Newly-onset type 1 diabetes mellitus precipitated by COVID-19 in an 8-month-old infant.

Type 1 diabetes mellitus (T1DM) is rare in infants and toddlers and is usually associated with a relatively high mortality when complicated with diabetic ketoacidosis (DKA). In infants, the classical symptoms of DKA are atypical and therefore many infants with DKA are mistreated for infections. We report a case of DKA precipitated by COVID-19 in an 8-month-old infant with newly diagnosed diabetes mellitus. This case is reported in view of its rarity and originality. The relation between T1DM and COVID19 infection is discussed.

A comprehensive update of ICET-A Network on COVID-19 in thalassemias: what we know and where we stand.

A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among  ß-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of  COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations.

Foreword: Research in times of pandemic COVID-19

Editorial.

Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics

The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress;a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults;however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.