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Please note: These are preprints and have not been peer reviewed. Data may be preliminary.
Spike Proteins of SARS –CoV-2: a detailed perspective on structure, receptor binding,...
Hamid Mukhtar
Zinnia Shah

Hamid Mukhtar

and 4 more

January 31, 2024
Spike proteins are heavily glycosylated, small protrusions located on the envelops of coronavirus. These proteins are the characteristic morphological features of coronavirus that give the virus family its name, and are alone responsible for the virulence, pathogenicity, and evolving tropism of these viruses. SARS-CoV-2 shows higher affinity towards its target, ACE-2 receptors in human subjects. This affinity is the result of mutations in its spike protein gene – as revealed through genomic sequencing. Being central to the viral structure, SARS-CoV-2 spike proteins and their receptor binding domains are the preferred platforms for vaccine development. The administration of neutralizing monoclonal antibodies is also being employed along with vaccines to accelerate viral shedding. Various expression and purification strategies are discussed in the paper to provide an updated overview of the SARS-CoV-2 therapeutic landscape. The development of antibody-dependent enhancement (ADE) is still a possible risk linked to the newly developed vaccines and needs to be studied. These challenges demand further research and an innovative approach to expand the therapeutic utility of coronavirus spike proteins.
Association Between Presence of Bacillus Calmette-Guerin Vaccine Scar and Coronavirus...
Buket Caliskaner Ozturk
Ilgim Vardaloglu

Buket Caliskaner Ozturk

and 10 more

January 31, 2024
Objective: Bacillus Calmette-Guerin (BCG) vaccine is administered for protection against tuberculosis and may also have beneficial effects against some viral respiratory tract infections. The low incidence and mortality of coronavirus disease (COVID-19) in countries that have BCG vaccination program is impressive, and some studies have shared contradictory results. In this study, it was aimed to investigate the relationship between BCG vaccination which is confirmed by BCG scar, and the frequency and course of COVID-19. Methods: Among 490 patients who applied to the outpatient clinic for Pulmonary and Enfectious Diseases between March 2021 and June 2021, 400 patients who accepted to participate in the study were included. After the consent of patients; age, gender, body mass index, comorbidities, smoking, history and the progress of COVID-19 of these patients were investigated; presence and number of BCG scar were recorded by physician. Data from groups with and without COVID-19 history were compared. Results: Of the 400 patients 228 (57%) were female. Mean age was 39.65 ± 13.53. 188 (47%) patients had a history of COVID-19. There was no relation between presence and number of the BCG scar and COVID-19 related hospitalization and intensive care unit admission. When groups with and without COVID-19 history compared, no statistically significant difference was found with the presence and number of BCG scars (p>0,05). Conclusion: No association was found between the presence or number of BCG scars and the frequency and course of COVID-19 in individuals with BCG vaccination history confirmed by the presence of BCG vaccine scars.
Transaminitis as a predictor of poor clinical outcomes in pregnant patients infected...
Julia Youssef
Sarah Weingarten

Julia Youssef

and 4 more

January 31, 2024
Objective: The objective of this study is to identify the effects of Coronavirus Disease 2019 (COVID-19) on liver enzymes in pregnant patients and to determine the significance of transaminitis as a predictor of worse clinical outcomes. Design: Case series. Setting: Tertiary care medical center. Population: 31 pregnant patients with a positive COVID-19 polymerase chain reaction (PCR) test and 20 infants who presented during March 25, 2020, to May 26, 2020. Methods: Maternal and neonatal outcomes were compared between patients with transaminitis and without transaminitis using one tailed Mann-Whitney test for nonparametric data and the fisher’s exact test for categorical data. Main outcome measures: Worse maternal outcomes between the groups were defined as need for intubation, oxygen supplementation, intensive care unit (ICU) admission, maternal death, and length of hospital stay. Results: Of the 31 patients with COVID-19, 10/29 (34.5%) were found to have transaminitis. The patients with transaminitis had increased oxygen requirements, increased rate of intubation and ICU admissions. Neonatal outcomes in patients with transaminitis included earlier gestational age at delivery and lower birth weights, but neither were statistically significant. Conclusion: Our study revealed that patients with COVID-19 and concomitant transaminitis had worse clinical outcomes in the mother when compared to those without transaminitis. Further studies should be conducted to explore this link between abnormal liver studies and poor outcomes in pregnant patients diagnosed with COVID-19. Keywords: Coronavirus, COVID-19, transaminitis, pregnancy Tweetable abstract: Pregnant patients with COVID-19 and transaminitis had worse outcomes than ones without transaminitis.
Allergic reactions to the Ad26.COV2.S Vaccine in South Africa
Jonny PETER
Cascia Day

Jonny PETER

and 12 more

January 31, 2024
Abstract ( n=254/250 words)   Background: The Janssen-Ad26.COV2.S vaccine is authorised for use in several countries with more than 30 million doses administered. Mild and severe allergic adverse events following immunisation(AEFI) have been reported. The aim of this report is to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. Methods: A single-dose of the Ad26.COV2.S vaccine was administered to 477234 South African Healthcare Workers between 17 February and 17 May 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy”. Anaphylaxis adjudication was performed using the Brighton Collaboration (BCC) and NIAID case definitions.  Results: A large cohort of South African healthcare workers received the Ad26.COV2.S vaccination. Only 250(0.052%) patients reported any allergic-type reaction(less than 1 in 2000), with four cases of adjudicated anaphylaxis (BCC level 1, n=3)(prevalence of 8.4 per million doses). All anaphylaxis cases had a prior history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest non-anaphylatic reactions and included: self-limiting, transient/localised rashes requiring no healthcare contact(n=91); or isolated urticaria and/or angioedema[n=70 median  onset 48(IQR 11.5-120) hours post vaccination] that necessitated healthcare contact(81%), antihistamine(63%), and/or systemic/topical corticosteroid(16%). All immediate (including adjudicated anaphylaxis) and the majority of delayed AEFI(65/69) cases resolved completely.   Conclusions: Allergic AEFI are rare following a single-dose of Ad26.COV with complete resolution in  all cases of anaphylaxis. Though rare, isolated, delayed onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.   Keywords: allergic reaction, anaphylaxis, COVID19 adenovirus vaccine; Janssen-Ad26.COV2.S vaccine, urticaria
Assessment of SARS-CoV-2 immunity in convalescent children and adolescents
Patrick Ip
Hing Wai Tsang

Patrick Ip

and 19 more

January 31, 2024
Background: Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Method: Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. Results: SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of recovery time. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, whereas higher level of CD8+ T cells in children aged ≥12 years, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Conclusion: Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.
Identification of Promising SARS-CoV-2 Main Protease (Mpro) and Spike Protein Inhibit...
Sukanth Kumar Enmozhi
Kavitha Raja

Sukanth Kumar Enmozhi

and 8 more

January 31, 2024
Coronaviruses infect lungs leading to death due to asphyxiation. SARS-CoV-2 is treated by targeting symptoms, repurposing drugs and plasma therapy. Several synthetic drugs are being prescribed that cause major side effects in liver, kidney and heart. Therefore new compounds with low toxicity must be investigated. We have identified antiviral compounds like Eritadenine, Gallic Acid, Ergosterol Peroxide and Pleuran from various edible mushrooms such as Lentinula edodes, Agaricus bisporus, Pleutorus ostreatus and Hericium erinaceus with evidence of literature review. The docking and simulation studies with the targets of SARS-CoV-2 such as Main Protease (M Pro) and Spike Protein were highly successful. In silico ADMET studies further proved that these compounds are druggable with low toxicity. These compounds have potential to prevent the cellular entry to prohibit assembly of new viruses inside the cell. But further studies are required to substantiate their bioactivity claim by in vitro and in vivo assay methods.
The Role of Serum Albumin and Blood Urea Nitrogen to Serum Albumin Ratio in Predictio...
Toktam Alirezaei
Saeede Hooshmand

Toktam Alirezaei

and 5 more

January 31, 2024
Background: Considering the role of higher blood urea nitrogen and lower serum albumin (SA) levels in deceased COVID-19 patients, increased blood urea nitrogen to SA (B/A) ratio may help to determine those at higher risk of becoming critically ill. This study evaluated the association of SA level and B/A ratio with disease severity and 30–day mortality and also their predictive value for disease severity in COVID–19 patients. Methods: 433 adult patients with COVID–19, admitted to a referral medical center in Tehran, Iran, from February to May 2020 were included. The laboratory markers were measured on admission. Disease severity was categorized into mild disease, severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock. The mortality was followed up for thirty days after admission. Results: Thirty–day mortality rate was 27.25%. The frequency of mild, severe pneumonia, ARDS, sepsis, and septic shock was 30.72%, 36.95%, 24.02%, 6.00%, and 2.31%, respectively. Mean B/A ratio was different among different disease severities. The odds of thirty-day mortality increased by 16% by each unit increase in B/A ratio and decreased by 57% by each unit increase in SA level. B/A ratio had the AUC of 0.45 for disease severity prediction with 71% sensitivity and 22% specificity. Conclusion: The results showed that B/A ratio and SA levels are associated with mortality in COVID–19 patient, while they had low predictive value for disease severity. High B/A ratio is, additionally, associated with disease severity. Therefore, we suggest to use this marker for clinical assessment of patients with COVID–19.
Physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling as a too...
Teerachat Saeheng
Juntra Karbwang

Teerachat Saeheng

and 2 more

January 31, 2024
Background and Purpose: Ritonavir-boosted lopinavir and chloroquine were withdrawn for COVID-19 treatment according to WHO recommendation. However, lopinavir is still being used for COVID-19 treatment in a clinical practice guideline without supportive evidence. We demonstrated the utility of physiologically-based pharmacokinetic (PBPK)/pharmacodynamic (PD) models to support clinical use of lopinavir and the withdrawal of chloroquine for COVID-19 treatment. Experimental approach: The developed whole-body PBPK models were validated against clinical data. Model validation was performed using acceptable methods. The inhibitory effect (%E) was calculated to demonstrate drug efficacy. The recommended drug regimen for COVID-19 was the combination of 400/100 mg lopinavir/ritonavir given twice daily and 300 mg base chloroquine given twice daily for 14 days. Key Results: This study successfully developed whole-body PBPK models (AAFEs of 1.2-fold). For patients with a 70 kg body weight, %E for chloroquine in epithelial lining fluid (ELF) and bronchial epithelial cells (BEC) were about 2% and 12%, respectively. The corresponding values for lopinavir were 66% and 87.4%, respectively. With the increased body weight to 90 kg, %E for lopinavir in BEC dramatically dropped to lower than 60%, while that in ELF was slightly decreased (86.87%). Conclusion and Implications: The results support the decision of withdrawing chloroquine and using lopinavir in asymptomatic (with positive antigen kit test) or mild COVID-19 cases. In addition, results support the administration of antiviral drugs within the ten days of infection to prevent treatment failure.
A novel comprehensive program combined optimal medical treatment and lifestyle for ty...
Chunsong Hu
Tengiz Tkebuchava

Chunsong Hu

and 2 more

October 26, 2021
This article introduces briefly current status in managing type 2 diabetes (T2D) and an updated classical standardized comprehensive program which combines optimal medical treatment (OMT) with lifestyle modification, that is, intervention of RT-ABCDEFG (iRT-ABCDEFG) for control and prevention of T2D, and discusses its advantages and prospects. Here, G means goals; F means follow-up; E means examination; D means disease & risk factors control; C means changing unhealthy “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] lifestyle & Chinese medicine or control the source of infection & cutting genetic or spreading pathways during the COVID-19 pandemic; B means biohazard control; And A means antagonistic treatment, such as optimal anti-diabetic agents, the glucagon-like peptide-1 receptor (GLPR) agonists, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, and the ultralong-acting, once-daily basal insulin. As a novel strategy for Intervention of diabetes, this program can be used as a Reverse, Right, and Routine Treatment in clinical practice. Moreover, the vital goals which include less major adverse cardiocerebrovascular events (MACCE) and diabetic complications, less medical costs, longer life expectancy, lower morbidity and mortality, and higher quality of life, will be realized by consistently practicing this program due to early diagnosis, OMT, and overall prevention. Whatever, this program is very helpful to manage or self-manage T2D and improve its outcomes since it highly links to cardiovascular disease (CVD), stroke, cancer, and other MACCEs.
Fractional system for the Study of Covid-19 in Latin America
Anderson Quintero
Hasbleidy  Parra Méndez

Anderson Quintero

and 3 more

January 31, 2024
The Covid-19 Pandemic has impacted all Latin American countries, which has become worse by having fragmented health systems and deep social inequalities, it is noteworthy that public policies are formulated based on general economic principles such as the law of dynamic equilibrium, assuming that all the processes that determine the socioeconomic evolution flow smoothly and continuously, taking out of consideration the occurrence of contingencies and emergent events that force all social action levels to adjust their plans and strategies, for which it is necessary to evaluate the impacts that this pandemic has caused in Latin American countries (Argentina, Brazil, Chile, and Colombia), which allow us to know the evolution of the disease in these countries. The objectives of this article are: Provide evidence that fractional models are easily adaptable to the evolution of the virus in populations from different socioeconomic contexts; Know the behavior of the disease in the study countries from the parameters of the best approximation of the model in contrast with the real data of the infection; For the modeling, systems of differential equations will be applied and for the calculation of the optimal coefficients, the method of Markov Monte Carlo chains (MCMC) will be implemented to estimate model parameters.
Estimating the Repercussions of Covid-19 in Pregnancy and Neonatal Complications
Sayali Patnekar

Sayali Patnekar

January 31, 2024
The chief goal of this article was to do a literature review on a sensitive topic that has affected many people worldwide. COVID-19 was declared as a pandemic as it crossed all the boundaries. The effects of COVID-19 infection were seen globally, affecting every individual of the society. But here, the main intention was to study the impact of COVID-19 illness in pregnancy since pregnancy is an immune-compromised condition. The effects that had on pregnancy were preterm labor, premature birth, pre-eclampsia, and miscarriages. The other objective was to study the neonatal outcomes, which showed fetal respiratory distress syndrome, Prolonged QT.
WHAT THE COVID-19 PANDEMIC TAUGHT US IN CHILDREN
MUSTAFA  GENÇELİ
Ozge Metin Akcan

MUSTAFA GENÇELİ

and 6 more

January 31, 2024
Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.
SARS-CoV-2 and the role of vertical transmission from infected pregnant women to thei...
Annette Plüddemann
Elizabeth Spencer

Annette Plüddemann

and 8 more

January 31, 2024
Background Vertical transmission of SARS-CoV-2 has been reported but appears uncommon. Objectives This study systematically reviewed the evidence on vertical transmission of SARS-CoV-2 from pregnant women to their neonates. Search strategy Literature searches in WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, search date to 20 December 2020; no language restrictions. Selection criteria Studies of any design reporting transmission. Data collection and analysis Two reviewers independently assessed article eligibility and extracted data. Results were reported descriptively; no meta-analyses were possible. Main results 106 studies were included: 40 reviews and 66 primary studies, most conducted in hospitals. 32 case reports were assessed as high risk of bias, due to the study design; across the 34 remaining primary studies, risk of bias was low to moderate. Sixteen case reports described vertical transmission. In cohort studies and case series, 65/2391 (2.7%) neonates born to mothers with a COVID-19 diagnosis tested positive for SARS-CoV-2 within 24 hours of birth; the proportion of positive neonates ranged from 0% to 22%. Twenty studies reported no vertical transmission. Maternal symptomatology and mode of delivery were not correlated with vertical transmission. 7/25 studies of placental tissue identified SARS-CoV-2; vertical transmission was infrequent. No study reported the results of viral culture to detect SARS-CoV-2. Conclusions These findings indicate that vertical transmission is possible, but not frequent. Further high-quality studies are needed to understand vertical transmission. Funding World Health Organization: WHO registration No 2020/1077093.
Health workers' perception and emotions of teleconsultation in pediatric cancer care
Pierluigi Calò
Amandine Bertrand

Pierluigi Calò

and 6 more

January 31, 2024
Background and aims: During the first lockdown of the novel Coronavirus pandemic (COVID-19), we developed a teleconsultation model to replace in-person visits. We conducted a survey-based study with the aim to evaluate satisfaction and emotions of health workers (HWs), to assess the feasibility of teleconsultations and to evaluate technical issues. Methods: This is a prospective monocentric exploratory study in which data were collected from March until May 2020 in the Lyon Pediatric Hematology and Oncology institute (IHOPe). We realized synchronous, video-based consultations between HWs and pediatric patients, treated for blood or solid malignancies or blood benign diseases. Every HW completed an online, pseudo-anonymized questionnaire which covered technical aspects, data concerning satisfaction, perception of the quality of the interaction with the patient and emotions felt after the teleconsultation. A score was calculated for each aspect. In order to study the relationship between the scores, the correlation coefficient method was used. Results: Eleven specialists participated in the study and we selected 84 questionnaires. With a satisfaction rate of 74%, HWs felt mostly calm (80%), relaxed (70%), stress-free (69%) and relieved (65%). We calculated the following median scores: an overall satisfaction score of 6.67 (0-10), a global feeling score of 8.79 (3.33-10.00), and a quality score of 7.34 (2.50-10.00). A strong correlation between the quality of the teleconsultation and the satisfaction of the HWs has been highlighted (r = 0,588). Conclusion: Our series is an encouragingly positive experience from the perspective of the HWs, their feelings and perceptions.
Cancer does not wait: safeguarding care for pediatric acute lymphoblastic leukemia pa...
Julia  Colunga-Pedraza
Perla Colunga-Pedraza

Julia Colunga-Pedraza

and 10 more

January 31, 2024
Introduction: Safeguarding care of acute lymphoblastic leukemia (ALL) patients during the COVID-19 pandemic has posed a significant challenge to health systems. We documented continuity (timeliness and compliance) of curative treatment in pediatric ALL patients, and the incidence and outcomes of patients infected with SARS-Cov2 in our institution. Materials and methods: We included all ALL patients aged <16 years who received treatment in “Hospital Universitario Dr. José Eleuterio Gonzalez” from March 2020 to June 2021. The causes of non-compliance and the outcomes of patients with COVID-19 were reported. Results: We analyzed 553 visits from 89 patients with ALL. Chemotherapy administration was timely and compliant with our treatment protocol in 83% (n=459) of the records reviewed. Treatment continuity goals of ≥80% were achieved for all treatment phases, except for the consolidation (66%) and intermediate maintenance phases (60%). The main causes of treatment delays or treatment modifications included lack of financial resources (2.5%), lack of inpatient beds (1.8%) and chemotherapy stock-outs (1.3%), and the treatment abandonment rate was 3.3%. Twenty-two patients (24.7%) were diagnosed with COVID-19. Of these, seven (32%) developed pneumonia, five (22.7%) required oxygen, and two (9%) developed multisystem inflammatory syndrome. For patients with COVID-19, the median length of stay was 9.5 days, and the 30-day mortality rate was 4.5%. Discussion: The continuity of curative treatment for ALL in the context of COVID-19 was >80% in our hospital. Adapting diagnosis and treatment protocols and implementing strategies to minimize the risk of infection were fundamental to safeguarding continuity care for cancer patients.
Sleep patterns and screen time in US school children during the first 6 months of the...
Amanda Hassinger
Alberto Monegro

Amanda Hassinger

and 2 more

January 31, 2024
Objective: This study compared sleep duration, screen exposure and sleep quality in school-aged children before COVID-19 to that during school closures and again when schools re-opened in fall 2020. Study design: Cross-sectional anonymous, online survey of parents of children 5-13 years old. Methods: Questions elicited information about sleep timing and quality, screen time, and schooling at three distinct periods: before the pandemic, when schools first closed in March 2020 and then re-opened in the fall. Results: Respondents described 101 children who were an average of 8.5 years old and 51% male. In lockdown, children slept an average of 25 minutes more (95%CI 00:13-00:38) due to delays in bedtime by 29 minutes (95%CI 0:00-0:58) and wake time by 75 minutes (95% CI 0:57-1:34). When schools re-opened, sleep duration returned to pre-pandemic levels, but sleep onset and offset times remained later. Despite more sleep, sleep quality and habits (e.g. bedtime refusal) worsened during lockdown and did not normalize in fall 2020. During lockdown, screen time increased in 65% of all children, and 96% of those in private schools. When school reopened in the fall, 78% of children in hybrid/virtual learning had screen time over 4 hours daily. Less daily screen time was associated with 2-fold higher odds of better sleep (OR 2.66, 95%CI 1.15-6.14). Conclusions: Although, school-aged children had an increase in sleep time when schools were closed, sleep quality and habits worsened. Upon return to school, sleep times and sleep quality did not normalize and were related to increased screen time.
Interleukin-2: an accurate biomarker for rapid testing of SARS-CoV-2 vaccine-induced...
Maria Oliver
Bryan Smith

Maria Oliver

and 3 more

January 31, 2024
Background: T cell responses to natural SARS-CoV-2 infection may be more robust and longer lived than antibody responses, thus preventing re-infection. Accurate assessment of vaccine-induced T cell responses is critical for understanding the magnitude and longevity of vaccine-induced immunity across patient cohorts. Aims: To establish a simple, accurate and rapid whole blood test to determine natural and vaccine-induced SARS-CoV-2 immunity via a cytokine release assay. Methods: Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with PCR-confirmed previous infection (n=29), suspected infection (n=30) or with no history of exposure (n=69); and in donors pre- and post-vaccination (n=32). Cytokines were measured by enzyme immunoassay and multiplex array. Results: Cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) were highly elevated in PCR-confirmed or suspected SARS-CoV-2 infected donors at 20->2000pg/ml and 20-1000pg/ml, respectively, compared to history negative controls (<20-90pg/ml). Receiver operating curves showed IL-2 as the superior biomarker with AUC of 0.99 compared to IFN-γ (0.94). Following vaccination, 100% of PCR-confirmed donors and 94% of unexposed individuals demonstrated a positive IL-2 response. Mean IL-2 levels increased ~18-fold from 12pg/ml pre-vaccination to 202pg/ml and 216pg/ml after the 1 st and 2 nd vaccine doses, respectively. No other cytokines were suitable biomarkers for distinguishing SARS-CoV-2 infection or vaccination responses. Conclusion: This rapid, whole blood-based T cell test can be utilised to make accurate and comparable assessments of vaccine-induced T cell immunity across multiple population cohorts, and aid decision making on public health policies and vaccine efficacy.
Whole Pulmonary Lavage: Treating Pulmonary Alveolar Proteinosis At The Time of COVID...
Katherine Powers
Vasanthi Avadhanula

Katherine Powers

and 5 more

January 31, 2024
Pulmonary alveolar proteinosis (PAP) is a rare syndrome due to increased production or decreased clearance of surfactant in alveoli and terminal bronchi that cause hypoxemic respiratory insufficiency. Here we present a patient with past medical history of PAP whose disease was exacerbated by superimposed COVID-19 pneumonia. He underwent whole pulmonary lavage (WPL). Evaluation of the viral count of the first and the last lavage of the left lung showed viral load in the alveolar space dropped by approximately 10-folds, however the magnitude of the viral load was substantial in both lavage samples. Whole pulmonary lavage may be used as a treatment option on patients with COVID pneumonia superimposed on a pulmonary alveolar proteinosis (PAP) exacerbation.
Pregnancy during respiratory pandemics: a comparison between 2009/10 H1N1 flu and 202...
Ana Beatrice Zanon
Elias Rosa Junior

Ana Beatrice Zanon

and 7 more

January 31, 2024
Background: Pregnant women undergo physiological changes that make them a challenging group of patients during pandemic respiratory diseases. Objective: To compare pregnant and non-pregnant women of childbearing age, regarding their demographic profile, clinical aspects, and mortality during the H1N1 and COVID-19 pandemics. Methods: Cross-sectional analysis of data from the SIVEP-Gripe, a Brazilian national surveillance database for respiratory viruses. Women of childbearing age with Severe Acute Respiratory Syndrome induced by H1N1 (2009/2010) and COVID-19 (2020/2021) were included. For each pandemic, women were divided into two groups according to their gestational status: pregnant or non-pregnant women. Groups were compared regarding epidemiological and clinical characteristics and their outcomes. Additionally, the effect of being pregnant was compared between both pandemics. Results: The analysis included 8,854 women for H1N1 flu pandemic (2,784 pregnant and 6,070 non-pregnant) and 69,607 women for COVID-19 pandemic (5,383 pregnant and 64,224 non-pregnant). In both pandemics, pregnant women were younger than non-pregnant women. Overall, pregnant women had lower frequencies of comorbidities and were less symptomatic. Nonetheless, notification due to hospitalization was more frequent in pregnant women in both pandemics. Among hospitalized women, pregnant women presented lower mortality rates than non-pregnant women (9.7% vs 12.6%, p=0.002 in H1N1 pandemic and 9.7% vs. 17.4%, p<0.001 in COVID-19 pandemic). Conclusion: In both pandemics, pregnant women had a higher rate of notification due to hospitalization than non-pregnant women. Nonetheless, among hospitalized subjects, pregnant women presented lower rates of death than non-pregnant women and this protection effect was more marked during the COVID-19 pandemic.
Risk factors of immunisation stress-related response to COVID-19 vaccination and hist...
Tomonori Takano
Masanori Hirose

Tomonori Takano

and 5 more

January 31, 2024
Abstract Background Safe vaccination worldwide is critical for eliminating the COVID-19 pandemic elimination. We aimed to evaluate adverse reactions to vaccination using a web-based questionnaire and to examine the risk factors for the occurrence of immunisation stress-related response (ISRR). Methods We conducted a questionnaire survey using Google Form® among employees of St. Marianna University Hospital who had received the COVID-19 vaccine between April 2021 and May 2021, 1 week after the first and second vaccinations. We developed and used a questionnaire to identify individuals with ISRR, according to the World Health Organization diagnostic criteria. A generalised linear mixed model was constructed with ISRR onset as the dependent variable, subjects as the random factor, and each parameter as a fixed factor. A multivariate model was constructed using the forced imputation method with factors that were significant in the univariate analysis. Results We enrolled 2,073 and 1,856 respondents in the first and second questionnaire surveys, respectively. Fifty-five and 33 ISRR cases were identified in the first and second vaccinations, respectively. In the univariate analysis, strong pre-vaccination anxiety (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.30–4.12, p=0·004) and history of allergy (OR, 1.6; 95% CI, 1.14–2.24, p=0·007) were significant risk factors. Multivariate analysis also showed that strong pre-vaccination anxiety (OR, 2.1; 95% CI, 1.15–3.80, p=0.016) and history of allergy (OR, 1.5; 95% CI, 1.09–2.15, p=0.014) were significant risk factors. Conclusions Confirmation of allergy prior to vaccination and subsequent action are essential for addressing ISRR.
Clinical Characteristics and Outcomes of Children and Adolescents with cancer infecte...
suleimman Al-Sweedan
Dua' Samara

suleimman Al-Sweedan

and 4 more

January 31, 2024
Background: Our knowledge about SARS-CoV2 infection is still evolving, its effects and complications on children and adolescents with cancer need to be studied more. The aim of this study is to present our experience with SARS-CoV2 infection in this population and to highlight specific complications and outcomes. Methods: This is a retrospective and prospective observational study, involved 21 cancer patients below the age of 18 years in north Jordan. Data regarding age, sex, cancer type, phase of treatment, duration between infection and chemotherapy and others were collected and reviewed. Results: A total of 21 patients with malignancy were included. Mean age of 8.5 years. Two patients (9.5%) had died; 4.7% is COVID related mortality and 4.7% related to cancer progression. Four patients had disease progression following SARS-CoV2 infection. Six cases developed hematological malignancy weeks to months after SARS-CoV2 infection and one patient was diagnosed with malignancy concomitantly with COVID-19 infection. Out of 15 patients with pre-existing malignancy, 1 patient (7%) developed pulmonary embolism, 4 (27%) patients were diagnosed with pneumonia and one patient was diagnosed with pericarditis (7%), 2 (13%) patients were admitted to pediatric intensive care unit. Regarding oxygen requirements; a total of 3 (20%) patients required some form of Oxygen supplementation. Conclusion: Diagnosis of COVID19 should not distract physicians from investigating new malignancy or relapse as they may come together or may be the result of COVID-19 infection. More studies and investigations are needed to identify the contribution of corona virus in pathogenesis of cancer.
Breakthrough SARS-CoV-2 infections after vaccination: A critical review
Zeinab Mohseni Afshar
Mohammad Barary

Zeinab Mohseni Afshar

and 8 more

January 31, 2024
At the beginning of the current pandemic, it was believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection would induce lifelong immunity and that reinfections would be unlikely. However, after several cases of reinfection were documented in previously infected patients, this was understood to be a false assumption, and this waning humoral immunity has raised significant concerns. Accordingly, long-term and durable vaccine-induced antibody protection against infection have also become a challenge, as several breakthroughs of COVID-19 infection have been identified in individuals who were fully vaccinated. This review discusses the current evidence on breakthrough COVID-19 infections occurring after vaccination.
A systematic review of molecular mechanism and therapeutic effect of Cannabidiol (CBD...
Wendong Huang
Jiangling Peng

Wendong Huang

and 5 more

January 31, 2024
Cannabidiol (CBD) is an abundant non-psychoactive phytocannabinoid in Cannabis extracts. Mechanic studies have indicated that CBD has high affinity on a series of receptors, including type 1 cannabinoid receptor (CB1), type 2 cannabinoid receptor (CB2), GPR55, transient receptor potential vanilloid (TRPV), peroxisome proliferator-activated receptor gamma (PPARγ). By modulating the activities of these receptor, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anti-cancer properties. Recently, according to some initial studies, CBD’s anti-inflammatory properties could be applied for treat or prevent COVID-19. CBD has gained increased attention in recent years because of its great potential to treat various human diseases. This review provides a current overview of CBD’s applications in human diseases, from mechanism of action to clinical trials.
Is there a Relationship between the COVID-19 Vaccine and Epistaxis?
Chiraag Karia
Mohammed Hussain

Chiraag Karia

and 5 more

January 31, 2024
Objectives: The aim of this study was to identify if there was a change in the incidence of epistaxis attendances following initiation of the COVID-19 vaccination programme. Design: A retrospective, cohort study. Setting: A large university teaching hospital with an emergency department (ED). Participants: A study group consisting of adults attending the emergency department for epistaxis over a 2-month period in 2021 and a control group consisting of adults attending the emergency for epistaxis over a 2-month period in 2019. Main outcome measures: The comparison of emergency department admission data with vaccination data between the control and study groups. Results: 187 (0.8% of total ED attendances) epistaxis attendances occurred in 2021 compared to 174 (0.6% of total ED attendances) epistaxis attendances in 2019 (p=0.002). No significant differences in platelet count were observed between the vaccinated (250.52 x109/L) and unvaccinated patients (214 x109/L) in the study group (p=0.117). The mean time between vaccination and presentation with epistaxis was 36 days ± 23.5 (n=102). Conclusion: The COVID-19 vaccine may be responsible for an increased proportion of epistaxis attendances to our emergency department. No evidence of thrombocytopenia was observed amongst patients presenting with epistaxis after vaccine administration. The mean time between vaccination and presentation with epistaxis was over five weeks.
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