SARS-CoV-2 Research Articles

Immunization against COVID-19: A Comprehensive Review on the Leading Vaccines

Abstract: The global impact of coronavirus disease (COVID-19) has prompted researchers and scientists to develop effective vaccines to contain the spread of the pandemic. This has led to the deployment of a range of vaccines from different pharmaceutical companies across the globe in a very short span of time. The current article provides a comprehensive record of all the vaccines developed against coronavirus with a specific focus on the mode of action and administration of the vaccines. The article also dwells on the composition, possible side effects and criteria for the choice of individuals for the administration of the vaccines. Vaccines against COVID-19 have been broadly categorized as mRNA vaccines, adenoviral vector-based vaccines and inactivated vaccines. Among the mRNA vaccines, the Pfizer vaccine and Moderna vaccines gained significant popularity. The Oxford Astro Zeneca vaccine and Sputnik V were the most effective viral vector vaccines. Inactivated vaccines such as Covaxin and Sinovac were also significant contributions to contain the pandemic. The review discusses the efficiency of vaccines against the variants of SARS CoV2. The review will provide a clear-cut idea about all kinds of exciting vaccines against COVID-19. At present, where the immediate crisis of the pandemic has been successfully contained, this article acts as a resource for future public health endeavors, policy makers, health care professionals and the general public to understand the diversity of COVID-19 vaccines.

Clinical Characteristics and Mortality Risk Factors of Hospitalized COVID-19 in Children: An Experience of Two Years Pandemic in Regional Referral Hospital

Coronavirus disease 2019 (COVID-19) has spread worldwide rapidly. COVID-19 in children is relatively mild compared to adults. However, several studies showed high mortality rates in children with underlying diseases. This study aimed to describe the clinical characteristics and outcomes of pediatric COVID-19 cases in regional referral hospital. This study was retrospective observational study using data from Medical Record Dr. Moewardi General Hospital between October 1st, 2020 and October 30th, 2022. The epidemiological and clinical data were extracted from the database and were compared with outcomes of patients. All statistical analyses were performed by SPSS software version 27. This study enrolled 371 (19,9%) children with confirmed RT-PCR SARS CoV-2 from 1856 hospitalized suspected children whereas 55% were males, and 63% aged under 5 years old. Moderate-severe patients accounted for 18% of the cases. Cough (74,4%), fever (66,6%) and shortness of breath (22,6) are the most common symptoms while 99 (26,7%) patients who had chronic diseases with the most common diseases being congenital heart disease, hematological malignancy and neurological disorders. Patient outcomes were significantly related to age, degree of severity and chronic disease with p=0.004, p< 0.001, and p< 0.001 respectively. After performing multivariate regression analysis, degree of severity [p<0.001; adjusted OR = 28.03, 95% CI (10.73–73.21)] was found to be significant predictors for mortality. The clinical and epidemiological data revealed that the majority symptom were cough, fever and shortness of breath. Mortality rate during hospitalization was higher in children with moderate-to-severe COVID-19.

The disappearing COVID-Naïve Population and comparative Roche vs. Abbott Test sensitivity: evidence from antibody seroprevalence in Milwaukee County, Wisconsin.

We study the prevalence of SARS-CoV-2 antibodies in a diverse population in Milwaukee County, Wisconsin from May 2021 to June 2022. We find that 99.4% (523/526) of the participants had positive results for antibodies to the SARS CoV2 spike protein over April-June 2022, soon after the early-2022 Omicron surge. Positive tests for spike protein antibodies were very high (86%; 19/22) even among unvaccinated persons who reported no knowledge of prior infection. Thus, by mid-2022, almost all persons were no longer COVID-naïve, defined as vaccination, infection (often without symptoms), or both. Nucleocapsid antibody tests, especially the Abbott test, were far less sensitive than spike protein tests, and Abbott test sensitivity faded with time since infection. Thus, studies which rely on nucleocapsid tests will understate prior infection rates. We also report large sample evidence on the performance of the Abbott and Roche spike and nucleocapsid protein tests in capturing prior vaccination, infection, or both. The Roche spike protein test outperforms the Abbott spike test, and the Roche nucleocapsid test greatly outperforms the Abbott nucleocapsid test.

Mapping Protein Conformational Landscapes from Crystallographic Drug Fragment Screens.

Proteins are dynamic macromolecules. Knowledge of a protein's thermally accessible conformations is critical to determining important transitions and designing therapeutics. Accessible conformations are highly constrained by a protein's structure such that concerted structural changes due to external perturbations likely track intrinsic conformational transitions. These transitions can be thought of as paths through a conformational landscape. Crystallographic drug fragment screens are high-throughput perturbation experiments, in which thousands of crystals of a drug target are soaked with small-molecule drug precursors (fragments) and examined for fragment binding, mapping potential drug binding sites on the target protein. Here, we describe an open-source Python package, COnformational LAndscape Visualization (COLAV), to infer conformational landscapes from such large-scale crystallographic perturbation studies. We apply COLAV to drug fragment screens of two medically important systems: protein tyrosine phosphatase 1B (PTP1B), which regulates insulin signaling, and the SARS CoV-2 Main Protease (MPro). With enough fragment-bound structures, we find that such drug screens enable detailed mapping of proteins' conformational landscapes.

Genomic characteristics, disease outcome and heterologous vaccine effectiveness among cases with SARS CoV-2 infection

BackgroundIn the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape.ObjectivesTo assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population.MethodsThis retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection.ResultsVaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies.ConclusionThe study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.

Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection

BackgroundRecovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support.MethodsWe characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12.ResultsNearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46–1.52; all p ≤ 0.05), those without a bachelor’s degree (RR = 1.33; 95% CI = 1.03–1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11–1.90; p < 0.01).ConclusionsLong COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.

Research on the evaluation of emergency management capability for urban public health emergencies under the perspective of resilience—a case study of Henan Province, China

With the rapid development of the economy and society, the likelihood of sudden public health emergencies in urban areas continues to rise. In particular, major infectious diseases that have gained global attention, such as the SARS virus, H1N1 influenza, Ebola outbreak, and COVID-19 pandemic, have presented significant challenges to urban emergency management systems. Evaluating emergency management capability is a fundamental requirement for developing emergency response capacity. To this end, this study combines the theory of resilience with the theory of full-process equilibrium emergency management, selects 31 evaluation indicators from six key aspects: preparedness, forewarning, mitigation, disposal, recovery, and learning. The indicator weights are determined using the AHP-Entropy Weight Method, and a TOPSIS model is constructed to assess the emergency management capability of urban public health emergencies. The model’s applicability is validated by examining 18 cities in Henan Province. The findings suggest that Jiaozuo, Hebi, Zhengzhou, and Luohe possess relatively robust emergency management capabilities for sudden public health incidents, whereas Kaifeng, Pingdingshan, and Shangqiu exhibit weaker capabilities.

Neurodevelopment in the First 2 Years of Life Following Prenatal Exposure to Maternal SARS-CoV-2 Infection

The effects of prenatal exposure to SARS-CoV-2 infection on child development throughout the first 2 years of life are unknown. To evaluate whether prenatal exposure to SARS-CoV-2 infection was associated with child neurodevelopmental outcomes during the first 2 years of life. This cohort study used data from the longitudinal, population-based pan-Canadian Pregnancy During the COVID-19 Pandemic cohort, which recruited participants from April 2020 to July 2022. Children were categorized as exposed to prenatal SARS-CoV-2 infection if their birthing parent had a positive polymerase chain reaction test performed by a health authority or as a healthy negative comparison if their birthing parent did not have SARS-CoV-2 antibodies in their postpartum dried blood spot sample. Prenatal SARS-CoV-2 infection. The birthing parent reported on their child's temperament at ages 6 and 24 months, developmental milestones at ages 12 and 24 months, and social-emotional milestones at ages 12 and 24 months. A total of 896 children were included, with 96 children who had been exposed to a prenatal SARS-CoV-2 infection (mean [SD] gestational age at birth, 39.20 [1.50] weeks; 45 [47%] male) and 800 were healthy negative comparisons (mean [SD] gestational age at birth, 39.47 [1.54] weeks; 388 [49%] male). In analyses of covariance adjusted for prepregnancy medical conditions and household socioeconomic status, prenatal exposure to SARS CoV-2 infection was associated with slightly higher regulatory control scores, indicating more regulation, at age 6 months (difference in means, 0.19 [95% CI, 0.02-0.36]; P = .03; ηp2 = 0.01). No significant differences were observed for the other neurodevelopmental outcomes. In mixed models adjusted for the same covariates that aimed to examine change in outcomes over time, prenatal SARS-CoV-2 infection exposure was not associated with developmental change in any neurodevelopmental outcomes between ages 6 and 24 months. In this longitudinal cohort study of multiple aspects of child neurodevelopment between ages 6 and 24 months, negligible associations between prenatal exposure to SARS-CoV-2 infection and child outcomes were observed. Follow-up research is warranted to determine whether these predominantly null effects persist into later childhood.

In silico exploration of phytocompounds from AYUSH-64 medicinal plants against SARS CoV-2 RNA-dependent RNA polymerase

BackgroundThe AYUSH 64 formulation helps to treat mild to moderate cases of COVID-19. Although several drugs have been proposed to combat COVID-19, no medication is available for SARS-CoV-2 infection. The RNA-dependent RNA polymerase (RdRp) is the pivotal enzyme of SARS-CoV-2 replication, so it could be considered a better drug target for experimental studies. ObjectiveThe AYUSH-64 formulation plants exhibited multiple therapeutic properties; thus, the present study aims to screen the phytocompounds of these plants against SARS CoV2 RdRp to identify specific compounds that could potentially affect COVID-19 infection. Materials and methodsPatchDock and AutoDock tools were used for docking experiments. MD simulations and Density Functional Theory (DFT) calculations of protein-ligand Picroside-I and Remdesivir complexes were carried out in GROMACS v2019.4 and Gaussian 09 software, respectively. ResultsAmong the tested, five phytocompounds (Picroside I, Oleanolic acid, Arvenin I, II, and III) from AYUSH-64 medicinal plants showed possible binding with RdRp catalytic residues (Ser759, Asp760, and Asp761). Of these, Picroside I exhibited hydrogen bond interactions with NTP entry channel residues (Arg553 and Arg555). The MM-PBSA free energy, RMSD, Rg, PCA, and RMSF analysis suggested that the Picroside I complex showed stable binding interactions with RdRp in the 50 ns simulation. In addition to this, Picroside I revealed its robust and attractive nature toward the target protein, as confirmed by DFT. ConclusionThe results of this study have proposed that Picroside I from AYUSH 64 medicinal plant compounds was the selective binder of catalytic and NTP entry channel residues of SARS-CoV2 RdRp thereby; it may considered as a potential inhibitor of SARS-CoV2 RdRp.

FASTER AND COST-EFFECTIVE EXTRACTION FREE METHOD FOR SARS-COV2 DETECTION BY RT-PCR

Background: The World Health Organization (WHO) declared an outbreak of febrile respiratory illness caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) in Wuhan City, China in December 2019. Within the immediate outbreak of three months, the global community was challenged with a devastating pandemic that caused heavy morbidities and mortalities around the globe. The expeditious spread of the virus, challenged the diagnostic laboratories to rapidly develop the accurate molecular diagnostic methods. As SARS CoV-2 assays became available for testing on existing molecular platforms, laboratories devoted unprecedented energy and resources to evaluating the analytical performance of the new tests and in some cases developed their diagnostic assays under FDA-EUA guidance. Aim: This study aims to compare the diagnostic efficacy of the extraction-free method of COVID-19 PCR and the conventional RT-PCR with extraction. Method: To get an accurate view of how an omission of RNA extraction step would perform in a real-world setting, a comparative study was performed using TATA MD CHECK RT-PCR DIRECT (Direct PCR) and LabGun Genomics for Conventional RT-PCR method. Result: From this study, direct RT-PCR correctly identified 92.3% of samples (n = 50) identified positive for SARS-CoV-2 RNA by conventional RT-PCR featuring an RNA extraction. Conclusion: Direct methods may represent a reasonable alternative to meet higher testing demands with low turnaround time as reverse transcription PCR includes traditionally time-consuming RNA extraction and purification procedures.

Humoral Immunity Profiling to Pandemic and Bat‐Derived Coronavirus Variants: A Geographical Comparison

AbstractDynamic pathogen exposure may impact the immunological response to SARS‐CoV‐2 (SCV2). One potential explanation for the lack of severe SCV2‐related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2‐related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat‐to‐human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre‐pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor‐binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre‐incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre‐pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2‐related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross‐reactive immunity to SCV2 prior to the global pandemic.

Life-Threatening Spontaneous Hematoma in Unusual Sites in Patients with COVID-19 on Anticoagulant Therapy: A Case Series

Thromboembolic manifestations are a common phenomenon in patients affected by corona virus (SARS CoV-2). Recent studies have shown that patients with acute renal failure are also at a greater risk of venous and arterial thromboembolism, 15-30% in ICU, and 7% inpatient care. However, frequently unjudicial use of anticoagulants may develop severe life-threatening hematoma. In our hospital settings we had a dedicated COVID Unit with a Hemodialysis facility. Our Nephrology department had managed 381 patients being COVID positive along with renal impairment from March 2020 to January 2022. Among these patients, four patients developed spontaneous non traumatic hematoma in unusual sites. On admission all the patients received treatment according to our national guidelines for COVID-19. Cases: It is a retrospective analysis in a single-centered hospital. Four cases with confirmed COVID-19 with acute kidney injury and on anticoagulant therapy had developed sudden concealed bleeding. These patients had no previous history of anticoagulant therapy before admission. Case 1 developed hemorrhage in Right lower anterior paramedian deep parietal wall of abdomen, Case 2 had hematoma in retroperitoneal space and in lower third of Iliopsoas, Case 3 developed hemorrhage in left cerebral hemisphere, Case 4 had Intramuscular Hematoma in left rectus abdominis. Out of these four patients two of them required Hemodialysis and one of them went into shock. All patients included were male. The mean age was 57±19.64years. All the four patients were initially managed conservatively with keen monitoring and with proper volume resuscitation, blood transfusion and discontinuation of the anticoagulants. Three of the patients survived with conservative management and one patient died due to sudden massive cardiac arrest. The use of therapeutic anticoagulant can increase the risk of bleeding in atypical sites and may exhibit higher patient death with COVID-19 if not identified at early stage. So a risk-benefit ratio of usage of anticoagulants should be kept in mind and further clinical trials needed to justify its random use in COVID-19. J Bangladesh Coll Phys Surg 2024; 42: 393-400

Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2.

During the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY. To characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs). A retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: "high dose dexamethasone" (daily dose greater than 12 mg and/or for longer than 10 days), "low dose dexamethasone" (daily dose 12 mg or less for 10 days or less), and "no dexamethasone" (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use. High-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74). Acknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.

Potential hypothesis for the increased risk of Parkinson´s disease following COVID-19.

Patients with severe COVID-19 may be more likely to develop PD as a result of shared biological pathways including a great expansion of MDSCs and an imbalance in Th17/Tregs ratio. We think that these shared pathogenic features may mechanistically explain the COVID-19 - PD axis. Thus, we assume that patients who recovered from critical COVID-19 should be selected based upon a potential higher risk of developing PD. Further studies are needed to better define the possible relationship between COVID-19 and neuroinflammation and identify whether some people are more likely to develop PD after contracting COVID-19 than others with special emphasis to ascertain possible vulnerable genetic backgrounds or epigenetic factors acting on brain which may promote PD during SARS COV-2 infection. Finally, we think that regular physical activity should be performed and encouraged in patients with PD.

SNaPshot minisequencing for SARS CoV 2 Variant Genotyping

Abstract Introduction/Objective The SNaPshot Multiplex System (Thermo Fisher) can investigate up to fifty SNP markers simultaneously by using PCR amplification and subsequent dideoxy single base extension of an unlabeled primer and capillary electrophoresis. After electrophoresis and fluorescence detection, the alleles of a single marker appear as different colored peaks at roughly the same size in the electropherogram plot. The size of the different allele peaks vary slightly due to differences in molecular weight of the dyes. We propose a new set of primers and probes to use this system to differentiate variants of SARs Cov 2 variants. Methods/Case Report SNAPSHOT analysis was performed using the primers designed internally and analysis was done of up to 7 mutation hot spots, which were 417, 4511, 478, 484, 501, 614, and 681. By implementing the algorithm of systems and methods herein with the traces depicted in Figures, true positive and true negative outcomes for the different COVID variants can be performed, based on the highlighted peaks, which are not necessarily the most intense peaks. 10 Positive controls achieved from in stro transcript plasmid was tested then 10 viral RNA obtained through BEI Resources, NIAID was tested after mixed into 30 pooled negative PCR-swab specimens. Genmapper was used for analysis of results. 40 Korean patient samples were tested as well. Results (if a Case Study enter NA) Both In vitro transcript and derived specimens of wild type, alpha, beta, delta, gamma, kappa, omicron, and pirola showed expected results in 78/80 of the specimens. For example,delta B.1.617.2 variant showed 1 = A (green) at Primer 452R-F, 2 = G (blue): Primer 484Q-F, and 3 = A (green) at Primer 614-F. Of note, hetero type was noted in a few of the patient strains but none of the BEI strains and this may be due to a transfromation of the virus and worth investigation. Conclusion The SNaPshot® Multiplex System is a accurate system that may be applied to multiple applications including viral strain anylsis and here we can show how it may be effectively used for SARS-Cov-2 gentotyping. Using this technique, it is possible to analyze more than 50 SNPs distributed throughout the genome in a single multiplex reaction, making it an advantage when compared with traditional sequencing reaction. This is a important study that shows that this technique may be used in multiple field applictions.

One-Year Surveillance of a Patient Cohort’s Lung Ultrasonography Findings Post Mild-Moderate COVID-19 Infection

Objective: Lung involvement due to COVID-19 infection relates to patient clinical outcomes. However, little evidence exists on whether an abnormal lung sonogram, during an initial outpatient infection, may signal an abnormal immunologic response and lasting abnormalities. The aim of this study was to observe whether high-risk outpatients, previously infected with SARS CoV-2 and found to have an initial abnormal lung sonogram, had persistent diagnostic findings at a 1-year re-examination. Materials and Methods: A prospective longitudinal cohort study was performed, based on a prior study completed in January 2022 wherein 55/201 (27%) of consecutive outpatients infected with SARS-CoV-2 received therapy at an outpatient monoclonal antibody clinic and had presented with an abnormal lung ultrasound containing at least 3 apical lung B-line artifacts (LUS+). One year later, the original 55 LUS+ patients were contacted for re-examination; as a result, 14 LUS+ patients consented to a repeat LUS tospecifically recheck the apical area of the lungs for persistent B-line artifacts. The same ultrasound equipment system and imaging methodology were used for this cohort of patients. Additional data was collected regarding COVID-19 test-positive re-infection, persistent pulmonary symptoms during the past year, and COVID-19 vaccination status. Results: Of the 14 LUS+ patients, the mean cohort age was 63 ± 9 years, of which 71% were men. Over the ensuing year, 43% had persistent symptoms, 71% had updated vaccination, and 36% had a self-reported re-infection. The re-infection was reported to have occurred a median of 7 months after the initial infection. The cohort was sub-divided into those with persistent LUS+ compared to those that reverted to a normal scan. The mean age was 69 ± 10 years among those LUS+ compared to 56 ± 8 years in the normalized group. The body mass index (BMI) was 32 kg/m2 in those LUS+ compared to 27 kg/m2 in the normalized group. The cohort has 6 men and 2 women in the LUS+ group compared to 4 men and 2 women in the normalized group. One LUS+ patient out of eight reportedly had been reinfected compared to four normalized patients out of six stated being reinfected. Three LUS+ patients out of eight reported having persistent symptoms compared to three normalized patients out of six complaining of continued COVID-19 symptoms. Conclusion: Based on the 1-year repeated LUS, for this cohort, there was a high prevalence of persistent symptoms and lung abnormalities, in those who had mild-moderate outpatient COVID-19 and received monoclonal antibody therapy. The longitudinal data collection on this cohort of COVID-19 positive outpatients may suggest that individual immune responses or viral virulence factors may play a role in B-line persistence. Certainly, future LUS results may be confounded by a previous COVID-19 infection.

Impact of mechanical power on ICU mortality in ventilated critically ill patients: a retrospective study with continuous real-life data

BackgroundOver the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not accurately reflect the impact of power throughout the period of mechanical ventilatory support on intensive care unit mortality.MethodsRetrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 h were included. We extracted the mechanical power values throughout the entire mechanical ventilation in controlled modes period from the clinical information system every 2 min. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with intensive care unit mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia.ResultsThe cut-off point of mechanical power at with there is a higher increase in intensive care unit mortality was 18 J/min. The greater the number of hours patients were under mechanical power > 18 J/min the higher the intensive care unit mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hypoxemic respiratory failure. The risk of death in the intensive care unit increases 0.1% for each hour with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay.ConclusionsThe number of hours with mechanical power > 18 J/min is associated with mortality in the intensive care unit in critically ill patients. Continuous monitoring of mechanical power in controlled modes using an automated clinical information system could alert the clinician to this risk.

A computational biology approach for the identification of potential SARS-CoV-2 main protease inhibitors from natural essential oil compounds.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions: Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.

Brugia malayi filarial helminth-derived extracellular vesicles suppress antigen presenting cell function and antigen-specific CD4+ T cell responses.

Live microfilariae (mf) and mf-derived extracellular vesicles (EVs) have been shown to modulate human antigen presenting cell (APC) function, most notably by suppressing the induction of IL-12 (and other pro-inflammatory cytokines) following activation with LPS and interferon-y. To explore further how EVs alter human APC function, we studied the effect ofmf and EVs on human elutriated monocyte-derived dendritic cells (DC) following exposure to Mf, mf-derived excretory/secretory (E/S) products, E/S depleted of EVs through ultracentrifugation and purified EVs. After demonstrating that the measurable responses induced by live mf could be recapitulated by EVs and EV-containing E/S, we next performed RNAseq analysis of human DC following exposure to live mf, EVs, E/S, or EV-depleted E/S. In our analyses of the data for the DC, using a false discovery rate (FDR)<0.05, EV-exposed DC had induced the expression of 212 differentially expressed genes (DEGs) when compared to unexposed DC and 157 when compared to E/S-depleted EVs. These genes were enriched in GO biological processes associated with neutrophil degranulation and 15 DEGs associated with KEGG Lysosome pathways. IPA analysis point to immune dysregulation. We next aimed to understand the intracellular processes altered by EVs and the effect these have on effector T cells. When SARS CoV-2 Membrane-specific CD4+ TCLs were assessed following EV conditioning of autologous DC and activation with the SARS CoV-2-Membrane peptide pool, we found conditioning reduced the frequency of SARS CoV-2 Membrane-specific CD3+ CD4+ CD154+ cells (p=.015). Similarly, EV-conditioning of SARS CoV-2 Membrane-specific CD3+ CD4+ cells induced fewer cell capable of producing IFN-γ (p=.045). Taken together, our data suggest a modulatory role of EVs on APC function that likely leads to defects in T cell effector function.

A-356 A hand-held microfluidic platform for rapid and sensitive identification of respiratory viruses from nasal swab samples

Abstract Background Identifying the infected individual with a fast and accurate test is essential to constrain the spread of viruses and provide the proper treatment. Antigen rapid test (ART) provides quick screening of infection for patients; however, it shows less promising in the detection of early infection and patent’s full recovery as its inferior sensitivity to the nucleic acid detection method. On the other hand, bulky and costly instrument, tedious and prolonged procedures in traditional nucleic acid testing is also unfavorable for the screening. Delta is developing a fully automated hand-held POC using molecular technology to simultaneously detect 4 targets in 20 mins. The POC can be stand-alone or linked to mobile or PC app for different application scenarios. The proprietary recipe of the lysis buffer could neutralize the inhibition in the sample with effective pathogen lysis in seconds. The microfluidic cartridge containing lyophilized reagent can be stored at room temperature. The amplification signal is detected via the optical system from the colorimetric LAMP. This study is to evaluate the performance of the POC system in detecting SARS-CoV2 (SC2), FluA and B viruses in nasal swab. In addition, the assay performance was further compared with other commercial products available. Methods The attenuated SC2 virus, FluA and B viruses were diluted with 1xTE into different concentrations. The diluted viruses were spiked into the lysis buffer in 5% v/v ratio. Nasal samples collected from donors were soaked and swirled inside the cartridges containing lysis buffer according to the manufacturers’ instructions. For commercial products without lysis buffer, direct swabs were used. The cartridges were then put into the respective devices for further testing. Results The lyophilized SC2 assay consistently detected the viruses at 1000 copies/ml (20 out of 20) in real nasal samples in the presence of Delta Lysis Buffer (containing lyophilized neutralizer). However, without Lysis buffer, there was no signal detected even in the presence of 240x LoD viruses. The whole workflow sensitivity was tested with SC2 positive samples at 1x, 4x, 10x LoD and negative samples in the nasal sample matrix on Delta hand-held system. The results were processed via embedded algorithm and displayed on device as well as on PC and mobile app respectively. Out of 79 positive samples tested, the detection rate was 100%. There was no false positive detection for 31 negative samples tested. Positive internal control indicated the valid runs. 5 major SC2 subtypes (99.8% in silico analysis of 366,707 strains), 10 FluA and 9 FluB subtypes were successfully detected. Further, Delta hand-held platform outperformed in the LoD of SC2 with 500 copies/swab comparing to the ≥50,000 copies/swab of the benchmarked commercial platforms. Conclusions The performance of the hand-held molecular detection system we developed demonstrated a rapid, sensitive, and competitive analytical performance in the respiratory panel detection. The capability of device linking to apps and clouds for data management and the extendable docking system for multiple devices to run samples simultaneously and independently, make it applicable for the infectious diseases screening in both clinical settings and for home-use.