Severe Acute Respiratory Coronavirus Research Articles

Clinical course and prognosis of patients with idiopathic pulmonary arterial hypertension after COVID-19

The coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus (SARS-CoV-2). This virus has many factors in its pathogenesis that affect the function of the right ventricle and pulmonary hemodynamics, which can negatively influence the clinical course of IPAH. According to the results of our study, the fact of getting over COVID-19 in patients with IPAH leads to some changes in laboratory and instrumental parameters. But no significant effect of COVID-19 on risk modification during the year was detected. This result can be explained by a combination of pathophysiological features of the pulmonary hypertension and the protective effect of constantly taken PAH-specific and anticoagulant therapy.

Polymorphism of RAAS genes in patients with COVID-19: comparison with frequency in population and relationship with severity of course

Evaluation of genes polymorphisms frequencies of angiotensinogen (AGT), angiotensin converting enzyme type 1 (ACE1) and angiotensin II receptors type 1 (AGTR1) and type 2 (AGTR2) in patients admitted with coronavirus disease (COVID-19) and its association the severity of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2). The study included 100 patients admitted to the hospital with a laboratory-confirmed diagnosis of COVID-19. All patients were identified with alleles and genotypes of polymorphic markers rs4762 of the AGT gene, rs1799752 of the ACE1 gene, rs5186 of the AGTR1 gene and rs1403543 of the AGTR2 gene. The frequencies of each polymorphisms were compared with population. Statistical processing was performed using the Statistica 8.0 software package. In evaluated cohort there was higher frequency of D-allele ACE1 rs1799752 compared to population. Depending on the availability of criteria for the severity of coronavirus infection, 44 (44%) patients were diagnosed with severe, 56 (56%) with moderate course. The groups did not significantly differ in age, gender, cardiovascular risk factors and comorbid pathology. In the groups with severe and moderate course, the same distribution of genotypes and alleles of AGT rs4762, AGTR2 rs1403543 and ACE1 rs1799752 was revealed. For the I/D alleles of the ACE1 rs1799752 gene, a significant deviation from the papulation was found in both the group of severe and moderate COVID-19. In the group with a severe course of the disease, a higher frequency of the mutant C-allele of the AGTR1 rs5186 gene was detected. In the same group, a deviation in the frequency ratio of A and C of the AGTR1 rs5186 alleles from Hardy-Weinberg Equilibrium was found. When calculating the risk of severe COVID-19 in the presence of the C-allele compared with the A-allele, an odds ratio 2.092 (95% confidence interval 1.066-4.108) was obtained. The data obtained suggest that the genes polymorphisms of the components of renin-angiotensin-aldosterone system, namely D-allele of ACE1 rs1799752 and C-allele of AGTR1 rs5186, may make it possible to identify groups of patients predisposed to the development of more severe COVID-19.

A-235 Systemic Inflammation is associated with worse outcomes from SARS-CoV-2 infection but not neutralizing antibody

Abstract Background Numerous studies have demonstrated an association between systemic inflammation and mortality in patients with COVID-19. However, it is unclear how neutralizing antibody to severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) associates with outcomes. Further, how systemic inflammation impacts neutralizing antibody production is relatively poorly understood. The aim of this study was to determine the association between the neutralizing antibody response to SARS-CoV-2, inflammatory markers, and clinical outcomes in a cohort of hospitalized patients without prior exposure/vaccination. Methods This prospective observational study approved by the Washington University IRB included adults admitted through the ED at Barnes Jewish Hospital between 10/2020 and 10/2021 with symptomatic RT-PCR confirmed SARS-CoV-2 infection. A total of 395 serial samples were assessed from 208 patients without previous vaccination or documented exposure to SARS-CoV-2. Neutralization of SARS-CoV-2 was assessed using the Architect ACE2 binding inhibition assay (Abbott, Research Use only) which measures the % inhibition of interactions between antibodies and the SARS-COV-2 viral Spike Receptor Binding Domain. While 12.5% inhibition of ACE2 was considered positive >80% neutralization is the expected standard. CRP was assessed using the Architect Multigent CRP assay with 9.6mg/dL as the categorical cutoff for risk and interleukin 6 (IL-6) was assessed using the Alinity IL-6 assay (Abbott, Research Use Only) using 30 pg/mL as the threshold for risk in categorical analyses. The electronic medical record (EPIC) was interrogated for comorbidities, age, gender, 30-day mortality, 10-day intubation, and pharmacological interventions. Correlation between biomarkers was assessed using Spearman r. Kaplan-Meier curves and Cox proportional hazards models were constructed for 30-day mortality and 10-day intubation. Results 37 of 208 (18%) of patients died within thirty days of ED presentation and 59 (28%) required intubation within 10-days. There was a significant correlation between IL-6 and CRP (r=0.34) but not with ACE-2 binding (Spearman r <0.06 for both IL-6 and CRP). There was significantly higher CRP in those that died (median = 14 mg/dL, IQR = 8-21) than those that survived (5 mg/dL, 2-11). IL-6 was higher in patients that died (344 pg/mL, 0-870) than those that survived (65 pg/mL, 28-140). Median ACE-2 inhibition trended higher in those that survived (18%, 0-65%) than those that died (3%, 0-48%). Survival curves demonstrated that patients with IL-6 > 30 pg/mL, CRP > 9.6 mg/dL, and ACE2 binding <12.5% at baseline were more likely to die within 30-days. Multivariate modeling found that only IL-6 (Hazard Ratio, 1.28, 95%CI 1.08-1.52 for each doubling) and age (1.04, 1.01-1.08) were significantly associated with 30-day mortality. Conclusions Systemic inflammation measured by IL-6 and CRP upon admission is highly associated with 30-day mortality from SARS-CoV-2 infection. While ACE-2 inhibition was lower in those that died from COVID-19 at admission, it was not independently associated with mortality or correlated with inflammatory markers. This implies an importance of other aspects of the immune response for mediating inflammation and reducing risk of mortality from SARS-CoV-2.

The SpO2/FiO2 Ratio Combined with Prognostic Scores for Pneumonia and COVID-19 Increases Their Accuracy in Predicting Mortality of COVID-19 Patients

Background: Identifying high-risk COVID-19 patients is critical for emergency department decision-making. Our study’s primary objective was to identify new independent predictors of mortality and their predictive utility in combination with traditional pneumonia risk assessment scores and new risk scores for COVID-19 developed during the pandemic. Methods: A retrospective study was performed in two Italian University Hospitals. A multivariable logistic model was used to locate independent parameters associated with mortality. Results: Age, PaO2/FiO2, and SpO2/FiO2 ratios were found to be independent parameters associated with mortality. This study found that the Pneumonia Severity Index (PSI) was superior to many of the risk scores developed during the pandemic, for example, the International Severe Acute Respiratory Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC 4C) (AUC 0.845 vs. 0.687, p < 0.001), and to many of the risk scores already in use, for example, the National Early Warning Score 2 (NEWS2) (AUC 0.845 vs. 0.589, p < 0.001). Furthermore, our study found that the Pneumonia Severity Index had a similar performance to other risk scores, such as CRB-65 (AUC 0.845 vs. 0.823, p = 0.294). Combining the PaO2/FiO2 or SpO2/FiO2 ratios with the risk scores analyzed improved the prognostic accuracy. Conclusions: Adding the SpO2/FiO2 ratio to the traditional, validated, and already internationally known pre-pandemic prognostic scores seems to be a valid and rapid alternative to the need for developing new prognostic scores. Future research should focus on integrating these markers into existing pneumonia scores to improve their prognostic accuracy.

Unveiling the Dynamic Mechanism of SARS-CoV-2 Entry Host Cells at the Single-Particle Level.

Understanding the dynamic features of severe acute respiratory coronavirus 2 (SARS-CoV-2) binding to the cell membrane and entry cells is crucial for comprehending viral pathogenesis and transmission and facilitating the development of effective drugs against COVID-19. Herein, we employed atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) to study the binding dynamics between the virus and cell membrane. Our findings revealed that the Omicron variant of SARS-CoV-2 virus-like particles (VLPs) exhibited a slightly stronger affinity for the angiotensin-converting enzyme-2 (ACE2) receptor compared with the Delta variant and was significantly higher than the wild-type (WT). Using a real-time force-tracing technique, we quantified the dynamic parameters for a single SARS-CoV-2 VLP entry into cells, showing that approximately 200 ms and 60 pN are required. The parameters aligned with the analysis obtained from coarse-grained molecular dynamics (CGMD) simulations. Additionally, the Omicron variant invades cells at a higher entry cell speed, smaller force, and higher probability. Furthermore, single-particle fluorescence tracking visually demonstrated clathrin-dependent endocytosis for SARS-CoV-2 entry into A549 cells. The dynamic features of endocytosis provide valuable insights into the SARS-CoV-2 entry mechanism and possible intervention strategies targeting the viral infection process.

Neurological Impact of Respiratory Viruses: Insights into Glial Cell Responses in the Central Nervous System.

Respiratory viral infections pose a significant public health threat, particularly in children and older adults, with high mortality rates. Some of these pathogens are the human respiratory syncytial virus (hRSV), severe acute respiratory coronavirus-2 (SARS-CoV-2), influenza viruses (IV), human parvovirus B19 (B19V), and human bocavirus 1 (HBoV1). These viruses cause various respiratory symptoms, including cough, fever, bronchiolitis, and pneumonia. Notably, these viruses can also impact the central nervous system (CNS), leading to acute manifestations such as seizures, encephalopathies, encephalitis, neurological sequelae, and long-term complications. The precise mechanisms by which these viruses affect the CNS are not fully understood. Glial cells, specifically microglia and astrocytes within the CNS, play pivotal roles in maintaining brain homeostasis and regulating immune responses. Exploring how these cells interact with viral pathogens, such as hRSV, SARS-CoV-2, IVs, B19V, and HBoV1, offers crucial insights into the significant impact of respiratory viruses on the CNS. This review article examines hRSV, SARS-CoV-2, IV, B19V, and HBoV1 interactions with microglia and astrocytes, shedding light on potential neurological consequences.

Advances in Engineering Circular RNA Vaccines.

Engineered circular RNAs (circRNAs) are a class of single-stranded RNAs with head-to-tail covalently linked structures that integrate open reading frames (ORFs) and internal ribosome entry sites (IRESs) with the function of coding and expressing proteins. Compared to mRNA vaccines, circRNA vaccines offer a more improved method that is safe, stable, and simple to manufacture. With the rapid revelation of the biological functions of circRNA and the success of Severe Acute Respiratory Coronavirus Type II (SARS-CoV-2) mRNA vaccines, biopharmaceutical companies and researchers around the globe are attempting to develop more stable circRNA vaccines for illness prevention and treatment. Nevertheless, research on circRNA vaccines is still in its infancy, and more work and assessment are needed for their synthesis, delivery, and use. In this review, based on the current understanding of the molecular biological properties and immunotherapeutic mechanisms of circRNA, we summarize the current preparation methods of circRNA vaccines, including design, synthesis, purification, and identification. We discuss their delivery strategies and summarize the challenges facing the clinical application of circRNAs to provide references for circRNA vaccine-related research.

Double testing with lateral flow antigen test devices for COVID-19: does a second test in quick succession add value?

Background/ObjectivesWe investigated if performing two lateral flow device (LFD) tests, LFD2 immediately after LFD1, could improve diagnostic sensitivity or specificity for detecting severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antigen. Study DesignIndividuals aged ≥16 years attending UK community testing sites (February–May 2021) performed two successive LFD tests and provided a nose-and-throat sample for a polymerase chain reaction (PCR) test. Using the PCR result as the reference diagnosis, we assessed whether improvements could be achieved in sensitivity (by counting a positive result in either LFD as a positive overall test result) or specificity (by using LFD2 as confirmatory test). ResultsOverall, 2231 participants were included with 159 (7 %) having a positive PCR test. Of 2223 participants who completed both LFD tests, LFD results were highly concordant both with each other and with PCR tests (>97 %). The proportion of discord LFD results decreased significantly over the study period. Combined LFD usage achieved a sensitivity of 68.6 %, versus 67.1 % for either LFD individually. The specificity increased from 99.5 % to 99.8 % when using LFD2 as confirmatory test. Observed increases in sensitivity and specificity were not statistically significant. Void results were recorded for 31 (1.4 %) LFD1s, 19 (0.9 %) LFD2s and 6 (0.3 %) combined LFD tests. ConclusionsLFD tests were highly reproducible even when they were performed by untrained users following only written instructions and without supervision. While performing two LFD tests of the same type in quick succession marginally increased sensitivity or specificity, statistically significant improvements were not detected in our study.

Zinc as a Possible Critical Element to Prevent Harmful Effects of COVID-19 on Testicular Function: a Narrative Review.

Research into innovative non-pharmacological therapeutic routes via the utilization of natural elements like zinc (Zn) has been motivated by the discovery of new severe acute respiratory syndrome-related coronavirus 2 (SARS-COV2) variants and the ineffectiveness of certain vaccination treatments during COVID-19 pandemic. In addition, research on SARS-COV-2's viral cellular entry and infection mechanism has shown that it may seriously harm reproductive system cells and impair testicular function in young men and adolescents, which may lead to male infertility over time. In this context, we conducted a narrative review to give an overview of the data pertaining to Zn's critical role in testicular tissue, the therapeutic use of such micronutrients to enhance male fertility, as well as in the potential mitigation of COVID-19, with the ultimate goal of elucidating the hypothesis of the potential use of Zn supplements to prevent the possible harmful effects of SARS-COV2 infection on testis physiological function, and subsequently, on male fertility.

Ensemble docking based virtual screening of SARS-CoV-2 main protease inhibitors.

During the first years of COVID-19 pandemic, X-ray structures of the coronavirus drug targets were acquired at an unprecedented rate, giving hundreds of PDB depositions in less than a year. The main protease (Mpro) of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is the primary validated target of direct-acting antivirals. The selection of the optimal ensemble of structures of Mpro for the docking-driven virtual screening campaign was thus non-trivial and required a systematic and automated approach. Here we report a semi-automated active site RMSD based procedure of ensemble selection from the SARS-CoV-2 Mpro crystallographic data and virtual screening of its inhibitors. The procedure was compared with other approaches to ensemble selection and validated with the help of hand-picked and peer-reviewed activity-annotated libraries. Prospective virtual screening of non-covalent Mpro inhibitors resulted in a new chemotype of thienopyrimidinone derivatives with experimentally confirmed enzyme inhibition.

SARS-CoV-2 and RSV bronchiolitis outcomes

BackgroundSevere acute respiratory syndrome related coronavirus (SARS-CoV-2) bronchiolitis has arisen with the SARS-CoV-2 pandemic. There is a paucity of literature on SARS-CoV-2 bronchiolitis. ObjectiveThe purpose of our paper was to review and compare outcomes in bronchiolitis due to severe acute respiratory syndrome related coronavirus 2 (SARS- CoV-2) and Respiratory Syncytial Virus (RSV). We also performed a subgroup analysis of two disrupted RSV seasons during the pandemic. MethodsThis was a retrospective study from a US TriNetX database from March 1, 2020-January 1, 2023. Propensity matching was utilized for confounders. ResultsThere was a total of 3,592 patients (1,796 in each group) after propensity matching.There was an increased risk of oxygen saturation ≤95 % (RR=1.50 95 % CI 1.58–1.94, p = 0.002) and ICU admission (RR=1.44 95 % CI 1.06–1.94, p = 0.02) in those with SARS- CoV-2 but not for oxygen saturation ≤90 % (RR=1.03 95 %CI 0.75–1.42, p = 0.85) or intubation (RR=0.73 95 % CI 0.35–1.47, p = 0.37). There was a decreased risk of a patient with SARS- CoV-2 bronchiolitis being hospitalized (RR=0.65 95 % CI 0.57–0.74, p < 0.0001), respiratory rate ≥60 (RR=0.64 95 % CI 0.48–0.88, p < 0.001) or ≥70 (RR=0.64 95 % CI 0.43–0.96, p = 0.03) when compared to RSV bronchiolitis. Specifically examining SARS- CoV-2 versus RSV bronchiolitis during the delayed RSV seasons, during the first season both infections were not severe, but during the second RSV bronchiolitis season, patients infected with RSV had less risk of ICU admission compared to those infected with SARS- CoV-2. ConclusionSARS- CoV-2 bronchiolitis patients appeared to have more severe outcomes since the risk of ICU admission was higher for these patients. Also, during the second delayed RSV season, SARS- CoV-2 bronchiolitis was more severe than RSV bronchiolitis.

Loss to Follow-Up: Patients with Type 1 Diabetes During the SARS-CoV-2 Pandemic.

The SARS-CoV-2 (severe acute respiratory syndrome related coronavirus 2) pandemic revealed many flaws in our health care system. This review aims to explore the significance of loss to follow-up on patients with type 1 diabetes during the pandemic, the morbidity and mortality associated, and strategies to prevent loss to follow-up or to re-engage patients in longitudinal care. [Pediatr Ann. 2024;53(7):e254-e257.].

The Role of Cytokines and T Cells as Mediators of Inflammatory Pathology in Type 1 Diabetes and COVID-19.

During the coronavirus disease 2019 (COVID-19) pandemic, reports of individuals experiencing new-onset type 1 diabetes (T1D) began to appear in the literature. This spurred subsequent epidemiological studies that demonstrated an increase in new diagnosis of T1D compared to prepandemic. Development of T1D is characterized by the development of an inappropriate T cell response directed against pancreatic beta-cells, leading to eventual loss of insulin secretion. This T cell response occurs in genetically susceptible individuals and may be triggered by viral illnesses. Abnormal cytokine production is another element of the pathogenesis of T1D. Infection with severe acute respiratory syndrome related coronavirus 2 induces a profound increase in the production of inflammatory cytokines and causes significant T-cell dysregulation. These disruptions of the immune system may be linked to the development of T1D following COVID-19. [Pediatr Ann. 2024;53(7):e264-e268.].

Molecular Docking of Phytochemicals from M. Charantia Targeting SARS-CoV-2 Main Protease

Coronavirus Disease 2019 (COVID-19) is a transmittable disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). The outbreak of the disease has affected the world in a negative manner. The development and on-going vaccination efforts has reduced the mortality rate in people with existing comorbidities and lowered virus transmission rate. However, there are still the needs for prescribed medicines that can be consumed by COVID-19 infected persons. Momordica charantia L. has been used in traditional medicines to treat various diseases including anti-diabetic and cancer. Pharmacological studies on Momordica charantia L. revealed that the plant stored many useful phytoconstituents that might be exploited for producing drug compounds to treat COVID-19. Nowadays, computational-aided drug methods are widely used in drug discovery process as it requires minimal compound design and improve the development pipeline. In this study, molecular docking of five phytochemicals from Momordica charantia L. were carried out against SARS-CoV-2 main protease (Mpro). The results obtained revealed that some of the phytochemicals showed a better dock score compared to the drug molnupiravir. Based on the dock score and the medicinal properties of each compound, it is suggested that these compounds can be further studied for potential drugs against COVID-19.

Implementation and effectiveness of non-pharmaceutical interventions, including mask mandates and ventilation, on SARS-CoV-2 transmission (alpha variant) in primary schools in the Netherlands.

There has been a lot of discussion about the role of schools in the transmission of severe acute respiratory coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, where many countries responded with school closures in 2020. Reopening of primary schools in the Netherlands in February 2021 was sustained by various non-pharmaceutical interventions (NPIs) following national recommendations. Our study attempted to assess the degree of regional implementation and effectiveness of these NPIs in South Limburg, Netherlands. We approached 150 primary schools with a structured questionnaire containing items on the implementation of NPIs, including items on ventilation. Based on our registry of cases, we determined the number of COVID-19 cases linked to each school, classifying cases by their source of transmission. We calculated a crude secondary attack rate by dividing the number of cases of within-school transmission by the total number of children and staff members. Two-sample proportion tests were performed to compare these rates between schools stratified by the presence of a ventilation system and mask mandates for staff members. A total of 69 schools responded. Most implemented NPIs were aimed at students, except for masking mandates, which preferentially targeted teachers over students (63% versus 22%). We observed lower crude secondary attack rates in schools with a ventilation system compared to schools without a ventilation system (1.2% versus 2.8%, p<0.01). Mandatory masking for staff members had no effect on the overall crude secondary attack rate (2.0% versus 2.1%, p = 0.03) but decreased the crude secondary attack rate among staff members (2.3% versus 1.7%, p<0.01). Schools varied in their implementation of NPIs, most of which targeted students. Rates of within-school transmission were higher compared to other studies, possibly due to a lack of proper ventilation. Our research may help improve guidance for primary schools in future outbreaks.

Medicinal Chemistry of Antisense Oligonucleotides for Therapeutic Use in SARS-CoV-2: Design Strategies and Challenges for Targeted Delivery

Background: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects. Objective: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations. Methods: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19. Results: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics. Conclusion: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics.

Mutations in the Receptor Binding Domain of Severe Acute Respiratory Coronavirus-2 Omicron Variant Spike Protein Significantly Stabilizes Its Conformation.

The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron's spike protein is examined in detail. The parent Omicron lineage has over ten mutations in the ACE2 binding region of the RBD that are specifically associated with its β hairpin loop domain. It is demonstrated through biophysical molecular computations that the mutations in the β hairpin loop domain significantly increase the intra-protein interaction energies of intra-loop and loop-RBD interactions. The interaction energy increases include the formation of new hydrogen bonds in the β hairpin loop domain that help stabilize this critical ACE2 binding region. Our results also agree with recent experiments on the stability of Omicron's core β barrel domain, outside of its loop domain, and help demonstrate the overall conformational stability of the Omicron RBD. It is further shown here through dynamic simulations that the unbound state of the Omicron RBD remains closely aligned with the bound state configuration, which was not observed for the wild-type RBD. Overall, these studies demonstrate the significantly increased conformational stability of Omicron over its wild-type configuration and raise a number of questions on whether conformational stability could be a positive selection feature of SARS-CoV-2 viral mutational changes.

Potential Usefulness of IgA for the Early Detection of SARS-CoV-2 Infection: Comparison With IgM.

Serological testing can be a powerful complementary approach to achieve timely diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, along with nucleic acid detection. Immunoglobulin (Ig) A antibodies are less frequently utilized to detect SARS-CoV-2 infection than IgM and IgG antibodies, even though IgA antibodies play an important role in protective immunity against SARS-CoV-2. This review discusses the differences in kinetics and assay performance between IgA and IgM antibodies and the factors influencing antibody responses. It highlights the potential usefulness of analyzing IgA antibodies for the early detection of SARS-CoV-2 infection. The early appearance of IgA and the high sensitivity of IgA-based immunoassays can aid in diagnosing coronavirus disease 2019. However, because of cross-reactivity, it is important to recognize the only moderate specificity of the early detection of SARS-CoV-2 IgA antibodies against spike antigens. Either the analysis of antibodies targeting the nucleocapsid antigen or a combination of antibodies against the nucleocapsid and spike antigens may strengthen the accuracy of serological evaluation.

Traditional Chinese Medicine as the Preventive and Therapeutic Remedy for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic still has tremendous impacts on the global socio-economy and quality of living. The traditional Chinese Medicines (TCM) approach showed encouraging results during previous outbreaks of Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). With limited treatment availability, TCM herbs and formulations could be useful to reduce COVID-19 symptoms and potential sources for discovering novel therapeutic targets. We reviewed 12 TCM herbs and formulations recommended for COVID-19 management by the National Health Commission and as National Administration of Traditional Chinese Medicine of the People's Republic of China. This article explored the Chinese national authorities' guidelines from 2003 to 2020, the scientific data in public databases for the recommended TCM remedies, and their potential mechanistic actions in COVID-19 management. Several TCM herbs and formulations could potentially benefit COVID-19 management. The recommended TCM oral preparations list includes Huoxiang zhengqi, Jinhua Qinggan, Lianhua Qingwen, and Shufeng jiedu; the recommended injection preparations comprise Xiyanping Xuebijing, Re-Du-Ning, Tanreqing, Xingnaojing, Shenfu, Shengmai, and Shenmai. TCM remedies are viable options for symptom alleviation and management of COVID-19. The current SARS-CoV-2 pandemic presents an opportunity to find novel therapeutic targets from TCM-active ingredients. Despite the recommendations in Chinese National guidelines, these remedies warrant further assessments in well-designed clinical trials to ascertain their efficacy in the treatment of COVID-19.

Study of different heterocycles showing significant anti-severe acute respiratory syndrome 2 activity in vitro and in vivo.

With the emergence of severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), antiviral drug development has gained increased significance due to the high incidence and potentially severe complications of the resulting coronavirus infection. Heterocycle compounds, acting as antimetabolites of DNA and RNA monomers, rank among the most effective antiviral drugs. These compounds' antiviral effects on various SARS-CoV-2 isolates, as found in existing data collections, form the basis for further research. The aim of this study was to examine the possible antiviral effect of some originally synthesized heterocyclic compounds. The main methods were cell culturing, cytotoxicity assay, qRT-PCR assay, tissue and blood cells analysis, and micro-computed tomography (micro-CT) imaging. In both in vitro and in vivo conditions, the elimination of SARS-Cov-2 occurred significantly earlier after administration of the compounds compared to the control group. In hamsters, the primary symptoms of coronavirus disease disappeared following administration of heterocycle compounds. Using delta and omicron strains of the SARS-CoV-2 virus, newly created heterocycle compound analogs dramatically reduced SARS-CoV-2 multiplication, resulting in a drop in viral RNA load in the supernatant under in vitro conditions. Improvements in pathological manifestations in the blood, bone marrow, and internal organs of hamsters demonstrated that heterocycle compounds inhibited SARS-CoV-2 replication both in vitro and in vivo.