Severe Acute Respiratory Syndrome Coronavirus Infection Research Articles

Exploring the viability of Zeatin as a prospective therapeutic candidate for investigating the complex interplay between severe acute respiratory syndrome coronavirus (SARS-CoV) and Alzheimer's disease.

The present research aims to explore the intricate link between SARS-CoV infection and susceptibility to Alzheimer's disease, focusing on the role of APOE4, a genetic factor associated with both conditions. Our research aims to uncover shared molecular pathways, considering APOE4's impact on lipid metabolism, immune responses, and neuroinflammation relevant to COVID-19 and AD. The Chyawanprash phytocompounds were subjected to in-silico ADMET profiling and Zeatin a neuroprotective cytokinin emerged as a promising regulator of the ACE2-SPIKE complex as it exhibits favourable pharmacological attributes, presenting as a non-substrate for Permeability glycoprotein, low Protein Binding Percentage, and distinctive toxicity endpoints. Therapeutic candidate. Zeatin's robust binding disrupts the intricate APOE4-ACE2-SPIKE interplay (AAS), offering a potential therapeutic avenue that is further corroborated by Molecular dynamic simulation as the system remained stable without any major fluctuation throughout the 100ns simulation. The AAS binding free energy, determined as -124.849 +/- 15.513 KJ/mol using MMPBSA assay, reveals significant contributions to complex stability from amino acids including, GLN41: 1.211kcal/mol, GLU340: 1.188kcal/mol, ALA344: 1.198kcal/mol, while ARG38: 2.011kcal/mol establishes pivotal strong bonds integral to the interaction between AAS and Zeatin. Rigorous cytotoxicity assessments reveal Zeatin's safety profile, highlighting its inhibitory effect on LN18 cell viability that sharply decreases to 32.47% at 200µg/ml, underscoring its modulatory impact on cellular metabolism. These findings enhance our understanding of the convergent mechanisms linking SARS-CoV and AD, providing valuable insights for potential therapeutic interventions. Further research is warranted to elucidate the specific pathways and molecular mechanisms through which zeatin exerts its protective effects.

Unique tRNA Fragment Upregulation with SARS-CoV-2 but Not with SARS-CoV Infection.

Unlike other coronaviruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly infected the global population, with some suffering long-term effects. Thanks to extensive data on SARS-CoV-2 made available through global, multi-level collaborative research, investigators are getting closer to understanding the mechanisms of SARS-CoV-2 infection. Here, using publicly available total and small RNAseq data of Calu3 cell lines, we conducted a comparative analysis of the changes in tRNA fragments (tRFs; regulatory small noncoding RNAs) in the context of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 infections. We found extensive upregulation of multiple tRFs in SARS-CoV-2 infection that was not present in SARS-CoV or other virus infections our group has studied. By comparing the total RNA changes in matching samples, we identified significant downregulation of TRDMT1 (tRNA methyltransferase), only in SARS-CoV-2 infection, a potential upstream event. We further found enriched neural functions among downregulated genes with SARS-CoV-2 infection. Interestingly, theoretically predicted targets of the upregulated tRFs without considering mRNA expression data are also enriched in neural functions such as axon guidance. Based on a combination of expression data and theoretical calculations, we propose potential targets for tRFs. For example, among the mRNAs downregulated with SARS-CoV-2 infection (but not with SARS-CoV infection), SEMA3C is a theoretically calculated target of multiple upregulated tRFs and a ligand of NRP1, a SARS-CoV-2 receptor. Our analysis suggests that tRFs contribute to distinct neurological features seen in SARS-CoV-2.

Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

Modulation of various host cellular machinery during COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID-19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID-19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS-CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular-level interaction between the host and the pathogen. In this review, we describe how SARS-CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post-transcription, translation, post-translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS-CoV2 infection.

Three-month antibody persistence of a bivalent Omicron-containing booster vaccine against COVID-19

We previously presented day 29 interim safety and immunogenicity results from a phase 2/3 study (NCT04927065) comparing the Omicron-BA.1-containing bivalent vaccine mRNA-1273.214 (50-µg) to the 50-µg mRNA-1273 booster in adults who previously received the mRNA-1273 primary series (100-µg) and mRNA-1273 first booster (50-µg) dose. Primary endpoints were safety, non-inferiority of the neutralizing antibody (nAb) and seroresponse against Omicron BA.1, superiority of the nAb response against Omicron-BA.1, and non-inferiority of the nAb response against ancestral SARS-CoV-2 for second boosters of mRNA-1273.214 versus mRNA-1273 at days 29 and 91. The key secondary endpoint was the seroresponse difference of mRNA-1273.214 versus mRNA-1273 against ancestral SARS-CoV-2 at days 29 and day 91. Participants were sequentially enrolled and dosed with 50-µg of mRNA-1273 (n = 376) or mRNA-1273.214 (n = 437) as second booster doses. Here we present day 91 post-booster results. In participants with no pre-booster, severe acute respiratory syndrome coronavirus 2-infection (SARS-CoV-2), mRNA-1273.214 elicited Omicron-BA.1-nAb titers (95% confidence interval [CI]) that were significantly higher (964.4 [834.4-1114.7]) than those of mRNA-1273 (624.2 [533.1-730.9]) and similar to those of mRNA-1273 against ancestral SARS-CoV-2 at day 91. mRNA-1273.214 also induced higher binding antibody responses against Omicron BA.1 and alpha, gamma and delta variants than mRNA-1273. Safety profiles were similar for both vaccines. The Omicron-BA.1 bivalent vaccine improved antibody responses compared to mRNA-1273 through 90 days post-booster.

SEVERE CORONAVIRUS INFECTIONS IN PREGNANCY: A SYSTEMATIC REVIEW

Introduction: A systematic literature review was undertaken to examine case reports pertaining to Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, in the context of pregnancy.
 Objective: The objective was to provide a comprehensive overview of the clinical manifestations, disease progression, and outcomes for both pregnant individuals and their neonates.
 Methods: A comprehensive search was conducted on the MEDLINE and ClinicalTrials.gov databases, covering the period from their establishment up until August 3, 2023. The author incorporated articles that present case-level data about the infection of pregnant women with MERS-CoV, SARS-CoV, and SARS-CoV-2. The course of sickness, markers of severe disease, maternal health outcomes, and pregnancy outcomes were extracted from the articles that were included.
 Results: A total of 1,328 distinct publications were found, with 1,253 articles being removed based on the evaluation of their titles and abstracts. A comprehensive examination was conducted on a total of 75 publications, out of which 29 papers were deemed ineligible and hence eliminated from the analysis throughout the full-text review process. Out of the 46 papers that provided case-level data, eight publications presented information on 12 instances of MERS-CoV infection, seven publications discussed 17 cases of SARS-CoV infection, and 31 publications detailed 98 cases of SARS-CoV-2 infection. The clinical presentation and progression of the illness varied over a spectrum, ranging from individuals who showed no symptoms to those who experienced severe and ultimately deadly disease. This pattern was consistent with what is typically observed in the broader population of patients. The occurrence of significant morbidity and mortality in women who contract MERSCoV, SARS-CoV, or SARS-CoV-2 during pregnancy has been documented. Adverse pregnancy outcomes such as pregnancy loss, preterm delivery, and laboratory findings indicating vertical transmission have also been recorded.
 Conclusion: The available data on SARS-CoV, MERS-CoV, and SARS-CoV-2 infections during pregnancy are currently inadequate. However, these data can still provide valuable insights for informing early public health interventions and clinical decision-making in the context of COVID-19. It is important to note that more comprehensive and systematically gathered data are needed to further enhance our understanding of this topic.

Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients?

From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it. In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were "Secondary Sclerosing Cholangiopathy", "SSC-CIP", "Secondary Sclerosing Cholangiopathy in critically ill patients", "Ketamine and cholangiopathy", "Ketamine abusers and liver disease", "Ketamine-related cholangiopathy", "SARS-CoV2 infection and liver disease", "post Covid-19 secondary sclerosing cholangitis", "Covid-19 cholangiopathy". Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out. Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.

Characteristics and management of patients with SARS-CoV2 infection admitted to pediatric intensive care units: Data analysis of the Spanish national multicenter registry.

The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) disease characteristics and management in children admitted to the pediatric intensive care units (PICU). The present study was based on a national multicentric prospective registry including PICU patients with SARS-CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS-C). A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS-C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios[IRR] 1.21, p < .012), pediatric sequential organ failure assessment score(p-SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS-C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS-C patients, their use was associated with higher p-SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS-C, it was associated with higher p-SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS-C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001). Severe SARS-CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS-C the most frequent cause of PICU admission related to SARS-CoV2. In most cases, the course of the disease was mild except in children with previous diseases.

SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study

BackgroundOne of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation. Materials and methodsPeripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-β, IL-17 and IL21 was assessed by ELISA method. ResultsThe population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-β, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group. ConclusionBased on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

Postnatal SARSCOV2 Infection in Neonates, Characteristics and Outcomes: An Observational Study

Background: Many aspects of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) pandemic in 2019 have been unclear, especially in newborns, and reports of neonatal diseases are usually associated with perinatal infection. Objectives: The purpose of this study was to evaluate clinical and para-clinical manifestations in newborns that contracted the infection after birth. Methods: This observational research was conducted from October 2020 to March 2022 to examine postnatal SARSCoV2 infection in infants admitted to the NICU or neonatal ward at the Children’s Medical Center in Tehran, Iran. Inclusion in the study was open to neonates who had positive RT-PCR results postnatally. Results: In total, 55 newborns were confirmed to have postnatal SARSCOV2. Fever was the most frequently observed symptom, with 35 (61%). Necrotizing enterocolitis was seen in 18% of neonates, and 30% of them were preterm. Neutropenia was seen in 34% of cases, with five cases having severe neutropenia. All neonates had a normal platelet count. Twenty percent of patients showed C - reactive protein higher than 6 mg/L. Two newborns had co-existing bacterial urinary tract infections. Our neonates didn't require antiviral, anticoagulant, or corticosteroid medications, and they recovered while receiving only supportive care. Everyone in the group of newborns was discharged without complications, and there were no deaths. Conclusions: The high rate of fever, high C- reactive protein, and neutropenia in SARSCoV2 neonates suggests that more observational research is needed to compare these symptoms to bacterial sepsis to avoid the overuse of antibiotics in these patients.

Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.

To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients. This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions. There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1-25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08-0.26). SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.

A Small Molecule That In Vitro Neutralizes Infection of SARS-CoV-2 and Its Most Infectious Variants, Delta, and Omicron.

The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages. In this brief report, we describe that the small molecule CD04872SC was able to neutralize SARS-CoV2 infection with a half-maximal effective concentration (EC50) = 248 μM. Serendipitously, we also were able to observe that CD04872SC inhibited the infection of the SARS-CoV-2 variants; Delta (EC50 = 152 μM) and Omicron (EC50 = 308 μM). These properties may define CD04872SC as a potential broad-spectrum candidate lead for the development of treatments for COVID-19.

Uncovering biomarkers for potential therapeutic targeting for COVID-19-related acute kidney injury: A bioinformatic approach

ABSTRACT Objective: The Coronavirus Disease 2019 (COVID-19) is a recently-emerging infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), posing a significant threat to public health around the world. In patients with COVID-19, acute kidney injury (AKI) is a common complication associated with poor prognoses. We analyzed co-expressed genes to explore relationships between SARS-CoV2 infection and AKI, and revealed potential biomarkers and therapeutic targets of the COVID-19-associated AKI (COVID-19-AKI). Methods: We utilized the GSE147507 and GSE139061 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in SARS-CoV-2 infection and AKI, respectively. This was followed by analyzing protein-protein interaction networks, Gene Ontology, and pathway enrichment to uncover the relationship between DEGs. DEGs in common (co-DEGs), as well as corresponding interactive transcription factors (TFs) and microRNAs, were identified from the above results, followed by drug molecules uncovered for managing COVID-19-AKI. Aims: To reveal potential biomarkers and therapeutic targets for COVID-19-AKI by bioinformatic approach. Results: We discovered 345 DEGs in the lung and 310 DEGs AKI samples from COVID-19 patients, respectively. IFIT1, ISG15, MX1, IFIT3, and IFIT2 were involved in SARS-CoV-2 pulmonary infection, while hub genes such as RPL23, EIF4A1, RPS8, RPL13, and UPF2 were associated with AKI. We further derived co-DEGs including ERRFI1, KLK10, NR4A1, PODXL, RASGEF1C, RNU11, SNORA12, SNORA74B, and VTRNA1-1 coupled with their predicted transcription factors, including BACH2, HNF4A, MYC, and microRNAs containing miR-637, miR-542-3p, and miR-224. These targets may correlate with COVID-19-AKI, for which candidate drugs were identified. Conclusions: ERRFI1, KLK10, NR4A1, PODXL, RASGEF1C, RNU11, SNORA12, SNORA74B, and VTRNA1-1 may be associated with COVID-19-AKI and serve as novel markers.

Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax".

messenger RNA (mRNA)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines such as BNT162b2 became available in late 2020, but hematological malignancy patients (HM pts) were not evaluated in initial registration trials. We hereby report the results of a prospective, unicentric, observational study Response to COVID-19 Vaccination in hEmatological malignancies (CERVAX) developed to assess the postvaccine serological and T-cell-mediated response in a cohort of SARS-CoV2-negative HM pts vaccinated with BNT162b2. Patients with lymphomas [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], chronic lymphocytic leukemia (CLL), and multiple myeloma (MM); off-therapy for at least 3 months; in a watch-and-wait program; or in treatment with ibrutinib, venetoclax, and lenalidomide were included. Different time points were considered to assess the serological response to the vaccine: before the second dose (T1), at 3-6-12 months after the first dose (T2-3-4, respectively). Since March 2021, 39 pts have been enrolled: 15 (38%) NHL, 12 (31%) CLL, and 12 (31%) MM. There were 13 of the 39 pts (33%) seroconverted at T1; an increase of the serological response was registered after the second dose (T2) (22/39 pts, 56%) and maintained after 6 months (22/39 pts, 56%) and 12 months (24/39 pts, 61%) from the first dose (T3-T4, respectively). Non-serological responders at T4 were 7/39 (18%): 0/15 NHL, 1/12 MM (8%), and 6/12 CLL (50%). All of them were on therapy (one lenalidomide, three ibrutinib, and three venetoclax). SARS-CoV2-reactive T-cell analysis (interferon gamma release assays) was available since June 2022 and was evaluated at 12 months (T4) from the first dose of vaccine in 31/39 pts (79%). T-cell-mediated-responders were 17/31 (55%): most of them were NHL and MM (47%, 41% and 12% for NHL, MM, and CLL, respectively). Both serological and T-cell non-responders were represented by pts on active therapy (venetoclax/ibrutinib). During the period of observation, eight (20.5%) pts developed mild SARS-CoV2 infection; no coronavirus disease 19 (COVID-19)-related deaths or hospitalizations were registered. In conclusion, in our cohort of lymphoproliferative pts receiving BNT162b2, CLL diagnosis and venetoclax/ibrutinib seem to be related with a lower humoral or T-mediated response. Nevertheless, the efficacy of mRNA vaccine in HM pts and the importance to continue the vaccine program even in non-responders after the first dose are supported in our study by demonstrating that a humoral and T-cell-mediated seroconversion should be observed even in the subsets of heavily immunocompromised pts.

Post-Covid Orofacial Mucormycosis: A Clinico-Radiological Classification System and Management Protocol.

In the wake of the second wave of the COVID-19 pandemic, a substantial number of individuals were afflicted by orofacial mucormycosis post-COVID. The immunocompromised state rendered by the SARS-COV2 (Severe Acute Respiratory Syndrome Corona Virus 2) infection provides a breeding ground for the opportunistic mucor invasion. Corticosteroid and COVID-induced hyperglycemia contribute to the unhindered progress of the mucor infection in these patients. The sino-nasal region serves as the entry point and rapid progress of the disease to the oral cavity, mid-face, orbits, and ultimately the brain proves fatal. The aim of this study was to present a definitive clinico-radiological staging/classification system for patients of post-covid mid-face mucormycosis based on combined radiographic and clinical features for subsequent convenient staging of maxillofacial mucormycosis. The objectives are being to lay down a comprehensive management protocol for these patients. This retrospective study consisted of a cohort of 31 patients presenting to a tertiary care center over a 12-month period and diagnosed as post-covid mucormycosis. Their clinical features at the time of presentation along with radiographic presentation/extent of anatomical destruction were combined to create a clinico-radiological staging system. Further, a comprehensive management protocol including cultures, surgery and chemotherapy has been laid down. This included 18 males and 13 females. Average age of the patients was 53.5years. As per the clinico-radiological system formulated by the authors, 2 patients (1 males and 1 females) displayed features of Stage 0, 12 patients (7 males and 5 females) of Stage 1-A, 8 patients (5 males and 3 females) of Stage 1-B, 6 patients (4 males and 2 females) and 3 patients (1 male and 2 females) of Stage 3. The lacuna of a comprehensive staging/classification system for patients of maxillofacial mucormycosis was felt by the authors while treating those affected by post-covid mucormycosis along with a detailed algorithm for management of the study population. It is to this effect that this clinic-radiological classification system has been suggested by the authors along with a management protocol.

S-39-1: COVID-19 AND HYPERTENSION IN JAPAN, AND KANAGAWA RASI COVID-19 STUDY

Severe acute respiratory syndrome coronavirus 2 (SARSCoV2) caused a global coronavirus disease-2019 (COVID19) pandemic, as declared by the World Health Organization on March 11, 2020. COVID19 was confirmed for the first time in January 2020, and despite epidemic prevention efforts, the number of patients with COVID19 continued to increase, primarily in metropolitan areas. To prevent the further spread of COVID19, the Japanese government announced a state of emergency on 7 April 2020, similar to the lockdowns impleme nted in other countries. We showed a significant increase in office BP with the white coat phenomenon was observed during the state of emergency, as well as an increase in related stress, thereby indicating that we should pay more attention to BP management during stressful global events, including the COVID19 pandemic, to prevent cardiovascular events (Kobayashi K, et al. Hypertens Res 2022; Kobayashi K, et al. Ito S, et al. J Diabetes Investig Apr 18 Epub, 2022). In addition, since the onset of the COVID19 pandemic, the possible roles of renin angiotensin system (RAS) inhibitors in COVID19 have been debated as favorable, harmful, or neutral. ACE2 not only is the entry route of SARSCoV2 infection but also triggers a major mechanism of COVID19 aggravation by promoting tissue RAS dysregulation, which induces a hyperinflammatory state in several organs, leading to lung injury, hematological alterations, and immunological dysregulation. ACE inhibitors and ARBs inhibit the detrimental hyperactivation of the RAS by SARSCoV2 and increase the expression of ACE2, which is a counterregulator of the RAS. Several studies have investigated the beneficial profile of RAS inhibitors in COVID19; however, this finding remains unclear. Further prospective studies are warranted to confirm the role of RAS inhibitors in COVID19 (Matsuzawa Y, et al. Hypertens Res 2020; Matsuzawa Y, et al. Hypertens Res, 202; Sato R, et al. Clin Exp Nephrol 2022).

Angiotensin converting enzyme 2 level and its significance in COVID-19 and other diseases patients.

Angiotensin-converting enzyme 2 (ACE2) expressions and its modulation are of great interest as being a key receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and the protective arm of the rennin-angiotensin axis, maintaining cardiovascular homeostasis. However, ACE2 expressions and their modulation in the healthy and disease background are yet to be explored. We performed a meta-analysis, extracting the data for ACE2 expression in human subjects with various diseases, including SARS-CoV2 infection without or with co-morbidity. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Out of 203 studies, 39 met the inclusion criteria with SARS-CoV2 patients without co-morbidity, SARS-CoV2 patients with co-morbidity, cardiovascular (CVD) patients, diabetes patients, kidney disorders patients, pulmonary disease patients, and other viral infections patients. Angiotensin-converting enzyme 2 expression was significantly increased in all diseases. There was an elevated level of ACE2, especially membrane-bound ACE2, in COVID-19 patients compared to healthy controls. A statistically significant increase in ACE2 expression was observed in CVD patients and patients with other viral diseases compared to healthy subjects. Moreover, subgroup analysis of ACE2 expression as soluble and membrane-bound ACE2 revealed a remarkable increase in membrane-bound ACE2 in CVD patients, patients with viral infection compared to soluble ACE2 and pooled standard mean difference (SMD) with the random-effects model was 0.37 and 2.23 respectively. It was observed that utilizing the ACE2 by SARS-CoV2 for its entry and its consequence leads to several complications. So there is a need to investigate the underlying mechanism along with novel therapeutic strategies.

Pathobiology and dysbiosis of the respiratory and intestinal microbiota in 14 months old Golden Syrian hamsters infected with SARS-CoV-2.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS2) affected the geriatric population. Among research models, Golden Syrian hamsters (GSH) are one of the most representative to study SARS2 pathogenesis and host responses. However, animal studies that recapitulate the effects of SARS2 in the human geriatric population are lacking. To address this gap, we inoculated 14 months old GSH with a prototypic ancestral strain of SARS2 and studied the effects on virus pathogenesis, virus shedding, and respiratory and gastrointestinal microbiome changes. SARS2 infection led to high vRNA loads in the nasal turbinates (NT), lungs, and trachea as well as higher pulmonary lesions scores later in infection. Dysbiosis throughout SARS2 disease progression was observed in the pulmonary microbial dynamics with the enrichment of opportunistic pathogens (Haemophilus, Fusobacterium, Streptococcus, Campylobacter, and Johnsonella) and microbes associated with inflammation (Prevotella). Changes in the gut microbial community also reflected an increase in multiple genera previously associated with intestinal inflammation and disease (Helicobacter, Mucispirillum, Streptococcus, unclassified Erysipelotrichaceae, and Spirochaetaceae). Influenza A virus (FLUAV) pre-exposure resulted in slightly more pronounced pathology in the NT and lungs early on (3 dpc), and more notable changes in lungs compared to the gut microbiome dynamics. Similarities among aged GSH and the microbiome in critically ill COVID-19 patients, particularly in the lower respiratory tract, suggest that GSHs are a representative model to investigate microbial changes during SARS2 infection. The relationship between the residential microbiome and other confounding factors, such as SARS2 infection, in a widely used animal model, contributes to a better understanding of the complexities associated with the host responses during viral infections.

Dysfunctional Metabolisms Of T Cells In Collegiate Football Players Infected With Sars-cov2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent ofCOVID19, which caused a global pandemic. One of the pathogenic hallmarks of COVID19 is adysregulation of immune cell metabolism accompanied by excessive inflammatory cytokineresponse, particularly in adults with underlying co-morbidities. However, the impact of SARS-CoV2 on metabolic function in discrete cellular populations, such as T cells, in young, otherwisehealthy, elite-level athletes who recovered from COVID19 is currently unknown. PURPOSE: Weexamined whether NCAA Division I Football Players exhibited altered T cell metabolism afterrecovering from COVID19. METHOD: We studied 9 PCR SARS-CoV2 post-positive (COVID19+)collegiate football players following 14-day quarantine and 4 COVID19 naïve players(COVID19-). Resting T cells were isolated and stimulated overnight with either: 1) SARS-CoV2peptivator pool of S + N + M peptides (JPT peptides), 2) T cell activator beads CD3/CD28, 3)SARS-CoV2 peptides+CD3/CD28 beads, or 4) T cells alone. Following overnight stimulation, Tcell bioenergetics were characterized using the Seahorse BioAnalzyzer (Agilent) to measureextracellular acidification rates (ECAR, a measure of glycolysis) and oxygen consumption rates(OCR, a measure of mitochondrial bioenergetics). Differences between groups were analyzedusing ANOVA and Dunnett’s post hoc tests. RESULTS: The ECAR of T cells isolated fromCOVID19+ participants was 32.5% lower when activated with CD3/CD28 beads and the SARS-CoV2 peptides, than that of T cells activated with beads alone (p < 0.05), but no difference wasobserved in T cells from COVID19- controls (p > 0.05). Similarly, OCR associated with ATPproduction was also 32.7% lower in COVID19+ participants (p < 0.001) when stimulated withSARS-CoV2 peptides, but not in COVID19- participants (p > 0.05). DISCUSSION: Our data suggestthat SARS-CoV2 infection is associated with impaired T cell bioenergetics, which coulddetrimentally impact T cell effector functions. As such, SARS-CoV2 infection appears to beassociated with hallmarks of T cell exhaustion even in elite collegiate athletes, which would beexacerbated in adults with pre-existing metabolic diseases (i.e., diabetes, obesity) and other co-morbidities.

Refractory Headaches.

Medication overuse headache (MOH), new daily persistent headache (NDPH), and persistent refractory headache attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection represent a significant burden in terms of disability and quality of life, and a challenge in terms of definition, pathophysiology, and treatment. Regarding MOH, prevention without withdrawal is not inferior to prevention with withdrawal. Preventive medications like topiramate, onabotulinumtoxinA, and calcitonin gene-related peptide (CGRP) monoclonal antibodies improve chronic migraine with MOH regardless of withdrawal. The differential diagnosis of NDPH is broad and should be carefully examined. There are no guidelines for the treatment of NDPH, but options include a short course of steroids, nerve blocks, topiramate, nortriptyline, gabapentin, CGRP monoclonal antibodies, and onabotulinumtoxinA. The persistence of headache 3 months after SARS-CoV2 infection is a predictor of poor prognosis.