Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus-pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.

Deep recurrent neural network-based Hadoop framework for COVID prediction with applications to big data in cloud computing

This paper proposes a particle squirrel search optimisation-based deep recurrent neural network (PSSO-based DRNN) to predict the coronavirus epidemic (COVID). Here, the cloud-based Hadoop framework is used to perform the prediction process by involving the mapper and reducer phases. Initially, the technical indicators are extracted from the time series data. Then, the deep belief network (DBN) is employed for feature selection from the technical indicators. After that, the COVID prediction is done by the DRNN classifier trained using the PSSO algorithm. The PSSO is developed by the integration of particle swam optimisation (PSO) and squirrel search algorithm (SSA). The PSSO-based DRNN is compared with existing methods and obtained minimal MSE and RMSE of 0.0523, and 0.2287 by considering affected cases. By considering death cases, the proposed method achieved minimal MSE and RMSE of 0.0010, and 0.0323 and measured minimum MSE of 0.0049 and minimum RMSE of 0.0702 for recovered cases.

Impact of social media on young bank employees during COVID-19 pandemic: A cross-sectional study

Background: During the COVID-19 pandemic, social media (SM) use saw a sharp raise, especially for obtaining information regarding COVID-19 during the lockdown. SM platforms also led to misinformation about the disease which caused negative psychological effects on individuals. Bank employees (BE) are special workgroups who experience various levels of mental stress at their workplace due to workload. During lockdown and till date many of the BE work from home which enabled them to use SM accordingly. Objective: The study was conducted to assess the stress levels and anxiety levels due to usage of SM in young BE during the COVID-19 pandemic. Materials and Methods: In this cross-sectional study, an online Google form questionnaire was distributed to the participants using convenient and snowball sampling method. The final sample consisted of 126 Goan young BE. Statistical analysis was performed using descriptive analysis. Results: The results of the study revealed that SM use had significant impact on the BE, with a potential negative effect on developing stress and anxiety. 10.3% (13) of the participants experienced low stress and 89.7% (113) experienced moderate stress. 51.6% (65) of the participants had mild anxiety, 10.3% (13) had moderate anxiety, and 38.1% (48) had severe anxiety. Conclusion: The present study concludes that increased SM use among the BE was associated with negative psychological outcomes. Anxiety and stress were associated with the time spent on using SM sites.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.

Robust T cell responses to Pfizer/BioNTech vaccine compared to infection and evidence of attenuated peripheral CD8+ T cell responses due to COVID-19

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer” peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust Spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring one week post the second vaccination (boost), whereas CD8+ T cells peaked two weeks later. These peripheral T cell responses were elevated compared to COVID-19 patients. We also found that prior SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that prior infection can influence the T cell response to vaccination. Graphical Our understanding of T cell responses in COVID-19 and vaccination is incomplete. Gao et al. examine SARS-CoV-2-specific T cell responses to infection and vaccination, revealing disparate kinetics between CD4+ and CD8+ T cells. Furthermore, compared to vaccination alone, circulating CD8+ T cells are attenuated during infection and in subsequent vaccination.

Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection.

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

Durability of immune responses to mRNA booster vaccination against COVID-19.

BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.ResultsThe booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.

Is Multi System Inflammatory Syndrome Secondary to Covid (Mis-C) Same as Sepsis Associated Secondary Hlh?

Purpose: COVID 19 infection in children is generally mild,however some of them develop an unique immunological phenomenon called MIS-C(multi-system inflammatory syndrome, which is a hyperimmune state resulting in vasculitis,mycarditis and end organ damage.We compared immune status of MIS-C with another viral infection triggered hyperinflammtory state;sepsis hemophagocyticlymphohistiocytosis (SHLH) to understand the pathogenses of this novel clinical syndrome Methods: We included patients with MIS-C, SHLH and viral sepsis(S) Blood samples were collected after written informed consent, utilizing protocols approved by our institution. We evaluated differential leukocyte counts, soluble markers of T cell and macrophage activation (sIL-2R, sCD163 and Ferritin) in plasma and did immunophenotyping of T cells and monocytes on cryopreserved peripheral blood mononuclear cells Results: Total of 62 children (MIS-C 27, Sepsis 27 &SHLH 8) were included with age ranging from 1 to 16 years. Total leukocyte counts did not differ across the groups. MISC had higher neutrophil counts as compared to SHLH and sepsis.(Median cu/mm : MIS-C -10062 SHLH-4434, S- 3138). Monocyte(M)and lymphocyte (L)numbers were comparable with SHLH but lesser than sepsis(Median M/L cummMISC- 390/1488, SHLH-252/1565, S-795/2841). Plasma levels of sIL-2R in MIS-C and SHLH were similarly elevated as opposed to sepsis(Median pg/ml MIS-C- 17824, SHLH- 25702, S - 3653). sCD163 levels was elevated highest in SHLH, followed by MIS-C and Sepsis (Median ng/ml SHLH- 2.18, MIS-C 0-96,S- 0.25). Similar trend was seen in proportions of activated T cells (HLADR+CD38+) across the groups (Median % SHLH 32.5, MIS-C- 4.31, S 1.14). Median CD4:CD8 in MIS-C (2.5) is comparable to sepsis (1.2) but significantly higher than SHLH (0.75) There was no difference inmonocyte activation Conclusion(s):MIS-C is a hyperimmune state but the immune profile has features overlapping with SHLH and sepsis. It is a different hyperimmune syndrome as compared to SHLH and needs more mechanistic studies.

COVID-19 Mortality Prediction using Machine Learning: A Deep Forest Approach

COVID-19 is an extremely deadly disease which has wreaked havoc worldwide. Initially, the first case was reported in the wet markets of Wuhan, China in the early 2020's. Though the mortality rate is low compared to other dangerous diseases, a lot of people have already succumbed to this virus. Vaccines have been successfully rolled out and it seems effective in preventing the severe symptoms of the coronavirus. However, a section of people (the elderly and people with existing comorbidities) still continue to die. It is extremely important to predict the patient vulnerability using machine learning since appropriate medicines and treatments can be given in time and precious lives can be saved. In this research, the deep forest classifier is utilized to predict the COVID-19 casualty status. This classifier requires extremely low hyperparameter tuning and can easily compete with the deep learning classifiers. This algorithm performed better than the traditional machine learning classifiers with an accuracy of 92%. The positive results obtained signifies the potential use of deep forest to prevent unwanted COVID-19 deaths by effectively deploying them in various medical facilities. Further, it can reduce the extreme burden already existing on healthcare systems caused by the novel coronavirus. © 2022 IEEE.

Outcomes of Covid-19 Infection among Hospitalized Patients by Their Stage of Chronic Kidney Disease

INTRODUCTION: Chronic kidney disease (CKD) is an important risk factor for severe COVID-19 disease associated with increased intensive care unit (ICU) admission and mortality. Studies demonstrate an increased mortality rate among advancing CKD stages in patients without COVID-19 infection. However, it is unknown whether a graded association exists between the stages of CKD and COVID-19 mortality. We aim to compare the rates of ICU admission, mechanical ventilation (MV), and survival amongst COVID-19 patients with Stage IIIb -V CKD. METHOD(S): We conducted a retrospective cohort study on non-dialysis adults with Stages IIIb, IV, and V CKD without previous renal transplant hospitalized for COVID-19 infection in a community hospital. Patients were categorized into two groups, Stage IIIb CKD and Stages IV&V CKD, based on their pre-admission glomerular filtration rate (GFR 30-44ml/ min vs < 30ml/min). The primary endpoints were rates of ICU admission, MV, non-invasive mechanical ventilation (NIMV), and survival. The Mann-Whitney U test for continuous variables and the chi-square test for categorical variables were used for analysis. RESULT(S): We screened 228 patients and 153 met the inclusion criteria. Baseline demographics were distributed equally between the two groups. There were statistically significant differences in the ICU admission rate (45.2% vs 25.3%,p-0.01), MV rate (37.1% vs 16.5%,p-0.004) and NIMV rate (50% vs 28.6%,p-0.007) in patients with Stage IIIb versus Stages IV&V CKD respectively. However, there was no significant difference in the survival rates (79.1% vs 67.7%,p-0.1128) between the two groups. CONCLUSION(S): The association between reduced baseline eGFR and increased risk of severe COVID-19 infection has been established with multiple studies evaluating the prognostic impact of pre-existing CKD in patients with COVID-19. Our study illustrates the greater incidence of adverse outcomes, such as ICU admission rate, MV rate, and NIMV rate, in patients with Stages IV&V CKD versus Stage IIIb CKD. With recent guidelines recommending management of COVID-19 infection based on the presence of risk factors, these results will aid in risk stratification among CKD patients with COVID-19, and encourage future prospective studies to explore disease-modifying treatments for the vulnerable CKD population.

Can Inflammatory Markers be used as an Early predictor for Mechanical ventilation in COVID-19 patients with Stages IIIb-V Chronic Kidney Disease?

Background. The clinical use of inflammatory markers soared during the COVID-19 pandemic. Though studies have shown C-reactive protein (CRP) to predict mechanical ventilation (MV) in patients with COVID-19, its utility is unknown in patients with chronic kidney disease (CKD), who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance of inflammatory cytokines. Our aim was to assess the association of inflammatory markers like CRP, ferritin, LDH, D dimer, and MV rate in patients with stages IIIb-V CKD and COVID-19. Methods. We conducted a cross-sectional study on inpatients in a community hospital from 12/1/19 to 1/1/22 with COVID-19 and stages IIIb-V CKD without a previous renal transplant. Primary endpoints were invasive MV(IMV) rates, noninvasive MV(NIMV) rates, and no MV. Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables. Cutoffs for variables were CRP 100 mg/L, ferritin 530ng/ml, D-dimer 0.5mg/L and LDH 590 U/L. Univariate analysis and Area under curve (AUC-ROC) between the covariates and outcomes were computed. Results. 290 patients were screened, and 118 patients met inclusion criteria. CRP, D dimer, and ferritin were significantly different among the three groups. On univariate analysis for IMV, CRP had an OR 5.44;ferritin, OR 2.8;LDH, OR 7.7;D-dimer, OR 3.9, WBC count, OR 4.2 (p< 0.05). Admission CRP level was 0.747 for the IMV group (AUC-ROC, sensitivity 80.8%, specificity 50%) and 0.663 for the NIMV group (AUC-ROC, sensitivity 69.2%, specificity 53%) Conclusion. Our results illustrate a positive correlation between CRP, ferritin, and D-dimer levels and MV and NIMV rates. The ROC demonstrates a good sensitivity for CRP levels in detectingMVthereby emphasizing the utility of these biomarkers as good predictive markers in COVID-19 patients with CKD. With increasing use of inflammatory markers to prognosticate disease severity in COVID, the applicability of these markers in different populations should be investigated. A similar pattern of elevated inflammatory markers predicting the rate of MV was found in patients with stages IIIb-V CKD. This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation due to CKD alone.

Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life (preprint)

The dynamics of innate and adaptive immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to SARS-CoV-2 infection in infants and young children in the first weeks and months of life by analyzing blood samples collected before, during, and after infection with Omicron and Non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, were stably maintained for >300 days. Antigen-specific memory B cell (MCB) responses were durable for 150 days but waned thereafter. Somatic hypermutation of V-genes in MCB accumulated progressively over 9 months. The innate response was characterized by upregulation of activation markers on blood innate cells, and a plasma cytokine profile distinct from that seen in adults, with no inflammatory cytokines, but an early and transient accumulation of chemokines (CXCL10, IL8, IL-18R1, CSF-1, CX3CL1), and type I IFN. The latter was strongly correlated with viral load, and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell transcriptomics. Consistent with this, single-cell ATAC-seq revealed enhanced accessibility of chromatic loci targeted by interferon regulatory factors (IRFs) and reduced accessibility of AP-1 targeted loci, as well as traces of epigenetic imprinting in monocytes, during convalescence. Together, these data provide the first snapshot of immunity to infection during the initial weeks and months of life.

Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2 (preprint)

The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (~4.4%) antibodies isolated at 1.4~6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates (preprint)

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly booster vaccine, and as a primary vaccine for pediatric use including in infants.

Durability of immune responses to the booster mRNA vaccination against COVID-19 (preprint)

Waning immunity to vaccination represents a major challenge in vaccinology. Whether booster vaccination improves the durability of immune responses is unknown. Here we show, using a cohort of 55 adult vaccinees who received the BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine against SARS–CoV–2, that a booster (i.e., 3rd immunization) dose at 6 – 10 months increased the half-life of serum neutralizing antibody (nAb) titers to 76 days from 56 – 66 days estimated after the primary two-dose vaccination series. A second booster dose (i.e., 4th immunization) more than a year after the primary vaccination increased the half–life further to 88 days. However, despite this modestly improved durability in nAb responses against the Wuhan strain, there was a loss in neutralization capacity against Omicron subvariants, especially the recently emerged variants, BA.2.75.2 and BQ.1.1 (35 and 50-fold drop in titers respectively, relative to the ancestral (WA.1) strain. While only 55 – 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (3rd dose), the response declined to below the detection limit in almost all individuals by 6 months. Notably, even against BA.1 and BA.5, the titers declined rapidly in a third of the vaccinees and were below the detection limit at 6 months. In contrast, booster vaccination induced antigen–specific memory B and T cells that persisted for at least 6 months. Collectively, our data show that the durability of immune responses improves following subsequent booster immunizations; however, the emergence of immune evasive variants reduces the effectiveness of booster doses in preventing infection.

Early immune markers of clinical, virological, and immunological outcomes in patients with COVID-19: a multi-omics study.

Background: The great majority of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunological outcomes in SARS-CoV-2-infected patients. Methods: Leveraging longitudinal samples and data from a clinical trial (N=108) in SARS-CoV-2-infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients. We characterized the association between early immune markers and subsequent disease progression, control of viral shedding, and SARS-CoV-2-specific T cell and antibody responses measured up to 7 months after enrollment. We further compared associations between early immune markers and subsequent T cell and antibody responses following natural infection with those following mRNA vaccination. We developed machine-learning models to predict patient outcomes and validated the predictive model using data from 54 individuals enrolled in an independent clinical trial. Results: We identify early immune signatures, including plasma RIG-I levels, early IFN signaling, and related cytokines (CXCL10, MCP1, MCP-2, and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2-specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine-learning models using 2-7 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset. Conclusions: Early immune signatures following infection can accurately predict clinical and immunological outcomes in outpatients with COVID-19 using validated machine-learning models. Funding: Support for the study was provided from National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) (U01 AI150741-01S1 and T32-AI052073), the Stanford's Innovative Medicines Accelerator, National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA) DP1DA046089, and anonymous donors to Stanford University. Peginterferon lambda provided by Eiger BioPharmaceuticals.

INCIDENTAL PULMONARY CAVITARY LESIONS AS AN UNCOMMON PRESENTATION OF LEMIERRE SYNDROME

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Pulmonary cavitary lesions can have varying etiologies. Among these, Lemierre syndrome is an uncommon disease which usually presents with symptoms of upper respiratory tract infection with unilateral neck pain, tenderness or swelling. In recent years, antibiotic stewardship for upper respiratory illnesses has led to its delayed diagnosis resulting in possible increased morbidity and mortality. There have been few reported cases of pulmonary cavitary lesions as the initial presentation of Lemierre syndrome. Our patient presented with incidental bilateral pulmonary cavitary lesions, which led to a diagnosis of Lemierre syndrome. CASE PRESENTATION: A 30-year-old gentleman with no significant past medical history visited urgent care for reproducible chest pain following motor vehicle accident. Chest x ray obtained for suspected rib fracture showed bilateral patchy and rounded opacities, confirmed by CT as bilateral cavitary nodules and consolidation. He was referred to our hospital for further care. Two weeks prior, following administration of COVID booster vaccine, he had developed fever, sore throat, tender lump behind left ear, left jaw and anterior left neck. Most symptoms self resolved in 3-5 days except persistent fever. On arrival, patient was febrile to 102F and hemodynamically stable. Physical examination revealed dry mucous membranes and erythematous pharynx. Labs were significant for leukocytosis of 24.5uL with bandemia and elevated inflammatory markers. Three sets of blood cultures were drawn and empirically started on vancomycin and piperacillin/tazobactam. Echocardiogram ruled out heart valve vegetations. CT angiography of neck showed intraluminal thrombi in left internal jugular vein. Blood cultures finalized to Fusobacterium nucleatum and antibiotics were tapered to metronidazole. Due to persistent fever, anticoagulation was initiated with apixaban 5mg twice daily. Pan CT showed improvement in size of many pulmonary septic emboli. After 48 hours of patient being afebrile, he was discharged on antibiotics and apixaban for at least 4 weeks until surveillance CT angiography showed non progression of thrombus. DISCUSSION: Lemierre syndrome is septic thrombophlebitis of internal jugular vein which presents within 1-3 weeks following upper respiratory tract infections with multi-system complications. Management involves prolonged antibiotic course with use of anticoagulation and vein stripping still being debated. Our patient came to the hospital with an incidental finding of bilateral cavitary pulmonary lesions which went on to be diagnosed as Lemierre syndrome from positive blood cultures and CT angiography findings. CONCLUSIONS: Lemierre syndrome is an uncommon disease with mortality up to 18%. A call out to health care providers to keep a low threshold for its diagnosis in patients with initial presentation of bilateral pulmonary cavitary lesions, warranting prompt management. Reference #1: Sinave CP, Hardy GJ, Fardy PW. The Lemierre syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection. Medicine (Baltimore). 1989 Mar;68(2):85-94. PMID: 2646510. Reference #2: Golpe R, Marín B, Alonso M. Lemierre's syndrome (necrobacillosis). Postgrad Med J. 1999 Mar;75(881):141-4. doi: 10.1136/pgmj.75.881.141. PMID: 10448489;PMCID: PMC1741175. Reference #3: Lee WS, Jean SS, Chen FL, Hsieh SM, Hsueh PR. Lemierre's syndrome: A forgotten and re-emerging infection. J Microbiol Immunol Infect. 2020 Aug;53(4):513-517. doi: 10.1016/j.jmii.2020.03.027. Epub 2020 Apr 4. PMID: 32303484. DISCLOSURES: No relevant relationships by Sumukh Arun Kumar No relevant relationships by Megna Machado No relevant relationships by Sushmita Prabhu No relevant relationships by PAWINA SUBEDI No relevant relationships by Mithil Gowda Suresh No relevant relationships by Bradley Switzer

Rosmarinic acid as a novel biomedical drug for inhibiting the replication of herpes and dengue viruses: An In-silico assessment (preprint)

Since ancient times to till now, viruses such as dengue, herpes virus, ebola, AIDS, influenza, ebola, chicken meat and SARS have been roaming around causing great health burdens. To fight against these contagious viruses, people rely heavily on medicinal plants to enhance their immune system of innate and adaptive. In this research, the preparation of ligands and proteins was performed using the Maestro V.13.2 module tool. This software, consisting of LigPrep, Grid Generation, SiteMap and Glide XP, has each contributed significantly to the preparation of ligands and proteins. Ultimately, the research found that (R)-(+)-rosmarinic acid was found to have significant docking scores of -10.847 for herpes virus, of -10.033 for NS5 and − 7.259 for NS1. In addition, the Pass Server prediction indicates that rosmarinic acid possesses a diverse spectrum of enzymatic activities, as Probability Active (Pa) values ​​start at > 0.751; whereas it has fewer adverse effects than the drugs prescribed for viruses. Accordingly, it was found that the rate of acute toxicity values ​​of rosamric acid. According to this analysis, we expect that the current research will reveal a clear route to finding a medicine that can successfully lessen the complications of numerous viruses without causing any harmful effects. Ultimately, we concluded that (R)-(+)-rosmarinic acid would expose significant antiviral effects in in-vitro and in-vivo experiments and also this research would be a valuable asset for future especially those who wish to discover a drug molecule for variety of viruses.