Designing a Conserved Immunogenic Peptide Construct from the Nucleocapsid Protein of Puumala orthohantavirus.

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides' immunogenic potential, which needs to be validated in different experimental systems.

Cross-reactivity of hantavirus antibodies after immunization with PUUV antigens.

Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross-reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross-reactive with serum from MVs immunized small mammals. These cross-reactive epitopes were located in oligomerization perinuclear targeting and Daxx-interacting domains. Most cross-reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross-reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

Zika virus precursor membrane peptides induce immune response in peripheral blood mononuclear cells.

Zika virus is a re-merging flavivirus allied to serious mental health conditions in the fetuses. There is currently no preventives or treatment available for Zika infection. In this work, we have extended the in silico analysis by performing the molecular docking of previous reported three conserved Zika virus precursor membrane (prM) peptides (MP1, MP2 and MP3) with HLA complex (pHLA) and T cell receptors (TCR) and also evaluated the peptide specific immune response in human peripheral blood mononuclear cells (PBMC). Most of the CD8+ and CD4+ T cell peptides-HLA complexes demonstrated good binding energies (ΔG) and HADDOCK scores in molecular docking analysis. Immunogenic response of peptides is measured as human peripheral blood mononuclear cell (PBMC) proliferation and interferon-gamma (IFN-γ) production using a 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and a sandwich enzyme-linked immunosorbent assay (ELISA) respectively on ten different healthy blood samples. Peptide MP3 exhibited significant results in eight (cell proliferation) and seven (IFN-γ secretion) healthy volunteers' blood samples out of ten. Additionally, peptides MP1 and MP2 presented significant cell proliferation and IFN-γ release in six healthy blood samples. Thus, the outcomes from in silico and in vitro studies showed the immunogenic potential of peptides which need to validated in different experimental system before considering as candidate vaccine against Zika virus infection.

Analysis of highly frequent point mutations in glycoprotein C, glycoprotein N, and nucleoprotein of CCHFV.

Crimean-Congo hemorrhagic fever virus (CCHFV) is classified among top 10 priority pathogens by World Health Organization. CCHFV belongs to Bunyaviridae family and negative sense ssRNA genome composed of three RNA segments: L, M, and S. RNA viruses show higher mutation rate as compared to DNA viruses. To gain deeper understanding of impact of point mutations in CCHFV M and S segment, mutation profiling, homology modeling, and molecular dynamic (MD) simulation were performed. Structural glycoproteins (glycoprotein C [Gc] and glycoprotein N [Gn]) of CCHFV are important for host-virus interaction and genome packaging, whereas CCHFV nucleoprotein (NP) is crucial for viral replication. Hence, current study is focused on evaluation of eight mutations in structural glycoproteins (Gc: 7 and Gn: 1) of M segment and seven mutations in NP of S segment. All these mutations were highly frequent, with mutation frequency between 0.81 and 1.0 and found to be persistent in the recent strains of CCHFV. Solubility analysis predicted that selected point mutations reduce solubility of Gc protein and increase solubility of Gn and NP proteins. MD simulation study deciphered that A1046V and G1158E in Gc protein, I778T in Gn protein, and H195R in NP protein displayed large deviation and fluctuation, and affected intramolecular interactions. In conclusion, we observed that point mutations could impact structure, stability, and host-virus interaction of protein, and might lead to evolution of new strains for better survival and drug resistance.

Understanding immune checkpoints and PD-1/PD-L1-mediated immune resistance towards tumour immunotherapy.

Immunotherapy has emerged as a transformative approach in the treatment of various cancers, offering new hope for patients previously faced with limited treatment options. A cornerstone of cancer immunotherapy lies in targeting immune checkpoints, particularly the programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway. Immune checkpoints serve as crucial regulators of the immune response, preventing excessive immune activity and maintaining self-tolerance. PD-1, expressed on the surface of T cells, and its ligand PD-L1, expressed on various cell types, including cancer cells and immune cells, play a central role in this regulatory process. Although the success rate associated with these immunotherapies is very promising, most patients still show intrinsic or acquired resistance. Since the mechanisms related to PD-1/PD-L1 resistance are not well understood, an in-depth analysis is necessary to improve the success rate of anti-PD-1/PD-L1 therapy. Hence, here we provide an overview of PD-1, its ligand PD-L1, and the resistance mechanism towards PD-1/PD-L1. Furthermore, we have discussed the plausible solution to increase efficacy and clinical response. For the following research, joint endeavours of clinicians and basic scientists are essential to address the limitation of resistance towards immunotherapy.

Assessment of kinetic and statistical models for predicting breakthrough curves of bio-colloid transport through saturated porous media.

The microbial contamination of groundwater and its prevention is a widespread concern in developing countries. The present study simulated the transportation and interception of bio-colloid, Escherichia coli in porous media experimentally using packed columns to address certain aspects of underexplored sorption potential and validated using several kinetic models. The breakthrough curves obtained through experiments are observed to be in good agreement with its prediction using kinetic models namely Thomas, Yoon-Nelson and Modified Dose-Response. The overall comparisons of R2 among all the three models suggest that the MDR model fits more perfectly to experimental results. The combined effect of independent factors (column depth, particle size and alumina content) on response factors (maximum relative concentration and time required to achieve peak concentration) was investigated by using Box-Behnken Design under Response Surface Methodology (RSM) to check statistical significancy of independent factors. The R2 values for both response factors are observed to be 0.94 and 0.99, indicating a very high correlation between predicted and actual values. The results obtained in the present study also confirms that the travel distance and particle size are the statistically significant parameters that efficiently impact on sorption of Escherichia coli during their transport whereas the alumina content also affects the sorption but is observed to be a statistically non-significant.

Identification of conserved immunogenic peptides of SARS-CoV-2 nucleocapsid protein.

The emergence of the new SARS-CoV-2 variants has led to major concern regarding the efficacy of approved vaccines. Nucleocapsid is a conserved structural protein essential for replication of the virus. This study focuses on identifying conserved epitopes on the nucleocapsid (N) protein of SARS-CoV-2. Using 510 unique amino acid sequences of SARS-CoV-2 N protein, two peptides (193 and 215 aa) with 90% conservancy were selected for T cell epitope prediction. Three immunogenic peptides containing multiple T cell epitopes were identified which were devoid of autoimmune and allergic immune response. These peptides were also conserved (100%) in recent Omicron variants reported in Jan-August 2023. HLA analysis reveals that these peptides are predicted as binding to large number of HLA alleles and 71-90% population coverage in six continents. Identified peptides displayed good binding score with both HLA class I and HLA class II molecules in the docking study. Also, a vaccine construct docked with TLR-4 receptor displays strong interaction with 20 hydrogen bonds and molecular simulation analysis reveals that docked complex are stable. Additionally, the immunogenicity of these N protein peptides was confirmed using SARS-CoV-2 convalescent serum samples. We conclude that the identified N protein peptides contain highly conserved and antigenic epitopes which could be used as a target for the future vaccine development against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Machine learning-based ensemble approach in prediction of lung cancer predisposition using XRCC1 gene polymorphism.

The employment of machine learning approaches has shown promising results in predicting cancer. In the current study, polymorphisms data of five single nucleotide polymorphisms (SNPs) of DNA repair gene XRCC1 (XRCC1 399, XRCC1 194, XRCC1 206, XRCC1 632, XRCC1 280) of the north Indian population along with four smoking status data is considered as an input to the proposed ensemble model to predict the risk of individual susceptibility to the lung cancer. The prediction accuracy of the proposed ensemble model for cancer predisposition was found to be 85%. The model performance is also evaluated using sensitivity, specificity, precision and the Gini index, which is found in the range of 0.83-0.87. The proposed model also outperformed in all evaluation parameters when compared with the individual Model (LM, SVM, RF, KNN and baseline neural net). Collectively, current results suggest the potential of the proposed ensemble model in predicting the risk of cancer based on XRCC1 SNPs data.Communicated by Ramaswamy H. Sarma.

Immunoinformatics-Based Identification of the Conserved Immunogenic Peptides Targeting of Zika Virus Precursor Membrane Protein.

Zika virus infections lead to neurological complications such as congenital Zika syndrome and Guillain-Barré syndrome. Rising Zika infections in newborns and adults have triggered the need for vaccine development. In the current study, the precursor membrane (prM) protein of the Zika virus is explored for its functional importance and design of epitopes enriched conserved peptides with the usage of different immunoinformatics approach. Phylogenetic and mutational analyses inferred that the prM protein is highly conserved. Three conserved peptides containing multiple T and B cell epitopes were designed by employing different epitope prediction algorithms. IEDB population coverage analysis of selected peptides in six different continents has shown the population coverage of 60-99.8% (class I HLA) and 80-100% (class II HLA). Molecular docking of selected peptides/epitopes was carried out with each of class I and II HLA alleles using HADDOCK. A majority of peptide-HLA complex (pHLA) have HADDOCK scores found to be comparable and more than native-HLA complex representing the good binding interaction of peptides to HLA. Molecular dynamics simulation with best docked pHLA complexes revealed that pHLA complexes are stable with RMSD <5.5Å. Current work highlights the importance of prM as a strong antigenic protein and selected peptides have the potential to elicit humoral and cell-mediated immune responses.

Association of MLH1-93G>A polymorphisms toward lung cancer susceptibility and its association with clinical outcome in North Indian patients treated with platinum-based chemotherapy.

Background: Lung cancer is one of the most prevalent and main causes of malignancy-related deaths worldwide, especially in developed countries. Epidemiological studies have demonstrated that individuals having alterations in a particular gene may have a high risk of developing certain types of cancer. Materials and Methods: In the present study, 500 Indian lung cancer patients and 500 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism method was used to identify the genotype of enrolled individuals and MedCalc statistical package was used for carrying out statistical analysis. Results: In this study, we found a reduced risk of developing adenocarcinoma in patients harboring variant (P = 0.0007) and combined type genotype (P = 0.008), whereas an increased risk for small-cell lung carcinoma (SCLC) development for those subject harboring GA genotypes (P = 0.03) was also observed. Further, heterozygous type and combined type genotype of heavy smokers for MLH1 polymorphism reported a 2-fold (P = 0.001) and 1.8-fold increased risk toward lung cancer development, respectively (P = 0.007). In case of females, the subjects harboring a variant allele have a significantly reduced risk for lung cancer development (P = 0.0001). For MLH1 polymorphism, reduced risk of developing tumor to T3 or T4 stage was observed (P = 0.04). Moreover, this is the first study reporting overall survival (OS) association for north Indian lung cancer patients with platinum-based doublet chemotherapy; for docetaxel, a three-fold increase in hazard ratio and corresponding low median standard survival time (8.4 months) for mutant and combined type genotype (P = 0.04) was observed. Conclusions: These results suggest that MLH1-93G>A polymorphism is involved in modulating the risk toward lung cancer. Our study also concluded a negative association of OS in patients undergoing carboplatin/cisplatin and docetaxel chemotherapy.

Mutational analysis of catalytic site domain of CCHFV L RNA segment.

INTRODUCTION: Crimean-Congo haemorrhagic fever virus (CCHFV) has tripartite RNA genome and is endemic in various countries of Asia, Africa and Europe. METHOD: The present study is focused on mutation profiling of CCHFV L segment and phylogenetic clustering of protein dataset into six CCHFV genotypes. RESULTS: Phylogenetic tree rooted with NCBI reference sequence (YP_325663.1) indicated less divergence from genotype III and the sequences belonging to same genotypes have shown less divergence among each other. Mutation frequency at 729 mutated positions was calculated and 563, 49, 33, 46 and 38 amino acid positions were found to be mutated at mutation frequency intervals of 0-0.2, 0.21-0.4, 0.41-0.6, 0.61-0.8 and 0.81-1.0 respectively. Thirty-eight highly frequent mutations (0.81-1.0 interval) were found in all genotypes and mapping in L segment (encoded for RdRp) revealed four mutations (V2074I, I2134T/A, V2148A and Q2695H/R) in catalytic site domain and no mutation in OTU domain. Molecular dynamic simulation and in silico analysis showed that catalytic site domain displayed large deviation and fluctuation upon introduction of these point mutations. CONCLUSION: Overall study provides strong evidence that OTU domain is highly conserved and less prone to mutation whereas point mutations recorded in catalytic domain have affected the stability of protein and were found to be persistent in the large population.

Hemorrhagic Fever with Renal Syndrome in Asia: History, Pathogenesis, Diagnosis, Treatment, and Prevention.

Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed.

Seasonal Changes in Serum Metabolites in Multiple Sclerosis Relapse.

Multiple sclerosis (MS) is a debilitating chronic disease of unknown etiology. There are limited treatment options due to an incomplete understanding of disease pathology. The disease is shown to have seasonal exacerbation of clinical symptoms. The mechanisms of such seasonal worsening of symptoms remains unknown. In this study, we applied targeted metabolomics analysis of serum samples using LC-MC/MC to determine seasonal changes in metabolites throughout the four seasons. We also analyzed seasonal serum cytokine alterations in patients with relapsed MS. For the first time, we can demonstrate seasonal changes in various metabolites in MS compared to the control. More metabolites were affected in MS in the fall season followed by spring, while summer MS was characterized by the smallest number of affected metabolites. Ceramides were activated in all seasons, suggesting their central role in the disease pathogenesis. Substantial changes in glucose metabolite levels were found in MS, indicating a potential shift to glycolysis. An increased serum level of quinolinic acid was demonstrated in winter MS. Histidine pathways were affected, suggesting their role in relapse of MS in the spring and fall. We also found that spring and fall seasons had a higher number of overlapping metabolites affected in MS. This could be explained by patients having a relapse of symptoms during these two seasons.

Epidemiology of Ebolaviruses from an Etiological Perspective.

Since the inception of the ebolavirus in 1976, 32 outbreaks have resulted in nearly 15,350 deaths in more than ten countries of the African continent. In the last decade, the largest (2013-2016) and second largest (2018-2020) ebolavirus outbreaks have occurred in West Africa (mainly Guinea, Liberia, and Sierra Leone) and the Democratic Republic of the Congo, respectively. The 2013-2016 outbreak indicated an alarming geographical spread of the virus and was the first to qualify as an epidemic. Hence, it is imperative to halt ebolavirus progression and develop effective countermeasures. Despite several research efforts, ebolaviruses' natural hosts and secondary reservoirs still elude the scientific world. The primary source responsible for infecting the index case is also unknown for most outbreaks. In this review, we summarize the history of ebolavirus outbreaks with a focus on etiology, natural hosts, zoonotic reservoirs, and transmission mechanisms. We also discuss the reasons why the African continent is the most affected region and identify steps to contain this virus.

Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by destruction of the myelin sheath structure. The loss of myelin leads to damage of a neuron's axon and cell body, which is identified as brain lesions on magnetic resonance image (MRI). The pathogenesis of MS remains largely unknown. However, immune mechanisms, especially those linked to the aberrant lymphocyte activity, are mainly responsible for neuronal damage. Th1 and Th17 populations of lymphocytes were primarily associated with MS pathogenesis. These lymphocytes are essential for differentiation of encephalitogenic CD8+ T cell and Th17 lymphocyte crossing the blood brain barrier and targeting myelin sheath in the CNS. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies. In later studies, aberrant function of Treg and Th9 cells was identified as contributing to MS. This review summarizes the aberrant function and count of lymphocyte, and the contributions of these cell to the mechanisms of MS. Additionally, we have outlined the novel MS therapeutics aimed to amend the aberrant function or counts of these lymphocytes.

In vitro evaluation of bioactive properties of banana sap.

Banana sap is currently designated as a waste subsequent to utilization of pseudo stem in pulp and paper industry as well as other applications which is contributing to the environmental pollution. In the present study, banana sap and its crude extracts were evaluated for antimicrobial, antioxidant and anticancer properties. The role of oxidized and un-oxidized banana sap for its antimicrobial potential against a microbial test panel comprising gram positive as well as gram negative bacteria and Candida albicans using in vitro micro broth dilution assay. The un-oxidized banana sap exhibited a significantly higher antibacterial potential as evident by a lower minimal inhibitory concentration (MIC) ranging between 15.625 to 62.5 mg/mL. In vitro radical scavenging activity of dichloromethane (DCM) extract of banana sap by DPPH method exhibited 54.62 ± 1.09 (µg/mL) IC50 value at the concentration of 1 mg/mL. Dichloromethane extract of banana sap showed maximum cytotoxic effect with human breast cancer (MCF-7) cell proliferation at the concentration of 100 µg/mL which was 78.37 ± 0.05% and the cytotoxic effect significantly increased with increasing concentration of banana sap extract. Furthermore, LCMS studies revealed the presence of bioactive compounds in dichloromethane extract of banana sap, such as rescinnamine derivative, dihydrorescinnamine and epimedin A. The present study suggested that banana sap is a promising source of bioactive compounds with relevant antimicrobial, antioxidant and anticancer properties.

Structural, functional analysis and association of MSH6 rs1800932, rs1042821 polymorphisms with clinical outcome in North Indian lung cancer patients treated with platinum-based doublet chemotherapy.

BACKGROUND: In this study, we have done structural and functional analysis of rs1800932 rs1042821 polymorphisms and tried to estimate any association of these polymorphisms with clinical outcomes in north Indian lung cancer patients. METHODS: Genotyping of 500 lung cancer patients was completed utilizing PCR-RFLP (Polymerase chain reaction- Restriction fragment length polymorphism). MedCalc statistical software was used to calculate adjusted and unadjusted odds ratios. Various computational tools like SIFT PROVEAN are used for functional analysis. Structural analysis was completed via MODELLER and CHIMERA. RESULTS: In our study, patients suffering from small cell lung cancer (SCLC) and harboring heterozygous genotype (AG) for MSH6 (rs1800932) polymorphism have reported a significant increase in median survival time (MST) (20.6 vs. 7.6 months, p = 0.03). Furthermore, for MSH6 rs1042821 polymorphism, patients undergoing docetaxel and carbo/cisplatin combination chemotherapeutic regimen and carrying heterogeneous genotype (CT) reported a significant increase in MST (16.6 vs.8.36 months, p = 0.03) and a corresponding decrease in hazard ratio 0.42 (95% CI= 0.18-1.03). Structural and Functional analysis of rs1042821 polymorphism revealed that it is present in the non-coding region of MSH6 protein and is significantly associated with increased overall survival. CONCLUSIONS: These results suggest that MSH6 rs1800932 rs1042821 polymorphisms are involved in increasing the overall survival of lung cancer patients, further confirmed by computational analysis.

Computational design of immunogenic peptide constructs comprising multiple human leukocyte antigen restricted dengue virus envelope epitopes.

Dengue virus (DENV) is endemic in 100 countries with the ability to impact nearly 50% of world population. DENV envelope (E) protein is responsible for viral attachment to host cells and has been target of various countermeasure development efforts. The current study focuses on a consensus computational approach to identify cross-reactive, immunogenic DENV-2 E peptides displaying promiscuity with a wide array of human leukocyte antigen (HLA) molecules. Four conserved peptides (FP-1, FP-2, FP-3 and FP-4) containing multiple CD8+ and CD4+ T cell epitopes were identified by employment of various immunoinformatics tools. FP-1, FP-2, FP-3 and FP-4 were estimated to bind with 227, 1787, 1008 and 834 HLA alleles, respectively. Root mean square deviation (RMSD) values obtained by molecular docking (CABS-Dock) with 20 HLA alleles (10 each of HLA classes I and II) resulted into comparable RMSD values of identified epitopes with native peptides, which represents the natural presentation of epitopes to HLA molecules. These peptides were also found to be part of previous experimentally validated immunogenic peptides. Further, a dengue immunogenic peptide construct was generated by linking the four peptides, an adjuvant and a 6× histidine tag. The construct showed strong binding and stability with Toll-like receptor. Collectively, these results provide strong evidence in the support of the immunogenic potential of the dengue immunogenic peptide construct.

Antibody and T Cell Immune Responses to SARS-CoV-2 Peptides in COVID-19 Convalescent Patients.

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19.

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.