Diagnosis of COVID-19 from the X-Ray images using BAT Algorithm with Deep Convolutional Neural Network

The COVID-19 widespread has posed a chief contest to the scientific community around the world. For patients with COVID-19 illness, the international community is working to uncover, implement, or invent new approaches for diagnosis and action. A opposite transcription-polymerase chain reaction is currently a reliable tactic for diagnosing infected people. This is a time- and money-consuming procedure. Consequently, the development of new methods is critical. Using X-ray images of the lungs, this research article developed three stages for detecting and diagnosing COVID-19 patients. The median filtering is used to remove the unwanted noised during pre-processing stage. Then, Otsu thresholding technique is used for segmenting the affected regions, where Spider Monkey Optimization (SMO) is used to select the optimal threshold. Finally, the optimized Deep Convolutional Neural Network (DCNN) is used for final classification. The benchmark COVID dataset and balanced COVIDcxr dataset are used to test projected model's performance in this study. Classification of the results shows that the optimized DCNN architecture outperforms the other pre-trained techniques with an accuracy of 95.69% and a specificity of 96.24% and sensitivity of 94.76%. To identify infected lung tissue in images, here SMO-Otsu thresholding technique is used during the segmentation stage and achieved 95.60% of sensitivity and 95.8% of specificity. © 2023 IEEE.

Animal Pre-Clinical Study of an Inactivated SARS-CoV-2 Vaccine candidate (Osvid-19 ): Immunogenicity, Protective, and Safety Aspects

Background: This study aimed to evaluate the outcomes of preclinical studies on the safety and immunogenicity of an inactivated COVID-19 vaccine candidate to warrant further clinical evaluation. Method(s): SARS-CoV-2 positive nasopharyngeal swab specimens were confirmed by real-time polymerase chain reaction and next-generation sequencing. The safety and immunogenicity tests of the COVID-19 vaccine were carried out in rats and Rhesus monkeys, and Balb/C mice and Rhesus monkeys, respectively. Result(s): The candidate vaccine was well tolerated and induced promising levels of SARS-CoV-2- specific IgG1, IgG2a, and Granzyme B in Balb/C mice, and anti-SARS-CoV-2 spike IgG and neutralizing antibodies in Rhesus monkeys. Based on cVNT results, the inactivated vaccine in 0.5 and 1 microg/100 microL doses was able to induce a neutralizing effect against the SARS-CoV-2 virus up to a dilution of 1:512 and 1:1000. The protective efficacy of the vaccine candidate was challenged with 2 x108 PFU of live viruses and confirmed by lung CT scan and histopathological evaluations compared to the control group. Repeated intramuscular injection of the candidate vaccine was generally well-tolerated in Rats and Rhesuses. No significant side effects were observed in rats injected with ten full human doses and in the Rhesus monkeys with three full human doses. Conclusion(s): Based on the findings presented in this study, it is recommended that this vaccine be moved into human testing commencing with a phase I clinical trial.Copyright © 2021 Muslim OT et al.

Accurate Machine Learning Algorithm for Monkey Pox Based on Covid-19

The Covid-19 virus is still marching all over the world. Many people are getting infected and a few are fatal to death. This research paper expressed that supervised learning has revealed supreme results than unsupervised learning in machine learning. Within supervised learning, random forest regression outplays all other algorithms like logistic regression (LR), support vector machine (SVM), decision tree (DT), etc. Now monkeypox is escalating in other countries at present. This virus is allied to human orthopox viruses. It can expand from one to one through contact person having rash or body fluids etc. The symptoms of monkeypox are much similar to covid19 virus-like fever, cold, fatigue, and body pains. Herewith we concluded that random forest regression shows possible foremost (97.15%) accuracy. © 2023 IEEE.

PROTECTION AGAINST HETEROLOGOUS CHALLENGE 1 YEAR AFTER INFANT SARS-CoV-2 IMMUNIZATION

Background: Although mRNA SARS-CoV-2 vaccines have received emergencyuse- authorization for infants age 6 months and older, vaccine uptake is slow, stressing that questions of safety and durability of vaccine efficacy remain prominent. Method(s): Infant rhesus macaques (RMs) (n=8/group) at 2 months of age, comparable to human toddler age, were immunized intramuscularly at weeks 0 and 4 with 30mug stabilized prefusion SARS-CoV-2 S-2P spike (S) protein (Washington strain) encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or 15mug S protein mixed with 3M-052 in stable emulsion (Protein). At 1 year, vaccinated and age-matched unvaccinated RM (n=8) were challenged intranasally (106pfu) and intratracheally (2x106pfu) with B.1.617.2. Lung radiographs and pathology were blindly assessed, viral N gene RNA (vRNA) copies were measured by qPCR in pharyngeal swabs and lung, and neutralizing antibody and peripheral blood T cell responses were measured. Result(s): At 1 year, D614G-specific neutralizing antibody (nAb) titers were still detectable in the Protein (ID50=755;range: 359-1,949) and mRNA-LNP groups (ID50=73;range: 41-240). Both vaccines also induced cross-neutralizing antibodies to B.1.617.2. Peripheral blood CD4+ T cell responses to the ancestral spike protein at week 52 did not differ between the groups. However, median CD8+ T cell responses were higher (p=0.002, Mann Whitney) in the mRNA-LNP group (2.8%;range: 0.9%-7.1%) compared to the Protein group (0.8%;range: 0.1%-1.6%). Control RMs had significantly higher median vRNA copies/ml (1.4+/-2.7x108) in day 4 pharyngeal swabs compared to Protein (3.8+/-6.8x103) or mRNA-LNP (4.4+/-9.7x105) vaccinated RMs. Severe lung pathology was observed in 7 of 8 controls compared to 1 of 8 or 0 of 8 RMs in the mRNA-LNP or Protein group respectively. Protection against lung inflammation was associated with nAb titers (r=-0.592, p=0.003) (Figure 1). Conclusion(s): These results demonstrate that despite lower vaccine doses compared to adults, both protein and mRNA vaccines were safe, induced durable immune responses and provided comparable protective efficacy against infection with a heterologous SARS-CoV-2 variant in infants, implying that early life vaccination of human infants may lead to durable immunity. Neutralizing ID50 antibody titers are a correlate of protection in infant RMs challenged with SARS-CoV-2.

A Review on Recent Monkey Pox Outbreak in 2022

Monkey pox, a zoonotic disease with clinical symptoms resembling smallpox, unexpectedly broke out and spread over the world after the outbreak of COVID-19, severely affecting several of the continents of the world. Monkey pox is currently a member of the genus otrhopox virus, which is a member of the sub family chorodoxvirinae. According to the available knowledge, small mammals and rodents have all been identified as potential sources of the monkey [ox virus]. The disease is characterized by a short febrile illness with lymphadenopathy followed by a rash which spreads centrifugally and passes through phases of macules, papules, vesicles, and pustules. Recovery occurs in most patients within 2-4 wk. Complications are more likely in children, pregnant women, and the immunocompromised. Specific diagnosis is by detection of viral DNA by PCR.Tecovirimat, brincidofovir, and cidofoviir are the medications used to treat monkey pox, immunoglobulin and new compounds are the vaccinations. This review will introduce a general overview of MPXV and describe the epidemiology, clinical features, evaluation, and treatment of monkey pox patients.Copyright © Journal of Global Trends in Pharmaceutical Sciences.

PROLONGED SARS-CoV-2 VIRAL BURDEN IN SIV-SARS-CoV-2 COINFECTED MACAQUES

Background: Individuals living with HIV are at increased risk of morbidity and mortality from COVID-19. Furthermore, SARS-CoV-2 infection in immunocompromised HIV infected individuals poses a risk to prolonged infection and viral shedding and the emergence of new variants of concern (VOCs). Using the SIV macaque model for AIDS, we are investigating the hypothesis that immune dysfunction during HIV infection will prolong SARSCoV- 2 viral infection, promote enhanced COVID-19 disease, and accelerate viral evolution. Here, we report the impact of SIV-CoV-2 co-infection on immune responses and pathogenesis. Method(s): Eight female rhesus macaques (aged 7-15 years, 5.5-9.9kg) were infected with SIVmac251 via low dose intravaginal challenge and then inoculated with 6.5x105 TCID50/mL SARS-CoV-2 (WA-1) at 17-34 weeks post-SIV infection via combined intranasal and intratracheal routes. Blood, bronchoalveolar lavage (BAL), stool, and nasal, oral, and rectal swabs were collected pre-infection through 14 days post-infection (DPI) to measure immune responses and viremia. ELISAs, ELISPOT, qRT-PCR, lung pathology, cytokine multiplex, and virus neutralization assays were performed to measure viral loads, pathogenesis, and immune responses. Result(s): Three days post-SARS-CoV-2 infection, we observed a transient decrease in CD4 counts, but there were no changes in clinical symptoms or plasma SIV viral loads. However, SARS-CoV-2 replication persisted in the upper respiratory tract, but not the lower respiratory tract. In addition, SARS-CoV-2 IgG seroconversion was delayed and antigen-specific T-cell responses were dampened. Notably, viral RNA levels in nasal swabs were significantly higher 7-14 DPI in SIV+ compared to previously published results using the same SARS-CoV-2 challenge virus in SIV- rhesus (PMCID: PMC8462335, PMC8829873). In addition, SIV/CoV-2 co-infected animals exhibited elevated levels of myeloperoxidase (MPO), a marker of neutrophil activation and increased lung inflammation. Conclusion(s): Here we provide evidence for the utility of the rhesus macaque in modeling human HIV-SARS-CoV-2 co-infection. Our results suggest that immunosuppression during SIV infection impairs de novo generation of anti-SARS-CoV-2 immunity, that may contribute to prolonged SARS-CoV-2 viral shedding, increased transmission windows, altered disease pathogenesis, and lower protection against subsequent SARS-CoV-2 exposures. Studies in progress will determine if SARS-CoV-2 viral evolution is accelerated in SIV-infected macaques.

HIGH FAT AND SUGAR DIET INDUCES GUT LEUKOCYTE DISRUPTIONS EXACERBATED BY SARS-CoV-2

Background: The disparity in COVID-19 disease burden between European, Asian, and African countries is notable, with considerably higher morbidity and mortality in many European countries as well as the U.S. Dietary differences between regions could play a role in differential COVID-19 pathogenesis, as Western diets high in fat and sugar have been implicated in enhancing gut damage and pathogenesis during viral infections. Here we investigate the effect of diet on gut immunity and SARS-CoV-2 infection. Method(s): Six pigtail macaques were fed a commercial monkey chow diet, then transitioned to a high fat and sugar chow diet (HFD) for approximately two months prior to infection with Delta strain SARS-CoV-2. Animals were sampled prior to HFD initiation, during HFD administration but prior to infection, and for approximately one month post-infection. HFD was maintained following infection and animals were euthanized at the study conclusion. Result(s): Viral RNA was detected for up to 28 days post-infection in nose swabs, with peak viral load at day 2 at a mean of 8.2x109 copies/mL of swab fluid. Subgenomic RNA (sgRNA, indicating viral replication) decayed more rapidly, with all animals having undetectable sgRNA by day 21, and a lower peak of 2.6x109 copies/mL swab fluid on day 2. Viral RNA load was approximately 3.5 logs greater and sgRNA load approximately 3 logs higher at day 2 than in rhesus macaques infected with WA2020 SARS-CoV-2 and fed standard monkey chow. Mucosal rectal biopsies indicated significantly lower B cell frequencies from baseline to approximately two months following HFD administration (p=0.04, Dunn's), and frequencies had not recovered approximately one month postinfection. GI tract-resident IgG+ B cells were nearly absent at necropsy, with mean frequency 0.03% of total B cells. B cell loss was coupled with modest T cell expansion during HFD administration, though frequencies declined following infection. Furthermore, NK cell frequencies tended to decline from baseline throughout HFD administration, and were further depleted at necropsy one month post-infection. Conclusion(s): SARS-CoV-2 infection can induce lymphopenia, and our sampling of gut mucosal tissue indicates B cell depletion and NK cell loss with a HFD that is further exacerbated by SARS-CoV-2 infection. Excess dietary fat and sugar may disrupt gut barrier integrity and immunity, in turn predisposing the tissue to pathology of viral infection.

Monkeypox Virus and Other Emerging Outbreaks: An Overview and Future Perspective.

Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.

Translational Model-Based Meta-Analysis -a Powerful Quantitative Tool in Developing Vaccines against Sars-Cov- 2 Variants

BACKGROUND: Quantitative models leveraging non-clinical data to predict clinical vaccine efficacy provide a translational framework to rapidly develop vaccines/ boosters against new strains of SARS-CoV- 2. METHOD(S): Previously, based on a systematic literature review, we performed a translational Model-Based Meta-Analysis (MBMA)1 integrating data of wild-type (WT) SARS-CoV- 2 from 13 rhesus macaques (RM) studies and eight clinical trials. The model is here updated with data from 32 additional RM studies including newer strains of SARS-CoV- 2 (e.g., omicron). Non-linear mixed-effects modeling was used to quantify the relationship in RM between serum neutralizing (SN) titers after vaccination and peak viral load (VL) post challenge in relevant tissue matrices. RESULT(S): The plot2 shows the model describes the relationship between SN titers and peak VL across all specimens well. The overlap between the confidence intervals across virus strains suggests that the model can be leveraged to describe RM data across viral SARS-CoV- 2 strains. CONCLUSION(S): The previous work1 demonstrated that RM VL is quantitatively predictive of clinical efficacy, and so this update provides a framework to predict clinical vaccine efficacy against newer variants using only RM data (Figure Presented).

Performance Analysis of Machine Learning Classification Approaches for Monkey Pox Disease Prediction

After covid-19 pandemic, many countries have the possibility of getting affected by Monkey Pox Virus. Monkey pox has the same symptoms of smallpox, chicken pox, and measles virus. In this work, the computational models are construed to predict the presence or absence of monkey pox virus. Eight different Classification algorithms including Decision Tree (DT), Random Forest Classification (RF), Naïve Bayes (NB), K-Nearest Neighbor algorithms (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Ada Boosting algorithm (AB), Gradient Boosting (GB) algorithm are used for the Classification of Monkey Pox disease. Four evaluation measures are used in this work to compute the accuracy of classification. Four measures F-Score, Accuracy, Precision, and Recall are used to compare the eight different types of classification algorithms. Based on experimental analysis, it was observed that highest accuracy of 71% is achieved by Gradient Boosting algorithm when compared to other algorithms. © 2022 IEEE.

In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes.

Type II transmembrane serine proteases represent pharmacological targets for blocking entry and spread of influenza or coronaviruses. In this study, the depletion rates of the 3-amidinophenylalanine (3-APhA)-derived matriptase/TMPRSS2 inhibitors MI-463, MI-472, MI-485 or MI-1900 were determined by LC-MS/MS measurements over a period of 300 min using suspensions of rat, dog and cynomolgus monkey primary hepatocytes. From these in vitro pharmacokinetic (PK) experiments, intrinsic clearance values (Clint) were evaluated, and in vivo pharmacokinetic parameters (hepatic clearance, hepatic extraction ratio and bioavailability) were predicted. It was found that rat hepatocytes were the most active in the metabolism of 3-APhA derivatives (Clint 31.9-37.8 mL/min/kg), whereas dog and monkey cells displayed somewhat lower clearance of these compounds (Clint 6.6-26.7 mL/min/kg). These data support elucidation of important PK properties of anti-TMPRSS2/anti-matriptase 3-APhAs using mammalian hepatocyte models and thus contribute to the optimization of lead compounds.

Elevated soluble urokinase plasminogen activator receptor is associated with renal dysfunction in a Chlorocebus atheiops COVID-19 model.

Increases of soluble urokinase plasminogen activator receptor (suPAR) were measured in both urine and plasma of a Chlorocebus aethiops (African green monkey; AGM) mucosal infected with SARS-CoV-2. The data indicate that elevated suPAR may be associated with renal dysfunction and pathology in the context of COVID-19.

Deep Learning Methods for Early Detection of Monkeypox Skin Lesion

As the world has not fully recovered from the aftermath of COVID-19, a new pandemic appears on the horizon. Monkey Pox is emerging as a new threat to the health of the world population. With the recorded spread over 40 countries worldwide it might be soon declared a pandemic. Monkey Pox shares common features with chickenpox and measles making it difficult to diagnose. Developing a new test kit at this early stage is a challenging task for the medical fraternity. This paper proposes the use of deep learning models that can be used to make the process of diagnosis automated. This paper tries to come up with a performance comparison of ResNet50, EfficientNetB3 and EfficientNetB7 algorithms. This study suggests a method for early detection of Monkey Pox Skin Lesion. Though an extensive study with other models on a larger dataset containing more images from various countries of the world needs to be carried out but this study gives some promising results on this limited dataset. © 2022 IEEE.

The 2022 Monkeypox Epidemic and What Has Led to the Current State of the Disease in the US: A Systematic Review.

Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The virus remains endemic to the Congo and West African regions, but non-endemic spreads have been cited. The most recent non-endemic outbreak in the spring of 2022 amidst the current COVID-19 pandemic is of interest due to its impact on global medical, economic, and societal climates. This literature review aims to highlight the virology, clinical signs and symptoms, diagnosis, prevention, and treatment of MPOX and discuss the social implications of the recent 2022 outbreak. We hope this review can pinpoint important clinical pearls of the MPOX virus and its societal impacts to further promote important discussion of this virus and its disease.

Preclinical Toxicity and Immunogenicity of a COVID-19 Vaccine (ZF2001) in Cynomolgus Monkeys.

Although the new coronavirus disease 2019 (COVID-19) outbreak occurred in late 2019, it is still endemic worldwide, and has become a global public health problem. Vaccination against SARS-CoV-2 is considered to be the most effective intervention to prevent the spread of COVID-19. ZF2001 is a recombinant protein vaccine based on SARS-CoV-2 receptor-binding domain (RBD) subunit which contains aluminum adjuvant. In order to advance our research on ZF2001 into clinical trial, we investigated the general toxicity and immunogenicity of ZF2001 in cynomolgus monkeys and assessed the possible target organs for vaccine-induced toxicity. In the present research, we observed no significant systemic toxicities and abnormal cardiovascular and respiratory events following four times injections of intramuscular ZF2001 in cynomolgus monkeys. Histological examination revealed recoverable inflammatory changes in quadricep muscle and adjacent lymph node at the vaccine injection site. As expected, the vaccine can produce a strongly specific binding antibody and neutralizing antibodies in cynomolgus monkeys after inoculation. Taken together, our regulatory toxicology research proves the safety and immunogenicity of the ZF2001 vaccine, supporting its entry into large scale clinical trials.

A perspective influence of the Epsilon variant of COVID-19 on Catechol-O-Methyltransferase Val158Met leads to the emergence of human papilloma virus-Gueye, which is wrongly described as monkey pox

A perspective study discussed how the epsilon variant of COVID-19 induced mutation to the existed human papilloma virus via mutagenic cadmium content of the COVID-19, and arsenic content of epsilon variant lead to appearance of new strain of human papilloma virus, we named it Human Papilloma Virus-Gueye. As this virus is most common among gay men, and due to the absence of infection with it among HIV-controlled patients. We suggest that this virus disturbs Catechol-O-Methyltransferase Val158Met which is the region which is responsible for male sexual orientation and has been linked to executive dysfunction, which might increase sexual risk behaviours favouring HIV transmission, which is damaged by mycotoxin of myecetoma fungal species and by cadmium contents of epsilon variant of COVID-19. We conclude that COVID-19 is not hazardous just because of its severe symptoms, but also because of its action as a mutagen on other microbes that may be present in a subclinical state. Also, we suggest that immunization against COVID-19 may lead to unexpected complications, especially mutations in other microbes. Finally, we claim that the scientific community named it monkey pox. Even among individuals who do not travel to the endemic, it is just mutant form of Human Papilloma virus.

Monkeypox virus: Future role in Human population.

BACKGROUND: Monkeypox viral infection is considered as global public health and a rare disease caused by Monkeypox virus (MPXV), which is caused by smallpox-like virus and it causes pustules all over the body. MPV is an emerging zoonotic infection with sporadic occurrence globally and multiple outbreaks have been reported in African regions. The story of MPXV has been started since 1970 in Democratic republic of Cargo. The high cases of MPXV was majorly detected in Congo Rain Forest region in Africa. Animal-human (Zoonotic) transmission occurred, although the individual infected animal was not recognized. Human-human transmission occurs and is difficult until bodily fluids or respiratory droplets are exchanged. If a specific individual uses an infected person's towels or bed sheets, infection may occur. AIM: The aim of this review is to document the methods of diagnosis, treatments (vaccines) and future role of MPXV in human population. OUTPUT: The diagnosis is confirmed mainly through clinical diagnosis and then laboratory diagnosis such as cell-culture, serological and Polymerase Chain Reaction tests. Presently, there is no vaccine for MPXV but the smallpox vaccine will protect. The old vaccine includes antivirals approved for use against Orthopoxvirus, such as tecovirimat, which can treat up to 85 % of MPXV in humans. MPXV is now considered as transmission virus which affects from human to humans. The fatality rate was documented to be 3-10 % in children and in adults it is very low. CONCLUSION: This review concludes MPXV is not as contagious as COVID-19 but proper measures should be taken as mentioned in this review to avoid MPXV. Presently, controlling MPXV presents unique challenges, and future prospective global studies in antivirals for this disease, as well as an MPXV vaccines, are recommended to eliminate this virus.

Monkeypox outbreak amidst COVID-19 reemergence in the European Region: Challenges, efforts, and recommendations.

Monkeypox (MPX), caused by the Monkeypox virus (MPXV), is an endemic disease in African countries and is currently causing outbreaks in several European regions, amidst a recent surge in new COVID-19 cases. This can significantly impact already exhausted healthcare services, adding on to the economic and social burdens in the region. A lack of sufficient laboratory diagnostics, antivirals, vaccines may hinder effective clinical management of affected patients. Therefore, it is essential to increase awareness about MPX and its transmission among the general population, to ensure necessary precautions are taken and new cases are reported swiftly. This article discusses the impact of MPXV on the current reemergence of COVID-19 in Europe, lessons learnt during the COVID-19 pandemic and recommendations to address potential challenges.

Sequence difference of angiotensin-converting enzyme 2 between nonhuman primates affects its binding-affinity with SARS-CoV-2 S receptor binding domain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused many deaths and contributed to a tremendous public health concern worldwide since 2020. Angiotensin-converting enzyme 2 (ACE2) binds to the SARS-CoV-2 virus as a receptor. The challenge of different nonhuman primate (NHP) species by SARS-CoV-2 virus demonstrated different effects on virus replication and disease pathology. This study characterizes differences between host ACE2 sequences of three NHP species: Macaca mulatta, Macaca fascicularis, and Chlorocebus sabaeus. In addition, the binding affinity between the ACE2 ectodomain and the SARS-CoV-2 S receptor-binding domain (RBD) was analyzed. Variation of ACE2 sequence among NHP species and the binding affinity may account for different susceptibility and responses to SARS-CoV-2 infection.