National Institute Of Allergy And Infectious Diseases Research Articles

A Robust Host-Response-Based Signature Distinguishes Bacterial and Viral Infections Across Diverse Global Populations

Background: Early and accurate diagnosis of acute infection has important consequences for antibiotic stewardship, resource allocation, and clinical outcomes. However, limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics have the potential to address these challenges, but accuracy varies widely across heterogeneous global patient populations. Methods: We performed a multi-cohort analysis of 4,200 unique samples across 69 retrospective blood transcriptome datasets from 20 countries. These samples were collected from patients with acute bacterial or viral infections representing a broad spectrum of biological (age, sex, race, ethnicity, pathogen, host genetics), clinical (severity, day of presentation), and technical (Affymetrix, Agilent, Illumina) heterogeneity. We also enrolled patients with infectious diseases in two cohorts from Laos and Nepal. Findings: Current host-response-based gene signatures distinguished intracellular bacterial infection from viral infections with substantially lower accuracy. Using 69 datasets, divided into training and validation datasets, we identified an 8-gene signature that distinguished intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) >0.91 (85.9% specificity, 90.2% sensitivity). In two prospective cohorts from Nepal and Laos, profiled using Fluidigm RT-PCR, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity, 91% sensitivity). Interpretation: The 8-gene signature met the target product profile (90% sensitivity, 80% specificity) proposed by the WHO and others for distinguishing bacterial and viral infections. The 8-gene signature should be considered for further validation and implementation. Funding Information: PK is funded in part by the Bill and Melinda Gates Foundation (OPP1113682); the National Institute of Allergy and Infectious Diseases (NIAID) grants 1U19AI109662, U19AI057229, and 5R01AI125197; Department of Defense contracts W81XWH-18-1-0253 and W81XWH1910235; and the Ralph & Marian Falk Medical Research Trust. DAR is supported by NIH/NIAID U19 AI109761 and the Thomas C. and Joan M. Merigan Endowment at Stanford University. LOMWRU is funded by the Wellcome Trust of Great Britain. AMR is funded by the National Science Foundation Graduate Research Fellowship and the Stanford Graduate Fellowship. This research was funded in whole, or in part, by the Wellcome Trust [Grant number 220211]. Declaration of Interests: AMR, SJP, TES, DAR, and PK are named as inventors on a patent application describing the 8-gene set, which has been licensed to Inflammatix. TES and SAT are employees of Inflammatix, and TES and PK are shareholders in Inflammatix. Inflammatix had no role in the design, funding, or reporting of this work. SD is currently employed by FIND. The other authors declare no conflicts of interest. Ethics Approval Statement: Ethical clearance was granted by the former Faculty of Medical Sciences Ethical Review Committee (now University of Health Sciences Ethics Committee), National University of Laos, the Oxford University Tropical Ethics Committee, and the Stanford University Institutional Review Board.

Viral Load in Non-Surviving Liberian Ebola Virus Disease Patients Is Underestimated by Diagnostic qRT-PCR: A Retrospective Observational Study

Background: Viral load in Ebola virus disease (EVD) correlates with case fatality rate (CFR) and is an important parameter used for diagnostic cutoffs, stratification in randomized controlled trials, and epidemiologic investigation. However, it is currently only estimated using cycle threshold (Ct) values from diagnostic qRT-PCR tests that were not developed or validated for quantitative purposes. Furthermore, during the 2013-2016 EVD epidemic in west Africa, numerous different diagnostic platforms and protocols were used and yielded inconsistent, often conflicting data. Methods: 727 whole blood samples, both positive and negative for Ebola virus (EBOV), that were collected for diagnostic purposes in Monrovia, Liberia between August 28 and December 18, 2014 were reanalyzed under highly controlled biosafety level 4 laboratory conditions. An optimized TRIzol-based extraction protocol was utilized, followed by a novel semi-strand specific two-step droplet digital PCR assay to quantify viral load as log10 EBOV RNA copies/mL. These data were then compared to the cycle threshold (Ct) values from the original diagnostic qRT-PCR testing, and a subset of the samples was also reanalyzed following re-extraction with the same diagnostic one-step PCR and instruments employed at the Ebola treatment unit for further assessment. Finally, for EBOV-positive patients, correlations between viral load, outcome, time from symptom onset, and other epidemiological parameters were evaluated utilizing a deidentified database. Findings: Survivors had significantly lower mean viral loads at presentation than non-survivors in both the reanalyzed dataset (5.61 [95% CI 5.34 to 5.87] versus 7.19 [95% CI 6.99 to 7.38] log10 EBOV RNA copies/mL, respectively; p < 0.0001) and diagnostic dataset (Ctvalue 28.72 [95% CI 27.97 to 29.47] versus 26.26 [95% CI 25.72 to 26.81], respectively; p < 0.0001). However, receiver operating characteristic curve analysis demonstrated the reanalyzed dataset to be superior to the diagnostic dataset (area under curve 0.80 [95% CI 0.75 to 0.85] versus 0.66 [95% CI 0.59 to 0.72], respectively) in distinguishing between survivors and non-survivors and the prognostic capacity of viral load increased substantially upon reanalysis (odds ratio [OR] of death 8.06, 95% CI 4.81 to 13.53, p < 0.0001 for viral loads above 6.71 log10 EBOV RNA copies/mL versus OR of death 2.02, 95% CI 1.27 to 3.20, p = 0.0028 for Ct values below 27.37). Diagnostic Ct values underestimated viral load in non-survivors by nearly 100-fold on average (mean difference between diagnostic Ct value and reanalyzed Ct value of 5.15 [95% CI 4.43 to 5.87]); substantially less discrepancy was observed for survivors (mean difference between diagnostic Ct value and reanalyzed Ct value of 1.79 [95% CI 1.16 to 2.43]). Six samples that were reported negative by diagnostic testing were found to be positive upon reanalysis, and had high viral loads. Non-survivors presented to the ETU significantly earlier as the epidemic progressed, from 6.8 days following symptom onset (95% CI 5.7 to 7.9), on average, during the first three weeks to 3.7 days (95% CI 2.4 to 5.0) during the last three weeks (p = 0.0006) and had significantly lower viral loads (7.6 log10 EBOV RNA copies/mL [95% CI 7.3 to 7.9] to 6.5 log10 EBOV RNA copies/mL [95% CI 5.8 to 7.2] for the same intervals (p = 0.0046). However, the CFR remained steady at approximately 60% throughout. Interpretation: Inaccurate viral load estimation from diagnostic Ct values is likely multifactorial, but unaddressed PCR inhibition from tissue damage in patients with fulminant EVD may largely account for the discrepancies between the datasets in this study. In light of these findings, testing protocols for EVD require further standardization and validation to produce accurate viral load estimates, minimize false negatives, and allow for reliable epidemiological investigation. Funding Information: This research was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The deidentified samples and data utilized for this study received a determination of ‘not human subjects research’ by the NIH Office of Human Subjects Research Protection and has been approved by the University of Liberia-Pacific Institute for Research and Evaluation IRB.

Post-Mrna Vaccination SARS-CoV-2 IGG Concentrations and Surrogate Virus Neutralization Response Compared by HIV Status and Type of Vaccine: A Matched Case-Control Observational Study

Background: Limited data is available on whether there are differences in the humoral response to mRNA SARS-CoV-2 vaccination by HIV status. We compared surrogate virus neutralization tests (sVNT) and anti-receptor-binding-domain (RBD) IgG concentrations by HIV status, as well as if responses differed by mRNA vaccine type. Methods: Remnant serum samples were collected during the month of May 2021 from all people living with HIV (PLWH) undergoing outpatient laboratory testing in a U.S. municipal health-care system. Samples from 100 PLWH were then matched on the same number of days following second mRNA vaccination, age (+/- 5 years), birth sex, and type of mRNA vaccine to samples from 100 adults receiving care for chronic conditions at the same hospital. Antibody responses were measured using a previously validated sVNT and anti-RBD IgG, with non-response defined as the limit of detection at <10 reciprocal titer and <10 relative fluorescent units respectively. Responses were compared by HIV status using mixed-effects models. Findings: In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine. There were 2.43-fold higher odds of sVNT non-response among PLWH [95% confidence interval (CI)=1.09-5.39]. Although few individuals did not mount an anti-RBD IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD concentrations were 43% lower among PLWH (GMR 0.57; 95% CI=0.36-0.88). After adjusting for age, sex, and days post-second-vaccination, receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower sVNT titers, each 100-cell increase in CD4+ T-cell count was associated with 22% higher titers (GMR 1.22; 95% CI=1.09-1.37), while unsuppressed RNA>200 copies/mL was associated with 89% lower titers (GMR 0.11; 95% CI=0.01-0.84). Interpretation: PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, particularly among those with low CD4+ T-cell counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Funding: This research was supported by U.S. National Institute of Allergy and Infectious Diseases (NIAID) R01AI158013 (M.A.S. and M.G.), and U.S. NIAID P30AI027763 (M.G.) Declaration of Interest: DVG reports personal fees from Gilead Sciences outside the submitted work. All other authors declare no competing interests. Ethical Approval: As only remnant samples were used, the University of California, San Francisco IRB did not require informed consent for study participation. The UCSF IRB # is 20-30387.

1238. The Novel Semisynthetic Saponin Adjuvant TQL1055 Enhances the Antibody Response to Pertussis Vaccine with an Improved Tolerability Profile over QS-21

BackgroundAcellular pertussis vaccines are better tolerated but less immunogenic than older whole cell vaccines. Novel adjuvants may be useful to enhance their immunogenicity. First-generation natural saponins are potent immuno-enhancers but are highly reactogenic. The novel semisynthetic saponin TQL1055 was evaluated for its potential to enhance the immunogenicity of a commercially available acellular pertussis vaccine as part of a National Institute of Allergy and Infectious Disease (NIAID) funded project.MethodsGroups of 10 female C57BL/6J mice were immunized subcutaneously (SC) with Adacel® (containing 0.5 mcg pertussis toxin antigen) alone or in combination with QS-21 at 20 mcg/dose or TQL1055 at 50 mcg/dose on Days 0 and 28. Serum antibody titer to pertussis antigen was determined by ELISA (Alpha Diagnostics) at Days 0, 28, and 42 and geometric mean titers (GMT) in IU/mL were determined. Body weights were measured serially for 7 days after dose 1.ResultsAt 28 days following dose 1, mice receiving TQL1055 had an anti-pertussis toxin IgG GMT of 8492, compared with 2263 in mice receiving QS-21 (p = 0.005). At Day 42, 14 days after dose 2, the GMTs increased to 18719 in the TQL1055 group and 10851 in the QS-21 group (p = 0.0653 vs TQL1055 dose 2; p = 0.6038 vs TQL1055 dose 1). Mice in the Adacel and TQL1055 groups gained weight steadily after dose 1, while mice in the QS-21 group had an average weight loss of 10% from baseline at 3 days after dose 1 (p < 0.0001).Figure 1: TQL1055 Enhances the Antibody Response to Adacel® (Commercial Acellular Pertussis Vaccine) in C57BL/6J Female Mice Figure 2: TQL1055 Shows Enhanced Tolerability (measured by decreased weight loss) Compared to QS-21 Following Subcutaneous Injection in C57BL/6J Female Mice ConclusionTQL1055 enhanced the antibody response to a commercial acellular pertussis vaccine to a greater degree than QS-21. Additionally, TQL1055 was better tolerated than QS-21, with no weight loss after vaccination. These findings suggested that TQL1055 may improve the performance of acellular pertussis vaccines without an increase in reactogenicity.DisclosuresChloe Buzz, BS, Adjuvance Technologies (Employee) Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Phil Livingston, MD, Adjuvance Technologies (Consultant, Shareholder) Eric Farris, PhD, Adjuvance Technologies (Employee) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)

Application of a Sanger-Based External Quality Assurance Strategy for the Transition of HIV-1 Drug Resistance Assays to Next Generation Sequencing.

The National Institute of Allergy and Infectious Diseases (NIAID) Virology Quality Assurance (VQA) established a robust proficiency testing program for Sanger sequencing (SS)-based HIV-1 drug resistance (HIVDR) testing in 2001. While many of the lessons learned during the development of such programs may also apply to next generation sequencing (NGS)-based HIVDR assays, challenges remain for the ongoing evaluation of NGS-based testing. These challenges include a proper assessment of assay accuracy and the reproducibility of low abundance variant detection, intra- and inter-assay performance comparisons among laboratories using lab-defined tests, and different data analysis pipelines designed for NGS. In collaboration with the World Health Organization (WHO) Global HIVDR Laboratory Network and the Public Health Agency of Canada, the Rush VQA program distributed archived proficiency testing panels to ten laboratories to evaluate internally developed NGS assays. Consensus FASTA files were submitted using 5%, 10%, and 20% variant detection thresholds, and scored based on the same criteria used for SS. This small study showed that the SS External Quality Assurance (EQA) approach can be used as a transitional strategy for using NGS to generate SS-like data and for ongoing performance while using NGS data from the same quality control materials to further evaluate NGS assay performance.

Exome sequencing study in a clinical research setting finds general acceptance of study returning secondary genomic findings with little decisional conflict.

The most appropriate strategies for managing secondary genomic findings (SF) in clinical research are being developed and evaluated. We surveyed patients at the National Institute of Allergy and Infectious Diseases (NIAID) to evaluate decisional conflict regarding enrolling in a study that returns SF. Responses were collected using a cross-sectional survey after informed consent but before return of SF. Sixty-six adults of 116 eligible participants responded. No participant explicitly declined because they did not want to possibly receive a SF. Sixty-five of 66 (98%) participants thought it was appropriate to return SFs in research; one participant was unsure. Decisional conflict regarding enrolling in a study returning SF was low overall with 68% of participants reporting a score of less than 10 on a 100-point decisional conflict scale, implying that they felt informed, clear on what they wanted, and supported. Lower genetic literacy was weakly associated with higher decisional conflict (Spearman's rho=-0.297, p=.015). Six participants reported confusion related to the choices about SFs. Our data suggest that participants in our study feel it is appropriate to receive SF and have little decisional conflict about potentially receiving such information; however, some participants may need further education and counseling.

Remdesivir is a Delayed Translocation Inhibitor of SARS CoV-2 Replication

Remdesivir is a nucleoside analog approved by the FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryoEM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of three copies of remdesivir monophosphate (RMP) and a partially incorporated fourth RMP in the active site. The structure reveals that RMP blocks RNA translocation after incorporation of three bases following RMP, resulting in delayed chain termination, which can guide the rational design of improved antiviral drugsFunding: This work was supported in part by Welch Foundation grantsF-1604 (to K.A.J.) and F-1938 (to D.W.T.), National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) R01AI110577 (to K.A.J) and National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) R01114223 (to K.A.J.) and R35GM138348 (to D.W.T.), Army Research Office Grant W911NF-15-1-0120(to D.W.T.), and a Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation Medical Research Award (to D.W.T.). D.W.T is a CPRIT Scholar supported by the Cancer Prevention andResearch Institute of Texas (RR160088) and an Army Young Investigator supported by the Army Research Office (W911NF-19-1-0021).Conflict of Interest: All authors declare no competing interests.

Peanut oral food challenges and subsequent feeding of peanuts in infants

The prevalence of peanut allergy has increased in recent years and affects approximately 1% to 3% of children in the United States.1 Peanut allergy presents a significant burden to caregivers and patients due to the anaphylaxis risk, lifelong allergy, increased financial costs, and worse quality of life. On the basis of the results of the Learning Early About Peanut Allergy (LEAP) study, the National Institute of Allergy and Infectious Diseases (NIAID) updated food allergy guidelines in 2017 to introduce peanut as early as 4 to 6 months of age into infant diets as a way to reduce the risk of peanut allergy.

Therapies Against COVID-19: a Running to a Treatment

There is no specific drug or therapy against COVID-19. Since the beginning of the pandemic, scientists are running to discover a drug or therapy that can treat the disease. What we found until now are a combined drug and therapies that can mitigate the effects of the disease in the human body and how to manage the patient better. In this article, we tried to join the new discoveries and presented the drugs and therapies and their mechanisms to combat the SARS-CoV-2. We showed the immunomodulators, parasiticides, antiviral drugs (focused on Remdesivir), antimalarial drugs, anti-cytokine drugs focused on the role of IL-6, Reumathological drugs, inhibitors of cell-receptors, antiinflammatory drugs, especially the role of corticosteroids (dexamethasone), antibiotics (azithromycin), anti-thrombotic drugs, blood derivates therapies and alternative therapies currently used against COVID-19. Also, we listed the main results of clinical trials of new therapies presented by Recommended Panel Treatment Guidelines [NIAID-RML (USA)]. We searched the data in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Excerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We used 302 articles from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-SARS-2, COVID-19, corona virus, coronaviruses, immunomodulators, parasiticides, antiviral, antimalarial, anti-thrombotic and anti-cytokine, antiinflammatory, Reumathological drugs, inhibitors of cell-receptors, antibiotics, blood derivates therapies and alternative therapies, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that despite there is no treatment or drugs against the COVID-19, a combined therapy can help and mitigate the effects of the disease, helping the immune system to combat the virus.&#x0D;

Vaccines’ Candidates Against SARS-CoV-2

Scientists, health organizations, and pharmaceutical companies are making a large global effort to develop vaccines against SARS-CoV-2, the virus of COVID-19 since the outbreak began. Until now, we have more than 150 candidates. However, 19 vaccine candidates have entered clinical trials in phase 2 and 3 trials (31 July 2020). In this article we aimed to present the platforms for COVID-19 vaccine, the types of vaccines (live, attenuated, inactivated, DNA/RNA, proteins subunits, viral vector), the antigen selection, adjuvants, and we focused on the phase 2/3 trial vaccines at this point (Sinopharm, Coronavac, Moderna, Oxford, Biontech). We searched the data in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Excerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We reviewed 216 articles and used 106 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-SARS-2, COVID-19, corona virus, coronaviruses, vaccine, platform, antigen, subunit, live and attenuated vaccine, RNA vaccine, live vaccine, inactivated vaccine, types of vaccines, adjuvants, replication, viral vector, phase 1-3, trial, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that although vaccines have shown safety in phase 1 and efficacy in phase 2 and the beginning of phase 3 is starting, the most renowned scientists believe that a vaccine will be available only in the middle of next year.&#x0D;

Real-life Infant Peanut Allergy Testing in the Post-NIAID Peanut Guideline World

S Volertas, M Coury, G Sanders, M McMorris, M Gupta. J Allergy Clin Immunol Pract. 2020;8(3):1091–1093.e2 To characterize the use of peanut allergy screening at a single center in infants with severe eczema and/or egg allergy and those not meeting high-risk National Institute of Allergy and Infectious Diseases (NIAID) screening criteria. This study included 112 infants (under the age of 12 months) who were tested for peanut sensitization. Of those tested, 84 infants were screened prior to first peanut introduction, and 28 were tested to evaluate a prior reaction upon peanut ingestion/exposure. A retrospective chart review was performed. Among the 84 infants who were screened prior to …

Diagnostic of COVID-19: Chest Computer Tomography or RT-PCR?

In this review article, we presented a gold-standard method to detect the SARS-CoV-2, the novel virus that is causing the COVID-19 outbreak, and the use of a computer tomography (CT) method to detect the complications of the disease. We showed the controversial analysis about which method is the best to detect the disease earlier due to the COVID-19 complications. We searched the articles in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Excerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We reviewed 96 articles and used 45 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-SARS-2, COVID-19, corona virus, coronaviruses, RT-PCR, computer tomography (CT), diagnostic methods, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that chest CT plays an important role in the timely detection of lung infection abnormalities in the early phase of COVID-19 infection. However, the RT-PCR is the gold standard method to detect SARS-CoV-2.&#x0D;

Services Marketing of COVID-19 Vaccines in the Present Scenario

The global COVID-19 vaccines market is projected to reach USD 1,401 million by 2025 from USD 2,273 million in 2022, at a CAGR of -14.9% during the forecast period. The growth of the COVID vaccines market is attributed majorly to the rising number of people infected with COVID-19 and increasing funding for vaccine development. On the other hand, the global COVID-19 drugs market is projected to reach USD 2 million by 2025 from USD 165 million in 2020, at a CAGR of -57.8% during the forecast period. The growth of the COVID drugs market is primarily attributed to use of repurposed drugs for compassionate use, and the emergence of alternative therapies such as convalescent plasma therapy which were earlier used for treating epidemic diseases such as SARS, MERS, and H1N1. Moreover, collaborations between global organizations and governments of various nations to promote the supply of essential drugs and medical supplies are fueling the market growth. Researchers worldwide are working around the clock to find a vaccine against SARS-CoV-2, the virus causing the COVID-19 pandemic. The Herculean effort means that a fast-tracked vaccine could come to market anywhere from the end of 2020 to the middle of 2021. To date, just two coronavirus vaccine has been approved. Sputnik V – formerly known as Gam-COVID-Vac and developed by the Gamaleya Research Institute in Moscow – was approved by the Ministry of Health of the Russian Federation on 11 August. Experts have raised considerable concern about the vaccine’s safety and efficacy given it has not yet entered Phase 3 clinical trials. A second vaccine in Russia, EpiVacCorona, has also been granted regulatory approval, also without entering Phase 3 clinical trials. Operation Warp Speed (OWS) is a collaboration of several US federal government departments including Health and Human Services and its subagencies, Agriculture, Energy and Veterans Affairs and the private sector. OWS has selected three vaccine candidates to fund for Phase 3 trials: Moderna’s mRNA-1273, University of Oxford and AstraZeneca’s AZD1222, and Pfizer and BioNTech's BNT162. Within OWS, the US National Institutes of Health (NIH) has partnered with more than 18 biopharmaceutical companies to accelerate development of drug and vaccine candidates for COVID-19 (ACTIV). The COVID-19 Prevention Trials Network (COVPN) has also been established, which combines clinical trial networks funded by the National Institute of Allergy and Infectious Diseases (NIAID): the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium (IDCRC), and the AIDS Clinical Trials Group.

The New Technologies in the Pandemic Era

The pandemic of the new coronavirus affected people’s lives by an unprecedented scale. Due to the need for isolation and the treatments, drugs, and vaccines, the pandemic amplified the digital health technologies, such as Artificial Intelligence (AI), Big Data Analytics (BDA), Blockchain, Telecommunication Technology (TT) as well as High-Performance Computing (HPC) and other technologies, to historic levels. These technologies are being used to mitigate, facilitate pandemic strategies, and find treatments and vaccines. This paper aims to reach articles about new technologies applied to COVID-19 published in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Excerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We reviewed 252 articles and used 140 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-SARS-2, COVID-19, corona virus, coronaviruses, New Technologies, Artificial Intelligence, Telemedicine, Telecommunication Technologies, AI, Big Data, BDA, TT, High-Performance Computing, Deep Learning, Neural Network, Blockchain, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that this pandemic lastly consolidates the new technologies era and will change the whole way of the social life of human beings. Also, a big jump in medicine will happen on procedures, protocols, drug designs, attendances, encompassing all health areas, as well as in social and business behaviors.

History of Pandemics and COVID-19: What We are Learning from this Pandemic to Be Prepared for the Next One

Since the beginning of human history, the pathogens affect the humankind. The emerge of the new outbreak of coronavirus-19 (COVID-19) is not new in the history of plagues. However, this pandemic has a huge difference from the others due to its ability to affect worldwide at the same time, which brings new perspectives to our future. In this review, we listed some of the worst epidemics and pandemics of human civilization and the new outbreak, listing the pathogens, the spread, and the consequences for mankind. Our search included articles in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Exerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews, and original articles in this order. We reviewed 192 articles and used 94 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, COVID, n-SARS-2, COVID-19, corona virus, coronaviruses, history of pandemics and epidemics, pathogens, plagues, with the tools MeSH (Medical Subject Headings), AND, OR, and the characters [,“,; /., to ensure the best review topics. We concluded that this pandemic will change the social and economic order, as well as it is the first that affects us quickly. So, the experience of COVID-19 could teach us how to be prepared for other outbreaks in the future.

Pathogenesis, Clinical Manifestations and Laboratory Findings of the COVID-19

Since the beginning of the pandemic of new coronavirus, scientists are trying to elucidate the mechanisms of SARS-CoV-2 replication in the human body, its genome, and the behavior of the virus into cells. Also, at the beginning of the outbreak, they found that the unique problem of the virus is the severe acute respiratory syndrome pneumonia, however, new discoveries revealed that the virus affects major organ systems in the human body, causing injuries and letal damages. In addtion, the tests for diagnosing the virus has became a priorty. So, based on the literature review, we showed in this articles the mechanisms of the virus into cells, the symptoms, the clinical course of the disease, and the main injuries caused in the human body’s systems by the SARS-Cov-2, and the laboratory findings. We based our research in the articles of the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Exerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews and original articles in this order. We reviewed more than 317 articles and used 235 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-Sars-2, COVID-19, corona virus, coronaviruses, Pathogenesis, clinical manifestations, symtoms, damage, injuries, laboratory, diagnosis, with the tools MeSH (Medical Subject Headings), AND, OR, and characters [,“,; /., to ensure the best review topics. We concluded that the virus could affect and damage the respiratory system, cardiovascular system, digestive system, urogenital system, and central nervous system. It makes the treatment harder than the physicians found at the beginning of the pandemic. We are initiating our understanding of this new virus and the effect in patients during the symptoms and after them. A deeper understanding of this virus from biomedical research and epidemiological observation will provide important clues to etiologic research, diagnosis, differential diagnosis, treatment, and prognostic assessment against COVID-19.

The Radiological Images and the Diagnostic of COVID-19

The gold-standard method to identify the presence of COVID-19 is the RT-PCR. However, the imaging diagnostic has been requested when there is suspicion of disease’s presence and/or the inflammatory phase of the disease begins. Ths artices described the most common manifestations and patterns of lung abnormality on computed X-Ray (CXR), computer tomography (CT) and Ultrasound of the chest in COVID-19. Notwithstanding the RT-PCR is the gold-standard diagnostic method for COVID-19, the CT has been shown an essential tool to identify pneumonia and the complications of COVID-19 in a patient. This review article aimed to summarize the radiological findings of COVID-19 researches for the following three principal areas: (1) radiological performance in the detection of COVID-19; (2) radiological role in the diagnosis of COVID-19; and (3) radiological function in the monitoring of COVID-19. We searched the articles in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Exerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews and original articles in this order. We reviewed 121 articles and used 57 for this paper from March to May 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-Sars-2, COVID-19, corona virus, coronaviruses, diagnostic, radiology, imaging, computed tomography, chest, CT, X-Ray, with the tools MeSH (Medical Subject Headings), AND, OR, and characters [,“,; /., to ensure the best review topics. We concluded that the imaging method to detect the features of COVID-19 plays an important role in the diagnosis and follow up of the patient with COVID-19 pneumonia. Despite CT has a better sensitivity when compared to CRX and ultrasound, the portable CRX and portable ultrasound could be a new tool with minimal risk of contamination and with good sensitivity.

The Epidemiology, Transmissions and Risk Factors of SARS-CoV-2

The outbreak of a novel coronavirus (SARS-CoV-2) and associated COVID-19 disease in late December 2019 has led to a global pandemic, spreading very quickly and causing a more than 500,000 deaths in less than six monhs of the ourbreak. The incidence differs by country and depends on many agents, such as population density, demography, the amount of testing people and reporting, and actions of mitigation strategies, provisions of sanitary and education of the society. In this article, we presented the current studies about the epidemiology of COVID-19, including the transmission routes of the SARS-CoV-2, the incubation period, the reproduction number (R0), the case fatality risks (CFR), comorbidities and measures prevention against COVID-19. We searched the articles in the main database (PubMed/Medline, Elsevier Science Direct, Scopus, Isi Web of Science, Embase, Exerpta Medica, UptoDate, Lilacs, Novel Coronavirus Resource Directory from Elsevier), in the high-impact international scientific Journals (Scimago Journal and Country Rank - SJR - and Journal Citation Reports - JCR), such as The Lancet, Science, Nature, The New England Journal of Medicine, Physiological Reviews, Journal of the American Medical Association, Plos One, Journal of Clinical Investigation, and in the data from Center for Disease Control (CDC), National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) and World Health Organization (WHO). We prior selected meta-analysis, systematic reviews, article reviews and original articles in this order. We reviewed 235 articles and used 131 from March to June 2020, using the terms coronavirus, SARS-CoV-2, novel coronavirus, Wuhan coronavirus, severe acute respiratory syndrome, 2019-nCoV, 2019 novel coronavirus, n-CoV-2, covid, n-Sars-2, COVID-19, corona virus, coronaviruses, epodemiology of COVID-19, risk factors, viral spreading, transmissions, routes, animals incubation, period, RO, CFR, comorbidities, prevention, with the tools MeSH (Medical Subject Headings), AND, OR, and characters [,“,; /., to ensure the best review topics. We concluded that the epidemiological data is very important to know the transmission risks rate, purpose public political policies of mitigating the disease, protect the vulnerable population. Also, it is important reconsider the legislation about wild animals, the potential intermediate host(s) of various viruses, as well as the conditions of live for animals for human comsuption to prevent future outbreaks.

The association of α4β7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

Backgroundα4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4+ T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID).MethodsMSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4β7 expression on CD4+ T cells. Multivariable conditional logistic regression was used to compare α4β7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of α4β7 expression pre-seroconversion with HIV disease progression.FindingsIn MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of α4β7 expression on CD4+ T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p = 0.246). Interestingly, in PWID (n = 49 cases, 143 controls), cases had significantly lower levels of α4β7 expression compared to their matched controls (adjOR = 0.80, 95% CI = 0.68, 0.93; p = 0.004). Among HIV-positive PWID (n = 47), there was no significant association in HIV disease progression in individuals above or below the median level of α4β7 expression (log-rank p = 0.84).InterpretationIn contrast to findings in heterosexual women, higher α4β7 expression does not predict HIV acquisition or disease progression in PWID or MSM.FundingThis study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.

The technology behind TB DEPOT: a novel public analytics platform integrating tuberculosis clinical, genomic, and radiological data for visual and statistical exploration.

ObjectiveClinical research informatics tools are necessary to support comprehensive studies of infectious diseases. The National Institute of Allergy and Infectious Diseases (NIAID) developed the publicly accessible Tuberculosis Data Exploration Portal (TB DEPOT) to address the complex etiology of tuberculosis (TB).Materials and MethodsTB DEPOT displays deidentified patient case data and facilitates analyses across a wide range of clinical, socioeconomic, genomic, and radiological factors. The solution is built using Amazon Web Services cloud-based infrastructure, .NET Core, Angular, Highcharts, R, PLINK, and other custom-developed services. Structured patient data, pathogen genomic variants, and medical images are integrated into the solution to allow seamless filtering across data domains.ResultsResearchers can use TB DEPOT to query TB patient cases, create and save patient cohorts, and execute comparative statistical analyses on demand. The tool supports user-driven data exploration and fulfills the National Institute of Health’s Findable, Accessible, Interoperable, and Reusable (FAIR) principles.DiscussionTB DEPOT is the first tool of its kind in the field of TB research to integrate multidimensional data from TB patient cases. Its scalable and flexible architectural design has accommodated growth in the data, organizations, types of data, feature requests, and usage. Use of client-side technologies over server-side technologies and prioritizing maintenance have been important lessons learned. Future directions are dynamically prioritized and key functionality is shared through an application programming interface.ConclusionThis paper describes the platform development methodology, resulting functionality, benefits, and technical considerations of a clinical research informatics application to support increased understanding of TB.