The Pandemic, Infodemic, and People's Resilience in India: Viewpoint.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused widespread fear and stress. The pandemic has affected everyone, everywhere, and created systemic inequities, leaving no one behind. In India alone, more than 34,094,373 confirmed COVID-19 cases and 452,454 related deaths have been reported as of October 19, 2021. Around May 2021, the daily number of new COVID-19 cases crossed the 400,000 mark, seriously hampering the health care system. Despite the devastating situation, the public response was seen through their efforts to come forward with innovative ideas for potential ways to combat the pandemic, for instance, dealing with the shortage of oxygen cylinders and hospital bed availability. With increasing COVID-19 vaccination rates since September 2021, along with the diminishing number of daily new cases, the country is conducting preventive and preparatory measures for the third wave. In this article, we propose the pivotal role of public participation and digital solutions to re-establish our society and describe how Sustainable Development Goals (SDGs) can support eHealth initiatives and mitigate infodemics to tackle a postpandemic situation. This viewpoint reflects that the COVID-19 pandemic has featured a need to bring together research findings across disciplines, build greater coherence within the field, and be a driving force for multi-sectoral, cross-disciplinary collaboration. The article also highlights the various needs to develop digital solutions that can be applied to pandemic situations and be reprocessed to focus on other SDGs. Promoting the use of digital health care solutions to implement preventive measures can be enhanced by public empowerment and engagement. Wearable technologies can be efficiently used for remote monitoring or home-based care for patients with chronic conditions. Furthermore, the development and implementation of informational tools can aid the improvement of well-being and dissolve panic-ridden behaviors contributing toward infodemics. Thus, a call to action for an observatory of digital health initiatives on COVID-19 is required to share the main conclusions and lessons learned in terms of resilience, crisis mitigation, and preparedness.

Iodine-based Dual-Energy CT of Traumatic Hemorrhagic Contusions: Relationship to In-Hospital Mortality and Short-term Outcome.

BackgroundTraumatic hemorrhagic contusions are associated with iodine leak; however, quantification of leakage and its importance to outcome is unclear.PurposeTo identify iodine-based dual-energy CT variables that correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.Materials and MethodsIn this retrospective study, consecutive patients with contusions from May 2016 through January 2017 were analyzed. Two radiologists evaluated CT variables from unenhanced admission head CT and follow-up head dual-energy CT scans obtained after contrast material-enhanced whole-body CT. The outcomes evaluated were in-hospital mortality, Rancho Los Amigos scale (RLAS) score, and disability rating scale (DRS) score. Logistic regression and linear regression were used to develop prediction models for categorical and continuous outcomes, respectively.ResultsThe study included 65 patients (median age, 48 years; interquartile range, 25-65.5 years); 50 were men. Dual-energy CT variables that correlated with mortality, RLAS score, and DRS score were iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusion. The single-energy CT variable that correlated with mortality, RLAS score, and DRS score was hematoma volume at follow-up CT. Multiple logistic regression analysis after inclusion of clinical variables identified two predictors that enabled determination of mortality: postresuscitation Glasgow coma scale (P-GCS) (adjusted odds ratio, 0.42; 95% confidence interval [CI]: 0.2, 0.86; P = 0.01) and iodine quantity in pseudohematoma (adjusted odds ratio, 1.4 per milligram; 95% CI: 1.02 per milligram, 1.9 per milligram; P = 0.03), with a mean area under the receiver operating characteristic curve of 0.96 ± 0.05 (standard error). For RLAS, the predictors were P-GCS (mean coefficient, 0.32 ± 0.06; P < .001) and iodine quantity in contusion (mean coefficient, -0.04 per milligram ± 0.02; P = 0.01). Predictors for DRS were P-GCS (mean coefficient, -1.15 ± 0.27; P < .001), age (mean coefficient, 0.13 per year ± 0.04; P = .002), and iodine quantity in contusion (mean coefficient, 0.19 per milligram ± 0.07; P = .02).ConclusionIodine-based dual-energy CT variables correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Talbott and Hess in this issue.

Comparison of neutralizing antibody responses elicited from highly diverse polyvalent heterotrimeric HIV-1 gp140 cocktail immunogens versus a monovalent counterpart in rhesus macaques.

Eliciting neutralizing antibodies capable of inactivating a broad spectrum of HIV-1 strains is a major goal of HIV-1 vaccine design. The challenge is that envelopes (Envs) of circulating viruses are almost certainly different from any Env used in a vaccine. A novel immunogen composed of a highly diverse set of gp140 Envs including subtypes A, B, C, D and F was developed to stimulate a more cross-neutralizing antibody response. Env heterotrimers composed of up to 54 different gp140s were produced with the aim of focusing the response to the conserved regions of Env while reducing the dominance of any individual hypervariable region. Heterotrimeric gp140 Envs of inter- and intra-subtype combinations were shown to bind CD4 and a panel of neutralizing monoclonal antibodies with similar affinity to monovalent UG37 gp140. Macaques immunized with six groups of heterotrimer mixtures showed slightly more potent neutralizing antibody responses in TZM-BL tier 1 and A3R5 tier 2 pseudovirus assays than macaques immunized with monovalent Env gp140, and exhibited a marginally greater focus on the CD4-binding site. Carbopol enhanced neutralization when used as an adjuvant instead of RIBI in combination with UG37 gp140. These data indicate that cross-subtype heterotrimeric gp140 Envs may elicit some improvement of the neutralizing antibody response in macaques compared to monovalent gp140 Env.

Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. RESULTS: It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies.

Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.

Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.

International network for comparison of HIV neutralization assays: the NeutNet report II.

BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, beta-galactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation.

Interactions and management issues in HSV and HIV coinfection.

Significant synergistic interactions have been observed between HIV and herpes simplex virus (HSV). HIV-induced immune compromise can cause frequent and persistent HSV disease, while poorly controlled HSV replication may influence HIV pathogenicity and transmission. HSV-2 seroprevalence is high in HIV-infected cohorts worldwide, with rates of over 80% for HSV-1 and ranging from 33% to more than 80% for HSV-2. As seen in HIV-negative individuals, HSV-2 coinfection is associated with female gender, older age and black ethnicity. HSV infection is commonly under-diagnosed in HIV-infected individuals, although the use of PCR for HSV detection in mucocutaneous swabs and HSV type-specific serology can improve the diagnostic yield. In HIV-1-infected patients with frequent clinical episodes of HSV reactivation, suppressive antiviral therapy may prove beneficial in controlling HSV disease while also reducing HSV-mediated promotion of HIV replication. Antiretroviral therapy leads to a gradual recovery of HSV-specific T-cell responses and a reduction in HSV-related morbidity, indicating that successful management of coinfection should target both HIV and HSV replication. The aim of this review is to address the more speculative issues surrounding the management of HSV/HIV coinfection and to summarize the data that inform them.

Reconstitution of herpes simplex virus-specific T cell immunity in HIV-infected patients receiving highly active antiretroviral therapy.

Production of herpes simplex virus (HSV)-specific interferon- gamma by peripheral-blood mononuclear cells (PBMCs) of HSV-seropositive healthy donors and human immunodeficiency virus-infected persons was determined by use of ELISPOT. The mean +/- SD number of spot-forming cells/10(6) PBMCs was 314 +/- 74 in 11 healthy donors, 360 +/- 69 in 3 long-term nonprogressors (LTNPs), 186 +/- 52 in 9 newly diagnosed patients, and 181 +/- 59 in 33 patients who were receiving highly active antiretroviral therapy (HAART) for a median period of 30 months (range, 1-109 months). In 9 patients monitored prospectively while receiving virologically and immunologically successful first-line HAART, the number of spot-forming cells increased by 5.6/month (95% confidence interval, 1.2-9.9 [P=.01]) and 21.3/100 CD4 cells/mm(3) gained (95% confidence interval, 13.8-28.7 [P<.0001]). Responses were correlated with LTNP status and CD4 cell count.

Herpes simplex virus type 2 (HSV-2) seroprevalence at the time of HIV-1 diagnosis and seroincidence after HIV-1 diagnosis in an ethnically diverse cohort of HIV-1-infected persons.

OBJECTIVE: The objective of this study was to determine herpes simplex virus type 2 (HSV-2) seroprevalence at HIV-1 diagnosis and seroincidence > or =1 year after HIV-1 diagnosis. METHODS: HSV type-specific antibodies were detected by enzyme immunoassay. RESULTS: The cohort comprised 850 adults diagnosed HIV-positive in 1986-2001 and followed for a median of 3 years. HSV-2 seroprevalence was 63% (95% confidence interval [CI], 60-66%) and was associated with female gender, heterosexual risk group, black ethnicity, and older age. HSV-2 seroincidence was 1.8 per 100 person-years (95% CI, 0.8-2.8) and was associated with other sexually transmitted diseases, including human papilloma virus infection (P = 0.005) and gonorrhea (P = 0.05). A diagnosis of genital herpes was made in 21% HSV-2-seropositive persons and was more likely in those who tested HIV-positive before 1997 (adjusted odds ratio, 5.11; 95% CI, 3.28-7.98; P = 0.0001). CONCLUSIONS: Results confirm the epidemiologic association between HIV-1 and HSV-2. HSV-2 seroconversion was a marker of high-risk sexual behavior. The likelihood of developing symptoms of genital herpes declined from 1997 onward.

Isolation and molecular detection of methylotrophic bacteria occurring in the human mouth.

Diverse methylotrophic bacteria were isolated from the tongue, and supra- and subgingival plaque in the mouths of volunteers and patients with periodontitis. One-carbon compounds such as dimethylsulfide in the mouth are likely to be used as growth substrates for these organisms. Methylotrophic strains of Bacillus, Brevibacterium casei, Hyphomicrobium sulfonivorans, Methylobacterium, Micrococcus luteus and Variovorax paradoxus were characterized physiologically and by their 16S rRNA gene sequences. The type strain of B. casei was shown to be methylotrophic. Enzymes of methylotrophic metabolism were characterized in some strains, and activities consistent with growth using known pathways of C1-compound metabolism demonstrated. Genomic DNA from 18 tongue and dental plaque samples from nine volunteers was amplified by the polymerase chain reaction using primers for the 16S rRNA gene of Methylobacterium and the mxaF gene of methanol dehydrogenase. MxaF was detected in all nine volunteers, and Methylobacterium was detected in seven. Methylotrophic activity is thus a feature of the oral bacterial community.

Detection and typing of herpes simplex DNA in genital swabs by real-time polymerase chain reaction.

The LightCycler polymerase chain reaction (PCR) is a sensitive assay for the detection of Herpes simplex virus (HSV) DNA in muco-cutaneous swabs. Software-based analysis of the probe melting temperature (Tm) can be used to discriminate between HSV types (HSV-1 and HSV-2). Among 76 HSV DNA positive genital swabs, atypical Tms were observed in 14 (18%). The 14 samples were all typed as HSV-2 by sequence alignment. In 4/14 samples, the atypical Tm was associated with sequence variation at the probe-binding site. Among 10 samples with conserved sequences, Tms were influenced by the specimen preparation method prior to PCR. These findings indicate that multiple factors including, but not limited to sequence variation complicate melting curve analysis following real-time PCR. Alternative typing methods are recommended for specimens with atypical melting curves.

Disseminated neonatal herpes simplex virus (HSV) type 2 infection diagnosed by HSV DNA detection in blood and successfully managed by liver transplantation.

UNLABELLED: We report a case of neonatal herpes presenting with liver failure and disseminated coagulopathy which followed unrecognised maternal primary genital herpes and was diagnosed by herpes simplex virus DNA detection in blood by polymerase chain reaction 2 weeks after initiation of empiric intravenous aciclovir. The child underwent liver transplantation while receiving suppressive antiviral therapy and remains well after 10 months of follow-up. CONCLUSION: our case highlights potential pitfalls in the diagnosis of neonatal herpes and indicates a role for blood herpes simplex virus polymerase chain reaction as a sensitive diagnostic tool in disseminated infection. It is one of very few reports where liver transplantation has been successfully carried out in a neonate with herpes simplex virus-induced liver failure.