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Background The reactogenicity and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines are well studied. Little is known regarding the relationship between immunogenicity and reactogenicity of COVID-19 vaccines. Methods This study assessed the association between immunogenicity and reactogenicity after 2 mRNA-1273 (100 µg) injections in 1671 total adolescent and adult participants (≥12 years) from the primary immunogenicity sets of the blinded periods of the Coronavirus Efficacy (COVE) and TeenCOVE trials. Associations between immunogenicity through day 57 and solicited adverse reactions (ARs) after the first and second injections of mRNA-1273 were evaluated among participants with and without solicited ARs using linear mixed-effects models. Results mRNA-1273 reactogenicity in this combined analysis set was similar to that reported for these trials. The vaccine elicited high neutralizing antibody (nAb) geometric mean titers (GMTs) in evaluable participants. GMTs at day 57 were significantly higher in participants who experienced solicited systemic ARs after the second injection (1227.2 [1164.4–1293.5]) than those who did not (980.1 [886.8–1083.2], P =.001) and were associated with fever, chills, headache, fatigue, myalgia, and arthralgia. Significant associations with local ARs were not found. Conclusions These data show an association of systemic ARs with increased nAb titers following a second mRNA-1273 injection. While these data indicate systemic ARs are associated with increased antibody titers, high nAb titers were observed in participants after both injections, consistent with the immunogenicity and efficacy in these trials. These results add to the body of evidence regarding the relationship of immunogenicity and reactogenicity and can contribute toward the design of future mRNA vaccines. [ABSTRACT FROM AUTHOR]

Background: Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains.Methods: This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365.Results: All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine.Conclusions: No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited.Clinical Trials Registration: NCT02218125. [ABSTRACT FROM AUTHOR]

The authors reflect on the potential of intentional drug development by citing the results of a phase three randomized controlled trial on the effectiveness of ritonavir and nirmatrelvir as treatment against SARS-CoV-2 infection in COVID-19 unvaccinated patients. Based on the results, the combination drug was linked with mild dysgeusia and diarrhea, but it is effective against COVID-19.

The article presents the discussion on suffering relatively low Covid-19 vaccine coverage. Topics include immunity resulting from either vaccination or previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and suggesting the possibility of a high prevalence of underlying seropositivity due to previous infection.

Background: A prophylactic HIV-1 vaccine is a global health priority.Objective: To assess a novel vaccine platform as a prophylactic HIV-1 regimen.Design: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149).Setting: United States, East Africa, and South Africa.Patients: Healthy adults without HIV infection.Intervention: 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.Measurements: Safety and immunogenicity and the effect of baseline vector immunity.Results: 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.Limitations: Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.Conclusion: Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.Primary Funding Source: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland. [ABSTRACT FROM AUTHOR]

An editorial is presented on various studies regarding the use of viruses to treat diseases. Topics discussed include the potential use of viruses to change the course of cancer, the capability of oncolytic viruses to infect or kill tumor cells, and the study by A. Desjardins and colleagues on the use of an engineered poliovirus, targeting glioblastoma.

An introduction is presented in which the authors discuss articles within the issue on topics such as the duration of detection of Ebola virus by polymerase-chain-reaction assay and the randomized controlled trial of standard of care for Ebola infection.

Background: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans.Methods: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed.Results: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry.Conclusions: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.Clinical Trials Registration: NCT01103687. [ABSTRACT FROM AUTHOR]

Background. We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA.Methods. Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 109 to 1011 viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed.Results. Self-limited reactogenicity was observed after the initial immunization in the highest (1011 vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 109, 1010, and 1011 vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5.Conclusions. Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions.Clinical Trials Registration. NCT00695877. [ABSTRACT FROM AUTHOR]

The article discusses that rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of known effective treatments for coronavirus disease 2019 have caused an unprecedented situation for patients and clinicians regimens. It mentions that pharmacologic treatments that have generated substantial interest: regimens based on remdesivir, hydroxychloroquine and lopinavir.

Background. We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans.Methods. Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 109–1011 vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed.Results. Self-limited reactogenicity was observed after the initial immunization at the highest (1011 vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 109, 1010, 1011 vp 3-dose and the 1010 and 5 × 1010 vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/106 peripheral blood mononuclear cells, respectively.Conclusion. This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 1010 vp or less. Ad26 is a promising new vaccine vector for HIV-1.Clinical Trials Registration. NCT00618605. [ABSTRACT FROM AUTHOR]

Background. To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig). Methods. This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5). Results. No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) &ggr; and IL-2 enzymelinked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/106 peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/106 PBMCs (P = .003; T4 vs T5) for the IFN-&ggr; ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4. Conclusions. Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies. [ABSTRACT FROM AUTHOR]

The article describes the case of a 60-year-old male renal transplant recipient who suffered from diabetic ketoacidosis and renal insufficiency as well as mental-status changes. The patient was suffering from chronic respiratory problems until two months before he got admitted to a hospital due to somnolence, increasing fatigue and intermittent mild confusion. It discusses the development of hypoattenuation in the posterior right lentiform nucleus in the brain of the patient.

Chemotherapy directed at acute leukemia (AL) causes predictable periods of neutropenia during which patients are at significant risk for bacterial infection and subsequent infection-related death. In an effort to diminish this risk, several studies have assessed the utility of prophylactic antibiotics during the neutropenic period. While prophylactic antibiotics have been associated with a decrease in the incidence of fever and bacterial infection, no placebo-controlled randomized trial has found a decrease in mortality. In addition, delayed adverse consequences associated with prophylaxis have emerged including increases in both colonization and infection with antimicrobial-resistant and unusual pathogens like quinolone-resistant Escherichia coli. To determine who would benefit most from prophylaxis, the immediate benefits including reduction in fever and infection must be balanced with the potential for emergence of resistant pathogens in this population. [ABSTRACT FROM AUTHOR]

Summary: We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0mg doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1-uninfected adults were enrolled. Using an interferon-γ ELISPOT assay, a response to PADRE was detected in one vaccine recipient. Three vaccine recipients raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was safe and well-tolerated, but only weakly immunogenic. [Copyright &y& Elsevier]

Infections with fungi cause significant morbidity in the immunocompromised host and invasion of the CNS may lead to devastating consequences. Vulnerable individuals include those with haematological malignancies, transplant recipients, and those infected with HIV. Potential pathogens include yeasts, Aspergillus spp., other moulds of an increasing variety, and a range of dimorphic fungi, often associated with particular geographical locations. Antifungal treatments include polyenes such as amphotericin B and its lipid formulations, azoles such as fluconazole and itraconazole, and the more recent voriconazole and posaconazole. The new antifungal class of echinocandins, such as caspofungin, micafungin and anidulafungin, typically lack CNS penetration. Amphotericin B and flucytosine are used to initiate treatment for CNS yeast infections caused by Candida and Cryptococcus neoformans. Voriconazole is preferred for aspergillus, although amphotericin B, particularly in lipid formulation, is also useful. Reliable treatment data are lacking for CNS infections with most of the non-aspergillus moulds; posaconazole holds promise for the zygomycetes and perhaps some of the rarer pigmented fungi, but amphotericin B preparations are still recommended. Oral fluconazole is effective for the CNS manifestations of coccidioides, while histoplasmosis and blastomycoses typically require amphotericin B therapy. Effective treatment requires a definitive diagnosis, which is often challenging in the population at risk of CNS fungal infections. [ABSTRACT FROM AUTHOR]

The article discusses group of researchers led by Cao B. have performed an urgent randomized clinical trial of the efficacy of lopinavir-ritonavir drugs in patients with Covid-19 in Wuhan, China. It mentions that lopinavir-ritonavir does not seem to be highly effective in patients with Covid-19; and also mentions that lopinavir is not particularly potent against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Abstract: The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-∞, 52.1 and 53.8 μg·h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-∞, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection. [Copyright &y& Elsevier]

An editorial is presented on the "Take" as a Biomarker. Topics include inoculation of smallpox vaccine and formation of a pox-like scar at the vaccination site; risk of live vaccinia virus for local infection; and attenuated virus, Modified vaccinia Ankara (MVA's) safety in weak immune systems including cancer, human immunodeficiency virus (HIV) infection, and skin conditions.

Presents a study to evaluate cross-reactivity of quinolone antimicrobials in common opiate screening assays and to assess the in vivo implications of this phenomenon, in light of how common medications may cross-react with frequently used testing assays and cause false-positive results. Context; Objective; Design, setting, and participants; Main outcome measure; Results; Conclusion that greater attention to cross-reactivity of quinolones with immunoassays for opiates is needed to minimize the potential for invalid test interpretation.

Vaccine clinical trials have been essential to developing effective severe acute respiratory syndrome coronavirus 2 vaccines. The challenges of supply chain disruptions, infection control, study designs, and participant factors that affect trial procedures are reviewed, with specific solutions to streamline the clinical trial process. [ABSTRACT FROM AUTHOR]

The authors argue that the value of intensive fluid management and care is the most important take-home message from the case reports of Ebola virus disease (EVD) patients outside Africa. They say that it will be very hard to examine the contribution of a drug without comparative trials unless a new drug is profoundly effective. They add that the benefits of routine care like intravenous fluid and electrolyte support should be brought to all patients.

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. Methods and findings: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days). Conclusions: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. Trial registration: ClinicalTrials.gov/NCT03387150 (posted on 21 December 2017). In a Phase 1 randomised clinical trial, Stephen Walsh and colleagues assess the safety and pharmacokinetics of VRC07-523LS which has been engineered for improved breadth, potency, and a longer half-life. Author summary: Why was this study done?: Broadly neutralizing antibodies (bnAbs), which can block HIV-1 infection in laboratory settings, have considerable promise for HIV-1 prevention in people. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site (CD4bs) targeting bnAb, VRC01, was found to have 75% prevention efficacy against highly neutralization-sensitive viruses. Most circulating isolates of HIV-1 are less sensitive, and VRC01 was ineffective against those viruses. Our clinical trial was done to assess the safety and drug levels of another CD4bs bnAb called VRC07-523LS, which has been engineered for improved breadth, potency, and a longer half-life. What did the researchers do and find?: We administered VRC07-523LS to healthy volunteers without HIV using multiple routes (intravenous [IV], subcutaneous [SC], and intramuscular [IM]) and at doses ranging from 2.5 mg/kg to 20 mg/kg. VRC07-523LS was safe and well tolerated over more than 30 months of follow-up. At any given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. VRC07-523LS has a half-life of about 42 days, which is over twice as long as VRC01 (15 days). What do these findings mean?: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. The main limitations of our study are the small sizes of the individual groups and missing blood draws at the later time points due to COVID-19 restrictions, both of which lead to uncertainty in our estimates of drug levels and pharmacokinetic parameters. Presented in part at: HIV R4P 2021 Virtual (Abstract OA03.01), Cape Town, South Africa, January 2021; and IAS 2022 (Abstract PESUA14), Montréal, Canada, July 2022. [ABSTRACT FROM AUTHOR]

There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer. [ABSTRACT FROM AUTHOR]

Vaccination reduces morbidity and mortality due to infections, but efficacy may be limited due to distinct immunogenicity at the extremes of age. This raises the possibility of employing adjuvants to enhance immunogenicity and protection. Early IFNγ production is a hallmark of effective vaccine immunogenicity in adults serving as a biomarker that may predict effective adjuvanticity. We utilized mass cytometry (CyTOF) to dissect the source of adjuvant-induced cytokine production in human blood mononuclear cells (BMCs) from newborns (~39-week-gestation), adults (~18-63 years old) and elders (>65 years of age) after stimulation with pattern recognition receptors agonist (PRRa) adjuvants. Dimensionality reduction analysis of CyTOF data mapped the BMC compartment, elucidated age-specific immune responses and profiled PRR-mediated activation of monocytes and DCs upon adjuvant stimulation. Furthermore, we demonstrated PRRa adjuvants mediated innate IFNγ induction and mapped NK cells as the key source of TLR7/8 agonist (TLR7/8a) specific innate IFNγ responses. Hierarchical clustering analysis revealed age and TLR7/8a-specific accumulation of innate IFNγ producing γδ T cells. Our study demonstrates the application of mass cytometry and cutting-edge computational approaches to characterize immune responses across immunologically distinct age groups and may inform identification of the bespoke adjuvantation systems tailored to enhance immunity in distinct vulnerable populations. An in vitro mass cytometry study focusing on age and adjuvant-specific activation of human blood mononuclear cells reveals NK cells as the key source of TLR7/8 agonist induced innate IFNγ responses. [ABSTRACT FROM AUTHOR]

The article focuses on the implications for U.S. emergency use authorizations following the end of a declared public health emergency (PHE). Topics include the authority granted to U.S. public health agencies under section 319 of the Public Health Service Act and section 564 of the Federal Food, Drug, and Cosmetic Act for emergencies; and the Food and Drug Association's decision-making process and evidentiary standard for issuing emergency use authorizations during the COVID-19 pandemic.

The author reflects on the prevention of Influenzavirus B. The author mentions that 1 to 46% of the circulating viruses each season are caused by influenza B viruses. According to the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, and World Health Organization in the U.S. that the possible solution to minimize the chance of a B-lineage mismatch is to include both B lineages in the influenza vaccines.

The article provides information on an audio interview conducted on December 9, 2020 with Doctors Eric Rubin, Lindsey R. Baden and Joshua A. Barocas about who should be first in line as Covid-19 vaccines are launched.