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JAMA Network Open May 2024SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.
IMPORTANCE
SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.
OBJECTIVE
To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.
DESIGN, SETTING, AND PARTICIPANTS
This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023.
MAIN OUTCOMES AND MEASURES
Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis.
RESULTS
Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity.
CONCLUSIONS AND RELEVANCE
In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.
Topics: Humans; COVID-19; Nasopharynx; Viral Load; Male; SARS-CoV-2; Female; Adult; Middle Aged; COVID-19 Vaccines; Randomized Controlled Trials as Topic; United States; Aged
PubMed: 38780941
DOI: 10.1001/jamanetworkopen.2024.12835 -
Emerging Microbes & Infections Dec 2024As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial....
As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.
Topics: Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19; Antibodies, Neutralizing; Antibodies, Viral; Immune Evasion; Angiotensin-Converting Enzyme 2; Cell Line; Mutation; Neutralization Tests
PubMed: 38779718
DOI: 10.1080/22221751.2024.2359004 -
BMC Public Health May 2024The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This...
BACKGROUND
The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010.
METHODS
We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE).
RESULTS
In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%).
CONCLUSIONS
There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.
Topics: Humans; European Union; Global Burden of Disease; Life Expectancy; Disability-Adjusted Life Years; Male; Health Status; Female; Cost of Illness
PubMed: 38778362
DOI: 10.1186/s12889-024-18529-3 -
International Journal of Infectious... Aug 2024This study investigated the association between Coronavirus Disease 2019 mRNA vaccination and stroke in Qatar.
OBJECTIVE
This study investigated the association between Coronavirus Disease 2019 mRNA vaccination and stroke in Qatar.
METHODS
Between December 1, 2020, and April 11, 2023, a matched case-control study was conducted to investigate the association between 3036 acute stroke cases and 3036 controls drawn from the entire population of Qatar.
RESULTS
The adjusted odds ratio (aOR) for vaccination among cases compared to controls was 0.87 (95% CI: 0.75-1.00). The aOR was 0.74 (95% CI: 0.45-1.23) for a single vaccine dose, 0.87 (95% CI: 0.73-1.04) for primary-series vaccination (two doses), and 0.91 (95% CI: 0.66-1.25) for booster vaccination (three or more doses). The aOR was 0.87 (95% CI: 0.72-1.04) for BNT162b2 and 0.86 (95% CI: 0.67-1.11) for mRNA-1273. Subgroup analyses, considering different durations since vaccination, also demonstrated no association. Subgroup analyses based on nationality, age, number of coexisting conditions, or prior infection status yielded similar results. Subgroup analysis, stratified by stroke type, suggested an association between vaccination and cerebral venous sinus thrombosis (aOR of 2.50 [95% CI: 0.97-6.44]), but it did not reach statistical significance.
CONCLUSION
There was no evidence of an increased risk of stroke following vaccination, both in the short term and in the long term, extending beyond a year after receiving the vaccine.
Topics: Humans; Qatar; Case-Control Studies; Male; Female; Middle Aged; COVID-19; Stroke; Aged; Adult; Vaccination; COVID-19 Vaccines; SARS-CoV-2; BNT162 Vaccine; Odds Ratio; 2019-nCoV Vaccine mRNA-1273; Risk Factors
PubMed: 38777080
DOI: 10.1016/j.ijid.2024.107095 -
JCI Insight Apr 2024Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2...
Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.
Topics: Humans; HIV Infections; Male; Female; Child; Meningococcal Vaccines; Child, Preschool; Meningococcal Infections; Antibodies, Bacterial; B-Lymphocytes; Infectious Disease Transmission, Vertical; Immunogenicity, Vaccine; Immunoglobulin G
PubMed: 38775152
DOI: 10.1172/jci.insight.177182 -
Archives of Internal Medicine Research 2024The Biden administration decided to end the COVID-19 National and Public Health emergencies on May 11, 2023. These emergency declarations were established by the Trump...
The Biden administration decided to end the COVID-19 National and Public Health emergencies on May 11, 2023. These emergency declarations were established by the Trump Administration in early 2020. Under the COVID-19 emergency declarations, US citizens were provided with COVID-19 testing, vaccines, and treatments at little or no cost. The declarations allowed the federal government the option of waiving and or modifying government programs such Medicare, Medicaid. The emergency declarations were directly tied to other COVID-19 related provisions that have also expired that includes Economic Security (CARES) Act, the American Rescue Plan Act (ARPA), the Families First Coronavirus Response Act (FFCRA), the Coronavirus Aid, Relief, and the Inflation Reduction Act (IRA), the Consolidated Appropriations Act, 2023 (CAA). In addition, there were other federal and state emergency programs that were provided and too numerous to report here. At the time of this writing, the state of Tennessee continues to have moderate and sporadic spikes in COVID-19 cases and hospitalizations. Tennessee has higher than the national average of uninsured and underinsured people in the US. In Tennessee, more than 600,000 people are uninsured or underinsured in 2023 according to a study by the Kaiser Family Foundation. The ending of the PHE greatly impact coverage, cost, and access to COVID related services that will disproportionately affect the uninsured and medically underserved populations in Tennessee, the south in general, and throughout the US. Medically underserved populations are those groups with disparities in primary care, living in poverty, older, or having higher than expected infant mortality.
PubMed: 38774576
DOI: 10.26502/aimr.0164 -
Nature Communications May 2024The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs)...
The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.
Topics: Humans; AIDS Vaccines; HIV-1; HIV Antibodies; Antibodies, Neutralizing; CD4 Antigens; Vaccines, DNA; Antibodies, Monoclonal; HIV Infections; Cryoelectron Microscopy; HIV Envelope Protein gp120; Binding Sites; Complementarity Determining Regions
PubMed: 38773089
DOI: 10.1038/s41467-024-48514-8 -
Vaccine May 2024Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy...
BACKGROUND
Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products.
METHODS
HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables.
RESULTS
More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (OR = 2.50, OR = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002).
CONCLUSION
Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity.
PubMed: 38772835
DOI: 10.1016/j.vaccine.2024.05.039 -
Drugs in Context 2024Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as...
BACKGROUND
Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as first-line treatment in 2017. Reported national surveillance data in the USA estimated INSTI-R to be 6.3% as of 2018. This article aims to describe estimated prevalence of INSTI-R within a single clinic network in Chicago, IL, USA, and identify risk factors for resistance and virological failure (VF).
METHODS
This was a retrospective, single-centre study of adults with HIV starting an INSTI-containing regimen between September 2017 and 2020. The primary endpoint was the difference in INSTI-R of the sample population compared with the national prevalence. Other outcomes included VF and documented INSTI-R mutations.
RESULTS
Of 948 participants screened, 321 were included. Eight people had baseline INSTI-R testing results available, of which five had INSTI-R at baseline for an estimated prevalence of 1.6%. This estimation was significantly less than the national estimated prevalence of 6.3% (<0.001). VF occurred in 26 (7.8%) individuals. Because no participants acquired INSTI-R during the study period, investigators were unable to identify risk factors associated with the development of INSTI-R. People with high pre-treatment viral loads had 1.21 (95% CI 1.05-1.39) higher odds of VF.
CONCLUSIONS
Amongst participants on INSTI-containing regimens, INSTI-R rates were estimated to be lower than the estimated national prevalence. Detectable pre-switch viral loads were more associated with VF than undetectable viral loads.
PubMed: 38770371
DOI: 10.7573/dic.2023-12-4 -
Virologica Sinica Jun 2024As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of...
As of December 2022, 2603 laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we generated two DNA vaccine candidates by integrating MERS-CoV Spike (S) gene into a replicating Vaccinia Tian Tan (VTT) vector. Compared to homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8 T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates, but also proposes a heterologous sequential immunization strategy worthy of further development.
Topics: Animals; Vaccines, DNA; Middle East Respiratory Syndrome Coronavirus; Immunity, Cellular; Antibodies, Viral; Mice; Antibodies, Neutralizing; Immunity, Humoral; Viral Vaccines; Female; Coronavirus Infections; Mice, Inbred BALB C; CD8-Positive T-Lymphocytes; Vaccinia virus; Immunization, Secondary; Spike Glycoprotein, Coronavirus
PubMed: 38768713
DOI: 10.1016/j.virs.2024.05.005