Publications by authors named "Jonathan Z Li"
Cross-neutralization of distant coronaviruses correlates with Spike S2-specific antibodies from immunocompetent and immunocompromised vaccinated SARS-CoV-2-infected patients.
Res Sq
December 2024
As of May 2023, the public health emergency of COVID-19 was lifted across the globe. However, SARS-CoV-2 infections continue to be recorded worldwide. This situation has been attributed to the ability of the virus to evade host immune responses including neutralizing antibody-derived Immunity.
View Article and Find Full Text PDFBackground: Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies.
Methods: Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene).
Purpose Of Review: This review focuses on the viral and immune factors influencing HIV posttreatment control (PTC), a rare condition where individuals maintain viral suppression after discontinuing antiretroviral therapy (ART).
Recent Findings: Studies demonstrate that early ART initiation leads to smaller HIV reservoirs and delayed viral rebound in PTCs. Virologically, PTCs harbor smaller HIV reservoirs and show lower levels of reservoir transcriptional activity compared with posttreatment noncontrollers.
Background: A key research priority for developing an HIV cure strategy is to define the viral dynamics and biomarkers associated with sustained post-treatment control. The ability to predict the likelihood of sustained post-treatment control or non-control could minimize the time off antiretroviral therapy (ART) for those destined to not control and anticipate longer periods off ART for those destined to control.
Methods: Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control using viral kinetics data from several studies in which participants interrupted ART.
Article Synopsis
- - Pregnancy may worsen the severity of SARS-CoV-2 and other respiratory infections, but the reasons behind this increased risk are not well understood.
- - A study involving 226 women, including 152 pregnant and 74 non-pregnant, showed that pregnant women experience significant changes in T cell responses and immune functions after SARS-CoV-2 infection.
- - The study found increased levels of interleukin-27 in pregnant women, which is linked to T cell exhaustion, suggesting that unique immune responses during pregnancy could make them more vulnerable to viral infections.
2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on the Management of COVID-19: Anti-SARS-CoV-2 Neutralizing Antibody Pemivibart for Pre-exposure Prophylaxis.
Clin Infect Dis
October 2024
Article Synopsis
- * It includes recommendations for using the anti-SARS-CoV-2 neutralizing antibody pemivibart as pre-exposure prophylaxis based on systematic review evidence.
- * The guidelines follow GRADE methodology for assessing evidence certainty and strength of recommendations, and pemivibart is included in the FDA's Emergency Use Authorization.
We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.
View Article and Find Full Text PDFObjectives: To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms.
Methods: Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from several days up to 14 months post-SARS-CoV-2 infection. The primary outcome measure was to quantify SARS-CoV-2 antigens, including the S1 subunit of spike, full-length spike, and nucleocapsid, in participant samples.
In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded.
View Article and Find Full Text PDFKey HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4 T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.
View Article and Find Full Text PDFImportance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood.
Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound.
Design, Setting, And Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023.
Article Synopsis
- A study investigated whether the monoclonal antibodies amubarvimab/romlusevimab could lower the risk of Long COVID in non-hospitalized high-risk adults treated soon after COVID-19 symptoms began.
- Results showed that while this treatment significantly reduced hospitalizations and deaths (4% vs. 13% in the placebo group), it did not decrease the incidence of Long COVID symptoms, with 16% of treated participants reporting Long COVID compared to 14% in the placebo group.
- The conclusion is that although amubarvimab/romlusevimab is effective for immediate COVID-19 outcomes, additional strategies are necessary to prevent Long COVID.
Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations.
View Article and Find Full Text PDFArticle Synopsis
- The study evaluates two different antibody detection assays (MSD and Bio-Plex Pro) for their effectiveness in measuring antibodies against SARS-CoV-2, focusing on various antibody types (IgG, IgM, IgA) and antigens (RBD, N).
- Results showed high concordance (90.5% for anti-RBD IgG and 87% for anti-N IgG) in determining sample status as positive or negative across the two assays, indicating they can reliably assess immune responses.
- The research also found that participants treated with the monoclonal antibody bamlanivimab showed reduced IgG responses compared to those given a placebo, suggesting the treatment affects immune response
Article Synopsis
- Most individuals with HIV-1 quickly experience a viral rebound after stopping antiretroviral therapy, but a small group can maintain viral remission for a longer time.
- Researchers created dynamic models to understand the immune response and viral interactions, using data from 24 people who paused their treatment.
- The study identified key factors, especially the rate of effector cell expansion, that differentiate between those who can maintain control of the virus after treatment interruption and those who cannot.
Background: We evaluated the fully human polyclonal antibody product SAB-185 in a phase 3 trial for COVID-19.
Methods: Nonhospitalized high-risk adults within 7 days of symptom onset were randomized 1:1 to open-label SAB-185 3840 units/kg or casirivimab/imdevimab 1200 mg. Noninferiority comparison was undertaken for pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active).
Background: Reliable biomarkers of coronavirus disease 2019 (COVID-19) outcomes are critically needed. We evaluated associations of spike antibody (Ab) and plasma nucleocapsid antigen (N Ag) with clinical outcomes in nonhospitalized persons with mild-to-moderate COVID-19.
Methods: Participants were nonhospitalized adults with mild-to-moderate COVID-19 enrolled in ACTIV-2 between January and July 2021 and randomized to placebo.
Background: We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs) among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with coronavirus disease 2019 (COVID-19).
Methods: We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020-September 2023). We evaluated the mutational landscape of SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs granted Food and Drug Administration Emergency Use Authorization in 2023.
Article Synopsis
- The study investigates how maternal infection with SARS-CoV-2 affects immune responses in the placenta and its implications for fetal brain development, particularly focusing on Hofbauer cells (HBCs), which act as fetal placental macrophages.
- Researchers analyzed HBCs from term placentas of pregnant individuals who tested positive or negative for SARS-CoV-2, finding notable differences in gene expression and impaired functions like phagocytosis in certain HBC subpopulations.
- The findings indicate that HBCs can be transformed into microglia-like cells, allowing for personalized models to study microglial programming in children affected by maternal SARS-CoV-2 infection.
Article Synopsis
- Outpatient treatment of COVID-19 using subcutaneous monoclonal antibodies (mAbs) could simplify logistics compared to intravenous delivery.
- In a clinical trial with 211 participants, the BMS mAbs did not show significant benefits in symptom improvement or viral load reduction compared to placebo, despite being safe with fewer severe adverse events reported.
- The results suggest that subcutaneous administration of BMS mAbs may not be effective for low-risk COVID-19 patients, potentially due to how the body absorbs mAbs through this method.
Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics.
View Article and Find Full Text PDFCharacterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.
J Infect Dis
August 2024
Article Synopsis
- Monoclonal antibodies are an important treatment for COVID-19, and a study compared the effects of single vs. dual mAb treatments, specifically amubarvimab and romlusevimab.
- The study found that dual-active mAbs resulted in a quicker reduction of viral load in patients, though hospitalizations and death rates were similar between the two treatment types.
- Additionally, dual-active therapy showed a lower incidence of resistance mutations compared to single-active treatment.
Article Synopsis
- Emergency use authorization allowed several monoclonal antibody (mAb) therapies to treat mild-to-moderate COVID-19 in high-risk patients, targeting the virus's spike protein to prevent infection.
- While mAb therapy can reduce viral loads and hospitalization rates, cases of viral resistance have led to significant viral rebounds in some patients.
- Researchers developed models to explain these rebounds, suggesting that replenishing target cells is necessary, and variations in immune response may determine who experiences these significant rebounds.