Journal of Infectious Diseases

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BACKGROUND: Despite effective prevention approaches, ongoing HIV-1 transmission remains a public health concern indicating a need for identifying its drivers. METHODS: We combine a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV-1 transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission. RESULTS: We find that only a minority of clusters and patients acquire links to new infections between 2007 and 2020...

When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary...

The EPCR-rs867186-G allele has been linked to high plasma level of soluble-EPCR and controversially associated with either susceptibility or resistance to severe and cerebral malaria. In this study, quantitative-ELISA and sequencing were used to assess sEPCR levels and EPCR-rs867186 polymorphism in blood samples from Beninese children with different clinical presentations of malaria. Our findings show that sEPCR levels were higher at admission to hospital than during convalescence and that EPCR-rs867186-G-allele was associated with increased sEPCR plasma levels, severe malaria and mortality (p-values < ...

In the northeastern and upper Midwestern United States, Babesia microti and Borreliella burgdorferi use Ixodes scapularis ticks as vector and Peromyscus leucopus mice as major reservoir host. We previously established, in a 5-year field trial, that a reservoir-targeted OspA vaccine reduces the prevalence of B. burgdorferi-infected ticks. We accessed ticks and mouse blood samples collected during the trial, extracted DNA and amplified the B. microti 18S rRNA gene. Vaccine deployment reduced the prevalence of ticks coinfected with B...

BACKGROUND: Understanding the immunity against omicron infection and severe outcomes conferred by Covid-19 vaccination, prior SARS-CoV-2 infection, and monoclonal antibody therapy will inform intervention strategies. METHODS: We considered 295,691 patients who were tested for SARS-CoV-2 at Cleveland Clinic between October 1, 2021 and January 31, 2022. We used logistic regression to investigate the association of vaccination and prior infection with the risk of SARS-CoV-2 infection and used Cox regression to investigate the association of vaccination, prior infection and monoclonal antibody therapy with the risks of intensive care unit (ICU) stay and death...

BACKGROUND: We assessed COVID-19 vaccination impact on illness severity among adults hospitalized with COVID-19 August 2021-March 2022. METHODS: We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness (CLI) and positive SARS-CoV-2 molecular testing. We calculated odds ratios for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation...

BACKGROUND: High-level BK polyomavirus (BKPyV) replication in allogeneic hematopoietic cell transplantation (HCT) predicts failing immune control and BKPyV-associated hemorrhagic cystitis (BKPyV-HC). METHODS: To identify molecular markers of BKPyV-replication and disease, we scrutinized BKPyV-DNA loads in longitudinal urine and plasma pairs from 20 HCT-patients using quantitative nucleic-acid-testing (QNAT), DNase-I treatment prior to QNAT, next-generation-sequencing (NGS) and tested cell-mediated immunity...

Asymptomatic blood donors can transmit human parvovirus B19 (B19V). We assessed the B19V prevalence amongst a large cohort of blood donations collected in Germany during 2015-2018. In total, 167,123 donations were screened for B19V DNA with 22 cases of viraemia identified (0.013% positive). Infections peaked at a four-year interval and the highest number of cases occurred in the summer months. All 22 infections were found in rhesus D-antigen positive donations, suggesting a protective factor in donors who lack this antigen...

Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant...

We assessed changes in sexual behaviour among people with HIV (PWH) over 20 years. Condom use with stable partners steadily declined from over 90% to 29% since the Swiss U = U statement with similar trajectories between men who have sex with men (MSM) and heterosexuals. Occasional partnership remained higher among MSM compared to heterosexuals even during COVID-19 social distancing.

BACKGROUND: Though Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®). vaccination is approved for smallpox and monkeypox prevention, immunological persistence and booster effects remain undescribed. METHODS: Participants naïve to smallpox vaccination were randomized to 1 dose MVA-BN (1×MVA, N = 181), 2 doses MVA-BN (2×MVA, N = 183), or placebo (N = 181). Participants with previous smallpox vaccination received 1 MVA-BN booster (HSPX+, N = 200)...

BACKGROUND: The impact variant-specific immune evasion and waning protection have on declining COVID-19 vaccine effectiveness remains unclear. Using whole-genome-sequencing (WGS), we examined the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluated the utility of calendar-period-based classification as an alternative to WGS. METHODS: We conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021...

SARS-CoV-2, the causative agent of COVID-19, has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40-100% of the population which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor...

BACKGROUND: The COVIH-study is a prospective SARS-CoV-2 vaccination study in 1154 people with HIV (PWH), of whom 14% showed a reduced or absent antibody response after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. METHODS: Consenting hyporesponders received an additional 100µg mRNA-1273 vaccination. The primary endpoint was the increase in antibodies 28 days thereafter. Secondary endpoints were the correlation between participant characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity...

BACKGROUND: Respiratory syncytial virus (RSV) is associated with acute respiratory infection. We sought to identify RSV variants associated with prolonged infection. METHODS: Among healthy term infants we identified those with prolonged RSV infection and conducted 1) a human GWAS to test the dependence of infection risk on host genotype, 2) a viral GWAS for association with prolonged RSV infection using RSV whole-genome sequencing, 3) an analysis of all viral public sequences, 4) an assessment of immunological responses, and 5) a summary of all major functional data...

BACKGROUND: Urine exosomal bkv-miR-B1-5p is associated with BK virus (BKV) nephropathy (BKVN); however, its post-transplantation changes and predictability for BKVN have not been determined in kidney transplant recipients (KTRs). METHODS: Urine exosomal bkv-miR-B1-5p and urine and plasma BKV DNA were measured at 2 weeks and 3, 6, and 12 months post-transplant in 83 KTRs stratified into biopsy-proven or presumptive BKVN, BKV viruria, and no evidence of BKV reactivation...

BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over two respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, HCoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households...

BACKGROUND: We previously demonstrated that an intranasal dose of 108 TCID50 M2SR (M2-deficient single replication) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection...

BACKGROUND: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. METHODS: This placebo-controlled, double-blind, phase 1/2a study (NCT02935686) enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo...