Journal of Infectious Diseases

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ISSN / EISSN : 0022-1899 / 1537-6613
Published by: Oxford University Press (OUP) (10.1093)
Total articles ≅ 35,668
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, Laurel E. Beaty, Tellen D. Bennett, Nichole E. Carlson, Christopher B. Davis, Bethany M. Kwan, David A. Mayer, Toan C. Ong, Seth Russell, Jeffrey Steele, et al.
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac206

Abstract:
It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is also effective in preventing the progression of severe disease and mortality following SARS-CoV-2 Delta variant infection. Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1st 2021 - December 11th 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. Of 10,036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1,563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% versus 5.7%; adjusted OR 0.37, 95% CI 0.19-0.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% versus 1.0%; adjusted OR 0.11, 95% CI 0.0-0.79), and may reduce respiratory disease severity among those hospitalized. Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.
, Harish Verma, Visalakshi Jeyaseelan, Yunus, Samarea Nowrin, Deborah D. Moore, Bernardo A. Mainou, Ondrej Mach, Roland W Sutter, K Zaman
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac205

Abstract:
Background: The polio eradication endgame called for the removal of trivalent oral poliovirus vaccine and introduction of bivalent (types 1&3) OPV (bOPV) and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies. Methods: We conducted an open-label randomized clinical trial assessing two interventions, full or fractional-dose IPV (fIPV, 1/5 of IPV), administered at age 9-13 months with a second dose given two-months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment. Results: A single fIPV dose at age 9-13 months yielded 75% (95%CI:68-82) seroconversion against type 2, whereas two fIPV doses resulted in 100% seroconversion compared with 94% (95%CI: 89-97) after a single full dose (p < 0.001). Two doses of IPV resulted in 100% seroconversion. Conclusions: Our study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either one full dose of IPV or two doses of fIPV could be used to vaccinate missed cohorts, two fIPV doses being antigen-sparing and more immunogenic. Clinical Trial Registry: This trial was registered with ClinicalTrials.gov, number NCT03890497
Sunali Padhi, Nisha Nayak, Surjyapratap Sarangi, Suraj Kumar Nahak, Abhijit Pati, Bidyutprabha Pradhan, Bishwaranjan Purohit,
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac202

, Dan Milner, Karl Seydel, Terrie Taylor
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac200

Abstract:
Cerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infections with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx. We used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from non-malarial comas. N-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule-1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients. Our findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.
, Mark Arya, Yuben Moodley, Anna Jaques, Qin Jiang, Kena A. Swanson, David Cooper, Mohan S. Maddur, Jakob Loschko, Alejandra Gurtman, et al.
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac189

Abstract:
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults 65 − 85 years. Primary Cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the Month 0,2 Cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at Months 0 and 2. All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the Month 0,2 Cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo. RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. NCT03572062.
Francis Mwimanzi, Hope R. Lapointe, Peter K. Cheung, Yurou Sang, Fatima Yaseen, Gisele Umviligihozo, Rebecca Kalikawe, Sneha Datwani, F. Harrison Omondi, Laura Burns, et al.
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac199

Abstract:
Background: Third COVID-19 vaccine doses are broadly recommended, but immunogenicity data remain limited, particularly in older adults. Methods: We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement, and virus neutralization against ancestral and Omicron (BA.1) strains from pre-vaccine up to one month following the third dose, in 151 adults aged 24-98 years who received COVID-19 mRNA vaccines. Results: Following two vaccine doses, humoral immunity was weaker, less functional and less durable in older adults, where a higher number of chronic health conditions was a key correlate of weaker responses and poorer durability. One month after the third dose, antibody concentrations and function exceeded post-second-dose levels, and responses in older adults were comparable in magnitude to those in younger adults at this time. Humoral responses against Omicron were universally weaker than against the ancestral strain after both the second and third doses. Nevertheless, after three doses, anti-Omicron responses in older adults reached equivalence to those in younger adults. One month after three vaccine doses, the number of chronic health conditions, but not age, was the strongest consistent correlate of weaker humoral responses. Conclusion: Results underscore the immune benefits of third COVID-19 vaccine doses, particularly in older adults.
, Ines Elakhal Naouar, David B. King, Jennifer L. Burns, Kenya N. Jackson, Stephen W. Krauss, Prabha Chandrasekharan, Melanie D. McCauley, Brittany L. Ober Shepherd, Samantha McHenry, et al.
The Journal of Infectious Diseases; https://doi.org/10.1093/infdis/jiac198

Abstract:
Background: Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Since viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. Methods: Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. Results: Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL 4.58 log10 RNA copies/mL or anti- SARS-CoV-2 signal-to-cutoff ratio < 1.38 (VL: sensitivity and specificity 93%; anti- SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. Conclusions: Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.
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