Friday, April 17, 2026

#Infection of the #bovine mammary #gland by avian #H5N1 subclade 2.3.4.4b #influenza viruses

 


Abstract

The emergence of the panzootic clade of highly pathogenic avian influenza H5N1 (2.3.4.4b) in 2020 marked a major expansion in the host range of influenza A viruses (IAVs), raising concerns about further cross‑species transmission events and zoonotic spillover. Introduction of 2.3.4.4b viruses into U.S. dairy herds has resulted in widespread circulation, accompanied by reduced milk yield, mastitis, and high viral loads in milk. Notably, virus circulation in dairy cattle represents a novel route for mammalian adaptation and transmission that has already led to more than 40 human cases in the U.S. since 2024. Here, we investigated whether avian clade 2.3.4.4b viruses could infect mammary tissue from Aberdeen Angus, Holstein Friesian, and Limousin cattle, three breeds commonly farmed in Europe, the Americas, and Oceania. Using mammary gland explants, we inoculated tissues with attenuated reassortant viruses expressing the haemagglutinin and neuraminidase glycoproteins of three 2.3.4.4b viruses that predated the emergence of H5N1 in US cattle: A/chicken/England/053052/2021 (AIV07), A/chicken/Scotland/054477/2021 (AIV09), and A/chicken/England/085598/2022 (AIV48). Infected epithelial cells were identified using immunohistochemistry in explants from both the teat and gland cistern for all three breeds following infection with AIV09 and AIV48, indicating that mammary tissue from each of the three tested cattle breeds cattle is permissive to H5N1 infection. Lectin staining showed expression of both α2,3‑linked and α2,6‑linked sialic acids in the mammary tissue of all donors showing that all three breeds have the potential to support infection with both avian-adapted and mammalian adapted IAVs. Together, these findings demonstrate that mammary glands from both beef and dairy cattle breeds are permissive to infection with avian‑adapted and mammalian-adapted H5N1 viruses and highlight the potential for this tissue to act as a mixing vessel for IAV reassortment, underscoring the need to include cattle in ongoing H5N1 surveillance and risk‑assessment frameworks.


Competing Interest Statement

The authors have declared no competing interest.


Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MR/Y03368X/1, MC_UU_0034/2, MC_UU_0034/3, MC_UU_0034/1

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/V004697/1

Source: 


Link: https://www.biorxiv.org/content/10.64898/2026.04.16.718897v1

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Acquisition of specific #human respiratory tract binding of 2.3.4.4b #H5N1 #hemagglutinins requires multiple #mutations

 


Abstract

It has been suggested that the hemagglutinin of the human-infecting cattle-derived 2.3.4.4b virus A/Texas/34 (H5TX) requires only one mutation, namely Q226L, to switch from binding avian-type to human-type receptor preference. In this study, we examined the binding of H5TX Q226L, along with other key mutations, to sections of human trachea. We conclude that, while H5TX Q226L can bind human-type receptors, more than a single mutation is required for this protein to bind to human respiratory tract tissue. We also report changes in receptor-binding specificity of another 2.3.4.4b HA mutant, H5FR Q226L, associated with the presence of a multibasic cleavage site. This study offers insight into the determinants of evolution towards human-type receptor binding in currently circulating H5Nx viruses. It also emphasizes the importance of testing individual strains using additional methods, including tissue-based approaches, alongside synthetic glycans.


Competing Interest Statement

The authors have declared no competing interest.


Funder Information Declared

NWO, OCENW.M20.106

Horizon, 862605

Source: 


Link: https://www.biorxiv.org/content/10.64898/2026.04.16.718875v1

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Thursday, April 16, 2026

Susceptibility of wild and domestic #songbirds to #Usutu virus



Abstract

Usutu virus (USUV) is an emerging mosquito-borne orthoflavivirus that can cause neuroinvasive disease in humans and wild birds. USUV clusters phylogenetically within the Japanese encephalitis virus serocomplex, sharing antigenic and ecological similarity with West Nile virus (WNV). USUV is maintained in an enzootic cycle primarily involving passerine birds and Culex spp. mosquitoes. USUV was first isolated in South Africa in 1959 and has since spread throughout Africa and Europe, causing mortality and disease in several wild bird populations, specifically the Eurasian blackbird (Turdus merula). To understand transmission and pathogenesis of USUV in birds, we sought to develop passerine bird models of infection using wild-caught house finches (Haemorhous mexicanus), wild-caught American robins (Turdus migratorius), domestic canaries (Serinus canaria domestica), and captive-bred zebra finches (Taeniopygia guttata). Birds were inoculated with one or two isolates of USUV and viremia was measured. House finches, American robins, and canaries were susceptible to USUV, with 100% of inoculated birds developing viremia. These avian species reach viremias that have the potential to infect Cx. quinquefasciatus mosquitoes. Clinical disease and histopathological evidence of disease were severe in American robins and moderate to severe in canaries, with limited disease in house finches. However, zebra finches inoculated with one isolate of USUV did not develop detectable viremia. These findings provide additional tools for studying USUV enzootic transmission and pathogenesis in passerine birds.

Source: 


Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014213

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#UK, #England - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification



{England, Lincoln Region} A commercial flock of 3,800 laying ducks. Samples taken were positive for HPAI H5N1. Birds presented clinical signs prior to testing.

Source: 


Link: https://wahis.woah.org/#/in-review/7440

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#IvoryCoast - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 


A poultry farm in Zanzan Region.

Source: 


Link: https://wahis.woah.org/#/in-review/7446

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Cross - #protection against highly pathogenic avian #influenza #H5N1 virus from seasonal influenza #vaccines: a systematic review and meta-analysis of #ferret studies

 


ABSTRACT

The recent surge in spillover events of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b to humans and mammals in North America has raised urgent pandemic concerns. Human H5N1 vaccines are unavailable in most countries. We synthesized data from ferret challenge trials to evaluate whether widely available seasonal influenza vaccines confer cross-protection against lethal H5N1 infection. We systematically searched PubMed, Embase, and Web of Science for ferret studies of lethal H5N1 challenge published up to 5 July 2025 (PROSPERO #CRD42024520346). Random-effects meta-analyses were conducted to compare vaccine efficacy (VE) of seasonal influenza vaccines and H5N1 vaccines against H5N1-related mortality. Seroprotection was defined as a neutralizing antibody titre of ≥1:40. We identified 35 studies (157 trials). Seasonal influenza vaccines without N1 did not confer significant cross-protection (five trials; VE 14.8%, 95% CI –3.6 to 30.0). In contrast, VE was 73% for N1-containing seasonal influenza vaccines (19 trials; 95% CI 54–84) and 77% for H5N1 vaccines overall (133 trials; 95% CI 72–82) (p = 0.52). The VE of N1-containing seasonal influenza vaccines was modestly lower than that of H5N1 vaccines with seroprotection (88%; 66 trials; 95% CI 84–91; p = 0.009), but comparable to H5N1 vaccines that did not achieve seroprotection (63%; 67 trials; 95% CI 52–71; p = 0.29). The VE of seasonal influenza vaccines against H5N1 was robust across sensitivity analyses, with no evidence of publication bias (p = 0.99). Seasonal influenza vaccines significantly reduce H5N1-associated mortality in ferret trials, suggesting the cross-protection potential of currently available vaccines. Human studies are warranted.

Source: 


Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2654278

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#SARS-CoV-2 #vaccination and #infection elicit cross-neutralizing responses against clade 3 and 4 #sarbecoviruses

 


Abstract

Two sarbecoviruses, SARS-CoV-1 and SARS-CoV-2 that engage ACE2 through their receptor-binding domains, have caused major human outbreaks. The pandemic potential of sarbecoviruses has prompted the discovery and classification of bat and other zoonotic sarbecoviruses that are also able to use human ACE2 or ACE2 ortholog receptors for infection. However, the current human immunological landscape reactive to these SARS-CoV-2-related viruses is not well profiled. Using a panel of pseudotyped lentiviruses expressing only spike proteins, we assess serum neutralization activity against clade 3 and 4 (also designated as clade 1c) receptor binding domain classified sarbecoviruses in a cohort who received a primary series of COVID-19 mRNA vaccines as well as individuals before and after infection with BA.5 or XBB.1.5 variants. Detectable neutralizing responses against clade 3 and 4 sarbecoviruses are observed in both vaccinees and convalescents and are comparable in magnitude to titers against SARS-CoV-2 variants. Infection with XBB.1.5 increases neutralization titers against SARS-CoV-2 variants as well as against clade 3 and 4 sarbecoviruses. Collectively, our findings suggest that the current immunologic landscape of vaccination and infection may confer some level of immunity against a variety of clade 3 and 4 sarbecoviruses, which should inform future pandemic response and pan-sarbecovirus countermeasure efforts.

Source: 


Link: https://www.nature.com/articles/s41467-026-71662-y

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The virus entry #inhibitor ARN-75039 provides therapeutic #protection against #Lassa virus infection in guinea pigs

 


Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV infection in outbred Hartley guinea pigs exposed to a guinea pig–adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039–treated animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV infection.

Source: 


Link: https://www.science.org/doi/10.1126/scitranslmed.adx0938

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Wednesday, April 15, 2026

Highly Pathogenic Avian #Influenza #H5N1 Virus #RNA in #Bovine #Semen, #California, #USA, 2024

 


Abstract

Since March 2024, highly pathogenic avian influenza (HPAI) A(H5N1) virus has infected dairy cattle in the United States, prompting concern about novel transmission routes. During an outbreak in California, HPAI H5N1 RNA was detected in an asymptomatic bull’s semen. Although infectious virus was not isolated, semen-associated transmission risks and biosecurity practices remain a concern.

Source: 


Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1639_article

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#SARS-CoV-2 and #MERS-CoV disrupt #host #protein synthesis via nsp1 with differential effects on the integrated stress response

 


Significance

Coronaviruses cause disease across a wide range of animal species and the human coronaviruses SARS-CoV-2 and MERS-CoV have caused epidemics of severe respiratory illness. Thus, it is imperative to understand how these viruses antagonize host responses and cause lethal disease. We show here that the betacoronavirus nonstructural protein 1 (nsp1) promotes shutdown of host protein synthesis while preserving viral protein synthesis and, in addition, promotes degradation of host mRNAs. However, SARS-CoV-2 and MERS-CoV differ in their ability to manipulate the host integrated stress response, indicating that it is important to understand detailed coronavirus–host interactions and how they differ even between lethal coronaviruses. Such insights will inform the development of antiviral therapeutics to treat and prevent current and future coronavirus outbreaks.


Abstract

Coronaviruses pose a serious threat to public health, driving the need for antiviral therapeutics and vaccines. Therefore, it is paramount to understand how this family of viruses evades cellular antiviral responses and establishes productive infection. The conserved coronavirus nonstructural protein 1 (nsp1) has been shown to inhibit host protein synthesis and, in some coronaviruses, promote host messenger RNA (mRNA) degradation while viral mRNAs are protected. We showed previously that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces activation of host integrated stress response (ISR) kinases protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK), which promote phosphorylation of eukaryotic initiation factor 2 (eIF2α) and consequent inhibition of host protein synthesis. In contrast, eIF2α remains unphosphorylated during Middle East respiratory syndrome coronavirus (MERS-CoV) infection. To investigate the interactions of nsp1 and the ISR kinases, we utilized recombinant SARS-CoV-2 and MERS-CoV expressing nsp1 with mutations in each of two conserved domains. Upon infection with SARS-CoV-2 nsp1 mutants, translation was shut down in wildtype (WT) and PKR knockout (KO) cells but rescued in PERK KO cells, likely due to reduced p-eIF2α. In contrast, translation was rescued during infection with the analogous MERS-CoV nsp1 mutants even in WT cells. Moreover, SARS-CoV-2 WT suppressed expression of GADD34, a negative regulator of eIF2α phosphorylation, while SARS-CoV-2 nsp1 mutants induced GADD34. In contrast, MERS-CoV WT induced GADD34. Utilizing single-molecule fluorescence in situ hybridization, we found that SARS-CoV-2 and MERS-CoV nsp1 promote host mRNA degradation during WT, but not nsp1 mutant, infection. Thus, SARS-CoV-2 and MERS-CoV differ in interactions with the ISR and nsp1 control of host protein synthesis.

Source: 


Link: https://www.pnas.org/doi/abs/10.1073/pnas.2536296123?af=R

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Tuesday, April 14, 2026

#Vaccine-Elicited #Antibody Responses to #Influenza #H3N2 Subclade K

 


{Summary}

Influenza A(H3N2) subclade K (J.2.4.1) is a genetic branch of H3N2 with 11 mutations in hemagglutinin compared with the A/H3N2/Croatia/10136RV/2023 (H3N2 CR/23) vaccine strain, of which 8 mutations are on the hemagglutinin head surface (...) (...). As of February 2026, influenza A viruses currently represent approximately 96.3% of circulating influenza strains in the US, with H3N2 accounting for 88.4% of influenza isolates and subclade K comprising 91.5% of H3N2 isolates. The rapid expansion of H3N2 subclade K represents a major public health concern. This study reports antibody responses to H3N2 subclade K and other influenza strains before and after influenza vaccination.

(...)

Source: 


Link: https://jamanetwork.com/journals/jama/article-abstract/2846268

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#Greece - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 


A wild Whooper Swan in Kastoria Region.

Source: 


Link: https://wahis.woah.org/#/in-review/7433

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Avian #Influenza #Report - Reporting period: April 5 – 11, '26 (Wk 15) (HK CHP April 14, 2026): 2 new #human #H9N2 influenza cases in #China

 


{Excerpt}

(...)

-- Avian influenza A(H9N2)

- Guangdong Province

1) A three-year-old boy with onset on January 20, 2026. 

- Guangxi Zhuang Autonomous Region

2) A 63-year-old man with onset on February 5, 2026. 

(...)

Source: 


Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk15.pdf

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Monday, April 13, 2026

#Population #immunity to clade 2.3.4.4b #H5N1 is dominated by anti - #neuraminidase #antibodies

 


ABSTRACT

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)- and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting antibodies were absent, we detected widespread binding and functional NA antibodies against N1 neuraminidases from clade 2.3.4.4b H5N1 viruses. Neuraminidase inhibition (NI) titers were highest against North American D1.1 genotype N1 viruses and correlated strongly with neutralizing activity, whereas HA-binding antibodies did not. An additional N-linked glycosylation site, as found in the NA of a human D1.1 isolate from British Columbia, reduced susceptibility to NI antibodies. Antibodies titer to N5 from H5N5 were low to minimal. These findings indicate that population-level immunity to clade 2.3.4.4b H5 viruses is dominated by NA-directed antibodies, with important implications for pandemic risk assessment.


IMPORTANCE

Understanding how pre-existing human immunity shapes susceptibility to emerging influenza viruses is central to pandemic preparedness. Here, we determined that human sera contain widespread, functional antibodies targeting H5N1 neuraminidase, which correlate with virus neutralization, whereas HA-directed responses are limited. We further show that acquisition of an NA glycosylation site reduces antibody inhibition, highlighting a potential pathway for immune evasion. These results identify neuraminidase-specific immunity as a major immunological barrier to severe H5N1 disease in humans and emphasize the need to incorporate NA antigenicity into influenza surveillance, risk assessment, and next-generation vaccine design.

Source: 


Link: https://journals.asm.org/doi/10.1128/mbio.00445-26

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#Genomic similarity to quantitatively evaluate the #reassortment #potential of #H7N9 with other subtypes of avian #influenza viruses

 


Abstract

Introduction

The H7N9 influenza virus poses a significant public health threat due to its potential for reassortment and cross-species transmission. This study aims to systematically evaluate the genomic similarity between H7N9 and other influenza A subtypes to identify strains with high reassortment potential and characterize their spatiotemporal and host distribution patterns.

Methods

We analyzed nearly 4,000 H7N9 sequences from GISAID and NCBI, alongside representative sequences of other influenza A subtypes. Open reading frames were extracted, and a genomic similarity index was constructed using Euclidean distance, dot product, and cosine similarity measures, with weights optimized via principal component analysis. The index was applied to quantify inter-subtype similarity and predict reassortment-prone strains.

Results

High sequence similarity was observed between H7N9 and cognate subtypes (e.g., H7N3, H15N9), with H7N3 exhibiting the highest similarity index (1.00). Validation using known reassortant strains, such as A/Yixing/805/2022 (H3N2), confirmed that strains with high reassortment potential showed significantly elevated similarity scores across all gene segments (p< 0.001). High-similarity outliers analysis identified 581 spillover events, temporally concentrated during 2014–2017, and spatially clustered in regions like the United States, Europe, and Hong Kong. Host analysis highlighted birds—especially chickens, ducks, and turkeys—as key reservoirs for reassortment.

Discussion

The genomic similarity index effectively identifies influenza A subtypes with high reassortment potential, supported by retrospective validation and spatiotemporal congruence with documented outbreaks. The concentration of high-similarity strains in specific hosts and regions underscores the role of ecological factors in viral evolution. These findings provide a predictive framework for monitoring emergent reassortants and inform targeted surveillance strategies.

Source: 


Link: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1777911/full

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ONWARD: a #OneHealth, pan - #European multidisciplinary #network advancing #surveillance, #research, clinical management and control of zoonotic #hepeviruses

 


Highlight

• HEV remains the leading cause of acute viral hepatitis in Europe

• Surveillance and diagnostics for HEV are heterogeneous across EU/EEA

• Zoonotic HEV circulates widely in pigs, wildlife and food chains

• Rat HEV expands the zoonotic spectrum and clinical burden in Europe

• ONWARD integrates One Health surveillance, research and capacity building


Abstract

Zoonotic hepeviruses, particularly hepatitis E virus (HEV, species Paslahepevirus balayani) represent a major yet underestimated public health challenge in Europe. Despite being the leading cause of acute viral hepatitis, surveillance, diagnostic practices and prevention strategies remain heterogeneous across EU/EEA countries, limiting comparability and hindering accurate burden estimates. Underdiagnosis is further compounded by extrahepatic manifestations and the growing impact of chronic HEV infection in immunocompromised patients. At the human–animal–environment interface, zoonotic HEV circulates widely in domestic pigs, wildlife and food products, while coordinated surveillance and control measures remain inconsistently implemented. The recent recognition of ratHEV (species Rocahepevirus ratti) as a cause of acute and chronic hepatitis in Europe further expands the spectrum of zoonotic hepevirus infections and underscores the need for integrated One Health approaches. To address these challenges, the One Health Zoonotic Hepevirus Network (ONWARD; COST Action CA24140) was launched in 2025 as a pan-European, multidisciplinary collaboration uniting experts across human, veterinary, food safety and environmental health sectors. ONWARD aims to harmonise diagnostic tools, strengthen clinical research, integrate multisectoral surveillance, promote capacity building and support evidence-based policy development. By fostering coordination with European stakeholders ONWARD provides a structured framework to strengthen preparedness, surveillance and response to zoonotic hepevirus threats across Europe.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S1386653226000338?dgcid=rss_sd_all

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Sunday, April 12, 2026

The Raising of Lazarus, Rembrandt (1630)

 


Public Domain.

Source: 


Link: https://www.wikiart.org/en/rembrandt/the-raising-of-lazarus-1630

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Saturday, April 11, 2026

Historical #Pandemic and Contemporary #Influenza A Viruses Reveal #PB2 M631L as a Convergent #Adaptation to #Human ANP32

 


Abstract

Understanding the genetic changes that allow avian influenza A viruses (IAVs) to switch their natural hosts and establish productive infection in humans is important for pandemic risk assessment. Adaptations in the IAV polymerase are required to overcome species-specific restrictions imposed by host ANP32 proteins. Notably, avian virus polymerase is generally only poorly supported by human ANP32 proteins due to species-specific differences. Consequently, efficient polymerase adaptation to the binding interface of human ANP32 requires distinct amino acid changes, such as PB2 E627K. A separate adaptation, PB2 M631L, has recently been reported in mammalian-adapted IAV; however, its functional role across divergent viral lineages and its relationship to host ANP32-dependent adaptation remain incompletely defined. Here, we examine PB2 M631L in the polymerases of a 1918 pandemic strain, a recombinant contemporary H1N1pdm09, and a recent clade 2.3.4.4b H5N1 virus. Using polymerase activity and protein-interaction assays, we show that PB2 M631L enhances polymerase activity and ANP32 binding in human—but not avian—contexts, and that this effect is conserved across multiple viral backgrounds. In H1N1pdm09, PB2 M631L also increased virus replication in mammalian cells. These findings indicate that PB2 M631L contributes to enhanced polymerase compatibility with human ANP32 proteins and are consistent with a role in adaptation across multiple influenza virus lineages. Our results highlight how analysis of historical pandemic strains can inform risk assessment for future emerging viruses.

Source: 


Link: https://www.mdpi.com/2076-2607/14/4/859

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History of Mass Transportation: The Vagónka Studénka Krokodýl (Crocodile) Autorail (1962–68)


By Vít Javůrek - http://www.mujweb.cz/www/mhd_jama/vlaky3/Krasa10/olrepc1.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=6311434

Source: 


Link: https://en.wikipedia.org/wiki/List_of_Czech_locomotive_classes

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#Coronavirus Disease Research #References (by AMEDEO, April 11 '26)

 


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    Short-Term Mortality and the Impact of Disability Type Following COVID-19 Among Individuals with Disabilities: A Population-Based Study.
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