Showing posts with label remdesivir. Show all posts
Showing posts with label remdesivir. Show all posts

Wednesday, June 3, 2026

Identification and characterization of a #SARS-CoV-2 #Mpro G23 deletion #ensitrelvir - #resistant mutant

 


ABSTRACT

Ensitrelvir is an antiviral drug that specifically targets the conserved main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, mutations in Mpro could confer resistance to antivirals, including ensitrelvir. Thus, identifying SARS-CoV-2 drug-resistant mutants and elucidating their mechanisms of resistance are critical for guiding the selection of effective antiviral therapies. Here, we utilized a recombinant luminescent attenuated SARS-CoV-2 lacking the open reading frames (ORF) 3a and 7b proteins (Δ3a7b-Nluc WT) to safely identify ensitrelvir drug-resistant mutants (DRM-E) without the need of using virulent forms of SARS-CoV-2. We isolated a DRM-E containing a Mpro G23 deletion (G23del) with high resistance (~1,000-fold) to ensitrelvir, but not to the Mpro inhibitor nirmatrelvir or to the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir. The contribution of G23del in ensitrelvir resistance was confirmed by generating a Δ3a7b-Nluc containing G23del in Mpro (Δ3a7b-Nluc G23del). Δ3a7b-Nluc G23del exhibited resistance to ensitrelvir in both cultured cells and in K18 hACE2 transgenic mice. Binding affinity revealed that the G23del mutation altered ensitrelvir, but not nirmatrelvir, binding to Mpro. Notably, while Δ3a7b-Nluc G23del was affected in viral fitness, serial passage of Δ3a7b-Nluc G23del in the absence of ensitrelvir resulted in the emergence of substitution L50F in Mpro that restored viral fitness loss caused by G23del without altering resistance to ensitrelvir. Our results demonstrate that G23del in Mpro can confer resistance to ensitrelvir. Positively, G23del in Mpro does not render SARS-CoV-2 resistant to nirmatrelvir or remdesivir, suggesting the feasibility of treating SARS-CoV-2 infections containing G23del Mpro with other approved antivirals.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.00584-26

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Thursday, May 28, 2026

Experts convened by #WHO advise on candidate #treatments and #vaccines for #Ebola disease caused by #Bundibugyo virus (WHO, May 28 '26)

 


    In response to the current outbreak of Ebola disease caused by Bundibugyo virus occurring in the Democratic Republic of the Congo, with cases also reported in Uganda, WHO convened several of its expert and advisory groups

    These groups assessed potential vaccines and therapeutics for both prevention and treatment of Bundibugyo virus disease (BVD). 

    The WHO advisory groups recommended that all the products identified and considered be used exclusively within clinical trials to generate robust data and ensure safe, ethical, and effective research.

    WHO convened a series of meetings with the WHO R&D Blueprint technical advisory groups on candidate vaccines and therapeutics for BVD.

    In parallel, WHO also convened the Strategic Advisory Group of Experts on Immunization (SAGE) and its Ebola vaccine working group to advise on the potential role of licensed Ebola vaccines during BVD outbreaks.


Key recommendations

    There are currently no licensed therapeutics or vaccines specifically approved for the prevention and treatment of BVD. 

    Nevertheless, WHO advisory groups considered several candidate products that are promising enough to warrant prioritization for evaluation in clinical trials. 

    WHO is now working closely with the governments of the Democratic Republic of the Congo and Uganda to facilitate the implementation of research evaluation of these products.

    For treatment of cases:

        ° For treatment, the independent experts recommended prioritizing three candidate therapeutics for evaluation in research (i.e. clinical trials) among confirmed BVD cases: the monoclonal antibodies MBP134 and Maftivimab®, as well as the antiviral remdesivir.

        ° Combination therapy using a monoclonal antibody and remdesivir is also recommended for evaluation.

    For prevention of cases:

        ° For post-exposure prophylaxis among contacts of confirmed and probable cases, the oral antiviral obeldesivir was determined to be a priority candidate, although experts noted that this approach depends on effective contact tracing, which remains operationally challenging in some of the affected areas of the Democratic Republic of the Congo. Research on post-exposure prophylaxis involves giving tablets of obeldesivir to contacts of cases to evaluate whether this prevents them from developing Ebola disease.

        ° The most promising candidate vaccine was determined by the experts to be the single-dose rVSV Bundibugyo vaccine (being developed by the International AIDS Vaccine Initiative or IAVI). The development of this single-dose vaccine candidate will likely require 7–9 months before it is ready to be assessed through a clinical trial for its ability to prevent BDV.

        ° Another candidate vaccine, ChAdOx1 Bundibugyo (being developed by Oxford University/Serum Institute of India) could potentially become available within 2–3 months for efficacy assessment through a clinical trial.  However, additional animal data are still required to support and confirm further prioritization. Experts noted that a single-dose vaccine approach of this candidate could be suitable for contacts of Ebola cases, whereas a two-dose strategy might be considered for high-risk but unexposed populations such as health-care workers and frontline responders.

        ° The convened experts also reviewed the potential role of Ervebo, the only licensed Ebola vaccine. It is approved for use during outbreaks caused by the most common Ebola virus in Africa, from the Orthoebolavirus family. Ervebo is not licensed for prevention of BVD and evidence on cross-protection to other Ebola virus species remains limited and inconclusive. WHO recommends that Ervebo should not be used outside carefully designed research settings, to allow for its performance against BDV to be assessed.


Ensuring ethical and safe clinical trials

    WHO, the governments of the Democratic Republic of the Congo and Uganda, the Africa Centres for Disease Control and Prevention (Africa CDC), the ANRS Emerging infectious diseases (French National Agency for Research on AIDS and Viral Hepatitis), and other scientific partners are working together to develop and implement appropriate protocols to assess the safety and efficacy of the prioritized therapeutics through clinical field trials.

    WHO calls for accelerated access to essential supplies, stronger community protection, engagement and trust, and coordinated investment in the research, development and evaluation of BVD countermeasures.

    All research must adhere to the highest ethical standards, under the leadership of the national health authorities and in close consultation with affected communities.

    In the meantime, our priority is to stop transmission with tools that we have used for decades of Ebola responses, which include disease surveillance, rapid testing and diagnosis, contact tracing, isolation and care for patients, infection prevention and control, community engagement, and safe and dignified burials.


Background

    The WHO R&D Blueprint is a global initiative that allows the rapid activation of research and development activities during epidemics. Its aim is to fast-track the availability of proven effective tests, vaccines, and medicines that can be used to save lives and avert large-scale crises.

    SAGE is the principal advisory group to WHO for vaccines and immunization. It is charged with advising WHO on overall global policies and strategies, ranging from vaccines and technology, research and development, to delivery of immunization and its linkages with other health interventions.


About WHO 

    Dedicated to the well-being of all people and guided by science, the World Health Organization leads and champions global efforts to give everyone, everywhere an equal chance at a safe and healthy life.

    We are the UN agency for health that connects nations, partners and people on the front lines in 150+ locations – leading the world’s response to health emergencies, preventing disease, addressing the root causes of health issues and expanding access to medicines and health care. Our mission is to promote health, keep the world safe and serve the vulnerable. 

    “Together for health. Stand with science”, the theme of World Health Day 2026 marks a year-long campaign to highlight science as the foundation for protecting health and well-being worldwide.

Source: 


Link: https://www.who.int/news/item/28-05-2026-experts-convened-by-who-advise-on-candidate-treatments-and-vaccines-for-ebola-disease-caused-by-bundibugyo-virus

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Monday, May 11, 2026

Technical note for disembarkation and onward #management of #passengers and crew in context of an #Andes virus-associated cluster MV Hondius cruise ship - Interim #guidance 8 May 2026 (WHO, edited)

 


Introduction

-- This technical note is intended for public health authorities, port health authorities, and partner agencies involved in the disembarkation, onward travel, monitoring, and follow-up of passengers and crew associated with the MV Hondius event.


Communication

-- Managed by: National health authorities / public health and medical evaluation team / risk communication specialists

-- Effective risk communication is essential to support the safe and orderly disembarkation and onward management of passengers and crew, and to maintain public trust during an evolving public health event

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note. 

-- Passengers and crew should receive clear, consistent and timely information before, during and after disembarkation, including explanations about public health measures, what to expect at each step, and next steps. 

-- Further considerations on risk communication are available in Annex 1.



1. Upon Arrival

Ship regulations

-- Managed by: Ship captain

• The required documentation should be provided to port health authorities, including the valid Ship Sanitation Certificate and the Ship Declaration of Health (or Maritime Declaration of Health).

• The ship should comply with the public health measures recommended by port health authorities, including for measures that need to be applied on board as well as during disembarkation, or medical evacuation.

• The ship captain should notify port health authorities of any person that meets the suspect case definition as assessed by physicians on board.


Communication to passengers and crew members

-- Managed by: captain / evaluation team / crew / communications officer

• Clearly communicate the steps that will be implemented.

• Inform that the disembarkation and onward travel of passengers and crew are being managed through coordinated and controlled public health measures, and that the risk to the general public remains very low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.


2. Upon disembarkation

-- Managed by: national authorities

- Considering the attention attracted by this event, national authorities should ensure arrangements for security and media management in the port receiving the ship.


Management of passengers with symptoms prior to disembarkation

-- Managed by: medical team on board / national health authorities at the port of call

• Duly equipped ambulances should be pre-positioned at the port.

• If a suspected case is identified prior to the arrival of the ship, their medical evacuation to designated health facilities on-shore should be facilitated first, prior to disembarkation of passengers and crew.

• A designated trained team should be able to provide immediate care and ensure the safe and timely transfer to designated health facilities equipped to provide the appropriate level of safe and quality care.

• Any member of the medical team at the port of disembarkation, including ambulance crews, should apply standard and transmission-based precautions when attending cases.

    Perform hand hygiene before putting on personal protective equipment (PPE).

    Put on PPE items including eye protection, respirator (e.g. N95, FPP2), gown, and gloves before assessing, and transferring the case to a designated health facility on shore.

    PPE should be removed once patient transfer has been completed, and hand hygiene performed after removal of PPE items. PPE should be managed as infectious waste.

• Ensure patients use a respiratory (e.g. N95, FPP2) during the transfer.

• Transport of patients should be carefully planned to ensure those sending the patient and receiving them are fully informed and prepared.

• See Annex 2 and 3 for further information.


Steps for disembarkation for passengers and crew members

-- Managed by: national health authorities at the port of call.

• Provide guidance to the crew on organizing the order of disembarkation (e.g. prioritizing passengers according to their location on the ship, followed by crew members, including instructions on how to wear a respirator).

• Staggering the disembarkation of passengers may be considered to ensure safe and efficient disembarkation. Individuals should disembark one by one from the ship.

• Respirators (N95, FPP2) should be provided prior to disembarkation to all passengers and crew members, under the assumption that it cannot be ruled out if contacts are symptomatic until they have been screened.

• All passengers and crew members disembarking should wear a well-fitted respirator{1} prior to disembarkation and until screening is undertaken.

• Individuals should ideally carry minimal hand luggage, with the remaining luggage handled separately by the ship’s company.

• Transport (ideally facilitated through boats or coach) should be available and ready to transport individuals to the onward location. Windows should be kept open for ventilation.


Screening area for passengers and crew members

-- Managed by: national health authorities at the port of call.

• National health authorities will define the best location to organize the screening of disembarking passengers and crew. It may be organized while passengers and crew are exiting the boat one by one or in a designated screening area on shore.

• Screening area(s) should be organized in a dedicated, pre-identified location in the port area, preferably outdoors but allowing for privacy, and with seats (distanced at least one meter apart), access to dedicated bathroom facilities, hand hygiene products and drinking water available in the waiting area.

• If indoors, the room should be well-ventilated (open windows), large enough to maintain distancing of at least one meter between people, have separate entrance and exits with one-way flow to maintain distancing and crowd control, and have provision for personal comfort i.e., toilets, seating (one meter apart), supply of individual water, and waste facilities.

• Toilet and rest facilities should be separate from those for reception and assessment staff.

• Administration and support staff should be allocated to ensure compliance with public health recommendations and are advised to wear medical masks, with access to hand hygiene facilities (soap and water or alcohol-based hand solutions).

• The screening area should ensure that at least one meter distance between the screener and the passenger/crew member is maintained. Temperature checks should be undertaken with non-touch thermometers.

• Respirators, masks and hand hygiene stations should be available in the screening area.

• Adequate environmental cleaning and disinfection of surfaces and shared equipment in the screening area should be performed between screenings.

• Equipped ambulances and their staff should be prepositioned prior to disembarkation, in case a medical evacuation is needed.


Screening and evaluation of passengers and crew members at disembarking

-- Managed by: national health authorities / evaluation team

Note: a team on the ship is currently assessing passengers and crew for exposure and health status. Coordination among this team and the evaluation team at disembarkation is strongly encouraged.

• In coordination with the ship, data on exposures should be examined to facilitate rapid exposure assessments.

• All passengers and crew should be provided with clear information including why measures are in place, what happens next (monitoring, travel, contact points), what symptoms to watch out for, and who to immediately contact 24/7 if any symptom develops.

• Investigation and medical teams should be mindful of the high-stress environment experienced by the passengers and crew and ensure empathy when conducting screening.

• All passengers and crew members are advised to wear a well-fitted respirator (e.g. FFP2, N95) while being assessed by port health authorities.

• During assessment, passengers and crew members will be checked for fever with non-touch thermometers, evaluated for their exposure and any symptoms they might have or have had.

• The above procedures shall be conducted by trained medical teams.

• During evaluation, any passenger or crew member with symptoms compatible with the suspected case definition (see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship) should be managed as described in the next section.

• Health personnel conducting screening should apply standard IPC precautions, including:

    Perform hand hygiene before and after the screening of contacts.

    Use of gloves if touching travelers and when handling potentially contaminated materials.

    Health personnel are advised to wear a medical mask and eye protection during screening of passengers and crew members at disembarking.

    Medical masks should be disposed of if they become soiled or wet.

    Adequate quantities of PPE items and hand hygiene material should be available in the evaluation area.

• Ideally, those disembarking should be pre-cleared by immigration authorities to avoid the need for contact with immigration staff. If they must pass through immigration, they should do so after screening, and immigration staff should wear a medical mask and have access to hand hygiene facilities (soap and water or alcohol-based hand solutions).


Management of passengers or crew members with symptoms identified at the time of screening

-- Managed by: national health authorities

• During evaluation, if a person presents symptoms compatible with ANDV infection (see case definition in Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship), the medical team should:

    Practice hand hygiene and ensure adequate PPE as described above and in annex 3.

    Isolate the patient in a designated area with a dedicated bathroom and dedicated linen/personal items while transfer for evacuation is organized.

    Initiate the medical evacuation of the person to a designated health facility as indicated above.

    PPE must be changed between patients, and hand hygiene should be performed before putting on PPE, and after removing PPE.

• When transferring, ensure the patient wears a respirator and the health worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Initial symptomatic treatment should be initiated for symptom control and if needed, any supportive care intervention, i.e. oxygen if hypoxemic. A monitoring plan should be put into place to ensure any clinical deterioration is noted in a timely fashion.

• See Annex 2 and 3 for further information.


Mental health and psychosocial support (MHPSS) for passengers and crew members

-- Managed by: MHPSS team, national health authorities.

• Mental health and psychosocial support should be considered for passengers and crew disembarking, as this situation may have generated significant stress in some.

• The availability of psychosocial support could help address anxiety or distress associated with the disembarkation process and perceived health risks.


Management of passenger and crew luggage and belongings

-- Managed by: conveyance operator / competent authorities

• Luggage will be handled after disembarkation by the conveyance operator, in collaboration with competent authorities.

• Passengers and crew members will be able to take their luggage back after screening is completed, in accordance with the protocols established by the competent authorities.


3. After disembarking

Onward travel of asymptomatic passengers and crew members

-- Managed by: national health authorities in country of repatriation

- For further guidance, see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship.

- Asymptomatic passengers may travel following repatriation from the Canary Islands, provided that

- they have completed the active monitoring and in designated facility or home quarantine. Which includes:

• Public health authorities should conduct daily follow-up for 42 days after disembarkation, during which time the passenger should be advised to avoid contact with other persons through remaining in a designated facilities or at home, depending on national guidelines and capacities. 

• Follow-up may occur by telephone, messaging, telehealth, or in person.

• Passengers who are healthcare workers should refrain from returning to work for designated period.

• Passengers should avoid contact with other household members, and where possible and remain in a separate room.

• In case social interactions are unavoidable, passenger should wear a FFP2 or N95 respirator, practice physical distancing, and observe regular hand hygiene.

• All travel, nationally and internationally, should be discouraged for 42 days.

• Movement of the passenger out of the jurisdiction of public health authorities in charge of their follow-up may be allowed for life-threatening or humanitarian reasons, provided that arrangements are made with the public health authorities in the jurisdiction at destination, including internationally through IHR channels.

• During daily follow-up, any symptoms: temperature, fever, fatigue or malaise, muscle ache, headache, gastrointestinal symptoms, respiratory symptoms, should be promptly reported using a contact follow-up form.

• Any passengers developing symptoms compatible with hantavirus infection should be promptly isolated, clinically evaluated and tested.

• Passengers should receive:

    Written information on symptoms to look out for.

    Emergency contact numbers.

    Instructions regarding healthcare seeking and testing.


Crew management

-- Managed by: cruise operator / competent authorities

• Medical care, including public health preventive measures, for crew members should be provided in accordance with the Maritime Labour Convention, 2006, as amended (MLC, 2006)

• Crew members should not resume duty on another ship until they complete the active monitoring and in designated facility or home quarantine (as above)


Management of deceased persons confirmed for ANDV infection on the ship

-- Managed: national authorities at port of call.

- Transmission of ANDV from deceased persons has not been documented, and viral load decreases before terminal illness; however, other respiratory pathogens (e.g., tuberculosis) have been transmitted from human remains. Thus, as exposure to bodily fluids and respiratory secretions may occur during handling of remains, standard IPC precautions should be applied when managing deceased suspected, probable, or confirmed cases.

• Personnel handling remains should apply standard IPC precautions and wear appropriate PPE, including gloves, gown, medical mask, and eye protection where exposure to bodily fluids or respiratory secretions is possible.

• Hand hygiene should be performed before and after PPE use and after contact with the body or contaminated materials.

• Unnecessary manipulation of the body and aerosol-generating procedures should be avoided.

• The body should be placed in a leak-proof body bag if needed and handled according to national procedures.

• Environmental cleaning and disinfection of potentially contaminated surfaces and equipment should be performed using appropriate disinfectants.

• International repatriation of remains may proceed according to national and international regulations.


Ship disinfection

-- Managed by conveyance operator and competent authorities

• The ship should be inspected for rodents, cleaned, disinfected and appropriate rodent control measures implemented, as appropriate, in accordance with the Integrated Management Plan of the Ship and WHO guidance, and as per advice of the competent authority.

• The ship shall cease to be regarded as affected when the competent authority is satisfied with the measures implemented, and there are no conditions on board that could constitute a public health risk.

• Staff involved in sanitary procedures on board the ship should wear adequate PPE (including eye protection, respirator, gown, and gloves).


Plans for updating

-- WHO continues to monitor the situation closely for any changes that may affect this interim guidance. 

-- Should any factors change, WHO will issue a further update. 

-- Otherwise, this interim guidance will expire one year after the date of publication.


References

1. World Health Organization. International Health Regulations (2005) – As amended in 2014, 2022 and 2024. https://apps.who.int/gb/bd/pdf_files/IHR_2014-2022-2024-en.pdf

2. World Health Organization. WHO Guideline on Contact Tracing; 2025. https://www.who.int/publications/i/item/9789240102965

3. World Health Organization. Handbook for Management of Public Health Events on Board Ships; 2016. https://www.who.int/publications/i/item/handbook-for-management-of-public-health-events-on-board-ships

4. World Health Organization. Vector Surveillance and Control at Ports, Airports, and Ground Crossings; 2016. https://www.who.int/publications/i/item/vector-surveillance-and-control-at-ports-airports-and-ground-crossings

5. World Health Organization. Guide to Ship Sanitation. 3rd edition; 2011. https://www.who.int/publications/i/item/9789241546690

6. World Health Organization. Handbook for inspection of ships and issuance of ship sanitation certificates; 2011. https://www.who.int/publications/i/item/handbook-for-inspection-of-ships-and-issuance-of-ship-sanitation-certificates

7. World Health Organization. Considerations for strengthening international information sharing for tracing and managing infectious disease cases and contact persons: Interim Guidance; 2026. https://www.who.int/southeastasia/internal-publications-detail/sewhe09022601

8. World Health Organization. World Health Organization. A decision framework for effective, equitable and context-specific public health and social measures during public health emergencies: decision navigator.

9. EU Healthy Sailing. Evidence-based guidelines for the specificities and needs of medical operations in expedition passenger ships. 2026

10. WHO and ICRC. Basic Emergency Care. Approach to the acutely ill and injured. 2018. https://www.who.int/publications/i/item/basic-emergency-care-approach-to-the-acutely-ill-and-injured


Annex 1. Risk communication

-- Effective risk communication is essential to support the safe, orderly, and dignified disembarkation and onward management of passengers and crew members, and to maintain public trust during an evolving public health event. 

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note.

• Ensure that passengers and crew receive clear, consistent and timely information before, during and after disembarkation, including explanations of public health measures, what to expect and next steps.

• Ensure communication materials are available in the relevant languages of passengers and crew and in accessible formats.

• Communicate clearly that the disembarkation and onward return of passengers and crew are being conducted through coordinated and controlled public health procedures, and that the risk to the wider public remains low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.

• Acknowledge openly what is known and what remains uncertain, that investigations are ongoing and that recommendations may be updated as new epidemiological or laboratory evidence becomes available.

• Explain that changes in guidance reflect standard precautionary public health practice.

• Provide passengers and crew with written and verbal information on symptoms to monitor, duration, procedures if symptoms develop and contact details for public health authorities responsible for follow-up.

• Promote early reporting of symptoms and cooperation with monitoring arrangements and any other public health measure advised while traveling home.

• Ensure communication materials and briefings emphasize respect for the dignity, privacy and rights of passengers and crew and explicitly discourage stigma, discrimination, or blame.

• Ensure that communication at points of entry (ports, airports, transit hubs) is coordinated across agencies and consistent in messaging to avoid confusion or contradictory messages.

• Provide host communities, transit authorities, and destination countries with clear public information on the rationale for measures in place, what to expect, and what actions are not required.

• Establish clear channels for two-way communication, allowing passengers and crew to ask questions, raise concerns, and seek clarification throughout disembarkation and onward management.

• Monitor public perceptions, media coverage, and misinformation related to the event and adapt communication content and tone as needed, in coordination with WHO and relevant partners.


Annex 2. IPC for healthcare workers caring for suspected or confirmed cases

• Suspected, probable or confirmed cases must be isolated in single rooms (one room per case).

• In addition to standard precautions, implement transmission-based precautions when providing care to suspected or confirmed cases.

• Those providing care should wear personal protective equipment prior to entering the isolation room.

    Perform hand hygiene before donning PPE.

    PPE items include: eye protection, respirator (e.g. N95, FPP2), gown, gloves when providing direct patient care.

    PPE should be removed and appropriately disposed of when exiting the isolation room, and hand hygiene must be performed after removal of PPE items.

• Ensure adequate indoor ventilation.

• Routine environmental cleaning and disinfection should be performed using regular disinfectants.

• Medical waste and used linen should be handled as per existing procedures.

• When transferring, ensure the patient wears a respirator and the healthcare worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Transport of patients should be carefully planned to ensure sending/receiving ends are fully informed and prepared.


Annex 3. Considerations on clinical management of suspected and confirmed patients

-- Medical management of a person with suspected, probable or confirmed hantavirus infection should be structured through standard protocols using appropriate PPE (see above), including:

• Severity-based triage of the condition using clinical and physiological measures (see WHO Basic Emergency Care).

• Systematic assessment, and rapid emergency action to address problems in Airway, Breathing, Circulation, Disability [ABCDE].

• Establishing a diagnosis is a priority (PCR and serology testing), but all patients should be managed according to the severity of disease. Outbreak case definitions are not a substitute for clinical judgment.

• High-quality and anticipatory supportive care should be provided.

    Oxygen and availability of respiratory support should be prioritised.

    * Deterioration after the prodromal phase can be precipitous (over hours). Anticipatory actions should include careful monitoring and ensuring proximity to intensive care facilities for cardiovascular support, mechanical ventilation, and ideally extracorporeal membrane oxygenation.

    * Shock should be treated according to existing clinical guidelines for sepsis.

    * Ensure monitoring of vital signs and renal function (through clinical and biochemical assays). Investigation and monitoring of platelet count and proteinuria should be in place as these provide early insight into adverse prognosis, and imminent acute kidney injury respectively.

    * There are no proven antiviral treatments for hantavirus. Off-label use of favipiravir, remdesivir and other existing drugs have been used. Such use must be accompanied by detailed clinical data capture under monitored use. Mechanistically, remdesivir is less favourable compared with favipiravir due to its relatively reduced action against segmented viruses such as hantavirus).

• Direct evidence related to the use of corticosteroids in hantavirus infection for pulmonary or renal syndromes is limited. A single randomized controlled trial of patients with Andes virus hantaviral infection with cardiopulmonary syndrome in Chile did not demonstrate a benefit from high dose corticosteroid treatment but was underpowered to detect a moderate difference between arms.

• Routine antibiotic administration is not indicated for known hantavirus disease. However, for those presenting with symptoms of acute respiratory infection, bacterial infection must be considered. Suspicion of superadded bacterial infection is also an indication for antibiotic treatment based on clinical assessment.


Annex 4. Considerations on laboratory diagnosis

NOTE. Further information on laboratory diagnosis will be provided in a separate document and will cover additional aspects.

• Laboratory diagnosis of hantavirus infection relies on either molecular detection of viral RNA and serological detection of antibodies, with the choice depending on the interval between symptom onset and sample collection.

• By the time symptoms develop, viremia is often already at or near its peak, and both IgM and IgG antibodies may be detectable. IgM levels begin to decline over the following weeks and typically disappear within about three months, whereas IgG appears slightly later and may remain elevated for many years.

• For molecular detection, whole blood is recommended, while serum and blood clot can also be used. Serum is the preferred specimen for serology, although plasma from whole blood is also acceptable. Samples should be collected in sterile plastic tubes with screw caps.


Testing of suspected cases

• Suspected cases should be tested using an Andes virus–specific RT-PCR protocol, as outlined in reference laboratory procedures posted on the WHO EIS Platform and in the WHO Disease Outbreak News. In the absence of Andes virus-specific RT-PCR, a pan-hantavirus PCR can be used, and sequencing should be performed to confirm Andes virus.

• Molecular detection by RT-PCR, whether conventional or real-time, can confirm infection at any point during the acute phase, up to approximately ten days after symptom onset.

• If a sample has been collected more than 10 days after onset, a negative RT-PCR result in a properly collected and preserved sample, only rules out infection when serological testing is also negative, provided that enough time since last exposure has elapsed to allow development of anti-Andes virus specific antibodies.

• Positive cases without an epidemiological link to a confirmed or probable case should be systematically sequenced.


Testing of asymptomatic contacts for research purposes

• Routine testing of asymptomatic contacts is not mandatory for public health purposes.

• Regular (e.g. weekly) RT-PCR testing of asymptomatic contacts, on specimens such as blood, saliva, oral swabs and nasopharyngeal swabs, could be considered for research purposes to better understand virus shedding and transmission dynamics.

• However, testing should NOT be used to determine the end of the follow-up period, which remains fixed at 42 days after last exposure regardless of test results.

• When testing capacity is limited, symptomatic contacts must always be prioritised for diagnostic testing because they are more likely to be infected and require timely clinical evaluation.

• Serological testing at the beginning and end of the follow-up period may also be considered to ascertain serological status of contacts.

© World Health Organization 2026. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license.

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{1} The recommendation for contacts to wear a well-fitted respirator (N95, FFP2) until screening is undertaken is a precautionary source control measure aimed at reducing the risk of onward transmission from individuals who might be symptomatic and pre-symptomatic.

Source: 


Link: https://www.who.int/publications/m/item/who-technical-note-for-the-disembarkation-and-onward-management-of-passengers-and-crew-in-the-context-of-an-andes-virus-associated-cluster-mv-hondius-cruise-ship

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Wednesday, April 22, 2026

#Ensitrelvir for the #treatment of hospitalized adults with #COVID19: an international phase 3 randomized placebo-controlled trial

 


Abstract

Background

Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity.

Methods

We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the Days to Recovery Scale through Day 60 (DRS-60), analyzed using a Van Elteren test.

Results

From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (p=0.19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; p<0.001). There was no difference in secondary clinical outcomes or pre-specified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively.

Conclusions

Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness severity in the Omicron era compared to earlier periods in the COVID-19 pandemic, and high use of remdesivir and corticosteroids, may have contributed to the lack of clinical benefit.

Source: 


Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag272/8660678?redirectedFrom=fulltext

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Tuesday, April 21, 2026

Timing of #Remdesivir Initiation and Clinical #Outcomes in Hospitalized Patients with #COVID19 Who Are at High Risk of Disease Progression in #Japan: A Health Insurance Claims Database Study

 


Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Source: 


Link: https://www.mdpi.com/1999-4915/18/4/479

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Monday, December 22, 2025

#Remdesivir as a potent #antiviral against prototype and current #epidemic #Oropouche virus #strains (BeAn19991 and PE-IAM4637)

 


Highlights

• We generated a recombinant reporter OROV that expresses the eGFP fluorescent protein in infected cells.

• We found that remdesivir efficiently inhibited the replication of Oropouche virus (OROV) using this reporter OROV.

• We demonstrated strain-dependent differences in the replication efficiency of OROV.


Abstract

The Oropouche virus (OROV), an orthobunyavirus transmitted by biting midges, is the causative agent of Oropouche fever, which has caused multiple outbreaks in South and Central America. During the most recent epidemic in 2023–2025, more than 25,000 laboratory-confirmed cases were reported in Brazil, and no licensed antivirals have been reported to be effective date. In this study, we generated a recombinant OROV-expressing enhanced green fluorescent protein (rOROV/GFP) to facilitate rapid and sensitive antiviral evaluation. Growth kinetics demonstrated that rOROV/GFP replicated less efficiently than wild-type rOROV and that the historical prototype strain (BeAn19991) exhibited higher replication efficiency than the recent epidemic isolate (PE-IAM4637) in both Vero E6 and Huh7 cells. Using this system, we evaluated the antiviral activity of ribavirin, favipiravir (T-705), and remdesivir against OROV. All three compounds inhibited OROV replication in a dose-dependent manner, with remdesivir showing the greatest potency (IC₅₀ values of 0.31 µM). Taken together, our findings highlight remdesivir as a promising candidate for the treatment of Oropouche fever caused by OROV. Furthermore, we established rOROV/GFP as a powerful tool for antiviral drug screening.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S0168170225001583?via%3Dihub

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Thursday, October 9, 2025

Molecular basis of #SARS-CoV-2 proofreading enzyme–mediated #resistance to #remdesivir

 


Abstract

SARS-CoV-2’s remarkable resistance to nucleotide analog antivirals such as remdesivir, which thwarts RNA synthesis by inhibiting viral polymerase (RdRp), challenges available therapies. We reveal that remdesivir incorporation destabilizes RdRp–RNA complex while enhancing RNA binding to the proofreading exoribonuclease (ExoN), facilitating remdesivir excision. Conserved ExoN determinants for remdesivir recognition and excision underpin ExoN-mediated resistance across all coronaviruses. These findings inform the design of next-generation antivirals and combination therapies capable of overcoming ExoN-mediated resistance.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/full/10.1073/pnas.2519755122

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Thursday, September 25, 2025

#Remdesivir: Effectiveness and Safety in Hospitalized #COVID19 #Patients—Analysis of Retrospectively Collected Data from Daily Practice in #Omicron Variant Era and Comparison with the Pre-Omicron Period

 


Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has impacted global health. Remdesivir was approved based on clinical trials demonstrating improved outcomes in hospitalized patients. The ReEs-COVID19 study provides real-world evidence on its effectiveness and safety across two periods: Pre-Omicron and Omicron. This retrospective, observational cohort study included 1610 patients hospitalized with COVID-19, treated with remdesivir during Pre-Omicron (September 2020–February 2021; n = 606) and Omicron (June 2022–March 2023; n = 1004) periods. Primary endpoint: time to discharge; Hepatic/renal function abnormalities were also investigated. In the Omicron period patients were older and had more comorbidities but remdesivir was initiated earlier (median: 2 days from symptom onset) compared to the Pre-Omicron period (8 days). ICU admissions rates and direct COVID-19-related deaths were significantly lower, but overall 30-day mortality was higher during the Omicron period. Earlier remdesivir administration was associated with faster discharge. Abnormal liver tests and acute kidney injury were rare across both periods. ReEs-COVID19 confirmed remdesivir’s effectiveness and safety in real-world clinical settings during both periods, underscoring its importance in treatment of hospitalized COVID-19 patients, especially when initiated earlier in the disease course. Further research is needed to evaluate its utility in specific subgroups (e.g., immuno-compromised) and in combination with other treatments.

Source: Microorganisms, https://www.mdpi.com/2076-2607/13/10/2242

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Thursday, September 11, 2025

#Marburg Virus #Disease in #Rwanda, 2024 — Public Health and Clinical Responses

 


Abstract

Background

On September 27, 2024, Rwanda reported an outbreak of Marburg virus disease (MVD), after a cluster of cases of viral hemorrhagic fever was detected at two urban hospitals.

Methods

We report key aspects of the epidemiology, clinical manifestations, and treatment of MVD during this outbreak, as well as the overall response to the outbreak. We performed a retrospective epidemiologic and clinical analysis of data compiled across all pillars of the outbreak response and a case-series analysis to characterize clinical features, disease progression, and outcomes among patients who received supportive care and investigational therapeutic agents.

Results

Among the 6340 patients with suspected MVD who underwent testing, 66 had laboratory-confirmed MVD, 51 (77%) of whom were health care workers. The median estimated incubation period was 10 days (interquartile range, 8 to 13), and symptom onset occurred a median of 2 days (interquartile range, 1 to 3) before hospital admission. The results of epidemiologic investigations were highly suggestive of a zoonotic origin of the outbreak: an index patient was identified who had been exposed to Egyptian fruit bats at a mining site. The case fatality rate in the outbreak was 23% (15 deaths among 66 patients). Remdesivir and the monoclonal antibody MBP091 were used under expanded access and clinical trial protocols. In addition, 1710 frontline workers and high-risk contacts received the chimpanzee adenovirus 3–vectored vaccine ChAd3-MARV under emergency use authorization in a phase 2 clinical trial.

Conclusions

Implementation of containment measures, advanced supportive care, and access to investigational countermeasures may have contributed to reduced mortality from MVD in this outbreak. Enhancing surveillance, improving infection prevention and control in health care settings, and ensuring timely deployment of medical countermeasures will be critical for mitigating the effects of future filovirus disease outbreaks.

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2415816?query=TOC

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Tuesday, July 29, 2025

#SARS-CoV-2 #Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug #Resistance

Abstract

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC50 and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC50). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance.

Source: Viruses, https://www.mdpi.com/1999-4915/17/8/1055

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Thursday, April 24, 2025

#Remdesivir, mAb114, REGN-EB3, and #ZMapp partially rescue nonhuman #primates infected with a low passage #Kikwit variant of #Ebola virus

Abstract

In 2018, a clinical trial of four investigational therapies for Ebola virus disease (EVD), known as the PALM trial, was conducted in the Democratic Republic of Congo. All patients received either the antiviral remdesivir (RDV) or a monoclonal antibody product: ZMapp, mAb114 (Ebanga), or REGN-EB3 (Inmazeb). The study concluded that both mAb114 and REGN-EB3 were superior to ZMapp and RDV in reducing mortality from EVD. However, the data suggested that some patients in the RDV and ZMapp groups might have been sicker at the time of treatment initiation. Here, we assessed the efficacy of each of these therapies in a uniformly lethal rhesus monkey model of EVD when treatment was initiated 5 days after Ebola exposure. Treatment with RDV, mAb114, REGN-EB3, and ZMapp each resulted in similar survival (approximately 40%). Survival was associated with circulating viral load at treatment initiation. A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 group. Our data show similar suboptimal efficacy of individual therapeutics in the uniformly lethal NHP model of EVD, supporting further clinical investigation of therapeutic combinations to maximize the overall therapeutic effect and improve patient outcomes, particularly for the treatment of advanced stage EVD.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59168-5

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Monday, January 27, 2025

Improving #clinical #care of patients in #Nipah #outbreaks: moving beyond ‘compassionate use’

Summary

The 2024 Nipah outbreak in Kerala, India—its fifth in six years—and the recurring annual outbreaks in Bangladesh underscore the persistent threat posed by the Nipah virus (NiV) in the region. With a high mortality rate, human-to-human transmission potential, and the widespread presence of Pteropus bats, the natural reservoir, NiV remains a significant epidemic threat. Despite being a WHO priority pathogen, there has been no systematic effort to improve patient care for NiVD, leading to consistently poor outcomes. Current care relies on supportive measures and the ‘compassionate use’ of unapproved drugs like ribavirin and remdesivir. Drugs used ‘off-label’ during outbreaks can become the ‘standard of care’ without robust evidence of their safety or efficacy, complicating the testing of new therapies and perpetuating uncertainty about their true effectiveness. To improve NiVD care, we propose four key strategies: 1) Enhance early case detection, 2) optimize supportive care to improve outcomes and create a standard for future trials, 3) adopt a syndromic approach centered on encephalitis, and 4) explore innovative trial designs tailored to low case numbers as an alternative to ‘compassionate use’. By integrating these strategies, healthcare systems in NiV-endemic regions will be better equipped to manage both current and future outbreaks.

Source: Lancet Regional Health South-East Asia, https://www.thelancet.com/journals/lansea/article/PIIS2772-3682(24)00177-X/fulltext

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Saturday, January 25, 2025

#Remdesivir and #Obeldesivir Retain Potent #Antiviral Activity Against #SARS-CoV-2 #Omicron Variants

Abstract

As new SARS-CoV-2 variants continue to emerge, it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.2.86, BF.7, BQ.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, JN.1.7, JN.1.18, KP.2, KP.3, LB.1, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF when compared with reference strains. Genomic analysis identified 29 Nsp12 polymorphisms in these and previous Omicron variants. Phenotypic analysis of these polymorphisms confirmed no impact on the antiviral activity of RDV or ODV and suggests Omicron variants containing these Nsp12 polymorphisms remain susceptible to both compounds. These data support the continued use of RDV in the context of circulating SARS-CoV-2 variants and the development of ODV as an antiviral therapeutic.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/168

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