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  1. Kurup A, Leo YS, Tan AL, Wong SY
    Ann Acad Med Singap, 1999 Jul;28(4):605-9.
    PMID: 10561784
    Penicillium marneffei has emerged as an important opportunistic pathogen in HIV-infected patients in Southeast Asia. We report the first 5 cases of P. marneffei diagnosed in Singapore. All the patients were HIV-infected and were either Thai nationals or had frequently travelled to Thailand. Fever, weight loss, anaemia and papular skin lesions were common clinical manifestations in our patients, all of whom had the organism isolated from blood. Skin biopsy specimens showed histological evidence of P. marneffei in 2 patients. In 1 patient each, the organism grew in cultures of specimens from bone marrow and respiratory secretions. Amphotericin B therapy followed by itraconazole were used in 3 of our 5 patients and was associated with good clinical response and outcome.
  2. Win MK, Chow A, Chen M, Lau YF, Ooi EE, Leo YS
    Ann Acad Med Singap, 2010 Jun;39(6):448-52.
    PMID: 20625620
    INTRODUCTION: Outbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control.

    MATERIALS AND METHODS: During the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples.

    RESULTS: The overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received.

    CONCLUSIONS: A mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks.

  3. Umapathi T, Kam YW, Ohnmar O, Ng BCJ, Ng Y, Premikha M, et al.
    J Peripher Nerv Syst, 2018 09;23(3):197-201.
    PMID: 30070025 DOI: 10.1111/jns.12284
    Although individuals with Zika virus (ZIKV) antibodies were reported in Malaya in mid-1950s, entomological and human surveillance in Singapore did not identify autochthonous transmission until the outbreak of August-November, 2016. A total of 455 cases from 15 separate clusters were identified. We asked if this ZIKV outbreak increased the incidence of Guillain-Barré syndrome (GBS) and aimed to characterize these cases. Eleven GBS cases, consecutively enrolled into our prospective GBS database from onset to 4 weeks after outbreak, and six controls, comprising three GBS patients enrolled before outbreak and three non-GBS patients, were examined for evidence of recent ZIKV infection. We performed serum, urine ZIKV RT-PCR, ZIKV serology, and virus neutralization assays, accounting for cross-reaction and co-infection with dengue (DENV). We found five GBS cases with only serological evidence of recent ZIKV infection (including one ZIKV-DENV co-infection). A temporal relationship with ZIKV outbreak was unlikely as two cases were GBS controls enrolled 3 months before outbreak. None reported symptoms of ZIKV infection. In addition, compared to last 10 years the national number of GBS hospitalizations did not increase during and immediately after outbreak. We conclude the 2016 Singapore ZIKV outbreak did not cause a change in GBS epidemiology.
  4. Ng KW, Chow A, Win MK, Dimatatac F, Neo HY, Lye DC, et al.
    Singapore Med J, 2009 Aug;50(8):785-90.
    PMID: 19710977
    Chikungunya is a re-emerging mosquito-borne viral infection that has spread from East Africa to Indian Ocean islands and re-emerged in India since 2004. In Malaysia, chikungunya re-emerged after a hiatus of seven years, causing a localised outbreak in a north-western coastal town in 2006 and subsequently widespread outbreaks in 2008. Since the first local outbreak of chikungunya in Singapore in January 2008, chikungunya infections have been increasingly reported in Singapore. In this case series, five patients aged 37-62 years, with chikungunya infection confirmed in August 2008, were reported. Three of the five were male, and only one had medical comorbidities. Two had a travel history to Johor, Malaysia, where local outbreaks of chikungunya had been reported. Fever, arthralgia and rash were the most common symptoms. Fever lasted four to five days while viraemia lasted four to 11 days, persisting two to three days after defervescence in three patients. A biphasic pattern of fever was observed in two patients. Leucopenia was noted in all patients, while mild thrombocytopenia and transaminitis occurred in three of five patients. Two patients had persistent polyarthralgia at two to three weeks after the onset of symptoms. Fever, arthralgia and rash should prompt consideration of acute chikungunya in Singapore. While taking the travel history, doctors should be mindful that indigenous chikungunya cases can occur.
  5. Ng KT, Ng KY, Khong WX, Chew KK, Singh PK, Yap JK, et al.
    PLoS One, 2013;8(12):e80884.
    PMID: 24312505 DOI: 10.1371/journal.pone.0080884
    HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
  6. Simarmata D, Ng DC, Kam YW, Lee B, Sum MS, Her Z, et al.
    Sci Rep, 2016 05 16;6:26097.
    PMID: 27180811 DOI: 10.1038/srep26097
    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.
  7. Lim CC, Lee WL, Leo YS, Lee KE, Chan KP, Ling AE, et al.
    J Neurol Neurosurg Psychiatry, 2003 Jan;74(1):131-3.
    PMID: 12486285
    The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.
  8. Ang LW, Gao Q, Cui L, Farwin A, Toh MPHS, Boudville IC, et al.
    BMC Infect Dis, 2022 Jan 25;22(1):88.
    PMID: 35078426 DOI: 10.1186/s12879-022-07066-2
    BACKGROUND: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore.

    METHODS: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT).

    RESULTS: A total of 2234 migrant workers aged 20-49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2-91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965-1989 than those born in 1990-1999 (95.3% vs. 86.6%, p 

  9. Ang LW, Gao Q, Cui L, Farwin A, Toh MPHS, Boudville IC, et al.
    BMC Public Health, 2022 Jan 16;22(1):111.
    PMID: 35033034 DOI: 10.1186/s12889-022-12528-y
    BACKGROUND: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore.

    METHODS: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure.

    RESULTS: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20-43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 - 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 - 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 - 15.4%) in Chinese workers to 23.0% (95% CI 17.1 - 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989.

    CONCLUSIONS: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks.

  10. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al.
    Clin Infect Dis, 2020 07 11;71(2):383-389.
    PMID: 31626692 DOI: 10.1093/cid/ciz850
    BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.

    METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.

    RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).

    CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.

    CLINICAL TRIALS REGISTRATION: NCT01030211.

  11. Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, et al.
    Lancet, 2017 Apr 22;389(10079):1611-1618.
    PMID: 28283286 DOI: 10.1016/S0140-6736(17)30269-6
    BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
    METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
    FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
    INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
    FUNDING: National Medical Research Council, Singapore.
    Study site: Hospitals, Singapore; University Malaya Medical Centre (UMMC). Kuala Lumpur, Malaysia
    Study protocol: https://clinicaltrials.gov/ct2/show/NCT01030211
  12. Pan DS, Huang JH, Lee MH, Yu Y, Chen MI, Goh EH, et al.
    BMC Fam Pract, 2016 11 03;17(1):148.
    PMID: 27809770 DOI: 10.1186/s12875-016-0547-3
    BACKGROUND: Patients' expectations can influence antibiotic prescription by primary healthcare physicians. We assessed knowledge, attitude and practices towards antibiotic use for upper respiratory tract infections (URTIs), and whether knowledge is associated with increased expectations for antibiotics among patients visiting primary healthcare services in Singapore.

    METHODS: Data was collected through a cross-sectional interviewer-assisted survey of patients aged ≥21 years waiting to see primary healthcare practitioners for one or more symptoms suggestive of URTI (cough, sore throat, runny nose or blocked nose) for 7 days or less, covering the demographics, presenting symptoms, knowledge, attitudes, beliefs and practices of URTI and associated antibiotic use. Univariate and multivariate logistic regression was used to assess independent factors associated with patients' expectations for antibiotics.

    RESULTS: Nine hundred fourteen out of 987 eligible patients consulting 35 doctors were recruited from 24 private sector primary care clinics in Singapore. A third (307/907) expected antibiotics, of which a substantial proportion would ask the doctor for antibiotics (121/304, 40 %) and/or see another doctor (31/304, 10 %) if antibiotics were not prescribed. The majority agreed "antibiotics are effective against viruses" (715/914, 78 %) and that "antibiotics cure URTI faster" (594/912, 65 %). Inappropriate antibiotic practices include "keeping antibiotics stock at home" (125/913, 12 %), "taking leftover antibiotics" (114/913, 14 %) and giving antibiotics to family members (62/913, 7 %). On multivariate regression, the following factors were independently associated with wanting antibiotics (odds ratio; 95 % confidence interval): Malay ethnicity (1.67; 1.00-2.79), living in private housing (1.69; 1.13-2.51), presence of sore throat (1.50; 1.07-2.10) or fever (1.46; 1.01-2.12), perception that illness is serious (1.70; 1.27-2.27), belief that antibiotics cure URTI faster (5.35; 3.76-7.62) and not knowing URTI resolves on its own (2.18; 1.08-2.06), while post-secondary education (0.67; 0.48-0.94) was inversely associated. Those with lower educational levels were significantly more likely to have multiple misconceptions about antibiotics.

    CONCLUSION: Majority of patients seeking primary health care in Singapore are misinformed about the role of antibiotics in URTI. Agreeing with the statement that antibiotics cure URTI faster was most strongly associated with wanting antibiotics. Those with higher educational levels were less likely to want antibiotics, while those with lower educational levels more likely to have incorrect knowledge.
  13. Lam SK, Burke D, Capeding MR, Chong CK, Coudeville L, Farrar J, et al.
    Vaccine, 2011 Nov 28;29(51):9417-22.
    PMID: 21864627 DOI: 10.1016/j.vaccine.2011.08.047
    Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now.
  14. Tomashek KM, Wills B, See Lum LC, Thomas L, Durbin A, Leo YS, et al.
    PLoS Negl Trop Dis, 2018 10;12(10):e0006497.
    PMID: 30286085 DOI: 10.1371/journal.pntd.0006497
    Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.
  15. Agarwal A, Hunt B, Stegemann M, Rochwerg B, Lamontagne F, Siemieniuk RA, et al.
    BMJ, 2020 Sep 04;370:m3379.
    PMID: 32887691 DOI: 10.1136/bmj.m3379
    UPDATES: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.

    CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19?

    CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.

    WHAT IS NEW?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.

    ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.

    FUTURE RECOMMENDATIONS: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

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