A living WHO guideline on drugs for covid-19

UPDATES: This is the twelfth version (eleventh 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 under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19. NEW OR UPDATED RECOMMENDATIONS: • Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use. UNDERSTANDING THE NEW RECOMMENDATIONS: When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted. PRIOR RECOMMENDATIONS: • Recommended for patients with severe or critical covid-19­strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation­a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19­a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation­a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19­a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity­a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial. 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, 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.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996–2020

Background The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). Methods A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. Results A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = −0.430, P = 0.036), H. influenzae (rs = −0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). Conclusion In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era. Graphical

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

Estimating the Neutralizing Effect and Titer Correlation of Semi-Quantitative Anti-SARS-CoV-2 Antibody Immunoassays.

For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND50 ≥ 20 was comparable among the four immunoassays (Cohen's kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND50 ≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson's R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.

Respiratory viruses in hematopoietic cell transplant candidates: impact of preexisting lower tract disease on outcomes.

Pretransplant respiratory virus infections (RVIs) have been shown to negatively affect hematopoietic cell transplantation (HCT) outcomes. The impact of and need for delay of HCT for pretransplant infection with human rhinovirus (HRV) or endemic human coronavirus (HCoV; 229E, OC43, NL63, and HKU1) remain controversial. We analyzed the impact of symptomatic RVI within ≤90 days before HCT on overall mortality, posttransplant lower respiratory tract disease (LRD), and days alive and out of hospital (DAOH) by day 100 post-HCT in multivariable models. Among 1,643 adult HCT recipients (58% allogeneic recipients), 704 (43%) were tested for RVI before HCT, and 307 (44%) tested positive. HRV was most commonly detected (56%). Forty-five (15%) of 307 HCT recipients had LRD with the same virus early after HCT. Pretransplant upper respiratory tract infection (URI) with influenza, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, HRV, or endemic HCoV was not associated with increased overall mortality or fewer DAOH. However, in allogeneic recipients who received myeloablative conditioning, LRD due to any respiratory virus, including HRV alone, was associated with increased overall mortality (adjusted hazard ratio, 10.8 [95% confidence interval, 3.29-35.1] for HRV and 3.21 [95% confidence interval, 1.15-9.01] for all other viruses). HRV LRD was also associated with fewer DAOH. Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

Differential Impact of Nonpharmaceutical Interventions on the Epidemiology of Invasive Bacterial Infections in Children During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Invasive bacterial infection (IBI) remains a major burden of mortality and morbidity in children. As coronavirus disease 2019 (COVID-19) emerged, stringent nonpharmaceutical interventions (NPIs) were applied worldwide. This study aimed to evaluate the impact of NPIs on pediatric IBI in Korea. METHODS: From January 2018 to December 2020, surveillance for pediatric IBIs caused by 9 pathogens (S. pneumoniae, H. influenzae, N. meningitidis, S. agalactiae, S. pyogenes, S. aureus, Salmonella species, L. monocytogenes and E. coli) was performed at 22 hospitals throughout Korea. Annual incidence rates were compared before and after the COVID-19 pandemic. RESULTS: A total of 651 cases were identified and the annual incidence was 194.0 cases per 100,000 in-patients in 2018, 170.0 in 2019 and 172.4 in 2020. Most common pathogen by age group was S. agalactiae in infants < 3 months (n = 129, 46.7%), S. aureus in 3 to < 24 months (n = 35, 37.2%), Salmonella spp. in 24 to < 60 months (n = 24, 34.8%) and S. aureus in children ≥ 5 years (n = 128, 60.7%). Compared with 2018 to 2019, the incidence rate in 2020 decreased by 57% for invasive pneumococcal disease (26.6 vs. 11.5 per 100,000 in-patients, P = 0.014) and 59% for Salmonella spp. infection (22.8 vs. 9.4 per 100,000 in-patients, P = 0.018). In contrast, no significant changes were observed in invasive infections due to S. aureus, S. agalactiae and E. coli. CONCLUSIONS: The NPIs implemented during the COVID-19 pandemic reduced invasive diseases caused by S. pneumoniae and Salmonella spp. but not S. aureus, S. agalactiae and E. coli in children.

SARS-CoV-2 transmission in schools in Korea: nationwide cohort study.

OBJECTIVE: There is an urgent public need to readdress the school closure strategies. We aimed to describe the epidemiology of COVID-19 in schools and school-aged children to understand their roles in transmitting SARS-CoV-2 in Korea. DESIGN: Retrospective cohort study. SETTING: All schools in Korea PATIENTS: All school-aged children in Korea. INTERVENTIONS: None (observational study). MAIN OUTCOME MEASURES: Incidence rate, proportion of affected schools. RESULTS: Between February and December 2020, the incidence rate was lower among school-aged children (63.2-79.8 per 100 000) compared with adults aged 19 and above (130.4 per 100 000). Household was the main route of transmission (62.3%), followed by community (21.3%) and school clusters (7.9%). Among the schools in Korea, 52% of secondary schools had COVID-19 cases, followed by 39% of primary schools and 3% of kindergartens. CONCLUSIONS: We found that schools and school-aged children aged 7-18 years were not the main drivers of COVID-19 transmission. The major sources of transmission were households.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARS-CoV-2 Monoclonal Antibody Treatment of Patients with COVID-19.

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine.

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20-71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0-18.0) compared to those in the ChAd group (median 23.0, IQR 8.0-43.0, P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0-9.0, P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL, P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL, P=0.002) and BNT (1.656 ± 1.925 IU/mL, P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.

Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients.

OBJECTIVES: To investigate antibody production in asymptomatic and mild COVID-19 patients. METHODS: Sera from asymptomatic to severe COVID-19 patients were collected. Microneutralization (MN), fluorescence immunoassay (FIA), and enzyme-linked immunosorbent assay (ELISA) were performed. RESULTS: A total of 70 laboratory-confirmed COVID-19 patients were evaluated, including 15 asymptomatic/anosmia, 49 mild symptomatic, and 6 pneumonia patients. The production of the neutralizing antibody was observed in 100% of pneumonia, 93.9% of mild symptomatic, and 80.0% of asymptomatic/anosmia groups. All the patients in the pneumonia group showed high MN titer (≥1:80), while 36.7% of mild symptomatic and 20.0% of asymptomatic/anosmia groups showed high titer (p < 0.001). Anti-SARS-CoV-2 antibodies could be more sensitively detected by FIA IgG (98.8%) and ELISA (97.6%) in overall. For the FIA IgG test, all patients in the pneumonia group exhibited a high COI value (≥15.0), while 89.8% of mild symptomatic and 73.3% of asymptomatic/anosmia groups showed a high value (p = 0.049). For the ELISA test, all patients in the pneumonia group showed a high optical density (OD) ratio (≥3.0), while 65.3% of mild symptomatic and 53.3% of asymptomatic/anosmia groups showed a high ratio (p = 0.006). CONCLUSIONS: Most asymptomatic and mild COVID-19 patients produced the neutralizing antibody, although the titers were lower than pneumonia patients. ELISA and FIA sensitively detected anti-SARS-CoV-2 antibodies.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19.

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Epidemiology and Clinical Features of Myocarditis/Pericarditis before the Introduction of mRNA COVID-19 Vaccine in Korean Children: a Multicenter Study.

BACKGROUND: Korean health authority plans to vaccinate adolescents against coronavirus disease 2019 (COVID-19) starting high school seniors during the summer vacation of 2021. However, the myocarditis/pericarditis following COVID-19 vaccine has been reported recently in adolescents and young adults. This study was performed to answer the urgent questions about the basic epidemiology and clinical course of myocarditis/pericarditis in hospitalized patients prior to the introduction of COVID-19 vaccines in pediatric population. METHODS: A retrospective medical record analysis including frequency, clinical characteristics, etiology and outcome of myocarditis/pericarditis was conducted in 17 years and younger patients who were hospitalized in two referral hospitals in Korea between 2010 and 2019. RESULTS: Total 142 patients with myocarditis (n = 119) and/or pericarditis (n = 23) were identified. Median age was 5.4 years (interquartile range, 0.6-12.9 years; range, 11 days-17.8 years), and male was 61%. In adolescents aged 12-17 years, the male to female ratio was 3.2. Myocarditis/pericarditis occurred 0.70 per 1,000 in-patients during the study period: 0.96 (< 1 year), 0.50 (1-5 years), 0.67 (6-11 years) and 1.22 (12-17 years) per 1,000 in-patients, respectively. There was an increasing tendency for the annual frequency from 0.34 in 2010 to 1.25 per 1,000 in-patients in 2019 (P = 0.021). Among the 56 (40%) proven pathogens at admission, Mycoplasma pneumoniae (n = 11, 8%) and enterovirus (n = 10, 7%) were most common. Of the 142 patients, 99 (70%) required pediatric intensive care unit care and 10 (7%) received heart transplantation. In addition, 61 patients (61/131, 47%) without heart medication at admission needed heart medication when they were discharged. Eleven (7.7%) patients died, of which five patients were previously healthy. The median age of deceased patients was lower than the survival group (0.8 vs. 6.3 years, P = 0.014). CONCLUSION: The frequency of myocarditis/pericarditis was highest among male adolescent in-patients; however, the outcome was favorable in this group without any mortality.

Updates on the coronavirus disease 2019 vaccine and consideration in children.

Humanity has been suffering from the global severe acute respiratory syndrome coronavirus 2 pandemic that began late in 2019. In 2020, for the first time in history, new vaccine platforms-including mRNA vaccines and viral vector-based DNA vaccines-have been given emergency use authorization, leading to mass vaccinations. The purpose of this article is to review the currently most widely used coronavirus disease 2019 vaccines, investigate their immunogenicity and efficacy data, and analyze the vaccine safety profiles that have been published, to date.

Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea.

BACKGROUND: This study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: After analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups. RESULTS: The first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50-64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations. CONCLUSION: This survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging.

Evaluation of six anti-SARS-CoV-2 antibody test kits and practical approaches to optimize the diagnostic performance.

In an investigation of six anti-SARS-CoV-2 antibody kits with different target antigen and methodology, each kit showed comparable performance. As false-positive reactions occurred independently with different kits, specificity increased to 100% when pairs of kits were used. With three-kit combination, both sensitivity (99.1%) and specificity (100%) increased.

A living WHO guideline on drugs to prevent covid-19.

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea.

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.