Impact of COVID-19 Treatment on Real-World Outcomes in Inflammatory Bowel Disease.

BACKGROUND: While there are multiple safe and effective agents for COVID-19 treatment, their impact in inflammatory bowel disease (IBD) remains uncertain. AIMS: Our objective was to assess the effects of these therapies on both IBD and COVID outcomes. METHODS: A single-center retrospective study of adult patients with IBD who contracted COVID-19 between 12/2020 and 11/2022 was performed. Patients were stratified by COVID-19 treatment (antivirals and/or intravenous antibodies) vs no therapy. The primary outcome was the development of severe COVID-19 infection, defined by need for supplemental oxygen, corticosteroids and/or antibiotics, or hospitalization. Secondary outcomes included rates of withholding advanced IBD therapy (defined as biologic agents or small molecules) and of post-COVID-19 IBD flare. RESULTS: Of 127 patients with COVID-19 infection, 70% were on advanced therapies, 35% received COVID-19 treatment, and 15% developed severe COVID-19. Those treated for COVID-19 were more likely to be on corticosteroids [odds ratio (OR) 4.61, 95% confidence interval (CI) 1.72-12.39, p = 0.002] or advanced IBD therapies (OR 2.78, 95% CI 1.04-7.43, p = 0.041). After adjusting for age, race, sex, corticosteroid use, obesity, COVID-19 vaccination status, and severe COVID-19 infection, those treated for COVID-19 were more likely to have IBD therapy held (OR 6.95, 95% CI 1.72-28.15, p = 0.007). There was no significant difference in rates of post-COVID-19 IBD flares or severe COVID-19 infection. There were no COVID-related deaths. CONCLUSIONS: Patients with IBD on advanced therapies were frequently treated for acute COVID-19. Although COVID-19 treatment was associated with temporary withholding of IBD therapy, it did not result in increased IBD flares.

Determining and Comparing the Real-World Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Patients Hospitalized With COVID-19.

BACKGROUND: Current guidelines recommend using nirmatrelvir-ritonavir for coronavirus disease 2019 (COVID-19) treatment, but its potential drug interactions and contraindications limit its applicability in certain categories of patients. The aim of the study was to evaluate the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in managing COVID-19 among hospitalized patients. METHODS: We conducted a retrospective cohort study among hospitalized COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir and did not require baseline supplemental oxygen from February 2022 to January 2023. We compared the effectiveness of molnupiravir and nirmatrelvir-ritonavir with a focus on disease progression. RESULTS: The study included 401 high-risk, hospitalized adult COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir. No significant difference was found in disease progression, the composite outcome of disease progression (4.0% vs. 1.4%, P = 0.782), and O2 supplementation via nasal prong (21.8% vs. 14.8%, P = 0.115) between the patients treated with molnupiravir and those treated with nirmatrelvir-ritonavir. This finding was similar after 1:1 propensity-score matching. In the multivariate analysis, molnupiravir treatment was not significantly associated with progression to severe disease. CONCLUSION: In conclusion, our findings suggest that similar to nirmatrelvir-ritonavir, molnupiravir has a distinct potential role in COVID-19 treatment, transcending its current perceived status as only a secondary option.

[Health alerts for substandard, falsified, and unregistered medical products at the onset of the COVID-19 pandemic in the AmericasAlertas de saúde para produtos médicos abaixo do padrão, falsificados e não registrados no início da pandemia de COVID-19 nas Américas]. / Alertas sanitarias de productos médicos subestándares, falsificados y no registrados al inicio de la pandemia de COVID-19 en las Américas.

Objective: Identify and analyze incidents of substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic. Methods: Detailed search of the websites of regulatory authorities in the Americas. Identification of incidents of substandard, falsified, unregistered, and stolen medicines and medical devices (including in vitro diagnostics). The types of products were determined, as were the stages in the supply chain where they were detected, and the actions taken by authorities. Results: A total of 1 273 incidents were identified in 15 countries (1 087 substandard, 44 falsified, 123 unregistered, and 19 stolen products). The largest number of incidents involved medical devices, disinfectants, and antiseptics. The most frequently reported point in the supply chain was online purchasing. The principal measures taken by the regulatory authorities were: alerts, prohibition of use, prohibition of advertising and manufacture, recall, and monitoring of adverse events. Conclusions: A substantial number of incidents involving substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic were identified. Shortages of supplies, easing of regulatory requirements, and increased demand are factors that may have led to an increase in the number of incidents. The national regulatory authorities of reference reported more frequent detection of incidents and more frequent application of health measures. A regulatory strategy is needed in order to address online sales and ensure the safe distribution of medical products.

Objetivo: Identificar e analisar incidentes de produtos médicos abaixo do padrão, falsificados, não registrados e roubados no início da pandemia de COVID-19. Métodos: Foi realizada uma busca detalhada nos sites das autoridades reguladoras das Américas. Foram identificados incidentes envolvendo medicamentos e dispositivos médicos (incluindo para diagnóstico in vitro) abaixo do padrão, falsificados, não registrados e roubados. Foram determinados os tipos de produtos, os estágios da cadeia de abastecimento em que foram detectados e as medidas tomadas pelas autoridades. Resultados: Foram identificados 1 273 incidentes em 15 países (1 087 produtos abaixo do padrão, 44 falsificados, 123 não registrados e 19 roubados). O maior número de incidentes estava relacionado a dispositivos médicos, desinfetantes e antissépticos. O ponto na cadeia de abastecimento com a maior frequência de relatos foi a de aquisição pela internet. As medidas tomadas pelas autoridades reguladoras foram principalmente alertas, proibições de uso, proibições de publicidade e fabricação, recolhimento de produtos do mercado e monitoramento de eventos adversos. Conclusões: Houve um número significativo de incidentes envolvendo produtos médicos abaixo do padrão falsificados, não registrados e roubados no início da pandemia de COVID-19. A escassez de insumos, a flexibilização das exigências regulatórias e o aumento da demanda são fatores que podem levar a um maior número de incidentes. As autoridades reguladoras nacionais de referência informaram um aumento na frequência de detecção de incidentes e implementação de medidas sanitárias. O canal de vendas pela internet precisa ser abordado com alguma estratégia regulatória para garantir a distribuição segura de produtos médicos.

Patients with moderate to severe COVID-19 outcomes on remdesivir according to baseline 4C mortality score.

BACKGROUND: Remdesivir was the first antiviral to show clinical benefit in patients with moderate-to-severe COVID-19. Previous trials demonstrated a faster time to recovery in hospitalized patients treated with remdesivir vs placebo. Current guidelines recommend treatment with remdesivir based on hospitalization status, oxygen requirements, and time from symptom onset. However, other factors may be evaluated to determine disease severity and risk for progression. The 4C mortality score is a validated, eight variable score that may be used to categorize patients by mortality risk at the time of hospital admission for COVID pneumonia. The objective of this study was to determine if the 4C mortality score may be used to predict which patients with moderate to severe COVID-19 would benefit the most from remdesivir at the time of hospital admission. METHODS: This was a single-center retrospective cohort study comparing time to recovery among hospitalized patients with moderate-to-severe COVID-19 who were treated with remdesivir compared to those who were treated with standard of care (SOC). The primary outcome was time to recovery, defined as discharge from the hospital or no longer requiring supplemental oxygen, stratified by the 4C mortality score risk group. Secondary outcomes included in-hospital mortality, hospital length of stay, and time to recovery in patients who were started on remdesivir within 7 days from symptom onset vs after 7 days from symptom onset. A survival analysis was used to analyze time to recovery outcomes. RESULTS: Data was collected and analyzed for a total of 300 patients, of which 200 received remdesivir and 100 received SOC. Patients in the remdesivir group had a longer time to recovery compared to patients in the SOC group (6 days vs 4 days). This finding was driven by patients who were categorized to the intermediate risk and high risk mortality groups. Additionally, patients who received remdesivir had a longer length of hospital stay compared to those who received SOC (12 days vs 9 days). Remdesivir was not associated with an increased rate of adverse events. CONCLUSIONS: This study of patients admitted with moderate-to-severe COVID-19 found that patients who were treated with remdesivir had a longer time to recovery and a longer length of stay compared to those who received SOC. These findings add to the body of evidence questioning the benefit of remdesivir therapy among patients hospitalized with COVID-19.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Racing to immunity: Journey to a COVID-19 vaccine and lessons for the future.

SARS-CoV-2 is the novel coronavirus behind the COVID-19 pandemic. Since its emergence, the global scientific community has mobilized to study this virus, and an overwhelming effort to identify COVID-19 treatments is currently ongoing for a variety of therapeutics and prophylactics. To better understand these efforts, we compiled a list of all COVID-19 vaccines undergoing preclinical and clinical testing using the WHO and ClinicalTrials.gov database, with details surrounding trial design and location. The most advanced vaccines are discussed in more detail, with a focus on their technology, advantages and disadvantages, as well as any available recent clinical findings. We also cover some of the primary challenges, safety concerns and public responses to COVID-19 vaccine trials, and consider what this can mean for the future. By compiling this information, we aim to facilitate a more thorough understanding of the extensive COVID-19 clinical testing vaccine landscape as it unfolds, and better highlight some of the complexities and challenges being faced by the joint effort of the scientific community in finding a prophylactic against COVID-19.

[Basic aspects of COVID-19 for management from primary care]. / Aspectos básicos de la COVID-19 para el manejo desde atención primaria.

SARS-CoV-2 is transmitted from person to person by inhalation or contact with respiratory droplets and aerosols. The median incubation period is 5.1 days. Fever, dry cough, dyspnea and fatigue are the most common symptoms. Almost half of the cases are asymptomatic. The spectrum of disease varies from mild (81%) to critical (5%). Older age, male gender and comorbidities negatively impact on the severity and mortality of COVID-19. The diagnosis of acute COVID-19 is made with RT-PCR or antigenic detection tests. In hospital patients, remdesivir reduces recovery time. Oral steroids are recommended for severe or critical cases requiring oxygen therapy or mechanical ventilation. Thromboprophylaxis is recommended in all severe and non-severe cases with high thrombotic risk. Antibiotherapy is limited to cases of high suspicion of bacterial superinfection. Mild-moderate and severe cases after discharge from hospital should be clinically monitored for a minimum period of two weeks.

Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19.

INTRODUCTION: Given the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug. BACKGROUND: The in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis. REVIEW RESULTS: Literature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes. CONCLUSION: As per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia. HOW TO CITE THIS ARTICLE: Shetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.

Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis.

BACKGROUND: The COVID-19 causing coronavirus is an enveloped RNA virus that utilizes an enzyme RNA dependent RNA polymerase for its replication. Favipiravir (FVP) triphosphate, a purine nucleoside analog, inhibits that enzyme. We have conducted this systematic review and meta-analysis on efficacy and safety of the drug FVP as a treatment for COVID-19. METHODS: Databases like Pubmed, Pubmed Central, Scopus, Embase, Google Scholar, preprint sites, and clinicaltirals.gov were searched. The studies with the standard of care (SOC) and FVP as a treatment drug were considered as the treatment group and the SOC with other antivirals and supportive care as the control group. Quantitative synthesis was done using RevMan 5.4. Clinical improvement, negative conversion of reverse transcription-polymerase chain reaction (RT-PCR), adverse effects, and oxygen requirements were studied. RESULTS: We identified a total of 1798 studies after searching the electronic databases. Nine in the qualitative studies and four studies in the quantitative synthesis met the criteria. There was a significant clinical improvement in the FVP group on the 14th day compared to the control group (RR 1.29, 1.08-1.54). Clinical deterioration rates were less likely in the FVP group though statistically not significant (OR 0.59, 95% CI 0.30-1.14) at the endpoint of study (7-15 days). The meta-analysis showed no significant differences between the two groups on viral clearance (day 14: RR 1.06, 95% CI 0.84-1.33), non-invasive ventilation or oxygen requirement (OR 0.76, 95% CI 0.42-1.39), and adverse effects (OR 0.69, 0.13-3.57). There are 31 randomized controlled trials (RCTs) registered in different parts of the world focusing FVP for COVID-19 treatment. CONCLUSION: There is a significant clinical and radiological improvement following treatment with FVP in comparison to the standard of care with no significant differences on viral clearance, oxygen support requirement and side effect profiles.

Review of adverse cutaneous reactions of pharmacologic interventions for COVID-19: A guide for the dermatologist.

The new coronavirus, severe acute respiratory syndrome coronavirus 2, is associated with a wide variety of cutaneous manifestations. Although new skin manifestations caused by COVID-19 are continuously being described, other cutaneous entities should also be considered in the differential diagnosis, including adverse cutaneous reactions to drugs used in the treatment of COVID-19 infections. The aim of this review is to provide dermatologists with an overview of the cutaneous adverse effects associated with the most frequently prescribed drugs in patients with COVID-19. The skin reactions of antimalarials (chloroquine and hydroxychloroquine), antivirals (lopinavir/ritonavir, ribavirin with or without interferon, oseltamivir, remdesivir, favipiravir, and darunavir), and treatments for complications (imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine and low molecular weight heparins) are analyzed. Information regarding possible skin reactions, their frequency, management, and key points for differential diagnosis are presented.

Treating COVID-19: Review of Drug Hypersensitivity Reactions.

The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since it was first reported in Wuhan, China in December 2019. Its severe clinical manifestations, which often necessitate admission to intensive care units, and high mortality rate represent a therapeutic challenge for the medical community. To date, no drugs have been approved for its treatment, and various therapeutic options are being assayed to address the pathophysiological processes underlying the clinical manifestations experienced by patients. New and old drugs administered as monotherapy or in combination to immunologically compromised patients may favor the development of adverse drug reactions, including drug hypersensitivity reactions, which must be identified and managed accordingly. Given the lack of herd immunity and the high rate of viral contagion, new cases are expected to emerge in the coming months. Thus, the probability of more adverse reactions or even new clinical manifestations may increase in parallel. Allergists must receive updated information on these treatments, as well as on the management of possible drug hypersensitivity reactions.

Past, Present, and Future of Remdesivir: An Overview of the Antiviral in Recent Times.

In the current COVID-19 pandemic, evidence to justify the use of any specific antiviral drug with proven efficacy is not yet available. Antiviral drug development always remains a challenge to the scientists. Remdesivir has emerged as a promising molecule, based on results of clinical trials and observational studies and has receieved marketing approval for COVID-19 treatment under "emergency use authorization" in countries such as United States. Remdesivir is a newer antiviral drug that acts as an RNA-dependent RNA polymerase (RdRp) inhibitor targeting the viral genome replication process. Therapeutic efficacy was first demonstrated by suppressing viral replication in Ebola-infected rhesus monkeys. It is available for parenteral use with reasonable safety and tolerability profile. Multiple clinical trials are going on in many countries to evaluate its safety, efficacy and tolerability. Positive outcome will make the drug capable of meeting the demand generated by both the current pandemic and future outbreak. HOW TO CITE THIS ARTICLE: Choudhury S, Chakraborty DS, Lahiry S, Chatterjee S. Past, Present, and Future of Remdesivir: An Overview of the Antiviral in Recent Times. Indian J Crit Care Med 2020;24(7):570-574.

The effects of remdesivir on mortality and the requirement for mechanical ventilation in patients with COVID-19: a systematic review stratified by disease severity.

BACKGROUND/AIMS: The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV. RESULTS: A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events. CONCLUSION: In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.

Therapeutic Impact of Tocilizumab in the Setting of Severe COVID-19; an Updated and Comprehensive Review on Current Evidence.

Introduction: The COVID-19 pandemic caused by SARS-CoV-2 has been the major health concern in 2019 globally. Considering the severity and phase of the disease, various pharmacotherapy schedules were proposed. Here, we set out to provide close-up insights on the clinical utility of Tocilizumab (TCZ), a biologic monoclonal antibody in this regard. Methods: In this comprehensive review, various databases, including Scopus, PubMed Central, Medline, Embase, Google Scholar, and preprint publishers (med/bioRxiv) were searched until January 30, 2024, according to the keywords and search criteria. Results: Besides the pros and cons, compelling evidence purported the safety and efficacy of TCZ and indicated that it exhibits great potential to reduce short-term and all-cause (28-30-day) mortality. TCZ significantly drops the adverse events if administered in the right time course (in the inflammatory phase) during critical/severe COVID-19 pneumonia. Despite contradictory results, the benefits of TCZ appear significant, especially in combination with add-on therapies, such as corticosteroids. Although the safety of TCZ is acceptable, solid data is lacking as to its benefits during pregnancy. There are limited data on TCZ combination therapies, such as hemoperfusion, intravenous immunoglobulin (IVIG), simple O2 therapy, vasopressor support, convalescent plasma therapy, and even in vaccinated patients and COVID-19 reinfection, especially in elderly persons. In addition, the impact of TCZ therapy on the long-lasting COVID-19 is unclear. Conclusion: Personalized medicine based on individual characteristics and pertinent clinical conditions must be considered in the clinicians' decision-making policy. Finally, to mitigate the risk-to-benefit ratio of TCZ, a treatment algorithm, based on available literature and updated national institute of health (NIH) and Infectious Diseases Society of America (IDSA) guidelines, is also proposed.

Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study.

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. DESIGN, PATIENTS AND SETTING: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). INTERVENTIONS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. MEASUREMENTS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. INTERPRETATION: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

Evaluating in vivo effectiveness of sotrovimab for the treatment of Omicron subvariant BA.2 versus BA.1: a multicentre, retrospective cohort study.

BACKGROUND: In vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2. METHODS: A multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status). RESULTS: Eighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (- 14.3%; 95% confidence interval (CI): - 32.6 to 4.0%), ICU admission (- 7.1%; 95%CI: - 20.6 to 6.3%), and mortality (- 7.1%; 95%CI: - 20.6 to 6.3%). CONCLUSIONS: No differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab's effectiveness against infections due to specific emerging COVID-19 variants.

Efficacy and Safety of Ensitrelvir for Asymptomatic or Mild COVID-19: An Exploratory Analysis of a Multicenter, Randomized, Phase 2b/3 Clinical Trial.

BACKGROUND: This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19). METHODS: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6-August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary. RESULTS: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein. CONCLUSIONS: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT2031210350.

Descriptions of Scientific Evidence and Uncertainty of Unproven COVID-19 Therapies in US News: Content Analysis Study.

BACKGROUND: Politicization and misinformation or disinformation of unproven COVID-19 therapies have resulted in communication challenges in presenting science to the public, especially in times of heightened public trepidation and uncertainty. OBJECTIVE: This study aims to examine how scientific evidence and uncertainty were portrayed in US news on 3 unproven COVID-19 therapeutics, prior to the development of proven therapeutics and vaccines. METHODS: We conducted a media analysis of unproven COVID-19 therapeutics in early 2020. A total of 479 discussions of unproven COVID-19 therapeutics (hydroxychloroquine, remdesivir, and convalescent plasma) in traditional and online US news reports from January 1, 2020, to July 30, 2020, were systematically analyzed for theme, scientific evidence, evidence details and limitations, safety, efficacy, and sources of authority. RESULTS: The majority of discussions included scientific evidence (n=322, 67%) although only 24% (n=116) of them mentioned publications. "Government" was the most frequently named source of authority for safety and efficacy claims on remdesivir (n=43, 35%) while "expert" claims were mostly mentioned for convalescent plasma (n=22, 38%). Most claims on hydroxychloroquine (n=236, 79%) were offered by a "prominent person," of which 97% (n=230) were from former US President Trump. Despite the inclusion of scientific evidence, many claims of the safety and efficacy were made by nonexperts. Few news reports expressed scientific uncertainty in discussions of unproven COVID-19 therapeutics as limitations of evidence were infrequently included in the body of news reports (n=125, 26%) and rarely found in headlines (n=2, 2%) or lead paragraphs (n=9, 9%; P<.001). CONCLUSIONS: These results highlight that while scientific evidence is discussed relatively frequently in news reports, scientific uncertainty is infrequently reported and rarely found in prominent headlines and lead paragraphs.

The Therapy of SARS-CoV-2 Infection in Children.

The impact of SARS-CoV-2 infections in children has fortunately been lower than what has been seen in adults. However, even previously healthy children have developed severe disease, sometimes with subsequent mortality, and those who are infants or adolescents, are from racial and ethnic minority groups, or have certain chronic conditions are at higher risk of these outcomes. During the pandemic, extensive studies of therapeutic agents, including antivirals and immunomodulators, were conducted in adults. Few trials included children, and most were in older children and adolescents. Thus, the potential benefits of therapies in children must be extrapolated from adult evidence. Despite these limitations, advisory committees of the National Institute of Health (NIH), the Infectious Disease Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS) were constituted, and expert consensus guidelines were developed. This review provides a synthesis of those comprehensive recommendations for therapy in children. These address treatment during the early infectious period with antiviral agents, including remdesivir and nirmatrelvir/ritonavir, as well as treatment in the later period of immune dysregulation with corticosteroids and immunomodulators. In addition, the therapeutic approach for multisystem inflammatory syndrome in children (MIS-C), also referred to as Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is also provided.