Effects of bamlanivimab alone or in combination with etesevimab on subsequent hospitalization and mortality in outpatients with COVID-19: a systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) has caused an enormous loss of life worldwide. The spike protein of the severe acute respiratory syndrome coronavirus 2 is the cause of its virulence. Bamlanivimab, a recombinant monoclonal antibody, has been used alone or in combination with etesevimab to provide passive immunity and improve clinical outcomes. A systematic review and meta-analysis was conducted to investigate the therapeutic effects of bamlanivimab with or without etesevimab (BAM/ETE) treatment. Methods: Our study was registered in PROSPERO (registry number CRD42021270206). We searched the following electronic databases, without language restrictions, until January 2023: PubMed, Embase, medRxiv, and the Cochrane database. A systematic review and meta-analysis was conducted based on the search results. Results: Eighteen publications with a total of 28,577 patients were identified. Non-hospitalized patients given bamlanivimab with or without etesevimab had a significantly lower risk of subsequent hospitalization (18 trials, odds ratio (OR): 0.37, 95% confidence interval (CI): [0.29-0.49], I2: 69%; p < 0.01) and mortality (15 trials, OR: 0.27, 95% CI [0.17-0.43], I2: 0%; p = 0.85). Bamlanivimab monotherapy also reduced the subsequent risk of hospitalization (16 trials, OR: 0.43, 95% CI [0.34-0.54], I2: 57%; p = 0.01) and mortality (14 trials, OR: 0.28, 95% CI [0.17-0.46], I2: 0%; p = 0.9). Adverse events from these medications were uncommon and tolerable. Conclusions: In this meta-analysis, we found the use of bamlanivimab with or without etesevimab contributed to a significantly-reduced risk of subsequent hospitalization and mortality in non-hospitalized COVID-19 patients. However, resistance to monoclonal antibodies was observed in COVID-19 variants, resulting in the halting of the clinical use of BAM/ETE. Clinicians' experiences with BAM/ETE indicate the importance of genomic surveillance. BAM/ETE may be repurposed as a potential component of a cocktail regimen in treating future COVID variants.

Safety and immunogenicity of SARS-CoV-2 vaccine MVC-COV1901 in Taiwanese adolescents: a randomized phase 2 trial.

Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12-17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic.ClinicalTrials.gov registration: NCT04951388.

Appendicitis as a Leading Manifestation of Kawasaki Disease in Older Children.

Kawasaki disease (KD) is a systematic inflammatory disease with multiple organ involvement. Timely diagnosis and prompt management are essential for successful treatment. KD, with an atypical presentation, remains a diagnostic challenge for physicians. We report a five-year-old boy who presented with appendicitis. An appendectomy was performed; however, his fever persisted. The boy was diagnosed with KD and intravenous immunoglobulin was administered. His symptoms resolved, and he had an uneventful recovery. Furthermore, we performed a literature review with 13 cases identified in the literature. Most cases were male, and the average age was older than typical for KD. In conclusion, KD may present with abdominal complaints and appendicitis may be a rare initial presentation of KD. Multidisciplinary cooperation and high awareness are warranted for timely diagnosis, especially in older children experiencing persistent fever after an appendectomy.

To mix or not to mix? A rapid systematic review of heterologous prime-boost covid-19 vaccination.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear. AREAS COVERED: Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2). EXPERT OPINION: Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.

Repurposing Colchicine in Treating Patients with COVID-19: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) had caused huge health losses worldwide. Several drugs had been applied to treat patients with COVID-19, and repurposing colchicine had been proposed for its anti-inflammatory properties via several pathways. In this systematic review, we evaluated the effects of colchicine treatment. From inception to May 31, 2021, databases, including PubMed, EMbase, medRxiv, and Research Square were searched, and 11 studies were enrolled. A total of 17,205 COVID-19 patients with male predominance (62.9%) were analyzed. Patients with colchicine treatment had a significantly lower risk of mortality (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.38-0.87, I2: 72%; p < 0.01) and a non-significantly lower rate of mechanical ventilation (OR: 0.67, 95%CI: 0.39-1.15). The side effects were mild and not significantly different (OR: 2.03, 95%CI: 0.51-8.09). Subgroup analysis with randomized controlled trials showed no statistically significant difference in the mortality (OR: 0.80, 95%CI: 0.44-1.46, I2: 33%; p = 0.22). In conclusion, our meta-analysis found that colchicine treatment was associated with a significantly lower risk of mortality in patients with COVID-19. However, this benefit was not observed in the subgroup analysis of randomized controlled trials. Further randomized controlled studies are required to confirm the potential benefits of colchicine treatment.

Discovery of Small Anti-ACE2 Peptides to Inhibit SARS-CoV-2 Infectivity (Adv. Therap. 7/2021)

SARS-CoV-2 infects human cells by binding its spike protein to the human ACE2 receptor. Using a peptide biopanning strategy, the authors have discovered small anti-ACE2 peptides that can effectively block the SARS-CoV-2/ACE2 interaction. The anti-ACE2 peptides can be potentially used as prophylactic or therapeutic agents for SARS-CoV-2 and other ACE2-mediated viruses. This is reported by Kun Cheng and co-workers in article number 2100087.

Discovery of Small Anti-ACE2 Peptides to Inhibit SARS-CoV-2 Infectivity.

COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects host cells by binding its viral spike protein receptor-binding domain (RBD) to the angiotensin converting enzyme 2 (ACE2) on host cells. Blocking the SARS-CoV-2-RBD/ACE2 interaction is, therefore, a potential strategy to inhibit viral infections. Using a novel biopanning strategy, a small anti-ACE2 peptide is discovered, which shows high affinity and specificity to human ACE2. It blocks not only the SARS-CoV-2-RBD/ACE2 interaction but also the SARS-CoV-1-RBD/ACE2 interaction. Moreover, it inhibits SARS-CoV-2 infection in Vero-E6 cells. The peptide shows negligible cytotoxicity in Vero-E6 cells and Huh7 cells. In vivo short-term lung toxicity study also demonstrates a good safety of the peptide after intratracheal administration. The anti-ACE2 peptide can be potentially used as a prophylactic or therapeutic agent for SARS-CoV-2 or other ACE2-mediated viruses. The strategy used in this study also provides a fast-track platform to discover other antiviral peptides, which will prepare the world for future pandemics.

The Effect of a Name-Based Mask Rationing Plan in Taiwan on Public Anxiety Regarding a Mask Shortage During the COVID-19 Pandemic: Observational Study.

BACKGROUND: The COVID-19 pandemic is a severe global health crisis. Wearing a mask is a straightforward action that can be taken, but shortage of stock and equity of allocation were important issues in Taiwan. Furthermore, increased anxiety leading to the stockpiling of masks has been common during the pandemic. OBJECTIVE: We aim to summarize the name-based mask rationing plan implemented in Taiwan and explore the public's perceived anxiety about mask shortages. METHODS: The government of Taiwan took action to control the supply and allocation of face masks. We summarize the timeline and important components of the mask rationing plan. A survey that aimed to investigate the overall response to the mask rationing plan was answered by 44 participants. RESULTS: The mask rationing plan was implemented in late January 2020. Daily production capacity was increased from 2 million masks to 16 million masks in April 2020. People could buy 9 masks in 14 days by verification via their National Health Insurance card. Digital face mask availability maps were created. Moreover, the mask plan safeguarded the purchase of masks and resulted in decreased anxiety about a mask shortage (4.05 [SD 1.15] points; 72.7% [n=32] of participants answered "agree" or "strongly agree"). The majority of people felt that the mask plan was satisfactory (4.2 [SD 0.92] points; 79.5% [n=35] of participants answered "agree" or "strongly agree"). CONCLUSIONS: We found that the unique name-based mask rationing plan allowed for control of the production and supply of masks, and contributed to the appropriate allocation of masks. The mask rationing plan not only provided the public with physical protection, but also resulted in reduced anxiety about mask shortages during the pandemic.

Taiwan Government-Guided Strategies Contributed to Combating and Controlling COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is highly contagious, and thus has become an emerging health crisis worldwide. The optimal strategies to prevent the spread of this disease are inconclusive, and therefore, the adopted measurements to combat COVID-19 varies in different countries. In mid-March and late-August 2020, we performed internet searches to collect relevant information, from sources such as the website of the World Health Organization. The epidemiological data of COVID-19 from several countries were collected and we found that Taiwan had a comparably successful story for combating the pandemic. As of mid-March, Taiwan had high rates of diagnostic testing (688.5 tests per million citizens) with a lower infection rate (49 cases, 2.1 cases per million people). As of late-August, there were 488 cases (20 cases per million people). Furthermore, Taiwanese government-guided strategies and hospital data were also reviewed. We summarized some important strategies to combat COVID-19, which include: (1) border control; (2) official media channel and press conferences; (3) name-based rationing system for medical masks; (4) TOCC-based rapid triage, outdoor clinics, and protective sampling devices; and (5) social distancing, delaying the start of new semesters, and religious assembly restriction. In conclusion, Taiwan had lower rates of COVID-19 compared with other countries, and Taiwan government-guided strategies contributed to the control of the disease's spread.

Impact of Wearing Masks, Hand Hygiene, and Social Distancing on Influenza, Enterovirus, and All-Cause Pneumonia During the Coronavirus Pandemic: Retrospective National Epidemiological Surveillance Study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic is an important health crisis worldwide. Several strategies were implemented to combat COVID-19, including wearing masks, hand hygiene, and social distancing. The impact of these strategies on COVID-19 and other viral infections remains largely unclear. OBJECTIVE: We aim to investigate the impact of implemented infectious control strategies on the incidences of influenza, enterovirus infection, and all-cause pneumonia during the COVID-19 pandemic. METHODS: We utilized the electronic database of the Taiwan National Infectious Disease Statistics System and extracted incidences of COVID-19, influenza virus, enterovirus, and all-cause pneumonia. We compared the incidences of these diseases from week 45 of 2016 to week 21 of 2020 and performed linear regression analyses. RESULTS: The first case of COVID-19 in Taiwan was reported in late January 2020 (week 4). Infectious control strategies have been promoted since late January. The influenza virus usually peaks in winter and decreases around week 14. However, a significant decrease in influenza was observed after week 6 of 2020. Regression analyses produced the following results: 2017, R2=0.037; 2018, R2=0.021; 2019, R2=0.046; and 2020, R2=0.599. A dramatic decrease in all-cause pneumonia was also reported (R2 values for 2017-2020 were 0.435, 0.098, 0.352, and 0.82, respectively). Enterovirus had increased by week 18 in 2017-2019, but this was not observed in 2020. CONCLUSIONS: Using this national epidemiological database, we found a significant decrease in cases of influenza, enterovirus, and all-cause pneumonia during the COVID-19 pandemic. Wearing masks, hand hygiene, and social distancing may contribute not only to the prevention of COVID-19 but also to the decline of other respiratory infectious diseases. Further studies are warranted to elucidate the causal relationship.

One-Seventh of Patients with COVID-19 Had Olfactory and Gustatory Abnormalities as Their Initial Symptoms: A Systematic Review and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) patients exhibited protean clinical manifestations. Olfactory and gustatory abnormalities (anosmia and ageusia) were observed in COVID-19 patients, but the reported prevalence varied. In this systematic review, the prevalence of olfactory and gustatory abnormalities (OGA) was evaluated in laboratory-confirmed COVID-19 patients. On 8 May 2020, 14,506 articles were screened, while 12 of them were enrolled. A total of 1739 COVID-19 patients were analyzed, with a wide range of prevalence observed (5.6-94%). The pooled prevalence was 48.5% with high heterogeneity (I2, 98.8%; p < 0.0001). In total, 15.5% had OGA as their first symptom (I2, 22.6%; p = 0.27) among the patients analyzed. Contradictory to COVID-19 negative controls, patients with COVID-19 had a higher risk of OGA (odds ratio, 5.3; I2, 66.5%; p = 0.03). In conclusion, approximately half of COVID-19 patients had OGA, and one-seventh of them had OGA as their initial symptoms. OGA were cardinal symptoms of COVID-19, which may serve as clues for early diagnosis. Diagnostic testing for SARS-CoV-2 was suggested in patients with OGA during the COVID-19 pandemic to ensure timely diagnosis and appropriate quarantine.

Clinical features of neonates born to mothers with coronavirus disease-2019: A systematic review of 105 neonates.

BACKGROUND: Despite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear. We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19. METHODS: We searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes in neonates born to mothers with COVID-19. Data were pooled using a random effects regression model. Primary and secondary outcomes were neonatal clinical outcomes and infectious status, respectively. RESULTS: Fourteen studies involving 105 neonates fulfilling the study criteria were identified. The rates of preterm neonates and those small for gestational age (SGA) were 25 (23.8%) and 10 (11.2%), respectively. Among 91 neonates who were tested, 8 (8.8%) were positive for nucleic acids or antibodies for SARS-CoV-2. Additionally, 28 (26.7%) of the neonates were symptomatic and two test-negative neonates died, including one stillbirth. Between test-positive and test-negative groups, the rates of SGA, preterm delivery, duration between maternal symptom onset and delivery, and perinatal complication were not significantly different; but the rate of symptomatic after birth reached significant difference (62.5% vs 20.5%, p = 0.008). CONCLUSIONS: Most neonates born to infected mothers had favorable outcomes. Although direct evidences of intrauterine infection were scarce, the risk of intrauterine infection should be considered based on a positive test in 8.8% of the neonates. Symptomatic neonates born to infected mothers should receive tests for SARS-CoV-2 to initiate appropriate treatment and quarantine. Further studies are warranted to assess the outcomes of COVID-19 in neonates.

COVID-19: Taiwan's epidemiological characteristics and public and hospital responses.

BACKGROUND: Coronavirus disease 19 (COVID-19) is a global health threat with significant medical, economic, social and political implications. The optimal strategies for combating COVID-19 have not been fully determined and vary across countries. METHODS: By the end of February 2020 in Taiwan, 2,150 patients received diagnostic COVID-19 testing and 39 confirmed cases were detected. This is a relatively lower rate of infection compared to other Asian countries. In this article, we summarize the epidemiological characteristics of the 39 infected patients as well as public and hospital responses to COVID-19. RESULTS: Thirty-nine COVID-19 cases and one death have been confirmed in Taiwan. Seventeen of these patients were infected by family members or in hospital wards, emphasizing how COVID-19 is mostly spread by close contact. We examined how hospital have responded to COVID-19, including their implementation of patient route control, outdoor clinics, hospital visit restrictions and ward and staff modifications. We also studied the public's use of face masks in response to COVID-19. These strategies may reduce the spread of COVID-19 in other countries. CONCLUSION: The emergence and spread of COVID-19 is a threat to health worldwide. Taiwan has reported lower infected cases and its strategies may contribute to further disease prevention and control.