Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

Sequelae of long COVID, known and unknown: A review of updated information.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Updated information regarding acute severe hepatitis of unknown origin in children: Viewpoints of and insights from pediatricians.

Recently, the morbidity of acute severe hepatitis of unknown origin in children (SHIC) has tended to decrease, but this condition should not be ignored because of its uncertain but severe nature. The current study briefly summarizes updated information regarding the epidemiological, clinical, and etiological aspects of SHIC based on the newest information available. Opinions from pediatricians are also presented. In light of the status quo of SHIC and COVID-19 globally, several suggestions are proposed to improve future studies, which could help to further explore the underlying mechanisms of SHIC in the context of COVID-19.

Immunological and metabolic characteristics of the Omicron variants infection.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.

Different clinical guidelines, common goal: To reduce COVID-19 mortality.

The tendency of the Omicron variant to rapidly became the dominant SARS-CoV-2 strain and its weaker virulence than other strains worldwide has prompted many countries to adjust their public health strategies. This work summarizes all appropriate clinical interventions to reduce the public health burden caused by COVID-19 according to guidelines from the World Health Organization and 10 countries, i.e., the United States of America (USA), India, France, Germany, Brazil, South Korea, Japan, Italy, the United Kingdom (UK), and China. Five stages of COVID-19 were identified: asymptomatic infection and mild, moderate, severe, and critical illness. Most guidelines recommend antivirals starting with mild cases for those from Germany and India. Since more drugs are being developed and are becoming available to COVID-19 patients, guidelines are increasingly being updated with new pharmacological intervention strategies. Thus, a global view needs to be adopted to provide helpful options and precise treatment strategies during the lasting fight against the COVID-19 pandemic.

Oral high-dose acetylcysteine: Effective against the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high rate of transmission and it exhibits immune escape characteristics. N-acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH), which can enter cells to play an antioxidant role, so it is better than glutathione. Patients tolerate NAC well, and adverse reactions are rare and mild, so this type of drug with multiple actions is considered to be a mucolytic agent as well as a drug for the prevention/treatment of various diseases, including COVID-19. Previous studies indicated that the clinical effectiveness of NAC is dose-dependent. Low-dose NAC (0.2 g tid for adults) is a mucolytic expectorant, high-dose NAC (0.6 g bid or tid) has expectorant action as well as antioxidant action, and extreme-dose NAC (300 mg/kg.d) is used for detoxification in cases of an acetaminophen overdose. Presumably, orally administered high-dose NAC (0.6 g tid for adults and 10 mg/kg tid for children) could be used as an adjuvant to treat an Omicron infection. It should reduce the time to negative conversion and prevent severe COVID-19, reducing the duration of hospitalization and increasing the bed turnover rate.

Long-term sequelae of different COVID-19 variants: The original strain versus the Omicron variant.

Although Omicron appears to cause less severe acute illness than the original strain, the potential for large numbers of patients to experience long COVID is a major concern. Little is known about the recovery phase in cases of Omicron, highlighting the importance of dynamically monitor long COVID in those patients. Subjects of the current study were patients available for a three-month follow-up who were admitted from January 13 to May 22, 2020 (period of the original strain) and from January 1 to May 30, 2022 (period of Omicron). Twenty-eight-point-four percent of patients infected with the original strain had long-term symptoms of COVID-19 and 5.63% of those infected with the Omicron strain had such symptoms. The most common symptom was a cough (18.5%), followed by tightness in the chest (6.5%), in patients infected with the original strain. Fatigue (2.4%) and dyspnea (1.7%) were the most commonly reported symptoms in patients infected with the Omicron strain. The respiratory system is the primary target of SARSCoV-2. Supportive treatment is the basis for the treatment of respiratory symptoms in patients with COVID-19. Quality sleep and good nutrition may alleviate fatigue and mental issues. Further knowledge about a long-term syndrome due to Omicron needs to be discussed and assembled so that healthcare and workforce planners can rapidly obtain information to appropriately allocate resources.

Verification of the efficiency of saline gargle sampling for detection of the Omicron variant of SARS-CoV-2, a pilot study.

A saline gargle (SG) has proven to be an efficient method of sampling to detect SARS-CoV-2. The aim of this pilot study was to verify the efficiency of SG sampling in detecting the Omicron variant of SARS-CoV-2. Subjects were a total of 68 patients with COVID-19 (Omicron variant), and 167 pairs of samples were collected. A conventional oropharyngeal swab (OPS) was obtained and SG sampling was performed immediately afterward; both were subjected to RT-qPCR. A subgroup analysis of symptomatic and asymptomatic patients was performed. Results revealed no significant differences in the distribution of patients and cycle threshold (CT) values between the SG and OPS in overall data and data on days 1-3, 4-7, and 8-14. The subgroup analysis revealed no significant differences between the SG and OPS results in symptomatic patients. In asymptomatic patients, the CT values for the SG were significantly lower than those for the OPS, implying that SG sampling had better sensitivity in the context of the Omicron variant. These data indicate that the SG had satisfactory efficiency (vs. the OPS). An SG is a simple and less invasive method of sampling that is suited to mass, frequent, and repeated sampling to detect SARS-CoV-2.

Can nasal irrigation with chlorine dioxide be considered as a potential alternative therapy for respiratory infectious diseases? The example of COVID-19.

Chlorine dioxide (ClO2) is a high-level disinfectant that is safe and widely used for sterilization. Due to the limitations on preparing a stable solution, direct use of ClO2 in the human body is limited. Nasal irrigation is an alternative therapy used to treat respiratory infectious diseases. This study briefly summarizes the available evidence regarding the safety/efficacy of directly using ClO2 on the human body as well as the approach of nasal irrigation to treat COVID-19. Based on the available information, as well as a preliminary experiment that comprehensively evaluated the efficacy and safety of ClO2, 25-50 ppm was deemed to be an appropriate concentration of ClO2 for nasal irrigation to treat COVID-19. This finding requires further verification. Nasal irrigation with ClO2 can be considered as a potential alternative therapy to treat respiratory infectious diseases, and COVID-19 in particular.

Analysis of 394 COVID-19 cases infected with Omicron variant in Shenzhen: impact of underlying diseases to patient's symptoms.

OBJECTIVES: The emergence of new variants of SARS-CoV-2 is continuously posing pressure to the epidemic prevention and control in China. The Omicron variant of SARS-CoV-2 having stronger infectivity, immune escape ability, and capability causing repetitive infection spread to many countries and regions all over the world including South Africa, United States and United Kingdom etc., in a short time. The outbreaks of Omicron variant also occurred in China. The aim of this study is to understand the epidemiological characteristics of Omicron variant infection in Shenzhen and to provide scientific basis for effective disease control and prevention. METHODS: The clinical data of 394 imported COVID-19 cases infected with Omicron variant from 16 December 2021 to 24 March 2022 admitted to the Third People's hospital of Shenzhen were collected and analyzed retrospectively. Nucleic acid of SARS-CoV-2 of nasopharyngeal swabs and blood samples was detected using 2019-nCoV nucleic acid detection kit. Differences in Ct values of N gene were compared between mild group and moderate group. The specific IgG antibody was detected using 2019-nCoV IgG antibody detection kit. Statistical analysis was done using SPSS software and graphpad prism. RESULTS: Patients were categorized into mild group and moderate group according to disease severity. The data on the general conditions, underlying diseases, COVID-19 vaccination and IgG antibody, viral load, laboratory examination results, and duration of hospitalization, etc., were compared among disease groups. Mild gorup had higher IgG level and shorter nucleic acid conversion time. Patients with underlying diseases have 4.6 times higher probability to progress to moderate infection. CONCLUSION: In terms of epidemic prevention, immunization coverage should be strengthened in the population with underlying diseases. In medical institutions, more attention needs to be paid to such vulnerable population and prevent further deterioration of the disease.

The 4Rs approach to COVID-19 emergency management during the post-pandemic period: What lessons can be learned from Shenzhen, China?

The Omicron variant of SARS-CoV-2 (or Omicron) is extremely contagious and has swept the world in a short period. Shenzhen—a new international city in China with a permanent population of 17.56 million and covering nearly 2000 square kilometers—was attacked by Omicron in 2022. However, the pandemic was controlled in a very short time as a result of prompt government reaction that prevented the variant's further spread. The total number of cases in this wave of the pandemic was more than 2600. Shenzhen's successful experience in tackling the Omicron wave deserves in-depth discussion. Proposed by American scholar Robert Heath, the 4Rs model aims to reduce the harm from a crisis through the measures of reduction, readiness, response, and recovery. This article presents the successful experience of Shenzhen's local government and the Shenzhen Third People's Hospital, the only hospital in Shenzhen designated to use the 4Rs emergency management model for the treatment of COVID-19 during the 2022 Omicron wave of the pandemic.

Neutralization of five SARS-CoV-2 variants of concern by convalescent and BBIBP-CorV vaccinee serum.

The prevalence of SARS-CoV-2 variants of concern (VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients' sera and convalescent sera against all VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain (WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3 and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100% (30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90% (18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.

Advances in acute severe hepatitis of unknown etiology in children

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a tremendous threat to global health. polymerase chain reaction (PCR) and antigen testing have played a prominent role in the detection of SARS-CoV-2-infected individuals and disease control. An efficient, reliable detection tool is still urgently needed to halt the global COVID-19 pandemic. Recently, the food and drug administration (FDA) emergency approved volatile organic component (VOC) as an alternative test for COVID-19 detection. In this case-control study, we prospectively and consecutively recruited 95 confirmed COVID-19 patients and 106 healthy controls in the designated hospital for treatment of COVID-19 patients in Shenzhen, China. Exhaled breath samples were collected and stored in customized bags and then detected by high-pressure photon ionization time-of-flight mass spectrometry for VOCs. Machine learning algorithms were employed for COVID-19 detection model construction. Participants were randomly assigned in a 5:2:3 ratio to the training, validation, and blinded test sets. The sensitivity (SEN), specificity (SPE), and other general metrics were employed for the VOCs based COVID-19 detection model performance evaluation. The VOCs based COVID-19 detection model achieved good performance, with a SEN of 92.2% (95% CI: 83.8%, 95.6%), a SPE of 86.1% (95% CI: 74.8%, 97.4%) on blinded test set. Five potential VOC ions related to COVID-19 infection were discovered, which are significantly different between COVID-19 infected patients and controls. This study evaluated a simple, fast, non-invasive VOCs-based COVID-19 detection method and demonstrated that it has good sensitivity and specificity in distinguishing COVID-19 infected patients from controls. It has great potential for fast and accurate COVID-19 detection.