Negative Conversion Time Research Articles

Characteristics and related factors of viral nucleic acid negative conversion in children infected with Omicron variant strain of SARS-CoV-2

Objective: To understand the characteristics and associated factors of viral nucleic acid conversion in children infected with Omicron variant strain of SARS-CoV-2 in Shanghai. Methods: The clinical symptoms, laboratory results and other data of 177 children infected with SARS-CoV-2 who were hospitalized in Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (designated hospital for SARS-CoV-2 infection in Shanghai) from April 25 to June 8, 2022 were retrospectively analyzed. According to the chest imaging findings, the children were divided into mild and common type groups. According to their age, the unvaccinated children were divided into<3 years old group and 3-<18 years old group. According to the vaccination status, the children aged 3-<18 year were divided into non-vaccination group, 1-dose vaccination group and 2-dose vaccination group. Comparison between groups was performed by independent sample t-test and analysis of variance, and multivariate linear regression analysis was used for multivariate analysis. Results: Among the 177 children infected with Omicron variant of SARS-CoV-2, 96 were males and 81 were females, aged 3 (1, 6) years. The time of viral nucleic acid negative conversion was (10.3±3.1) days. The 177 children were 138 cases of mild type and 39 cases of common type. Among the children aged 3-<18 years old, 55 cases were not vaccinated, 5 cases received 1-dose and 36 cases received 2-dose vaccination. Among the 36 children who received 2 doses of vaccination, the time of viral nucleic acid negative conversion was shorter in those vaccinated within 6 months than those over 6 months ((7.1±1.9) vs. (10.8±3.0) d, t=-3.23, P=0.004). Univariate analysis showed that the time of nucleic acid negative conversion of SARS-CoV-2 was associated with age, underlying diseases, gastrointestinal symptoms, white blood cell count, proportion of neutrophils, proportion of lymphocytes, and the number of doses of SARS-CoV-2 vaccine (t=3.87, 2.55, 2.04, 4.24, 3.51, 2.92, F=16.27, all P<0.05). Multiple linear regression analysis showed that older age (β=-0.33, 95% CI -0.485--0.182, P<0.001) and more doses of vaccination (β=-0.79, 95% CI -1.463--0.120, P=0.021) were associated with shortened nucleic acid negative conversion time in children, while lower lymphocyte proportion (β=-0.02, 95% CI -0.044--0.002, P=0.031) and underlying diseases (β=1.52, 95% CI 0.363-2.672, P=0.010) were associated with prolonged nucleic acid negative conversion time in children. Conclusion: The children infected with Omicron variant of SARS-CoV-2 with reduced lymphocyte proportion and underlying diseases may have longer time of viral nucleic acid negative conversion,while children with older age and more doses of vaccination may have shorter time of viral nucleic acid negative conversion.

Influencing factors of nucleic acid negative conversion in patients with mild and common COVID-19 induced by the Omicron variant of SARS-COV-2.

To observe the clinical characteristics of mild and common COVID-19 patients infected with the Omicron variant, and to analyze related factors affecting the time to negative conversion of viral nucleic acid detection. Clinical data of 1781 patients with coronavirus disease 2019 (COVID-19) admitted to a cabin hospital in Shanghai from April 12 to May 26, 2022, were retrospectively analyzed, including age, gender, height, weight, clinical symptoms, comorbid diseases, COVID-19 vaccination, treatment, and nucleic acid negative conversion time. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of nucleic acid negative conversion time. Among the 1781 patients, 995 were male and 786 were female, with a median age of 39 (30, 52) years. There were 727 patients (40.8%) with overweight and obesity [body mass index (BMI) > 24 kg/cm 2) and 413 patients (23.2%) had comorbid diseases. 205 cases (11.5%) were not vaccinated while 1576 cases were vaccinated. There were 1233 cases (69.2%) with one or more symptoms. The main clinical symptoms were cough (60.3%), expectoration (50.4%) and fever (36.9%). 1444 cases (81.0%) were treated with Chinese medicine, 78 cases (4.4%) were treated with western medicine, 14 cases (0.8%) were treated with integrated Chinese and western medicine, and 245 cases (13.8%) did not receive any medical treatment. All patients improved and were discharged. The median nucleic acid negative conversion time was 10.3 (7.4, 12.4) d. Univariate and multivariate analysis showed that, age ≥ 60 years ( OR＝1.537, 95% CI: 1.116 - 2.115, P<0.01), BMI > 24 kg/cm 2 ( OR＝1.344, 95% CI: 1.106 - 1.634, P<0.01 ) and hypertension ( OR＝1.518, 95% CI: 1.094 - 2.106, P<0.05) were independent risk factors for prolonged nucleic acid negative conversion. COVID-19 vaccination ( OR=0.548, 95% CI: 0.398 - 0.755, P<0.01) was a protective factor, that is, vaccination shortened the time for the nucleic acid test to become negative. The symptoms of the Omicron variant infection were relatively mild and occult. Age ≥ 60 years old, comorbid hypertension, no vaccination and BMI > 24 kg/cm 2 are independent influencing factors for prolonged nucleic acid negative conversion.

Efficacy and safety of Reyanning mixture in patients infected with SARS-CoV-2 Omicron variant: A prospective, open-label, randomized controlled trial

A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p=0.012), coughing (12.2% vs. 14.8%, p=0.046), and expectoration (6.0% vs. 8.0%, p=0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

Vaccination, symptomatic infection and negative conversion of viral RNA by body mass index, diabetes, and age: An observational study

BackgroundThe associations of doses of vaccine received with symptomatic infection with SARS-CoV-2 and negative conversion rate of viral RNA by BMI, diabetes, and age are unclear. MethodsIncluded were adult cases of SARS-CoV-2 infection hospitalized at a makeshift hospital in Shanghai (N = 38,592). Each case received a real-time reverse transcriptase–polymerase chain reaction (RT-PCR) test every day until discharge. Symptomatic cases had ≥1 pre-specified symptoms. Negative conversion time (NCT) was the duration between the specimen collection date associated with the first positive RT-PCR test and the first test date of the two consecutive negative tests at least 24 h apart. BMI-, diabetes- and age-stratified multivariable logistic and Poisson regressions were applied. FindingsCoexistence of overweight/obesity and diabetes was associated with a higher risk of symptomatic infection and a longer NCT compared with coexistence of normal weight and without diabetes, but this association was primarily attributed to underlying comorbidities. Compared with absence of vaccination, booster vaccination, but not full vaccination, was consistently associated with a 42 %–56 % lower odds of symptomatic infection and ∼1.6–1.8 days of shorter NCT across different strata separately for weight and diabetes. Age-stratified analyses found that the effectiveness of booster vaccination did not attenuate with age, except for preventing symptomatic infection among adults with diabetes. InterpretationBMI and diabetes co-determined their associations with symptomatic infection and NCT. Booster vaccination but not full vaccination was associated a lower risk of symptomatic infection, a shorter NCT or both regardless of BMI, diabetes status and age.

Clinical efficacy of Jingyin granules, a Chinese patent medicine, in treating patients infected with coronavirus disease 2019

BackgroundJingyin granules (JY), one patented Chinese herbal formula, have been advised for treating coronavirus disease 2019 (COVID-19) in China. As of now, the safety and effectiveness of JY in treating COVID-19 patients were still to be evaluated. PurposeTo investigate the safety and clinical effectiveness of JY in treating mild COVID-19 patients. Study designWe carried out a prospective cohort study, as the highly infectious COVID-19 omicron variant ranged in Shanghai (ClinicalTrial.gov registration number: ChiCTR2200058692). MethodsParticipants infected with COVID-19, who were diagnosed as mild cases, were assigned to receive either JY (JY group) or traditional Chinese medicine placebo (placebo group) orally for 7 days. The primary clinical indicators were the RNA negative conversion rate (NCR) and the incidence of severe cases. The secondary clinical indicators were the negative conversion time (NCT), inpatient length of stay (ILOS), and the disappearance rates of clinical symptoms. ResultsNine hundred participants were recruited in this clinical trial study, and 830 patients met the eligibility criteria. Seven hundred and ninety-one patients, accomplished the following-up assessment, including 423 cases of JY group and 368 cases of placebo group. NCR in JY group at 7-day posttreatment was considerably greater compared with placebo group (89.8% [380/423] vs 82.6% [304/368], P = 0.003). None of the patients with mild COVID-19 developed into severe cases. The median NCT of SARS-CoV-2 and ILOS in JY group were lesser than that in placebo group (4.0 [3.0,6.0]vs 5.0 [4.0,7.0] days, P < 0.001; 6.0 [4.0, 8.0] vs 7.0 [5.0, 9.0] days, P < 0.001). In both groups, the obvious improvement in clinical symptoms was observed, but the difference was not significant. In the subgroup of age ≤ 60 years, JY promoted SARS-CoV-2 RNA negative conversion (HR=1.242; 95% CI: 1.069-1.444, P < 0.001). No patients in both groups were reported as the case of serious adverse event. ConclusionJY maybe the potential medicine for treating mild COVID-19 patients, which had beneficial effects on increasing NCR, and shortening NCT and ILOS.

Effectiveness and safety analysis of SanHanHuaShi granules for the treatment of coronavirus disease 2019: Study protocol and statistical analysis plan for a randomized, parallel-controlled, open-label clinical trial.

Background: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020 by the World Health Organization (WHO). As of July 2, 2022, COVID-19 has caused more than 545 million infections and 6.3 million deaths worldwide, posing a significant threat to human health. Currently, there is still a lack of effective prevention and control strategies for the variation and transmission of SARS-CoV-2. Traditional Chinese medicine (TCM), which has a unique theoretical system, has treated various conditions for thousands of years. Importantly, recent studies have revealed that TCM contributed significantly to COVID-19. SanHanHuaShi (SHHS) granules, a Chinese herbal medicine, which has been included in Protocol for the Diagnosis and Treatment of Novel Coronavirus Disease 2019 (6th to 9th editions) issued by the National Health Commission of China and used to prevent and treat COVID-19 disease. A previous retrospective cohort study showed that SHHS could significantly reduce the severity of mild and moderate COVID-19. However, there is an absence of high-quality randomized controlled clinical studies to confirm the clinical effectiveness of SHHS. Therefore, a clinical study protocol and a statistical analysis plan were designed to investigate the efficacy and safety of SHHS for the prevention and treatment of COVID-19. This study will increase the integrity and data transparency of the clinical research process, which is of great significance for improving the practical application of SHHS granules in the future. Methods and analysis: The study was designed as a 7-day, randomized, parallel controlled, open-label, noninferiority clinical trial of positive drugs. A total of 240 patients with mild and moderate COVID-19 will be enrolled and randomly assigned to receive SanHanHuaShi granules or LianHuaQingWen granules treatment in a 1:1 ratio. Disease classification, vital signs, SARS-CoV-2 nucleic acid testing, symptoms, medications, adverse events, and safety evaluations will be recorded at each visit. The primary outcome will be the clinical symptom recovery rate. Secondary outcomes will include the recovery time of clinical symptoms, negative conversion time of SARS-CoV-2 nucleic acid test negative conversion rate, hospitalization time, antipyretic time, rate of conversion to severe patients, and time and rate of single symptom recovery. Adverse incidents and safety assessments will be documented. All data will be analyzed using a predetermined statistical analysis plan, including our method for imputation of missing data, primary and secondary outcome analyses, and safety outcomes. Discussion: The results of this study will provide robust evidence to confirm the effectiveness and safety of SHHS in the treatment of COVID-19. Clinical Trial Registration: http://www.chictr.org.cn. Trial number: ChiCTR2200058080. Registered on 29 March 2022.

Factors Influencing the Delay in Negative Conversion of PCR Swab Test Results in Patients with COVID-19

Background : The negative conversion duration of SARS-CoV-2 RNA was related to disease progression, and a prolonged negative conversion could provide early warning signal for poor prognosis in patients with COVID-19. The objectives of this study was to identify the factors influencing the delay in negative conversion of PCR swab test results in patients with COVID-19 as a consideration in determining the COVID-19 prevention policy in the community Methods : A retrospective cross-sectional study involving 68 patients diagnosed with COVID-19 that was treated in Dr. Kariadi General Hospital Medical Center Semarang from June 1st to December 30th 2020. Negative conversion was evaluated based on the results of the RT-PCR swab test on day 7, 14 and 21. Results : Mean negative conversion time for all patients was 11.63±5.08 days. Thirty-one factors were evaluated in the initial univariate Cox and Kaplan-Meier analysis. Older age (&gt;59 years), overweight (&gt;25 kg/m2), fever (&gt;38°C), shortness of breath, diabetes mellitus, neutrophilia, hypoalbuminemia, CRP and antiviral treatment showed significant association with negative conversion time. These factors were then included in a multivariate regression analysis. Hypoalbuminemia or albumin level of &lt;3.0 g/dL was found as an independent factor associated with negative conversion time of viral RNA (HR:1.986; 95%CI:1.098–3.594), and hypoalbuminemia was presumed to cause prolonged viral clearance time in patients with COVID-19. Conclusion : The factors influencing the prolong in negative conversion of viral RNA in patients with COVID-19 were older age, overweight, fever, shortness of breath, diabetes mellitus, neutrophilia, hypoalbuminemia, CRP and antiviral treatment. Hypoalbuminemia was an independent predictor for prolonged negative conversion of viral RNA in patients with COVID-19.

Analysis of clinical characteristics of patients with different vaccines and underlying diseases infected with novel coronavirus Omicron variant

To analyze the clinical characteristics of patients inoculated with different vaccines and underlying diseases, infected with the novel coronavirus Omicron variant. The data of 430 patients infected with the novel coronavirus Omicron variant who were admitted to Tianjin First Center Hospital from January 21, 2022 to March 7, 2022 were collected. A total of 108 patients with Omicron variant infection with underlying diseases were selected and enrolled. The gender, age, body mass index (BMI), history of underlying diseases, vaccination status (vaccination times, vaccination type), clinical symptoms, laboratory test indicators, imaging data, hospitalization time, nucleic acid negative conversion time, re-positivity and antibody titer from the two groups of the patients were collected and analyzed. In the 108 patients, 93 cases received inactivated vaccine and 15 cases received adenovirus vaccine. There was no statistically significant difference between the two groups in terms of gender, age, BMI, disease types, whether completed the fully vaccinated, whether had prime boost and underlying diseases. Both groups had fever, dry cough, sore throat, runny nose and other clinical symptoms, but there were no statistical difference between the two groups. There were no statistically significant differences in laboratory blood routine tests, biochemical indexes, C-reactive protein (CRP) level and the results of chest computed tomography (CT) imaging between the two groups. There were no statistically significant differences in hospitalization days, nucleic acid negative conversion time, whether admission to intensive care unit (ICU), turn re-positive on nucleic acid tests and immunoglobulin M (IgM) antibody titer expression between the two groups, but immunoglobulin G (IgG) antibody titer in adenovirus group was higher than that in inactivated group (g/L: 229.67±26.13 vs. 194.33±61.56, P = 0.020). There were also no significant differences in laboratory examinations, hospitalization days, nucleic acid negative conversion time, turn re-positive on nucleic acid tests and Novel coronavirus antibody titers expression of the patients with booster shots between the inactivated vaccine group and the adenovirus vaccine group. The protection of inactivated virus vaccine is equivalent to adenovirus vaccine in patients with underlying disease Omicron variant infection, and the titer of IgG antibody in patients with adenovirus vaccine is higher than that in patients with inactivated virus vaccine after one week of recovery.

Analysis of differences and influencing factors of liver injury associated with different strains of 2019-nCoV infection

Objective: To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection. Methods: Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results: A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group (P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [OR, 2.667 (CI: 1.389-5.122); P=0.003], increased CK [OR, 2.544 (CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] (CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [OR, 0.424 (CI: 0.254-0.709); P=0.001]. Conclusion: Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

Effectiveness and Safety of Baidu Jieduan Granules for COVID-19: A Retrospective Observational Multicenter Study.

ObjectiveTo evaluate the effectiveness and safety of Baidu Jieduan Granules (BDJDG) to treat common type coronavirus disease 2019 (COVID-19).MethodsThis multicenter, retrospective, and observational clinical trial included 230 common COVID-19 patients in Leishenshan, Huangshi, and Laohekou Hospitals in Wuhan from January 21 to March 26, 2020. The included patients were further divided into two subgroups according to the use of supplemental oxygen, mild and moderate groups. During the first 14 d of hospitalization, all patients were administered BDJDG combined with conventional Western medicine, and observed for continuous 28 d. Primary outcomes were disease progression rate and discharge rate. Secondary outcomes included negative conversion time of nucleic acid, hospitalization duration, clinical symptom subsidence time, and symptom regression rate.ResultsA total of 230 common COVID-19 patients were analyzed (138 in moderate group and 92 in mild group). By day 28, the disease progression rate was 4.3% and the discharge rate was 95.7%. All mild cases recovered and were discharged from hospital. The median negative conversion time of nucleic acid of all 230 COVID-19 patients was 12 d [inter-quartile range (IQR) 3.5–17], the median hospitalization duration was 15 d (IQR 12–20). The median time to fever, cough, and fatigue recovery was 4 d (IQR 2–6), 8 d (IQR 5–12), and 8 d (IQR 5–11). The recovery rate of fever, cough, and fatigue was 94.6%, 90.5%, and 93.5%. The median time to clinical improvement was 12 d (IQR 10–17). Compared with the baseline, total leukocyte counts, neutrophil counts, lymphocyte counts, and platelet counts were increased significantly on days 7 and 14 (P<0.01). C-reactive protein markedly increased on day 3 and significantly decreased on days 7 and 14 (P<0.01). No serious adverse events occurred during treatment.ConclusionBDJDG may be effective and safe for treatment of common type COVID-19. (Registration No. ChiCTR2000030836)Electronic Supplementary MaterialSupplementary material (Appendices 1—4) is available in the online version of this article at 10.1007/s11655-022-3673-x.

Analysis of clinical characteristics and prognosis of 4 264 patients with asymptomatic and mild novel coronavirus infections in Shanghai

To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment. Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed. A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37:1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.

The Value of Early Positive Nucleic Acid Test and Negative Conversion Time of SARS-CoV-2 RNA in the Clinical Outcome of COVID-19 Patients

BackgroundThe outbreak of coronavirus disease (COVID-19) poses a great threat to global public health. At present, the number of newly confirmed COVID-19 cases and deaths is increasing worldwide. The strategy of comprehensive and scientific detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through quantitative real-time polymerase chain reaction (qRT-PCR) for special populations and environments provides great support for the prevention and control of this pandemic in China. Our study focused on determining the factors associated with the length of time from symptom onset to the first positive nucleic acid test of throat swabs in COVID-19 patients, evaluating the effect of early positive nucleic acid detection on the disease severity and its significance in prognosis, and predicting the factors associated with the time from positive SARS-CoV-2 RNA test to negative conversion (negative conversion of SARS-CoV-2 virus) in COVID-19 patients.MethodsThis study included 116 hospitalized patients with COVID-19 from January 30, 2020 to March 4, 2020 in Wuhan, China. Throat swab samples were collected for qRT-PCR testing of SARS-CoV-2 RNA, and all patients included in this study were positive for this test.ResultsThe multivariate Cox proportional hazards model showed that disease severity (HR = 0.572; 95% CI 0.348–0.942; p = 0.028) was a protective factor for the time from symptom onset to positive nucleic acid detection. Meanwhile, the time from symptom onset to positive nucleic acid detection (HR = 1.010; 95% CI 1.005–1.020; p = 0.0282) was an independent risk factor for the delay in negative conversion time of SARS-CoV-2 virus. However, the severity of the disease (HR=1.120; 95% CI 0.771–1.640; p = 0.544) had no correlation with the negative conversion time of SARS-CoV-2 virus.ConclusionsPatients with more severe disease had a shorter time from symptom onset to a positive nucleic acid test. Prolonged time from symptom onset to positive nucleic acid test was an independent risk factor for the delay in negative conversion time of SARS-CoV-2 virus, and the severity of the disease had no correlation with negative conversion time of SARS-CoV-2 virus.

Demographic, Virological Characteristics and Prognosis of Asymptomatic COVID-19 Patients in South China.

BackgroundAsymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases.MethodsAll COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed.ResultsTotal 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004).ConclusionsThe asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.

Not Only High Number and Specific Comorbidities but Also Age Are Closely Related to Progression and Poor Prognosis in Patients With COVID-19.

Background: Some patients with comorbidities and rapid disease progression have a poor prognosis.Aim: We aimed to investigate the characteristics of comorbidities and their relationship with disease progression and outcomes of COVID-19 patients.Methods: A total of 718 COVID-19 patients were divided into five clinical type groups and eight age-interval groups. The characteristics of comorbidities were compared between the different clinical type groups and between the different age-interval groups, and their relationships with disease progression and outcomes of COVID-19 patients were assessed.Results: Approximately 91.23% (655/718) of COVID-19 patients were younger than 60 years old. Approximately 64.76% (465/718) had one or more comorbidities, and common comorbidities included non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes mellitus (DM), chronic hepatitis B (CHB), hyperuricaemia, and gout. COVID-19 patients with comorbidities were older, especially those with chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Hypertension, DM, COPD, chronic kidney disease (CKD) and CVD were mainly found in severe COVID-19 patients. According to spearman correlation analysis the number of comorbidities was correlated positively with disease severity, the number of comorbidities and NAFLD were correlated positively with virus negative conversion time, hypertension, CKD and CVD were primarily associated with those who died, and the above-mentioned correlation existed independently of age. Risk factors included age, the number of comorbidities and hyperlipidaemia for disease severity, the number of comorbidities, hyperlipidaemia, NAFLD and COPD for the virus negative conversion time, and the number of comorbidities and CKD for prognosis. Number of comorbidities and age played a predictive role in disease progression and outcomes.Conclusion: Not only high number and specific comorbidities but also age are closely related to progression and poor prognosis in patients with COVID-19. These findings provide a reference for clinicians to focus on not only the number and specific comorbidities but also age in COVID-19 patients to predict disease progression and prognosis.Clinical Trial Registry: Chinese Clinical Trial Register ChiCTR2000034563.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

IntroductionThis study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19.MethodsWe retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone.ResultsThirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05).ConclusionsRopeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01998-y.

Duration of infectious virus shedding in patients with severe coronavirus disease 2019 who required mechanical ventilation

BackgroundApproximately 5% of patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 develop severe COVID-19. Severe COVID-19 requires respiratory management with mechanical ventilation and an extended period of treatment. Prolonged infectious virus shedding is a concern in severe COVID-19 cases, but few reports have examined the duration of infectious virus shedding. Therefore, we investigated the duration of infectious virus shedding in patients transferred to Hiroshima University Hospital with severe COVID-19 requiring mechanical ventilation. MethodsNasopharyngeal swab specimens were collected and analyzed using both viral culture and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) tests between December 2020 and February 2021. ResultsOf the 23 patients tested, the proportions of those with positive test results at first specimen collection (the median number of days to first specimen collection after symptom onset was 10) on RT-qPCR and viral culture tests were 95·7% and 30·4%, respectively. All six patients with positive viral culture test results who were followed-up tested negative 24 days after symptom onset but remained positive on RT-qPCR. Viral loads based on PCR testing did not decrease over time, but those determined via culture tests decreased over time. The longest negative conversion time was observed in a dialysis patient on immunosuppressive drugs. ConclusionsThis study indicated that patients with severe COVID-19 remain culture positive for ≥ 10 days after symptom onset. Additionally, immunosuppressed patients with severe COVID-19 could consider isolation for ≥ 20 days.

Efficacy and safety of arbidol (umifenovir) in patients with COVID-19: A systematic review and meta-analysis.

ObjectiveTo provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID‐19 treatment.MethodsA literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle–Ottawa scale were used to assess the quality of included studies. Meta‐analysis was performed using RevMan 5.3.ResultsSixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non‐antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR‐PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78–1.14) and Day 14 (RR: 1.10; 95% CI: 0.96–1.25), and PCR negative conversion time (PCR‐NCT; mean difference [MD]: 0.74; 95% CI: −0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06–4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p < .05). Adding arbidol to lopinavir/ritonavir also led to better efficacy in terms of NR‐PCR on Day 7 and PCR‐NCT (p < .05). There was no significant difference between arbidol and chloroquine in primary outcomes (p > .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05).ConclusionThe present meta‐analysis showed no significant benefit of using arbidol compared with non‐antiviral treatment or other therapeutic agents against COVID‐19 disease. High‐quality studies are needed to establish the efficacy and safety of arbidol for COVID‐19.

The correlation between mental health status, sleep quality, and inflammatory markers, virus negative conversion time among patients confirmed with 2019-nCoV during the COVID-19 outbreak in China: An observational study.

The 2019 coronavirus disease (COVID-19) has spread to the whole world. Psychological and sleep problems among confirmed patients have drawn extensive attention which may be highly related to immune function and inflammatory responses of people. The aim of this study is to examine the correlation of mental health status, sleep quality, and inflammatory markers, virus negative conversion time (NCT) among confirmed patients during the COVID-19 outbreak.A cross-sectional survey was conducted in this study. Data from 66 patients assessed with demographic information, anxious symptom, depressive symptom, stress, and sleep quality were collected using a smartphone-based questionnaire platform and then clinical characteristics and laboratory indicators were collected using case review.Nearly 30% of the participants reported depression, anxiety, perceived pressure, and poor sleep quality. Compared with the group without depression, neutrophil count, and ratio of neutrophil count to lymphocyte count (NLR) in the depression disorder group were increased (P = .028, 0.043). There was also a significant difference in NLR and NCT between the anxiety group and the non-anxiety group (P = .021, .024). Similarly, compared with the good sleep quality group, NLR in the poor sleep quality group was increased (P = .011). Correlation analysis indicated that Self-Rating Depression Scale score was positively related to neutrophil count and NLR (r = 0.366, 0.330, P = .016, .031). The total score of Pittsburgh Sleep Quality Index (PSQI) was negatively related to lymphocyte count (r = −0.317, P = .049), and the sleep disturbance as 1 of the 7 dimensions of PSQI scale was positively correlated with NCT and NLR (r = 0.370, 0.340, P = .020, .034).In our study, confirmed patients were prone to have psychological and sleep problems. The level of inflammation in patients with psychological and sleep problems was higher than that in patients without corresponding problems. The inflammatory level increased with the increase of Self-Rating Depression Scale score, and the lymphocyte count decreased with the increase of the PSQI score. NCT was prolonged in the anxiety group and sleep disturbance was positively correlated with NCT.

He-Jie-Shen-Shi Decoction as an Adjuvant Therapy on Severe Coronavirus Disease 2019: A Retrospective Cohort and Potential Mechanistic Study.

Combination therapy using Western and traditional Chinese medicines has shown notable effects on coronavirus disease 2019 (COVID-19). The He-Jie-Shen-Shi decoction (HJSS), composed of Bupleurum chinense DC., Scutellaria baicalensis Georgi, Pinellia ternata (Thunb.) Makino, Glycyrrhiza uralensis Fisch. ex DC., and nine other herbs, has been used to treat severe COVID-19 in clinical practice. The aim of this study was to compare the clinical efficacies of HJSS combination therapy and Western monotherapy against severe COVID-19 and to study the potential action mechanism of HJSS. From February 2020 to March 2020, 81 patients with severe COVID-19 in Wuhan Tongji Hospital were selected for retrospective cohort study. Network pharmacology was conducted to predict the possible mechanism of HJSS on COVID-19-related acute respiratory distress syndrome (ARDS). Targets of active components in HJSS were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases. The targets of COVID-19 and ARDS were obtained from GeneCards and Online Mendelian Inheritance in Man databases. The key targets of HJSS in COVID-19 and ARDS were obtained based on the protein–protein interaction network (PPI). Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) was conducted to predict the pathways related to the targets of HJSS in COVID-19 and ARDS. A “herb-ingredient-target-pathway” network was established using Cytoscape 3.2.7. Results showed that the duration of the negative conversion time of nucleic acid was shorter in patients who received HJSS combination therapy. HJSS combination therapy also relieved fever in patients with severe COVID-19. Network pharmacology analysis identified interleukin (IL) 6, tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), catalase (CAT), mitogen-activated protein kinase (MAPK) 1, tumor protein p53 (TP53), CC-chemokine ligand (CCL2), MAPK3, prostaglandin-endoperoxide synthase 2 (PTGS2), and IL1B as the key targets of HJSS in COVID-19-related ARDS. KEGG analysis suggested that HJSS improved COVID-19-related ARDS by regulating hypoxia-inducible factor (HIF)-1, NOD-like receptor, TNF, T cell receptor, sphingolipid, PI3K-Akt, toll-like receptor, VEGF, FoxO, and MAPK signaling pathways. In conclusion, HJSS can be used as an adjuvant therapy on severe COVID-19. The therapeutic mechanisms may be involved in inhibiting viral replication, inflammatory response, and oxidative stress and alleviating lung injury. Further studies are required to confirm its clinical efficacies and action mechanisms.

Cash Conversion Cycle of food and beverage Product industry

Working capital is significant because of the effects it has on profitability and value. The conventional relationship between the cash conversion cycle and firm profitability is that reducing the cash conversion cycle improves firm profitability. Shortening the cash conversion time, on the other hand, can hurt the firm's operations and reduce profitability. This may occur when a firm takes steps to shorten the inventory conversion time; when a firm reduces the receivable settlement period, a firm could lose its good credit customers; and when a firm lengthens the payable deferral period, a firm may damage its own credit credibility. Identifying optimum levels of inventory, receivables, and payables where net keeping and opportunity costs are reduced and recalculating the cash turnover time based on these optimal stages, on the other hand, gives more full and precise insights into the performance of working capital management. According to the findings, the chosen firms have a poor average return on asset and return on equity, as well as a slightly negative cash conversion time. After adjusting for heteroskedasticity of data to minimise the effects of outliers, regression results revealed that cash conversion cycle has a significantly positive association with both return on assets and equity, indicating that it is not always necessary that the lower the cash conversion cycle, the greater the profitability measured through return on assets and equity. If the company will sell the goods and recover the receivables before paying the payables, the case would be somewhat different.