Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Long-term outcomes of COVID-19 convalescents: An 18.5-month longitudinal study in Wuhan.

OBJECTIVES: This study aimed to describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among COVID-19 survivors. METHODS: We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (interquartile range [IQR]: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We, in addition, explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. RESULTS: We observed continuous improvement of sequelae symptoms, lung function, chest computed tomography (CT), 6-minute walk test, and the Borg dyspnea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of participants at 18.5 months, respectively. Anxiety and depression disorders were alleviated for the convalescents, although depression status was sustained for a longer duration. CONCLUSIONS: Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

Case report: Treatment with Pien-Tze-Huang for prolonged positive SARS-CoV-2 test results in COVID-19 patients: A report of five cases.

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world since December 2019, becoming a global pandemic. Atypical cases of COVID-19, manifesting as prolonged positive SARS-CoV-2 test results during the convalescence period, have been encountered. These cases increase the difficulty of COVID-19 prevention and treatment. Here, we report five cases of COVID-19 patients who demonstrated prolonged positive SARS-CoV-2 tests after regular traditional Chinese medicine and western medicine treatments. After administration of Pien-Tze-Huang and cessation of previous treatments, SARS-CoV-2 tests results of the patients turned and remained negative. We believe the finding will contribute to a better understanding of atypical COVID-19 cases and hope to offer a potential therapy. Since this is a preliminary case series, larger-scale clinical trials are warranted.

Case report: Treatment with Pien-Tze-Huang for prolonged positive SARS-CoV-2 test results in COVID-19 patients: A report of five cases

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world since December 2019, becoming a global pandemic. Atypical cases of COVID-19, manifesting as prolonged positive SARS-CoV-2 test results during the convalescence period, have been encountered. These cases increase the difficulty of COVID-19 prevention and treatment. Here, we report five cases of COVID-19 patients who demonstrated prolonged positive SARS-CoV-2 tests after regular traditional Chinese medicine and western medicine treatments. After administration of Pien-Tze-Huang and cessation of previous treatments, SARS-CoV-2 tests results of the patients turned and remained negative. We believe the finding will contribute to a better understanding of atypical COVID-19 cases and hope to offer a potential therapy. Since this is a preliminary case series, larger-scale clinical trials are warranted.

The KIR2DL2/HLA-C1C1 Gene Pairing Is Associated With an Increased Risk of SARS-CoV-2 Infection.

SARS-CoV-2 is the causative agent for the global COVID-19 pandemic; however, the interaction between virus and host is not well characterized. Natural killer cells play a key role in the early phase of the antiviral response, and their primary functions are dependent on signaling through the killer cell immunoglobulin-like receptor (KIR). This study measured the association between KIR/HLA class I ligand pairings and the occurrence and development of COVID-19. DNA of blood samples from 257 COVID-19 patients were extracted and used to detect KIR and HLA-C gene frequencies using single strain sequence-specific primer (SSP) PCR. The frequency of these genes was compared among 158 individuals with mild COVID-19, 99 with severe disease, and 98 healthy controls. The frequencies of KIR2DL2 (P=0.04, OR=1.707), KIR2DS3 (P=0.047, OR=1.679), HLA-C1C1 (P<0.001, OR=3.074) and the KIR2DL2/HLA-C1C1 pairing (P=0.038, OR=2.126) were significantly higher in the COVID-19 patients than the healthy controls. At the same time, the frequency of KIR2DL3+KIR2DL2-/HLA-C1+Others+ was lower in COVID-19 patients than in healthy individuals (P=0.004, OR=0.477). These results suggest that the protective effect of KIR2DL3 against SARS-CoV-2 infection is related to the absence of the KIR2DL2 gene. This study found no correlation between the frequencies of these genes and COVID-19 pathogenesis. Global statistical analysis revealed that the incidence of COVID-19 infection was higher in geographic regions with a high frequency of KIR2DL2. Together these results suggest that the KIR2DL2/HLA-C1C1 gene pairing may be a risk factor for SARS-CoV-2 infection.

Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance.

Asymptomatic infection with SARS-CoV-2 is a major concern in the control of the COVID-19 pandemic. Many questions concerning asymptomatic infection remain to be answered, for example, what are the differences in infectivity and the immune response between asymptomatic and symptomatic infections? In this study, based on a cohort established by the Wuchang District Health Bureau of Wuhan in the early stage of the COVID-19 pandemic in Wuhan in 2019, we conducted a comprehensive analysis of the clinical, virological, immunological, and epidemiological data of asymptomatic infections. The major findings of this study included: 1) the asymptomatic cohort enrolled this study exhibited low-grade but recurrent activity of viral replication; 2) despite a lack of overt clinical symptoms, asymptomatic infections exhibited ongoing innate and adaptive immune responses; 3) however, the immune response from asymptomatic infections was not activated adequately, which may lead to delayed viral clearance. Given the fragile equilibrium between viral infection and host immunity, and the delayed viral clearance in asymptomatic individuals, close viral monitoring should be scheduled, and therapeutic intervention may be needed.

Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases

Gut microbiota composition is suggested to associate with coronavirus disease 2019 (COVID-19) severity, but the impact of gut microbiota on health outcomes is largely unclear. We recruited 81 individuals from Wuhan, China, including 13 asymptomatic infection cases (Group A), 24 COVID-19 convalescents with adverse outcomes (Group C), 31 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-positive cases (Group D), and 13 non-COVID-19 healthy controls (Group H). The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid (SCFA)-producing species than Group C. Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production. The abundance of SCFA-producing species was negatively correlated, while Escherichia coli was positively correlated with adverse outcomes. All three groups (A, C, and D) were enriched with the mucus-degrading species Akkermansia muciniphila, but decreased with Bacteroides-encoded carbohydrate-active enzymes. The pathways of vitamin B6 metabolic and folate biosynthesis were decreased, while selenocompound metabolism was increased in the three groups. Specifically, the secondary bile acid (BA) metabolic pathway was enriched in Group A. Antibiotic resistance genes were common among the three groups. Conclusively, the gut microbiota was related to the health outcomes of COVID-19. Dietary supplementations (SCFAs, BA, selenium, folate, vitamin B6) may be beneficial to COVID-19 patients.

Efficacy of Jinhua Qinggan Granules Combined With Western Medicine in the Treatment of Confirmed and Suspected COVID-19: A Randomized Controlled Trial.

Objective: To conduct a randomized controlled clinical trial to evaluate the clinical efficacy and prognostic value of Jinhua Qinggan granules in patients with confirmed and suspected coronavirus disease 2019 (COVID-19). Methods: A total of 123 suspected and confirmed COVID-19 patients participated in this clinical trial and were randomly divided into Jinhua and Western medicine groups. For 14 days, the Jinhua group was treated with Jinhua Qinggan granules and antiviral drugs, and the Western medicine group was treated with antiviral drugs alone. We collected information on clinical symptoms, disease aggravation rates, and negative conversion rates of nucleic acids in patients, and observed the effects of anti-infective drugs. Results: There was no significant difference in symptom improvement rates between the two groups, both confirmed and suspected patients (P > 0.05). Both treatments relieved symptoms such as fever, fatigue, and diarrhea. However, the Jinhua treatment was superior in relieving fever and poor appetite. Anti-infective drug use rates were significantly lower in the Jinhua group than in the control group. Conclusion: Jinhua Qinggan granules combined with Western medicine could relieve the clinical symptoms of fever and poor appetite in COVID-19 patients, reduce the use of antibiotics to a certain extent. Clinical Trial Registration: The registration number at China Clinical Trial Registry is ChiCTR2000029601.

Trans-ethnic genome-wide association study of severe COVID-19.

COVID-19 has caused numerous infections with diverse clinical symptoms. To identify human genetic variants contributing to the clinical development of COVID-19, we genotyped 1457 (598/859 with severe/mild symptoms) and sequenced 1141 (severe/mild: 474/667) patients of Chinese ancestry. We further incorporated 1401 genotyped and 948 sequenced ancestry-matched population controls, and tested genome-wide association on 1072 severe cases versus 3875 mild or population controls, followed by trans-ethnic meta-analysis with summary statistics of 3199 hospitalized cases and 897,488 population controls from the COVID-19 Host Genetics Initiative. We identified three significant signals outside the well-established 3p21.31 locus: an intronic variant in FOXP4-AS1 (rs1853837, odds ratio OR = 1.28, P = 2.51 × 10-10, allele frequencies in Chinese/European AF = 0.345/0.105), a frameshift insertion in ABO (rs8176719, OR = 1.19, P = 8.98 × 10-9, AF = 0.422/0.395) and a Chinese-specific intronic variant in MEF2B (rs74490654, OR = 8.73, P = 1.22 × 10-8, AF = 0.004/0). These findings highlight an important role of the adaptive immunity and the ABO blood-group system in protection from developing severe COVID-19.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Positive RT-PCR Test Results in 420 Patients Recovered From COVID-19 in Wuhan: An Observational Study.

OBJECTIVE: During the follow-up of patients recovered from coronavirus disease 2019 (COVID-19) in the quarantine and observation period, some of the cured patients showed positive results again. The recurrent positive RT-PCR test results drew widespread concern. We observed a certain number of cured COVID-19 patients with positive RT-PCR test results and try to analyze the factors that caused the phenomenon. METHODS: We conducted an observational study in COVID-19 patients discharged from 6 rehabilitation stations in Wuhan, China. All observed subjects met the criteria for hospital discharge and were in quarantine. Data regarding age, sex, body mass index (BMI), course of disease, comorbidity, smoking status and alcohol consumption, symptoms in and out of quarantine, and intervention were collected from the subjects' medical records and descriptively analyzed. The main outcome of this study was the RT-PCR test result of the observed subjects at the end of quarantine (negative or positive). Logistic regression analysis was used to identify the influencing factors related to recurrent positive RT-PCR test results. RESULTS: In this observational study, 420 observed subjects recovered from COVID-19 were included. The median age was 56 years, 63.6% of the subjects were above 50 years old, and 50.7% (213/420) were female. The most common comorbidities were hypertension [26.4% (111/420)], hyperlipidemia [10.7% (45/420)], and diabetes [10.5% (44/420)]. 54.8% (230/420) manifested one or more symptoms at the beginning of the observation period, the most common symptoms were cough [27.6% (116/420)], shortness of breath 23.8% (100/420)], and fatigue [16.2% (68/420)], with fever rare [2.6% (11/420)]. A total of 325 subjects were exposed to comprehensive intervention; 95 subjects were absence of intervention. The recurrence rate of positive RT-PCR test results with comprehensive intervention was 2.8% (9/325), and that with no intervention was 15.8% (15/95). The results of logistic regression analysis showed that after adjusted for factors such as age, sex, and comorbidity and found out that comprehensive intervention was correlated with the recurrent positive RT-PCR test results. There was appreciably less recurrence in the comprehensive intervention group. CONCLUSIONS: The factors related to positive RT-PCR test results in observed subjects recovered from COVID-19 were age, comorbidity, and comprehensive intervention, among which comprehensive intervention might be a protective factor. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, identifier ChiCTR2000030747.