COVID-19 in pediatrics: Genetic susceptibility.

The uptick in SARS-CoV-2 infection has resulted in a worldwide COVID-19 pandemic, which has created troublesome health and economic problems. We performed case-control meta-analyses in both African and European ethnicity COVID-19 disease cases based on laboratory test and phenotypic criteria. The cases had laboratory-confirmed SARS-CoV-2 infection. We uniquely investigated COVID infection genetics in a pediatric population. Our cohort has a large African ancestry component, also unique to our study. We tested for genetic variant association in 498 cases vs. 1,533 controls of African ancestry and 271 cases vs. 855 controls of European ancestry. We acknowledge that the sample size is relatively small, owing to the low prevalence of COVID infection among pediatric individuals. COVID-19 cases averaged 13 years of age. Pediatric genetic studies enhance the ability to detect genetic associations with a limited possible environment impact. Our findings support the notion that some genetic variants, most notably at the SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1 loci, play a role in COVID-19 infection susceptibility. The pediatric cohort also shows nominal replication of previously reported adult study results: CCR9, CXCR6, FYCO1, LZTFL1, TDGF1, CCR1, CCR2, CCR3, CCR5, MAPT-AS1, and IFNAR2 gene variants. Reviewing the biological roles of genes implicated here, NFIA looks to be the most interesting as it binds to a palindromic sequence observed in both viral and cellular promoters and in the adenovirus type 2 origin of replication.

CCR5 Receptor Occupancy Analysis Reveals Increased Peripheral Blood CCR5+CD4+ T Cells Following Treatment With the Anti-CCR5 Antibody Leronlimab.

CCR5 plays a central role in infectious disease, host defense, and cancer progression, thereby making it an ideal target for therapeutic development. Notably, CCR5 is the major HIV entry co-receptor, where its surface density correlates with HIV plasma viremia. The level of CCR5 receptor occupancy (RO) achieved by a CCR5-targeting therapeutic is therefore a critical predictor of its efficacy. However, current methods to measure CCR5 RO lack sensitivity, resulting in high background and overcalculation. Here, we report on two independent, flow cytometric methods of calculating CCR5 RO using the anti-CCR5 antibody, Leronlimab. We show that both methods led to comparable CCR5 RO values, with low background on untreated CCR5+CD4+ T cells and sensitive measurements of occupancy on both blood and tissue-resident CD4+ T cells that correlated longitudinally with plasma concentrations in Leronlimab-treated macaques. Using these assays, we found that Leronlimab stabilized cell surface CCR5, leading to an increase in the levels of circulating and tissue-resident CCR5+CD4+ T cells in vivo in Leronlimab-treated macaques. Weekly Leronlimab treatment in a chronically SIV-infected macaque led to increased CCR5+CD4+ T cells levels and fully suppressed plasma viremia, both concomitant with full CCR5 RO on peripheral blood CD4+ T cells, demonstrating that CCR5+CD4+ T cells were protected from viral replication by Leronlimab binding. Finally, we extended these results to Leronlimab-treated humans and found that weekly 700 mg Leronlimab led to complete CCR5 RO on peripheral blood CD4+ T cells and a statistically significant increase in CCR5+CD4+ T cells in peripheral blood. Collectively, these results establish two RO calculation methods for longitudinal monitoring of anti-CCR5 therapeutic antibody blockade efficacy in both macaques and humans, demonstrate that CCR5+CD4+ T cell levels temporarily increase with Leronlimab treatment, and facilitate future detailed investigations into the immunological impacts of CCR5 inhibition in multiple pathophysiological processes.

[Moxibustion on mental disorder in close contacts of coronavirus disease 2019: a randomized controlled trial].

OBJECTIVE: To observe the effect of moxibustion combined with Daiwenjiu plaster on mental disorder and self rating symptoms in close contacts of coronavirus disease 2019 (COVID-19) during quarantine. METHODS: A total of 240 close contacts of COVID-19 were randomized into an observation group (120 cases, 18 cases dropped off) and a control group (120 cases, 58 cases dropped off). Conventional observation was adopted in the control group. Moxibustion combined with Daiwenjiu plaster was given in the observation group, moxibustion was applied at Zusanli (ST 36), Hegu (LI 4) and Shenque (CV 8), 10 min each acupoint, once a day; Daiwenjiu plaster was applied at Dazhui (GV 14) and Feishu (BL 13) for 3 to 6 h each time, once every 2 days, the treatment was required for 2 weeks. Before and after treatment and in the follow-up of 2 weeks after treatment, self-reporting questionnaire 20 (SRQ-20), self-rating anxiety scale (SAS) scores and self rating symptoms were evaluated in the two groups. RESULTS: In the follow-up, SRQ-20 score was decreased compared before treatment (P<0.01), SAS score was decreased compared before and after treatment (P<0.01, P<0.05) in the observation group. After treatment and in the follow-up, SRQ-20 scores in the observation group were lower than those in the control group (P<0.05, P<0.01). After treatment, the case proportion of fatigue in the observation group was higher than that in the control group (P<0.05). In the follow-up, the case proportion of tension was lower than that in the control group (P<0.05). CONCLUSION: Moxibustion combined with Daiwenjiu plaster can effectively improve the mental disorder in close contacts of COVID-19.

[Analysis on the theory and clinical ideas of acupuncture and moxibustion for the prevention and treatment of coronavirus disease 2019].

Acupuncture and moxibustion has a wealth of experience in the prevention and control of epidemic disease since ancient times, which was used for all kinds of acute infectious diseases in modern times and its efficacy has been clearly and reliably reported. This article proposes the theoretical feasibility and reliability of acupuncture and moxibustion interventional prevention and treatment by discussing the recognition of coronavirus disease 2019 (COVID-19) from the perspective of acupuncture and moxibustion. The unique "acupuncture and moxibustion program" for COVID-19 is presented including treatment in different stages, selecting acupoints by distinguishing meridians, applying needle technique by various methods. The article also proposes a new understanding of acupuncture and moxibustion at related acupoints on the surface of the body that can directly affect the "moyuan" to treat the disease.

Carry forward advantages of traditional medicines in prevention and control of outbreak of COVID-19 pandemic.

Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper mainly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10 + 3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation.

Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. OBJECTIVE: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. RESULTS AND LIMITATIONS: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. CONCLUSIONS: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. PATIENT SUMMARY: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.

[Significance and operation mode of moxibustion intervention for the group under quarantine after close contact with COVID-19].

On the base of the idea of traditional Chinese medicine as "disease prevention", the mode and the protocol of the moxibustion intervention for the group under quarantine after close contact with coronavirus disease 2019 (COVID-19) were explored. The group under quarantine after close contact with COVID-19 was taken as the subjects. By the non-contact physician-patient communication network platform co-developed by China Association of Acupuncture-Moxibustion, Hunan Provincial Association of Acupuncture-Moxibustion, Data Center of China Academy of Chinese Medical Sciences and Yuge Medicine Company, an exploratory randomized controlled trial was designed. A total of 100 cases were included and randomized into a moxibustion group and a conventional intervention group, 50 cases in each one. In the moxibustion group, moxibustion intervention was used. In the conventional intervention group, the conventional observation was adopted without moxibusiton intervention applied. The outcomes included the symptoms changes, e.g. anxiety, emotional disturbance, fatigue, headache and diarrhea, as well as whether quarantine release and the case confirmed or not, etc. The results were evaluated before intervention, in 14 days of intervention and 2 weeks after intervention separately. In this research, on the base of internet plus technology and with the internet communication platform adopted, through mobile phone WeChat App, it was to implement the subject screen, the random allocation and the instruction of moxibustion intervention as well as the quality control of patient's diary and data collection. It is anticipated that the significance and the implementation mode of moxibustion intervention can be assessed preliminarily for the group under quarantine after close contact with COVID-19.

Pay attention to situation of SARS-CoV-2 and TCM advantages in treatment of novel coronavirus infection.

Since the outbreak of the new coronavirus epidemic, novel coronavirus has infected nearly 100,000 people in more than 110 countries. How to face this new coronavirus epidemic outbreak is an important issue. Basic reproduction number (R0) is an important parameter in epidemiology; The basic reproduction number of an infection can be thought of as the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. Epidemiology dynamics is a mathematical model based on a susceptibility-infection-recovery epidemic model. Researchers analyzed the epidemiological benefits of different transmission rates for the establishment of effective strategy in prevention and control strategies for epidemic infectious diseases. In this review, the early use of TCM for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have wide application in treating infectious and non-infectious diseases. The TCM theoretical system of treating epidemic diseases with TCM and the treatment scheme of integrated Chinese and Western medicine have proved their effectiveness in clinical practice. TCM can cure COVID-19 pneumonia, and also shows that the role of TCM in blocking the progress of COVID-19 pneumonia.