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.

Oral-Gut Microbiome Analysis in Patients With Metabolic-Associated Fatty Liver Disease Having Different Tongue Image Feature.

Objective: The objective of this study was to identify the biological correlation between the tongue coating color and oral and gut micro-characteristics in metabolic-associated fatty liver disease (MAFLD) patients. Method: The characteristics of the tongue coating were examined using an automatic tongue diagnosis system. Tongue coating and stool samples were collected from 38 MAFLD patients, and 16S rDNA full-length assembly sequencing technology (16S-FAST) was used for bioinformatic analysis. Results: Twenty-two and 16 subjects were included in two distinct clusters according to the white/yellow color of the tongue coating, which was assessed by the L*a*b* values of the image. Upon analyzing the microorganisms in the tongue coating, 66 and 62 pathognomonic bacterial genera were found in the White and Yellow Coating Groups, respectively. The abundance of Stomatobaculumis positively correlated with the a* values of the tongue coating in the White Coating Group, while Fusobacterium, Leptotrichia, and Tannerella abundance was significantly correlated with the b* values in the Yellow Coating Group. Function prediction mainly showed the involvement of protein families related to BRITE hierarchies and metabolism. The MHR (MONO%/high-density lipoprotein cholesterol) of the Yellow Coating Group was higher than that of the White Coating Group. Conclusion: In MAFLD patients, lower a* values and higher b* values are indicators of a yellow tongue coating. There were also significant differences in the flora of different tongue coatings, with corresponding changes in the intestinal flora, indicating a correlation between carbohydrate metabolism disorders and inflammation in the oral microbiome.

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.

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.