Thoughts on Coronavirus Disease 2019 Based on JingFang Medicine (Classical Chinese Formula) Solutions for COVID-19

This article aims to provide some thoughts on the prevention and treatment of Coronavirus Disease 2019 (COVID-19) from the perspective of JingFang Medicine (Classical Chinese Formula). It is believed that the vague theoretical understanding of COVID-19 in Traditional Chinese Medicine does not hinder the precise treatment of the disease by following the rule of “With this Zheng, prescribe this Fang.” According to the principle of “Fang-Zheng Correlation” and the knowledge gained from the thousands of years of experience in treating febrile diseases, Xiao Chai Hu Decoction () and its modifications are recommended with the emphasis on individualized treatment. As another form of practicing “Fang-Zheng Correlation,” generalized group treatment should also be paid attention to. Giving considerations to the historical medical data, Jing Fang Bai Du Powder () and Shi Shen Decoction () are recommended for group prevention treatment. Assisting the Zheng (Upright) Qi and using tonic formulas are two entirely different concepts. According to the principle of “Fang-Zheng Correlation,” tonics abuse should be avoided in the prevention of COVID-19, and the using of Huang Qi (Radix Astragali seu Hedysari) should also be very carefully done.

Kinetics of Severity Biomarkers and Immunological Features of Methylprednisolone Therapy for Severe COVID-19 Patients

In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the “core signature” cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The “core signature” cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed “core signature” cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.

Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

Prognostic Factors for COVID-19 Pneumonia Progression to Severe Symptoms Based on Earlier Clinical Features: A Retrospective Analysis.

Approximately 15-20% of COVID-19 patients will develop severe pneumonia, and about 10% of these will die if not properly managed. Earlier discrimination of potentially severe patients basing on routine clinical and laboratory changes and commencement of prophylactical management will not only save lives but also mitigate the otherwise overwhelming healthcare burden. In this retrospective investigation, the clinical and laboratory features were collected from 125 COVID-19 patients who were classified into mild (93 cases) or severe (32 cases) groups according to their clinical outcomes after 3-7 days post-admission. The subsequent analysis with single-factor and multivariate logistic regression methods indicated that 17 factors on admission differed significantly between mild and severe groups but that only comorbidity with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10 mg/L), and lactate dehydrogenase (LDH >250 U/L) were independently associated with the later disease development. Finally, we evaluated their prognostic values with receiver operating characteristic curve (ROC) analysis and found that the above four factors could not confidently predict the occurrence of severe pneumonia individually, though a combination of fast respiratory rate and elevated LDH significantly increased the predictive confidence (AUC = 0.944, sensitivity = 0.941, and specificity = 0.902). A combination consisting of three or four factors could further increase the prognostic value. Additionally, measurable serum viral RNA post-admission independently predicted the severe illness occurrence. In conclusion, a combination of general clinical characteristics and laboratory tests could provide a highly confident prognostic value for identifying potentially severe COVID-19 pneumonia patients.

Application of high-flow nasal cannula oxygen therapy in patients with severe COVID-19

Objective: To investigate the clinical value of high-flow nasal cannula oxygen therapy(HFNC) in patients with severe coronavirus disease 2019 (COVID-19).

Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019.

To describe the epidemiological and clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) in Beijing. To analyze the application of corticosteroids in patients with severe pneumonia. We collected information on demographic characteristics, exposure history, clinical characteristics, corticosteroids use, and outcomes of the 65 confirmed cases of COVID-19 at Fifth Medical Center of PLA General Hospital from Jan 20 to Feb 23, 2020. The final follow-up date observed was April 15th, 2020. The number of patients with mild, general, severe, and critical type were 10 (15.38%), 32 (49.23%), 8 (12.31%), and 15 (23.08%), respectively. The median incubation period was 6 days. Notable outliers were 1 patient at 16 days and 1 patient at 21 days. In lymphocyte subgroup analysis, decreases in total, T, CD4, and CD8 lymphocytes were more common as the disease worsened (All P < 0.05). Methylprednisolone (mPSL) was applied to 31 (47.69%) patients with pneumonia, including 10 (31.25%) general, 8 (100%) severe, and 13 (86.67%) critical patients, respectively. Corticosteroids inhibited Interleukin-6(IL-6) production (P = 0.0215) but did not affect T lymphocyte (P = 0.0796). There was no significant difference between patients using lower dose (≤ 2 mg/kg day) and higher dose (> 2 mg/kg day) mPSL in inhibiting IL-6 production (P = 0.5856). Thirty of 31 patients (96.77%) had stopped mPSL due to improvement of pneumonia. Virus RNA clearance time lengthened with disease progression (P = 0.0001). In general type, there was no significant difference in virus clearance time between patients with (15, 12-19 days) and without (14.5, 11-18 days) (P = 0.7372) mPSL use. Lymphocyte, especially T lymphocyte, in severe and critical patients showed a dramatic decrease. Application of lower dose corticosteroids (≤ 2 mg/kg day) could inhibit IL-6 production (a representative of cytokines) as effectively as a higher dose. Proper use corticosteroids in general type patients did not delay virus clearance.

An increased pretreatment neutrophil-to-lymphocyte ratio predicts severe novel coronavirus-infected pneumonia (preprint)

Objective The aim of this study was to identify early warning signs for severe novel coronavirus-infected pneumonia (COVID-19).Methods We retrospectively analyzed the clinical data of 90 patients with COVID-19 at the Guanggu District of Hubei Women and Children Medical and Healthcare Center comprising 60 mild cases and 30 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory blood test results were compared between the two groups. Logistic regression analysis was performed to identify the independent risk factors that predicted severe COVID-19. The receiver-operating characteristic (ROC) curve of independent risk factors was calculated, and the area under the curve (AUC) was used to evaluate the efficiency of the prediction of severe COVID-19.Results The patients with mild and severe COVID-19 showed significant differences in terms of cancer incidence, age, pretreatment neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) and the serum albumin (ALB) level (P<0.05). The severity of COVID-19 was correlated positively with the comorbidity of cancer, age, NLR, and CRP but was negatively correlated with the ALB level (P<0.05). Multivariate logistic regression analysis showed that the NLR and ALB level were independent risk factors for severe COVID-19 (OR=1.319, 95% CI: 1.043-1.669, P=0.021; OR=0.739, 95% CI: 0.616-0.886, P=0.001), with AUCs of 0.851 and 0.128, respectively. An NLR of 4.939 corresponded to the maximum joint sensitivity and specificity according to the ROC curve (0.700 and 0.917, respectively).Conclusion An increased NLR can serve as an early warning sign of severe COVID-19.

Increased pretreatment C-reactive protein-to-albumin ratio predicts severe coronavirus disease 2019 (preprint)

Objective The aim of this study was to identify early warning signs for severe coronavirus disease 2019 (COVID-19). Methods We retrospectively analysed the clinical data of 90 patients with COVID-19 from Guanggu District of Hubei Women and Children Medical and Healthcare Center, comprising 60 mild cases and 30 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory blood test results were compared between the two groups. The cutoff values were determined by receiver operating characteristic curve analysis. Logistic regression analysis was performed to identify the independent risk factors for severe COVID-19. Results The patients with mild and severe COVID-19 had significant differences in terms of cancer incidence, age, pretreatment neutrophil-to-lymphocyte ratio (NLR), and pretreatment C-reactive protein-to-albumin ratio (CAR) ( P =0.000; P =0.008; P=0.000; P =0.000). The severity of COVID-19 was positively correlated with comorbid cancer, age, NLR, and CAR ( P <0.005). Multivariate logistic regression analysis showed that age, the NLR and the CAR were independent risk factors for severe COVID-19 (OR=1.086, P =0.008; OR=1.512, P =0.007; OR=17.652, P =0.001). Conclusion An increased CAR can serve as an early warning sign of severe COVID-19 in conjunction with the NLR and age.

Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis (preprint)

Background Approximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Methods 125 COVID-19 patients enrolled in this study were classified into mild (93 cases) and severe (32 cases) groups, basing on their 3 to 7-days clinical outcomes. Patients' gender, age, comorbid with underlying diseases, epidemiological history, clinical manifestations, and laboratory tests on admission were collected and subsequently analyzed with single-factor and multivariate logistic regression methods. Finally, we evaluate their prognostic values with the receiver operating characteristic curve (ROC) analysis. Results Seventeen factors on admission differed significantly between mild and severe groups. Next, only four factors, including the comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were found to be independently associated with the later disease development. Prognostic value analysis by ROC indicated that individual factors could not confidently predict the occurrence of severe pneumonia, but that the combination of fast respiratory rate and elevated LDH significantly increase the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). Three- or four-factors combinations, including elevated LDH and fast respiratory rate, further increased the prognostic value. Additionally, measurable serum viral RNA post-admission could independently predict the severe illness occurrence. Conclusions General clinical characteristics and laboratory tests, such as combinations consisting of elevated LDH and fast respiratory rate, and detectable viral RNA in serum post-admission could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients.