Communication Pattern Changes Along With Declined IGF1 of Immune Cells in COVID-19 Patients During Disease Progression

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19) pandemic, represents a global crisis. Most patients developed mild/moderate symptoms, and the status of immune system varied in acute and regulatory stages. The crosstalk between immune cells and the dynamic changes of immune cell contact is rarely described. Here, we analyzed the features of immune response of paired peripheral blood mononuclear cell (PBMC) samples from the same patients during acute and regulatory stages. Consistent with previous reports, both myeloid and T cells turned less inflammatory and less activated at recovery phase. Additionally, the communication patterns of myeloid-T cell and T-B cell are obviously changed. The crosstalk analysis reveals that typical inflammatory cytokines and several chemokines are tightly correlated with the recovery of COVID-19. Intriguingly, the signal transduction of metabolic factor insulin-like growth factor 1 (IGF1) is altered at recovery phase. Furthermore, we confirmed that the serum levels of IGF1 and several inflammatory cytokines are apparently dampened after the negative conversion of SARS-CoV-2 RNA. Thus, these results reveal several potential detection and therapeutic targets that might be used for COVID-19 recovery.

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.

Functions of Traditional Chinese Medicine Combined with Recombinant Human Interferon α2b in Cervical Intraepithelial Neoplasias Patients

Cervical cancer is a common malignant neoplasm in women, and its incidence is increasing year by year. This study explored the effects of traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients. 178 cervical intraepithelial neoplasias (CIN) combined with high-risk HPV-positive patients from June 2017 to August 2020 were divided into the study group (n = 89 cases) and the control group (n = 89 cases) by the random number table method. Patients in the control group were treated with recombinant human interferon α2b, and the study group was treated with traditional Chinese medicine (TCM) on the basis of the control group. After treatment, the recurrence rate in the study group was significantly decreased while the human papillomavirus (HPV) negative conversion rate was significantly increased. 3 months after treatment, the TCM symptom scores in the study group were lower than in the control group. Moreover, serum levels of inflammatory factors decreased in both groups, and the decrease was more significant in the study group. After treatment, the ultrasound parameters were significantly decreased in the study group than in the control group. In conclusion, traditional Chinese medicine combined with recombinant human interferon α2b in cervical cancer patients could effectively improve the negative conversion rate of HPV infection, the level of inflammatory factors, reduce the degree of cervical erosion, and enhance the immunity of patients with high safety and significantly improve the quality of life.

Efficacy of chloroquine and hydroxychloroquine for the treatment of hospitalized COVID-19 patients: a meta-analysis

Aims: To evaluate the efficacy and safety of hydroxychloroquine/chloroquine, with or without azithromycin, in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in a random-effects meta-analysis. Primary outcomes included time to negative conversion of SARS-CoV-2 tests, length of stay, mortality, incidence of mechanical ventilation, time to normalization of body temperature, incidence of adverse events and incidence of QT prolongations. Results: Fifty-one studies (n = 61,221) were included. Hydroxychloroquine/chloroquine showed no efficacy in all primary efficacy outcomes, but was associated with increased odds of QT prolongations. Conclusion: Due to a lack of efficacy and increased odds of cardiac adverse events, hydroxychloroquine/chloroquine should not be used for treating hospitalized COVID-19 patients.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Effectiveness of a case management model in newly treated smear-positive pulmonary tuberculosis patients

Introduction: To investigate the effectiveness of the case management mode on the application of smear-positive pulmonary tuberculosis patients. Methodology: This was a randomized control trial. A total of 70 newly diagnosed smear-positive pulmonary tuberculosis patients were recruited and been randomly divided into experimental group and control group, with 35 participants in each group. In the experimental group, patients received the tuberculosis case management mode based on the conventional management mode. In the control group, patients received the routine management mode. We compared the knowledge, attitude, and practice score; sputum-negative conversion rate, effective imaging rate of the two groups at the time of initial admission, discharge, and one month after discharge. Results: The results showed that there was no significant difference in baseline data between the two groups (p > 0.05); at the time of discharge and one month after discharge, the knowledge, belief, behavior, sputum-negative conversion rate, and imaging examination effective rate of the experimental group were higher than those of the control group (p < 0.05). Conclusions: The case management mode can improve the knowledge, attitude, and practice level; sputum-negative conversion rate; and imaging efficiency of newly treated smear-positive pulmonary tuberculosis patients.

Short Observation Period and Aggressive Discharge of Patients With Head Injury and Serial CT Scans

Background: Many patients undergo two head computed tomography (CT) scans after mild traumatic brain injury (TBI). Radiographic progression without clinical deterioration does not usually alter management. Evidence-based guidelines offer potential for limited repeat imaging and safe discharge. This study characterizes patients who had two head CTs in the Emergency Department (ED), determines the change between initial and repeat CTs, and describes timing of repeat scans. Methods: This retrospective series includes all patients with head CTs during the same ED visit at an urban trauma center between May 1st, 2016 and April 30th, 2018. Radiographic interpretation was coded as positive, negative, or equivocal. Results: Of 241 subjects, the number of positive, negative, and equivocal initial CT results were 154, 50, and 37, respectively. On repeat CT, 190 (78.8%) interpretations were congruent with the original scan. Out of the 21.2% of repeat scans that diverged from the original read, 14 (5.8%) showed positive to negative conversion, 1 (.4%) showed positive to equivocal conversion, 2 (.88%) showed negative to positive conversion, 20 (8.3%) showed equivocal to negative conversion, and 14 (5.8%) showed equivocal to positive conversion. Average time between scans was 4.4 hours, and median length of stay was 10.2 hours. Conclusions: In this retrospective review, most repeat CT scans had no new findings. A small percentage converted to positive, rarely altering clinical management. This study demonstrates the need for continued prospective research to update clinical guidelines that could reduce admission and serial CT scanning for mild TBI.

Clinical efficacy of thymosin alpha 1 combined with multi-modality chemotherapy and its effects on immune function of patients with pulmonary tuberculosis complicated with diabetes

Objective: To observe the clinical efficacy of thymosin alpha 1 (Tα1) combined with multi-modality chemotherapy in patients with pulmonary tuberculosis (PTB) complicated with diabetes and discuss the effects of such combination therapy on lymphocyte subsets and sputum levels of cytokines. Methods: A total of 120 patients with PTB complicated with diabetes admitted to the Affiliated Hospital of North China University of Science and Technology from January 2017 to January 2018 were included in this study and randomly divided into an experimental group (Tα1 group, n=60) and a control group (n=60). Clinical efficacy and adverse drug reactions were observed and compared between the two groups. Blood samples were collected for lymphocyte (NK cell and T cell subsets) levels by flow cytometry, and sputum samples were collected for cytokine (IL-2, IFN-γ, IL-4 and TNF-α) levels by ELISA. Results: Two groups showed no statistically significant difference in sputum culture-negative conversion rate, chest lesion absorption rate, and cavity closure rate (P>0.05) after 6 months of treatment. However, after 12 months, the sputum culture-negative conversion rate, chest lesion absorption rate, and cavity closure rate in the Tα1 group increased compared with the control group, and the differences were statistically significant (P<0.05). There was a significant increase in CD3+, CD4+, NK-cells lymphocytes after six months in the Tα1 group than in the control group, whereas the CD8+, Th17, Treg lymphocytes in the Tα1 group were substantially lower than in the control group, with the differences showing statistical significance (P<0.05, respectively). After six months of treatment, the sputum supernatant levels of interleukin-4 (IL-4) and tumor necrosis factor α (TNF-α) in the Tα1 group were lower than in the control group, whereas the sputum supernatant levels of interleukin-2 (IL-2) and interferon gamma (IFN-γ) in the Tα1 group were higher than in the control group, and the differences were statistically significant (P<0.05, respectively). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Tα1 combined with multi-modality chemotherapy has a visible curative effect on PTB patients with diabetes as it can regulate immune function and reduce the levels of inflammatory cytokines. As a safe combination therapy, it seems promising for further use in clinical practice. doi: https://doi.org/10.12669/pjms.38.1.4419 How to cite this:Wu L, Luo P, Tian Y, Chen L, Zhang Y. Clinical efficacy of thymosin alpha 1 combined with multi-modality chemotherapy and its effects on immune function of patients with pulmonary tuberculosis complicated with diabetes. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4419 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Antiviral Therapy with Entecavir following Antituberculosis Therapy Alleviates Liver Injury and Restores Innate Immunity in Tuberculosis Patients Coinfected with Hepatitis B Virus

Objective. Coinfection of tuberculosis (TB) and viral hepatitis may increase the risk of antituberculosis treatment-induced hepatotoxicity, which is regarded as a common cause of termination of the first-line antituberculosis drugs. The study aimed at investigating the protective effects of antiviral therapy on the liver and innate immunity in patients with TB-HBV coinfection. Methods. A total of 100 patients with TB-HBV coinfection were recruited and split into antituberculosis and antiviral groups, 50 per group, according to odd or even date of hospital admission from December 2019 to October 2020. The patients in the anti-TB group received antituberculosis therapy, and those in the antiviral group received antiviral therapy. The clinical effectiveness; HBV-DNA negative conversion rate; liver function assessment involving alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL); immune function evaluation including CD4+, CD8+, CD4+/CD8+, and CD3+ T cells; inflammatory cytokines containing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ); and intestinal microflora including bifidobacterium, lactobacillus, enterobacterium, enterococcus, and clostridium were main outcome measures after treatment. Results. It was found that the total response rate in the antiviral group was significantly higher than the anti-TB group after treatment (χ2 = 3.157, P = 0.017 ). There was a significant difference in HBV-DNA negative conversion rates between the antiviral group and anti-TB group (82% vs. 58%, χ2 = 6.384, P = 0.001 ). The ALT, AST, and TBIL in the two groups were all increased after treatment ( P < 0.05 ), but the antiviral group indicated a rise of the above indices compared to the anti-TB group ( P < 0.05 ). The two groups showed a rise on the concentration of CD3+, CD4+, and CD4+/CD8+ T cells and a decline on the CD8+ T cells after treatment ( P < 0.05 ), but these changes in the antiviral group were more evident to those in the anti-TB group ( P < 0.05 ). There was an increase on the IFN-γ level and decrease on the TNF-α and IL-6 levels in both groups after treatment ( P < 0.05 ), but the antiviral group revealed a higher level of IFN-γ with lower levels of TNF-α and IL-6 compared to the anti-TB group ( P < 0.05 ). After treatment, the number of bifidobacteria and lactobacilli was increased, and the number of enterobacteria, enterococci, and clostridium were decreased in the two groups ( P < 0.05 ), while these changes in the antiviral group were more remarkable compared to the anti-TB group ( P < 0.05 ). There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 0.267, P = 0.731 ). Conclusion. Antiviral therapy for tuberculosis-HBV coinfected patients could inhibit HBV replication, providing protection against liver damage, improving innate immunity, and balancing intestinal microflora.

EVALUATION OF EFFECTIVENESS OF AROGYA KASHAYAM-20 IN COVID-19 CASES - A RANDOMIZED CONTROLLED STUDY

Introduction: The characteristic clinical features of Covid-19 disease range between asymptomatic to mild-moderate symptoms. Studies suggest that a large population (80%) presents its asymptomatic or milder form. Remaining 20 percent, owing to severity of the diseases, need hospital-based care. Many treatment protocols and strategies have been promoted and recommended by authorities including WHO, but nothing has actually been finalized till date. The present study was planned to evaluate the effectiveness of an Ayurvedic formulation viz. Arogya Kashayam-20 in the hospitalized cases of Covid-19.Aim: To evaluate the effectiveness of Arogya Kashayam-20 in the cases of COVID-19 particularly the negative conversion of RTPCR in 10 days duration.Material and Methods: This was a randomized controlled trial conducted at COVID-19 Care Center, Pt. Khushilal Sharma Government Ayurveda College &amp; Institute, Bhopal, Madhya Pradesh with a sample size of 112 participants, aged between 16 to 60 years of either sex. Participants were divided in two groups viz. group A and B. Both the groups received Hydroxychloroquine (HCQ), vitamin C and Zinc as per the prevailing ICMR guidelines and group 'A' received additionally Arogya Kashayam-20 for 10 days. Outcome measure of the study was to see the negative conversion RT-PCR test after intervention period of 10 days. CTRI Registration: CTRI/2020/06/026221. Results: Among the 60 cases registered in study group (group A), 51 cases (85.00%) were reported with negative RTPCR on 10th day. Out of 52 cases registered in control group (group B); 39 cases (75.00%) were tested negative RTPCR on 10th day. In both the groups all the cases were discharged asymptomatically on 10th day as per the prevailing ICMR guidelines. No ADR/AE observed during the intervention period.Conclusion: The study observes that the add on intervention group has a better outcome in terms of RT-PCR negative reports after 10 days comparing to the control group.