Moderate Coronavirus Disease 2019 Patients Research Articles

The Progression of Symptoms in Post COVID-19 Patients: A Multicentre, Prospective, Observational Cohort Study

Background: Although the coronavirus disease 2019 (COVID-19) pandemic is no longer a public health emergency of international concern, 30% of COVID-19 patients still have long-term complaints. A better understanding of the progression of symptoms after COVID-19 is needed to reduce the burden of the post COVID-19 condition. Objective: This study aims to investigate the progression of symptoms, identify patterns of symptom progression, and assess their associations with patient characteristics. Methods: Within the P4O2 COVID-19 study, patients aged 40–65 years were recruited from five Dutch hospitals. At 3–6 and 12–18 months post COVID-19, medical data were collected, and pulmonary function tests were performed. In between, symptoms were assessed monthly with a questionnaire. Latent class mixed modelling was used to identify symptom progression patterns over time, with multinomial logistic regression to examine associations with patient characteristics. Results: Eighty-eight patients (aged 54.4 years, 48.9% males) were included. Three trajectories were identified for fatigue and dyspnoea: decreasing, high persistent, and low persistent. The odds of “decreasing fatigue” was higher for never smokers and participants in the lifestyle intervention and lower for those having a comorbidity. The odds of “decreasing dyspnoea” was higher for moderate COVID-19 patients and lifestyle intervention participants and lower for males, mild COVID-19 patients, and those with a higher age. Conclusions: Three distinct trajectories were identified for fatigue and dyspnoea, delineating patterns of symptom persistence following COVID-19. Sex, age, smoking status, participation in lifestyle interventions and COVID-19 severity were associated with the likelihood of belonging to different trajectories. These findings highlight the heterogeneity of the long-term symptoms experienced by post COVID-19 patients and emphasise the importance of personalised treatment strategies.

Total Antioxidant Status and Oxidative Stress in Patients with COVID-19 Infection.

Oxidative stress (OS) may have a role in the pathogenesis and severity of the coronavirus disease 2019 (COVID-19) disease. The present study was conducted to estimate the association of inflammatory markers, total antioxidant status (TAS), and malondialdehyde (MDA) levels with the severity of the disease and to identify their trends after recovery. Adult patients admitted with moderate or severe COVID-19 were included after obtaining written informed consent from patient or next of kin. Patients who were critically ill, on ventilator, or in sepsis/septic shock were excluded. Levels of inflammatory markers, TAS, and OS as measured by MDA were estimated within 24 hours of admission and reevaluated at 12 weeks following discharge. The mean age of the 40 patients (42.5% females) was 55 ± 15 years. TAS values (in trolox equivalents/L) were significantly reduced in severe compared to moderate COVID-19 patients at admission (7.2 ± 4.19 vs 12.3 ± 5.21). These increased at 12 weeks after discharge. The MDA levels (in nmol/mL) were significantly higher in severe in comparison to moderate disease (7.1 ± 2.68 vs 4.1 ± 1.81). These values showed a downward trend 12 weeks after discharge in severe disease group. Admission levels of interleukin-6 (IL-6), D-dimer, and lactate dehydrogenase (LDH) were statistically higher in severe COVID-19 patients in contrast to moderate disease. Moderate and severe COVID-19 are associated with a state of high OS and a low total antioxidant levels which tend to recover at 3 months following discharge.

The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study.

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65-56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.

Effectiveness of dolutegravir in moderate severity COVID-19 patients: A single-center, randomized, double-blind, placebo-controlled trial

Introduction: Drug repurposing as a low-cost, time-saving, and often less risky strategy has been attractive for the treatment of coronavirus disease 2019 (COVID-19) during the pandemic. This trial aimed to evaluate the effectiveness of dolutegravir, an HIV-1 integrase inhibitor, in admitted patients with moderate COVID-19. Methods: This study was a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy of dolutegravir in adults admitted to a hospital in Ghaemshahr, Mazandaran Province, Iran. Patients aged 18-80 years with early symptoms of moderate COVID-19, which was confirmed based on reverse transcription polymerase chain reaction (RT-PCR) and/or chest computed tomography (CT) scan, were considered to be included in this study. Patients were randomly assigned in a 1:1 ratio to receive 50 mg dolutegravir plus the standard treatment regimen or the same value of placebo plus the standard treatment regimen, daily for 7 days. The standard treatment regimen was remdesivir 200 mg on day 1 followed by 100 mg for five days or until discharge. The primary endpoint was recovery 10 days after the beginning of the study. Results: Between August 22 and October 23, 2021, of 120 patients who were enrolled, 93 patients were randomly assigned to receive 50 mg dolutegravir (n = 46) or the placebo regimen (n = 47). No significant difference was observed between the two intervention groups based on the obtained results including frequency of respiratory modes during the first five days of admission, respiratory rate, and O2 saturation during six time periods. Conclusion: The results showed that in adult patients admitted to the hospital with moderate COVID-19, treatment with dolutegravir was not associated with improvement in clinical recovery. Larger randomized trials are required to provide more robust evidence about the effectiveness of dolutegravir.

Effects of toll-like receptor agonists and SARS-CoV-2 antigens on interferon (IFN) expression by peripheral blood CD3+ T cells from COVID-19 patients

BackgroundSignaling by toll-like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro. Material & methods30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex-matched healthy control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8, and 9 agonists, the spike protein (SP) of SARS-CoV-2, and the receptor binding domain (RBD) of SP. Frequencies of CD3+IFN-β+ T cells, and CD3+IFN-γ+ T cells were evaluated by flow cytometry. Interferon (IFN)-β gene expression was assessed by qRT-PCR. ResultsThe frequency of CD3+IFN-β+ T cells was higher in PBMCs from moderate (p < 0.0001) and severe (p = 0.009) patients at baseline in comparison with HCs. The highest increase in the frequency of CD3+IFN-β+ T cells in cell from moderate patients was induced by TLR8 agonist and SP (p < 0.0001 for both) when compared to HC, while, the highest increase of the frequency of CD3+IFN-β+ T cells in sample of severe patients was seen with TLR8 and TLR7 agonists (both p = 0.002). The frequency of CD3+IFN-γ+ T cells was significantly increased upon stimulation with TLR agonists in cell from patients with moderate and severe COVID-19, compared with HC (all p < 0.01), except with TLR7 and TLR8 agonists. The TLR8 agonist did not significantly increase the frequency of CD3+IFN-γ+ T cells in PBMCs of severe patients, but did so in cells from patients with moderate disease (p = 0.01). Moreover, IFN-β gene expression was significantly upregulated in CD3+T cells from moderate (p < 0.0001) and severe (p = 0.002) COVID-19 patients, compared to HC after stimulation with the TLR8 agonist, while, stimulation of T cells with SP, significantly up-regulated IFN-β mRNA expression in cells from patients with moderate (p = 0.0003), but not severe disease. ConclusionStimulation of PBMCs from COVID-19 patients, especially patients with moderate disease, with TLR8 agonist and SP increased the frequency of IFN-β-producing T cells and IFN-β gene expression.

Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients

Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.

The correlation of lymphocytes with disease progression of COVID-19.

The aim of this study is to evaluate the potential of lymphocytes as biomarkers to predict the decline of coronavirus disease 2019 (COVID-19). Lymphocytes were counted in 164 moderate COVID-19 patients in Shenzhen, China. Among the moderate infected patients, 12.2% (20/164) progressed to severe cases after admission. Compared with the stable patients, the counts of lymphocytes, both total T lymphocytes and CD4+ T lymphocytes, in the severe patients, were lower. The aggravation of moderate infected patients was significantly associated with lymphocyte count (hazard ratio [HR] = 0.91; 95% confidence interval [CI]: 0.84-0.99), total T lymphocyte count (HR = 0.91; 95% CI: 0.84-0.99), and CD4+ T lymphocyte count (HR = 0.91; 95% CI: 0.85-0.98). Total T lymphocytes and CD4+ T lymphocytes could be important biomarkers to evaluate the risk of aggravation for moderate infected COVID-19 patients. The patients with low percentages of total T lymphocytes and CD4+ T lymphocytes need more attention.

Clinical outcomes of mild to moderate coronavirus disease 2019 patients treated with Regdanvimab in delta-variant outbreak: Retrospective cohort study.

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation.

Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients

BackgroundIn 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient’s viral load and promote recovery.MethodsVolunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR).ResultsThe study’s primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious adverse events.ConclusionThe pandemic is not being effectively controlled and is causing multiple waves of infection that require extensive medical resources. However, FNC has demonstrated potential to reduce the treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. This makes FNC a promising candidate for COVID-19 treatment.Clinical trial registration: [clinicaltrials.gov], identifier [NCT04668235].

Long non-coding RNAs ANRIL, THRIL, and NEAT1 as potential circulating biomarkers of SARS-CoV-2 infection and disease severity

The current outbreak of coronavirus disease 2019 (COVID-19) is a global emergency, as its rapid spread and high mortality rate, which poses a significant threat to public health. Innate immunity plays a crucial role in the primary defense against infections, and recent studies have highlighted the pivotal regulatory function of long non-coding RNAs (lncRNAs) in innate immune responses. This study aims to assess the circulating levels of lncRNAs namely ANRIL, THRIL, NEAT1, and MALAT1 in the blood of moderate and severe SARS-CoV-2 infected patients, in comparison to healthy individuals. Additionally, it aims to explore the potential of these lncRNAs as biomarkers for determining the severity of the disease. The blood samples were collected from a total of 38 moderate and 25 severe COVID-19 patients, along with 30 healthy controls. The total RNA was extracted and qPCR was performed to evaluate the blood levels of the lncRNAs. The results indicate significantly higher expression levels of lncRNAs ANRIL and THRIL in severe patients when compared to moderate patients (P value = 0.0307, P value = 0.0059, respectively). Moreover, the expression levels of lncRNAs ANRIL and THRIL were significantly up-regulated in both moderate and severe patients in comparison to the control group (P value < 0.001, P value < 0.001, P value = 0.001, P value < 0.001, respectively). The expression levels of lncRNA NEAT1 were found to be significantly higher in both moderate and severe COVID-19 patients compared to the healthy group (P value < 0.001, P value < 0.001, respectively), and there was no significant difference in the expression levels of NEAT1 between moderate and severe patients (P value = 0.6979). The expression levels of MALAT1 in moderate and severe patients did not exhibit a significant difference compared to the control group (P value = 0.677, P value = 0.764, respectively). Furthermore, the discriminative power of ANRIL and THRIL was significantly higher in the severe patient group than the moderate group (Area under curve (AUC) = 0.6879; P-value = 0.0122, AUC = 0.6947; P-value = 0.0093, respectively). In conclusion, the expression levels of the lncRNAs ANRIL and THRIL are correlated with the severity of COVID-19 and can be regarded as circulating biomarkers for disease progression.

Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity

BackgroundThere is no doubt about the cardiovascular complications of coronavirus disease 2019 (COVID-19). Several genetic studies have demonstrated an association between genetic variants in a region on chromosome 9p21 and in a region on chromosome 16q22 with myocardial infarction (MI) and atrial fibrillation (AF) accompanied by cerebral infarction (CI), respectively.ObjectivesMI and CI susceptibility in patients with CDKN2B-AS1 and ZFHX3 polymorphisms, respectively, may have an effect on COVID-19 severity. We aimed to investigate whether there is an association between the cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) rs1333049 and zinc finger homeobox 3 (ZFHX3) rs2106261 single nucleotide polymorphisms (SNPs) and the degree of COVID-19 severity.Subjects and methodsThis current work was carried out on 360 subjects. They were classified into three groups: 90 severe COVID-19 cases, 90 moderate COVID-19 cases and 180 age- and gender-matched healthy controls. All subjects underwent genotyping of CDKN2B-AS1 (rs1333049) and ZFHX3 (rs2106261) by real-time PCR.ResultsThe frequency of G/C in CDKN2B-AS1 (rs1333049) was higher in severe and moderate COVID-19 patients than in controls (71.1% and 53.3% vs. 37.8%). The frequency of the C/C of CDKN2B-AS1 (rs1333049) was higher in moderate COVID-19 patients than in controls (26.7% vs. 13.3%). There were no significant differences regarding genotype frequency and allelic distribution of ZFHX3 (rs2106261) between COVID-19 patients and healthy controls.ConclusionCDKN2B-AS1 (rs1333049) gene polymorphism may play a role in determining the degree of COVID-19 severity. Further studies on its effect on cyclins and cyclin-dependent kinases (CDKs) [not measured in our study] may shed light on new treatment options for COVID-19.

The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial

N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A randomized controlled clinical trial was conducted among severe and moderate COVID-19 patients. The treatment group received oral 1200 mg daily of N-acetylcysteine (three times a day) and the standard care for COVID-19, while the control group received standard care for COVID-19 and a placebo. The NLR was determined on the first day of admission and after the seventh day of treatment. A paired Student t-test was used to compare the NLR before and after treatment while independent Student t-test was used to compare the NLR between treatment and control groups. A total of 40 severe and moderate COVID-19 were enrolled, 20 people in each group, with a mean age was 44.68±13.24 years old. The mean NLR on the first day was 9.44 in the treatment group and 8.84 in the control group. After the seventh day, the mean NLR was 4.27 and 11.54 in the treatment group and control group, respectively. The mean changes of NLR (the pre-treatment compared to post-treatment) in the treatment and control group were reduced 4.05 and increased 3.34, respectively. The NLR in treatment group significantly decreased compared to the control group (p&lt;0.001). In conclusion, N-acetylcysteine 1200 mg daily could reduce the NLR in severe and moderate COVID-19 patients.

Clinical characteristics of moderate or severe COVID-19 infection in patients with rheumatic diseases and analysis of risk factors leading to severe disease.

To explore the clinical characteristics of rheumatic disease (RD) patients who suffered from moderate or severe coronavirus disease 2019 (COVID-19) infection and to evaluate risk factors of COVID-19 infection in RD patients. A retrospective analysis was conducted on 148 moderate or severe COVID-19 patients admitted to the First People's Hospital of Suqian Affiliated to Nanjing Medical University, including 74 RD patients and 74 non-RD patients. Clinical data were collected including clinical characteristics and laboratory tests. The RD group showed a higher proportion of females with a higher incidence of interstitial lung disease and kidney disease than the non-RD group. Also, the incidence of fatigue, olfactory dysfunction and musculoskeletal pain was higher in the RD group, but the incidence of cough, wheezing, and fever was lower compared with non-RD patients. The hospitalized course of the RD group (12.7 days ± 6.55) was significantly longer than that in the non-RD group (8.07 days ± 3.40). Also, patients in the RD group had higher levels of erythrocyte sedimentation rate, interleukin (IL)-2, and IL-4 than the non-RD group. The logistic regression analysis showed that dizziness and headache, C-reactive protein (CRP) > 8 mg/L and lactate dehydrogenase (LDH) > 248 μ/L were independent risk factors for severe COVID-19 infections of RD patients. RD patients who suffered from moderate or severe COVID-19 infections have a higher risk of comorbidities, higher levels of inflammation, and longer hospitalized course. Dizziness and headache, CRP > 8 mg/L and LDH > 248 μ/L are risk factors for severe COVID-19 infections in RD patients.

The role of N-acetylcysteine in decreasing neutrophil-lymphocyte ratio in COVID-19 patients: A double-blind, randomized controlled trial.

N-acetylcysteine has antioxidant and anti-inflammatory activities that could potentially improve the clinical outcomes of coronavirus disease 2019 (COVID-19) patients. N-acetylcysteine potentially inhibits NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and results in control oxidative stress and cytokine release in COVID-19 patients. The aim of this study was to assess the effect of N-acetylcysteine in reducing the neutrophil-lymphocyte ratio (NLR) in COVID-19 patients. A randomized controlled clinical trial was conducted among severe and moderate COVID-19 patients. The treatment group received oral 1200 mg daily of N-acetylcysteine (three times a day) and the standard care for COVID-19, while the control group received standard care for COVID-19 and a placebo. The NLR was determined on the first day of admission and after the seventh day of treatment. A paired Student t-test was used to compare the NLR before and after treatment while independent Student t-test was used to compare the NLR between treatment and control groups. A total of 40 severe and moderate COVID-19 were enrolled, 20 people in each group, with a mean age was 44.68±13.24 years old. The mean NLR on the first day was 9.44 in the treatment group and 8.84 in the control group. After the seventh day, the mean NLR was 4.27 and 11.54 in the treatment group and control group, respectively. The mean changes of NLR (the pre-treatment compared to post-treatment) in the treatment and control group were reduced 4.05 and increased 3.34, respectively. The NLR in treatment group significantly decreased compared to the control group (p<0.001). In conclusion, N-acetylcysteine 1200 mg daily could reduce the NLR in severe and moderate COVID-19 patients.

#2974 SERUM CHEMOKINE CC-MOTIF LIGAND 17 IS A PREDICTIVE MARKER OF SEVERE COVID-19 IN HAEMODIALYSIS PATIENTS

Abstract Background and Aims Maintenance haemodailaysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. Method This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalisation (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19 which is defined as partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio &amp;lt;300 or SpO2 &amp;lt;94%. Multi-variate logistic regression models were used to investigate the association of CCL17 level with the development of severe COVID-19. Furthermore, to evaluate the degree of improvement in predicting performance in the pre-existing model with the addition of CCL17 compared to the pre-existing model, we calculated net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Results During hospitalisation, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including LDH and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/ml. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/ml) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017–0.227; P &amp;lt; 0.001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase, that are variables incorporated in multivariate logistic model, significantly improved classification performance for severe COVID-19 using the NRI (1.16, 95% CI: 0.82–1.50, P &amp;lt; 0.001) and IDI (0.18, 95% CI: 0.09–0.26, P &amp;lt; 0.001). Conclusion CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.

Efficacy of the Unani Regimen as an Add-On to Standard Treatment in Hospitalised RT-PCR-Confirmed Mild to Moderate COVID-19 Patients: An Open-Label Randomized Controlled Trial.

Background The coronavirus disease 2019 (COVID-19) pandemic resulted in mortality and morbidity worldwide. Many treatment modalities have beenexperimented with limited success. Therefore, the traditional system of medicine needs to be explored. Objective To evaluate the benefits of Unani regimensTiryaq-e-Arba and Unani Joshanda, as adjuvant therapy, were compared to standard treatment alone among reverse transcription polymerase chain reaction (RT-PCR)-confirmed mild to moderate COVID-19 cases. Materials and methods An open-label, double-arm, randomized, controlled interventional clinical study was conducted among 90 RT-PCR-confirmed mild to moderate COVID-19 inpatientsadmitted to a tertiary care hospital in New Delhi, India. Participants who fulfilled the criteria for inclusion were randomly assigned to two arms, with 43 subjects allocated to the Unani add-on armand 47 subjects to the control arm receiving standard treatment alone. Results Clinical recovery was achieved in all patients of the Unani arm, while in the control arm, three (6.4%) patients deteriorated and had to be shifted to ICU following admission. In the intervention arm, a shorter duration of hospitalization was observed (mean 5.95 days {SD = 1.99})than in the control arm (mean 7.62 days {SD, 4.06}); which was a statistically significant difference (p-value 0.017). The majority of the patients recovered within 10 days in the Unani add-on arm. The number of days taken for the reduction of symptoms was significantly less in the intervention arm (mean 5.14 days {SD, 2.39})as compared with standard treatment (mean 6.53 days {SD, 3.06})(p < 0.02). Renal and liver safety parameters were within the normal limits in both arms and no serious adverse event was reported. Conclusion Adding Unani formulations to standard treatment significantly reduced the duration of hospital stayand showed early recovery in COVID-19 patients compared with the control arm. It may be concluded that the synergistic effect of the Unani add-on with standard treatment gave more promising results in mild to moderate COVID-19 patients.

Evaluation of infliximab/tocilizumab versus tocilizumab among COVID-19 patients with cytokine storm syndrome

Coronavirus Disease 2019 (COVID-19) continues to spread rapidly. Monoclonal antibodies as well as anti-tumor necrosis factor are considered promising treatments for COVID-19. A prospective cohort study in which patients are divided into three groups. Group 1: moderate and severe COVID-19 patients received standard treatment; Group 2: moderate and severe COVID-19 patients received tocilizumab; Group 3: moderate and severe COVID-19 patients received treatment with infliximab and tocilizumab. 153 patients were recruited in the study. 40 received standard treatment alone, 70 received tocilizumab with standard treatment, and 43 received tocilizumab/infliximab with standard treatment. There was a significant difference in length of hospital stay (10.3, 8.9, and 7.6 days respectively P = 0.03), need for a non-invasive mechanical ventilator (4, 5, and one patient; P = 1.2E−8), intensive care admission (32, 45, and 16 patients; P = 2.5E−5), the occurrence of sepsis (18, 12, and 10 patients; P = 0.005) and in death (42.5%, 14.2%, and 7%; P = 0.0008) which were significantly lower in tocilizumab/infliximab group compared to tocilizumab and standard of care groups. Our study showed that tocilizumab/ infliximab in addition to standard of care was considered a promising treatment for moderate and severe COVID-19 patients.Trial registration number: ClinicalTrials.gov NCT04734678; date of registration: 02/02/2021.

Quantitative proteomics analysis of COVID-19 patients: Fetuin-A and tetranectin as potential modulators of innate immune responses

Treatment of severe cases of coronavirus disease 2019 (COVID-19) is extremely important to minimize death and end-organ damage. Here we performed a proteomic analysis of plasma samples from mild, moderate and severe COVID-19 patients. Analysis revealed differentially expressed proteins and different therapeutic potential targets related to innate immune responses such as fetuin-A, tetranectin (TN) and paraoxonase-1 (PON1). Furthermore, protein changes in plasma showed dysregulation of complement and coagulation cascades in COVID-19 patients compared to healthy controls. In conclusion, our proteomics data suggested fetuin-A and TN as potential targets that might be used for diagnosis as well as signatures for a better understanding of the pathogenesis of COVID-19 disease.

All-cause mortality in moderate and severe COVID-19 patients with myocardial injury receiving versus not receiving azvudine: a propensity score-matched analysis.

Patients with confirmed and suspected coronavirus disease 2019 (COVID-19) admitted to Wuhan Union Hospital from December 7, 2022, to December 30, 2022, were included in this study. Cox regression was conducted to identify risk factors for all-cause mortality. A propensity score-matched analysis was performed at a 1:1 ratio with a caliper of 0.1 pooled standard deviations of relevant confounders. The final analysis included a total of 332 patients (167 confirmed cases and 165 suspected cases), 42.77% (142/332) of the patients were 80 years of age or older and 68.67% (228/332) of them were men, 158 patients were treated with azvudine. In the matched cohort, the total mortality was 30.30% (60/198), 40 (20.20%, 40/198) patients received noninvasive ventilation and 22 (11.11%, 22/198) received invasive ventilation, 34 (17.17%, 34/198) patients were admitted to intensive care unit (ICU). The rate of shock, multiple organ damages and arrhythmia were 11.62% (23/198), 20.20% (40/198), and 12.12% (24/198), respectively. There was no significant difference on these clinical outcomes in patients treated with azvudine or not. Azvudine reduced early mortality (within 14 days from admission) (hazard ratio: 0.37, 95% confidence interval: 0.18-0.77) even after adjusting for other treatments including glucocorticoids, immunoglobin and anticoagulant therapy, but not the final in-hospital mortality of patients. Patients with COVID-19-related myocardial injury had a high mortality of about 30.30% (60/198). Azvudine improved the early survival of the patients but not final mortality.

Comparison of T Lymphocyte Subsets and Natural Killer Lymphocytes in Moderate Versus Severe COVID-19 Patients.

Severe respiratory involvement that follows a process of immune dysregulation and intense cytokine production remains to be the most dreaded complication of Coronavirus Disease-2019 (COVID-19) infection. The aim of this study was to analyze T lymphocyte subsets and natural killer (NK) lymphocytes in moderate and severe cases of COVID-19 infection and assess their significance in disease severity and prognosis. Twenty moderate cases and 20 severe cases of COVID-19 were studied and compared regarding blood picture, biochemical markers, T lymphocyte population subsets, and NK lymphocytes, which were determined by flow cytometric analysis. On analyzing the flow cytometric data of T lymphocyte cells and their subsets and NK cells in two groups of COVID-19 infection (one group moderate and the other severe cases), some immature NK lymphocyte relative and absolute counts were higher in the severe patients with worse outcome and death, while some mature NK lymphocyte relative and absolute counts were depressed in both groups. Also, interleukin (IL)-6 was significantly higher in severe cases when compared to moderate cases, and there was a positive significant correlation between immature NK lymphocyte relative and absolute counts and IL-6. There was no statistically significant difference between T lymphocyte subsets (T helper and T cytotoxic) with disease severity or outcome. Some immature NK lymphocyte subsets contribute to the widespread inflammatory response that complicates severe cases of COVID-19; therapeutic approaches directed to enhancing NK maturation or drugs that block NK cell inhibitory receptors have a potential role in controlling COVID-19 induced cytokine storm.