Vaccination increased host antiviral gene expression and reduced COVID-19 severity during the Omicron variant outbreak in Fuyang City, China.

BACKGROUND: The differences in host antiviral gene expression and disease severity between vaccinated and non-vaccinated coronavirus disease 2019 (COVID-19) patients are not well characterized. We sought to compare the clinical characteristics and host antiviral gene expression patterns of vaccinated and non-vaccinated cohorts at the Second People's Hospital of Fuyang City. METHODS: In this case-control study, we retrospectively analyzed 113 vaccinated patients with a COVID-19 Omicron variant infection, 46 non-vaccinated COVID-19 patients, and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We compared host antiviral gene expression profiles between healthy controls and COVID-19 patients who were either vaccinated or non-vaccinated at the time of infection. RESULTS: In the vaccinated group, most patients were asymptomatic, with only 42.9 % of patients developing fever. Notably, no patients had extrapulmonary organ damage. In contrast, 21.4 % of patients in the non-vaccinated group developed severe/critical (SC) disease and 78.6 % had mild/moderate (MM) disease, with fever occurring in 74.2 % patients. We found that Omicron infection in COVID-19 vaccinated patients was associated with significantly increased expression of several important host antiviral genes including IL12B, IL13, CXCL11, CXCL9, IFNA2, IFNA1, IFNγ, and TNFα. CONCLUSION: Vaccinated patients infected with the Omicron variant were mostly asymptomatic. In contrast, non-vaccinated patients frequently developed SC or MM disease. Older patients with SC COVID-19 also had a higher occurrence of mild liver dysfunction. Omicron infection in COVID-19 vaccinated patients was associated with the activation of key host antiviral genes and thus may play a role in reducing disease severity.

Myocardial Injury at Early Stage and Its Association With the Risk of Death in COVID-19 Patients: A Hospital-Based Retrospective Cohort Study.

Background: There are growing evidence demonstrating that coronavirus disease 2019 (COVID-19) is companied by acute myocardial injury. However, the associations of SARS-CoV-2-induced myocardial injury with the risk of death and prognosis after discharge in COVID-19 patients are unclear. Methods: This prospective cohort study analyzed 355 COVID-19 patients from two hospitals in different regions. Clinical and demographic information were collected and prognosis was followed up. Results: Of 355 hospitalized patients with COVID-19, 213 were mild, 90 severe, and 52 critically ill patients. On admission, 59 (16.7%) patients were with myocardial injury. Myocardial injury was more popular in critically ill patients. Univariate and multivariate logistic regression revealed that male, older age and comorbidity with hypertension were three crucial independent risk factors predicting myocardial injury of COVID-19 patients. Among 59 COVID-19 patients with myocardial injury, 25 (42.4%) died on average 10.9 days after hospitalization. Mortality was increased among COVID-19 patients with myocardial injury (42.4 vs. 3.38%, RR = 12.542, P < 0.001). Follow-up study observed that 4.67% COVID-19 patients with myocardial injury were not fully recovered in 14 days after discharge. Conclusion: Myocardial injury at early stage elevates mortality of COVID-19 patients. Male elderly patients with hypertension are more vulnerable to myocardial injury. SARS-CoV-2-induced myocardial injury has not completely recovered in 14 days after discharge.

Differentially expressed immune response genes in COVID-19 patients based on disease severity.

BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.

Renal dysfunction and prognosis of COVID-19 patients: a hospital-based retrospective cohort study.

INTRODUCTION: Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. MATERIALS AND METHODS: All 154 patients with COVID-19 were recruited from the Second People's Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. RESULTS: There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. CONCLUSION: Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.

Liver Dysfunction and Its Association with the Risk of Death in COVID-19 Patients: A Prospective Cohort Study.

Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed. Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p<0.01). Moreover, the fatality rate was higher in patients with cholestasis than those without cholestasis (relative risk=2.182, p<0.05). Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge. Conclusions: LD at early disease stage elevates the risk of death of COVID-19 patients. COVID-19-associated LD does not recover completely by 14 days after discharge.

Assessing SARS-CoV-2 RNA levels and lymphocyte/T cell counts in COVID-19 patients revealed initial immune status as a major determinant of disease severity.

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokine profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied, but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission, significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.

COVID-19 induced liver function abnormality associates with age.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease that may cause fever, dry cough, fatigue and shortness of breath. The impact of COVID-19 on liver function is not well described. RESULTS: We found that the overall frequency of LFT abnormality was 17.6%. Frequency of LFT abnormality was significantly greater in patients with severe/critical (SC) COVID-19 compared to those with mild/moderate (MM) COVID-19 (32.4% vs 11.6%, p=0.011). Among patients with LFT abnormality, the median age was significantly higher in the SC group compared to the MM group (52 vs 39 years, p=0.021). CONCLUSION: COVID-19 is frequently associated with mild liver function abnormality, particularly in individuals with severe/critical COVID-19 who were older. Liver function should be monitored carefully during infection, with judicious use of hepatotoxic agents where possible and avoidance of prolonged hypotension to minimize liver injury in older patients. METHODS: The No. 2 People's Hospital of Fuyang City in China has admitted a total of 159 patients with confirmed COVID-19 since the outbreak from January 2020 to March 2020. We analyzed the incidence of liver function test (LFT) abnormality in these patients with confirmed COVID-19 infection.

Effective treatment of severe COVID-19 patients with tocilizumab.

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19.

The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated 43 adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin-6 (IL-6), d-dimer (d-D), glucose, thrombin time, fibrinogen, and C-reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL-6 were 24.3 and 0.795 µg/L, respectively, while those of d-D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL-6 combined with d-D was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and d-D tandem testing was up to 93.3%, while the sensitivity of IL-6 and d-D by parallel test in the severe COVID-19 was 96.4%. IL-6 and d-D were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value.