Predictors of clinical deterioration in non-severe patients with COVID-19: a retrospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains pandemic with considerable morbidity and mortality around the world. The aim of this study was to identify the predictors for clinical deterioration in patients with COVID-19 who did not show clinical deterioration upon hospital admission. METHODS: Two hundred fifty-seven patients with confirmed COVID-19 pneumonia admitted to Guangzhou Eighth People's Hospital between 23 January and 21 March 2020 were retrospectively enrolled. Demographic data, symptoms, laboratory values, comorbidities and treatments were all collected. The study endpoint was clinical deterioration within 20 days from hospital admission. Univariate and multivariable logistic regression methods were used to explore the risk factors associated with clinical deterioration. RESULTS: A total of 49 (19%) patients showed clinical deterioration after admission. Compared with patients that did not experience clinical deterioration, clinically deteriorated patients had more dyspnea, cough and myalgia (65.3% versus 29.3%) symptoms and more had comorbidities (89.8% versus 36.1%). Clinical and laboratory characteristics at admission that were associated with clinical deterioration included senior age, diabetes, hypertension, myalgia, higher temperature, systolic blood pressure, C-reactive protein (CRP), procalcitonin, activated partial thromboplastin time, aspartate aminotransferase, alanine transaminase, direct bilirubin, plasma creatinine, lymphocytopenia, thrombocytopenia, decreased albumin and bicarbonate concentration. Medical history of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers and metformin were also risk factors. CONCLUSION: The four best predictors for clinical deterioration were CRP, procalcitonin, age and albumin. A "best" multivariable prediction model, resulting from using a variable selection procedure, included senior age, presentation with myalgia, and higher level of CRP and serum creatinine (bias-corrected c-statistic = 0.909). Sensitivity and specificity corresponding to a cut point of CRP ≥18.45 mg/L for predicting clinical deterioration were 85% and 74%, respectively.

Clinical characteristics of coronavirus disease 2019 infected with Delta variant in Guangzhou:A real-world study / 中华急诊医学杂志

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Longitudinal peripheral blood transcriptional analysis of COVID-19 patients captures disease progression and reveals potential biomarkers

COVID-19, caused by SARS-CoV-2, is an acute self-resolving disease in most of the patients, but some patients can develop a severe illness or even death. To characterize the host responses and identify potential biomarkers during disease progression, we performed a longitudinal transcriptome analysis for peripheral blood mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset to recovery. We found that PBMCs at different COVID-19 disease stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia may exacerbate disorders in blood coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression and predicting the risk of severity.

An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI)

BackgroundAntiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. MethodsOur study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FindingsThis study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical(P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. ConclusionsLPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FundingThis study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).

Temporal dynamics in viral shedding and transmissibility of COVID-19

We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.

The effect of inhaling bromide to patients with chronic obstructive pulmonary disease on resting pulmonary func- tion / 中国实用内科杂志

Objective To evaluate the effect of inhaling Ipratropium bromide to patients with chronic obstructive pulmo- nary disease(COPD)on resting pulmonary function,ventilation and exercise capacity during exercise.Methods All 12 stable patients were diagnosed as COPD.Before and after inhaling single-dose lpratropium bromideis,resting pul- monary function and Symptom-limited progressive cycle ergometer exercise tests were proceed.Results No obvious change in resting pulmouary function after inhaling Ipratropium bromide solution of four times the standard dose,but the maximal rate of work,maximal oxygen uptake,the maximal volume of ventilation per minute and the maximal ratio of tidal volume to inspiratory capacity increase significantly.The maximal dead space/tidal volume ratio and the maximal ventilatory equivalent for CO_2 have no change.There is a significant correlation between the amount of the maximal ratio of tidal volume to inspiratory capacity improved and amount of maximal oxygen uptake improved(r=0.598,P

Acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation.</p><p><b>METHODS</b>Twenty rats were exposed to hypoxic conditions for 3 weeks. Ten rats were used as normoxic controls. We administered Tet pulmonary targeting microspheres to 10 hypoxic rats and Tet aqueous solution to 10 hypoxic rats and the 10 control rats. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization.</p><p><b>RESULTS</b>Rats exposed to hypoxia developed pulmonary hypertension. The decrease in mPAP in rats treated with Tet pulmonary targeting microspheres was significantly greater than that in rats receiving Tet aqueous solution (P < 0.05), and the effects were longer with Tet pulmonary targeting microspheres. Moreover, Tet pulmonary targeting microspheres, unlike Tet aqueous solution, did not decrease mSBP.</p><p><b>CONCLUSION</b>Tet pulmonary targeting microspheres were more effective than Tet aqueous solution treating hypoxic pulmonary hypertension and acted selectively on the pulmonary circulation.</p>