Clinical observation and management of COVID-19 patients

Three leading infectious disease experts in China were invited to share their bedside observations in the management of COVID-19 patients. Professor Taisheng Li was sent to Wuhan to provide frontline medical care. He depicts the clinical course of SARS-CoV-2 infection. Furthermore, he observes the significant abnormality of coagulation function and proposes that the early intravenous immunoglobulin and low molecular weight heparin anticoagulation therapy are very important. Professor Hongzhou Lu, a leader in China to try various anti-viral drugs, expresses concern on the quality of the ongoing clinical trials as most trials are small in scale and repetitive in nature, and emphasizes the importance of the quick publication of clinical trial results. Regarding the traditional Chinese medicine, Professor Lu suggests to develop a creative evaluation system because of the complicated chemical compositions. Professor Wenhong Zhang is responsible for Shanghai’s overall clinical management of the COVID-19 cases. He introduces the team approach to manage COVID-19 patients. For severe or critically ill patients, in addition to the respiratory supportive treatment, timely multiorgan evaluation and treatment is very crucial. The medical decisions and interventions are carefully tailored to the unique characteristics of each patient

Benefits of high-dose intravenous immunoglobulin on mortality in patients with severe COVID-19: An updated systematic review and meta-analysis

BackgroundThe clinical benefits of high-dose intravenous immunoglobulin (IVIg) in treating COVID-19 remained controversial.MethodsWe systematically searched databases up to February 17, 2022, for studies examining the efficacy of IVIg compared to routine care. Meta-analyses were conducted using the random-effects model. Subgroup analysis, meta-regression, and trial series analysis w ere performed to explore heterogeneity and statistical significance.ResultsA total of 4,711 hospitalized COVID-19 patients (1,925 IVIg treated and 2786 control) were collected from 17 studies, including five randomized controlled trials (RCTs) and 12 cohort studies. The application of IVIg was not associated with all-cause mortality (RR= 0.89 [0.63, 1.26], P= 0.53; I2 = 75%), the length of hospital stays (MD= 0.29 [-3.40, 6.44] days, P= 0.88; I2 = 96%), the needs for mechanical ventilation (RR= 0.93 ([0.73, 1.19], P= 0.31; I2 = 56%), or the incidence of adverse events (RR= 1.15 [0.99, 1.33], P= 0.06; I2 = 20%). Subgroup analyses showed that overall mortality among patients with severe COVID-19 was reduced in the high-dose IVIg subgroup (RR= 0.33 [0.13, 0.86], P= 0.02, I2 = 68%; very low certainty).ConclusionsResults of this study suggest that severe hospitalized COVID-19 patients treated with high-dose IVIg would have a lower risk of death than patients with routine care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231040, identifier CRD42021231040

CD4+ T cell counts and soluble programmed death-1 at baseline correlated with hepatitis B surface antigen decline in HIV/HBV coinfection during combined antiretroviral therapy

BackgroundSeveral studies have described the rapid decline and clearance of hepatitis B surface antigen (HBsAg) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection after initiating combined antiretroviral therapy (cART). Early decline of HBsAg levels is associated with HBsAg seroclearance in the treatment of chronic HBV infection. This study aims to evaluate the HBsAg kinetics and the determinants of early HBsAg decline in patients with HIV/HBV coinfection during cART.MethodsA total of 51 patients with HIV/HBV coinfection were enrolled from a previously established HIV/AIDS cohort and followed for a median of 59.5 months after cART initiation. Biochemical tests, virology and immunology assessments were measured longitudinally. The kinetics of HBsAg during cART were analyzed. Soluble programmed death-1 (sPD-1) levels and immune activation markers (CD38 and HLA-DR) were measured at baseline, 1-year and 3-year during treatment. HBsAg response was defined as a decline of more than 0.5 log10 IU/ml at 6 months from the baseline after initiation of cART.ResultsHBsAg declined faster (0.47 log10 IU/mL) in the first six months and attained a decrease of 1.39 log10 IU/mL after 5-year therapy. Seventeen (33.3%) participants achieved a decline of more than 0.5 log10 IU/ml at the first 6 months of cART(HBsAg response) of which five patients achieved HBsAg clearance at a median of 11 months (range: 6-51 months). Multivariate logistic analysis showed the lower baseline CD4+ T cell levels (OR=6.633, P=0.012) and sPD-1 level (OR=5.389, P=0.038) were independently associated with HBsAg response after cART initiation. The alanine aminotransferase abnormality rate and HLA-DR expression were significantly higher in patients who achieved HBsAg response than in those who did not achieve HBsAg response after cART initiation.ConclusionLower CD4 + T cells, sPD-1, and immune activation were related to a rapid HBsAg decline in patients with HIV/HBV-coinfection after the initiation of cART. These findings imply that immune disorders induced by HIV infection may disrupt immune tolerance to HBV, leading to a faster decline in HBsAg levels during coinfection

Multiple Methods to Partition Evapotranspiration in a Maize Field

Partitioning evapotranspiration (ET) into soil evaporation E and plant transpiration T is important, but it is still a theoretical and technical challenge. The isotopic technique is considered to be an effective method, but it is difficult to quantify the isotopic composition of transpiration δT and evaporation δE directly and continuously; few previous studies determined δT successfully under a non-steady state (NSS). Here, multiple methods were used to partition ET in a maize field and a new flow-through chamber system was refined to provide direct and continuous measurement of δT and δE. An eddy covariance and lysimeter (EC-L)-based method and two isotope-based methods [isotope combined with the Craig–Gordon model (Iso-CG) and isotope using chamber measurement (Iso-M)] were applied to partition ET. Results showed the transpiration fraction FT in Iso-CG was consistent with EC-L at both diurnal and growing season time scales, but FT calculated by Iso-M was less than Iso-CG and EC-L. The chamber system method presented here to determine δT under NSS and isotope steady state (ISS) was robust, but there could be some deviation in measuring δE. The FT varied from 52% to 91%, with a mean of 78% during the entire growing season, and it was well described by a function of LAI, with a nonlinear relationship of FT = 0.71LAI0.14. The results demonstrated the feasibility of the isotope-based chamber system to partition ET. This technique and its further development may enable field ET partitioning accurately and continuously and improve understanding of water cycling through the soil–plant–atmosphere continuum

Nevirapine Plasma Concentrations Are Associated with Virologic Response and Hepatotoxicity in Chinese Patients with HIV Infection

BACKGROUND: Limited information is available on the relationship between nevirapine plasma concentrations and virologic response or liver toxicity in Chinese patients with HIV infection. The objective of this prospective study was to test this relationship and to determine the minimal therapeutic trough concentration of nevirapine for Chinese patients. METHODS: A total of 227 HIV-infected, treatment naïve patients were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) and C(2) (2 hr postdose) for measurement of nevirapine concentrations 6 months after treatment initiation. Therapeutic outcomes, viral load and CD4 cell count, were assessed at 3 and 6 months after starting therapy, while the evaluation of hepatotoxicity was undertaken 12 months after nevirapine treatment. RESULTS: A significant correlation between nevirapine trough concentrations and viral load was noticed after 6 months of treatment, particularly in patients with partial response and viral failure (p<0.01). The therapeutic C(trough) of nevirapine for Chinese patients was determined to be 3.9 µg/ml using the receiver operating characteristic curve. Virologic failure was observed in 21% (6/29) of patients with low nevirapine concentrations (<3.9 µg/ml) versus 5% (4/87) in patients with concentrations higher than 3.9 µg/ml (p = 0.015). Hepatotoxicity was significantly associated with the median nevirapine trough concentrations among male patients (8.20 vs. 5.48 µg/ml, p = 0.015) and hepatitis C virus co-infection (p = 0.039). CONCLUSIONS: Among Chinese patients with HIV infection, the therapeutic C(trough) of nevirapine was 3.9 µg/ml, higher than the recommended 3.0 µg/ml. The correlation between nevirapine concentrations, efficacy and hepatotoxicity suggests the benefit of dosage adjustment based on therapeutic drug monitoring among Chinese HIV-infected patients to optimize nevirapine containing antiretroviral therapy

Characteristics of spontaneous nystagmus and its correlation to video head impulse test findings in vestibular neuritis

ObjectiveTo explore the direction and SPV (slow phase velocity) of the components of spontaneous nystagmus (SN) in patients with vestibular neuritis (VN) and the correlation between SN components and affected semicircular canals (SCCs). Additionally, we aimed to elucidate the role of directional features of peripheral SN in diagnosing acute vestibular syndrome.Materials and methodsA retrospective analysis was conducted on 38 patients diagnosed with VN in our hospital between 2022 and 2023. The direction and SPV of SN components recorded with three-dimensional videonystagmography (3D-VNG) and the video head impulse test (vHIT) gain of each SCC were analyzed as observational indicators. We examined the correlation between superior and inferior vestibular nerve damage and the direction and SPV of SN components, and vHIT gain values in VN patients.ResultsThe median illness duration of between symptom onset and moment of testing was 6 days among the 38 VN patients (17 right VN and 21 left VN). In total, 31 patients had superior vestibular neuritis (SVN), and 7 had total vestibular neuritis (TVN). Among the 38 VN patients, all had horizontal component with an SPV of (7.66 ± 5.37) °/s, 25 (65.8%) had vertical upward component with a SPV of (2.64 ± 1.63) °/s, and 26 (68.4%) had torsional component with a SPV of (4.40 ± 3.12) °/s. The vHIT results in the 38 VN patients showed that the angular vestibulo-ocular reflex (aVOR) gain of the anterior (A), lateral (L), and posterior (P) SCCs on the ipsilesional side were 0.60 ± 0.23, 0.44 ± 0.15 and 0.89 ± 0.19, respectively, while the gains on the opposite side were 0.95 ± 0.14, 0.91 ± 0.08, and 0.96 ± 0.11, respectively. There was a statistically significant difference in the aVOR gain between the A-, L-SCC on the ipsilesional side and the other SCCs (p &lt; 0.001). The aVOR gains of A-, L-, and P-SCC on the ipsilesional sides in 31 SVN patients were 0.62 ± 0.24, 0.45 ± 0.16, and 0.96 ± 0.10, while the aVOR gains on the opposite side were 0.96 ± 0.13, 0.91 ± 0.06, and 0.98 ± 0.11, respectively. There was a statistically significant difference in the aVOR gain between the A-, L-SCC on the ipsilesional side and the other SCCs (p &lt; 0.001). In 7 TVN patients, the aVOR gains of A-, L-, and P-SCC on the ipsilesional side were 0.50 ± 0.14, 0.38 ± 0.06, and 0.53 ± 0.07, while the aVOR gains on the opposite side were 0.93 ± 0.17, 0.90 ± 0.16, and 0.89 ± 0.09, respectively. There was a statistically significant difference in the aVOR gain between the A-, L-, and P-SCC on the ipsilesional side and the other SCCs (p &lt; 0.001). The aVOR gain asymmetry of L-SCCs in 38 VN was 36.3%. The aVOR gain asymmetry between bilateral A-SCCs and bilateral P-SCCs for VN patients with and without a vertical upward component was 12.8% and 8.3%, which was statistically significant (p &lt; 0.05). For VN patients with and without a torsional component, the aVOR gain asymmetry of bilateral vertical SCCs was 17.0% and 6.6%, which was statistically significant (p &lt; 0.01). Further analysis revealed a significant positive correlation between the aVOR gain asymmetry of L-SCCs and the SPV of the horizontal component of SN in all VN patients (r = 0.484, p &lt; 0.01), as well as between the asymmetry of bilateral vertical SCCs and the SPV of torsional component in 26 VN patients (r = 0.445, p &lt; 0.05). However, there was no significant correlation between the aVOR gains asymmetry of bilateral A-SCCs and P-SCCs and the SPV of the vertical component in 25 VN patients.ConclusionThere is a correlation between the three-dimensional direction and SPV characteristics of SN and the aVOR gain of vHIT in VN patients. These direction characteristics can help assess different SCCs impairments in patients with unilateral vestibular diseases

Association Between Gut Microbiota and CD4 Recovery in HIV-1 Infected Patients

Composition of the gut microbiota has been linked with human immunedeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Evidence suggests that ART-treated patients with poor CD4+ T-cell recovery have higher levels of microbial translocation and immune activation. However, the association of the gut microbiota and immune recovery remains unclear. We performed a cross-sectional study on 30 healthy controls (HC) and 61 HIV-infected individuals, including 15 immunological ART responders (IRs), 20 immunological ART non-responders (INRs) and 26 untreated individuals (VU). IR and INR groups were classified by CD4+ T-cell counts of ≥350 cells/mm3 and &lt;350 cells/mm3 after 2 years of ART, respectively. Each subject’s gut microbiota composition was analyzed by metagenomics sequencing. Levels of CD4+ T cells, CD8+HLA-DR+ T cells and CD8+CD38+ T cells were measured by flow cytometry. We identified more Prevotella and fewer Bacteroides in HIV-infected individuals than in HC. Patients in INR group were enriched with Faecalibacterium prausnitzii, unclassified Subdoligranulum sp. and Coprococcus comes when compared with those in IR group. F. prausnitzii and unclassified Subdoligranulum sp. were overrepresented in individuals in VU group with CD4+ T-cell counts &lt;350 cells/mm3. Moreover, we found that the relative abundance of unclassified Subdoligranulum sp. and C. comes were positively correlated with CD8+HLA-DR+ T-cell count and CD8+HLA-DR+/CD8+ percentage. Our study has shown that gut microbiota changes were associated with CD4+ T-cell counts and immune activation in HIV-infected subjects. Interventions to reverse gut dysbiosis and inhibit immune activation could be a new strategy for improving immune reconstitution of HIV-1-infected individuals