The impact of COVID-19 non-pharmaceutical interventions on HIV care continuum in China: An interrupted time series analysis.

Background: China implemented strict non-pharmaceutical interventions to contain COVID-19 at the early stage. We aimed to evaluate the impact of COVID-19 on HIV care continuum in China. Methods: Aggregated data on HIV care continuum between 1 January 2017 and 31 December 2020 were collected from centers for disease control and prevention at different levels and major infectious disease hospitals in various regions in China. We used interrupted time series analysis to characterize temporal trend in weekly numbers of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, HIV diagnoses, median time intervals between HIV diagnosis and antiretroviral therapy (ART) initiation (time intervals, days), ART initiations, mean CD4+ T cell counts at ART initiation (CD4 counts, cells/µL), ART collections, and missed visits for ART collection, before and after the implementation of massive NPIs (23 January to 7 April 2020). We used Poisson segmented regression models to estimate the immediate and long-term impact of NPIs on these outcomes. Findings: A total of 16,780 PEP prescriptions, 1,101,686 HIV tests, 69,659 HIV diagnoses, 63,409 time intervals and ART initiations, 61,518 CD4 counts, 1,528,802 ART collections, and 6656 missed visits were recorded during the study period. The majority of outcomes occurred in males (55·3-87·4%), 21-50 year olds (51·7-90·5%), Southwestern China (38·2-82·0%) and heterosexual transmission (47·9-66·1%). NPIs was associated with 71·5% decrease in PEP prescriptions (IRR 0·285; 95% CI 0·192-0·423), 36·1% decrease in HIV tests (0·639, 0·497-0·822), 32·0% decrease in HIV diagnoses (0·680, 0·511-0·904), 59·3% increase in time intervals (1·593, 1·270-1·997) and 17·4% decrease in CD4 counts (0·826, 0·746-0·915) in the first week during NPIs. There was no marked change in the number of ART initiations, ART collections and missed visits during the NPIs. By the end of 2020, the number of HIV tests, HIV diagnoses, time intervals, ART initiations, and CD4 counts reached expected levels, but the number of PEP prescriptions (0·523, 0·394-0·696), ART collections (0·720, 0·595-0·872), and missed visits (0·137, 0·086-0·220) were still below expected levels. With the ease of restrictions, PEP prescriptions (slope change 1·024/week, 1·012-1·037), HIV tests (1·016/week, 1·008-1·026), and CD4 counts (1·005/week, 1·001-1·009) showed a significant increasing trend. Interpretation: HIV care continuum in China was affected by the COVID-19 NPIs at various levels. Preparedness and efforts to maintain the HIV care continuum during public health emergencies should leverage collaborations between stakeholders. Funding: Natural Science Foundation of China.

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.

Elevated levels of fructosamine are independently associated with SARS-CoV-2 reinfection: A 12-mo follow-up study.

BACKGROUND: The association between blood levels of fructosamine (FMN) and recurrent coronavirus disease 2019 (COVID-19) is currently unclear. AIM: To investigate a prospective relationship between blood levels of FMN and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. METHODS: A total of 146 Chinese hospitalized patients infected with SARS-CoV-2 were consecutively collectively recruited and followed from January 2020 to May 2021. Diagnosis of COVID-19 and SARS-CoV-2 reinfection was based on the diagnostic criteria and treatment protocol in China. The levels of FMN were determined in blood and divided into tertiles based on their distribution in the cohort of COVID-19 patients. Multivariate-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for SARS-CoV-2 reinfection across the tertiles of FMN levels. A Cox regression model was used to generate the HR for SARS-CoV-2 reinfection in the participants in the top tertile of FMN levels compared with those at the bottom. Disease-free survival was used as the time variable, and relapse was used as the state variable, adjusted for age, gender, influencing factors such as diabetes mellitus, hypertension, and corticosteroid therapy, and clinical indexes such as acute liver failure, acute kidney failure, white blood cell (WBC) count, C-reactive protein, prognostic nutritional index (PNI), and blood lipids. Kaplan-Meier analysis with log-rank tests was used to compare the survival rate between patients with elevated FMN levels (FMN > 1.93 mmol/L, the top tertile) and those with nonelevated levels. RESULTS: Clinical data for the 146 patients with confirmed COVID-19 [age 49 (39-55) years; 49% males] were analyzed. Eleven patients had SARS-CoV-2 reinfection. The SARS-CoV-2 reinfection rate in patients with elevated FMN levels was significantly higher than that in patients with nonelevated FMN (17% vs 3%; P = 0.008) at the end of the 12-mo follow-up. After adjustments for gender, age, diabetes mellitus, hypertension, corticosteroid therapy, WBC count, PNI, indexes of liver and renal function, and blood lipids, patients with nonelevated FMN levels had a lower risk of SARS-CoV-2 reinfection than those with elevated FMN levels (HR = 6.249, 95%CI: 1.377-28.351; P = 0.018). Kaplan-Meier analysis showed that the cumulative survival rate of patients infected with SARS-CoV-2 was higher in patients with nonelevated FMN levels than in those with elevated FMN levels (97% vs 83%; log rank P = 0.002). CONCLUSION: Elevated levels of FMN are independently associated with SARS-CoV-2 reinfection, which highlights that patients with elevated FMN should be cautiously monitored after hospital discharge.

Development of the TOA-Related Models for PM2.5 Prediction Pre- and Post-COVID-19 Outbreak over Yangtze River Delta Region of China

The lockdown and the strict regulation measures implemented by Chinese government due to the outbreak of the COVID-19 pandemic not only decelerated the spread of the virus but also brought a positive effect on the nationwide atmospheric quality. In this study, we extended our previous research on remotely sensed estimation of PM2.5 concentrations in Yangtze River Delta region (i.e., YRD) of China from 2019 to the strict regulation period of 2020 (i.e., 24 Jan, 2020-31 Aug, 2020). Unlike the method using aerosol optical depth (AOD) developed in previous studies, we validated the possibility of moderate resolution imaging spectroradiometer (MODIS) top-of-atmosphere (TOA) reflectance (i.e., MODIS TOA) at 21 bands in estimating the PM2.5 concentrations in YRD region. Two random forests (i.e., TOA-sig RF and TOA-all RF) incorporated with different MODIS TOA datasets were developed, and the results showed that the TOA-sig RF model performed better with R2 of 0.81 (RMSE=8.07 μg/m3) than TOA-all RF model with R2 of 0.79 (RMSE=9.13 μg/m3). The monthly averaged PM2.5 exhibited the highest value of 50.81 μg/m3 in YRD region in January 2020 and sharply decreased from February to August 2020. The annual mean PM2.5 concentrations derived by TOA-sig RF model were 47.74, 32.14, and 21.04 μg/m3 in winter, spring, and summer in YRD during the strict regulation period of 2020, respectively, showing much lower values than those in 2019. Our research demonstrated that the PM2.5 concentrations could be effectively estimated by using MODIS TOA reflectance at 21 bands and the random forest.

The Neutrophil-to-Lymphocyte Ratio is Associated with the Requirement and the Duration of Invasive Mechanical Ventilation in Acute Respiratory Distress Syndrome Patients: A Retrospective Study.

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality and most ARDS patients require ventilatory support. Applying appropriate ventilation strategies based on patients' individual situations has a direct impact upon patients' outcome. The neutrophil-to-lymphocyte ratio (NLR) has been shown to predict the early requirement of invasive mechanical ventilation (IMV) in patients with coronavirus disease 2019 (COVID-19). Our study aimed to investigate the relationship between baseline NLR and IMV in ARDS. Methods: A retrospective study was performed on patients who were diagnosed with ARDS using the Berlin definition and admitted to the First Affiliated Hospital of Soochow University from 2017 to 2022. Clinical data within 24 h after the ARDS diagnosis were collected from the medical record system. Based on the ventilation strategies during hospitalization, patients were divided into three groups and their clinical characteristics were compared. Furthermore, logistic regression analysis was used to screen the independent risk factors for IMV. STROBE checklist was used for this manuscript. Results: 520 ARDS patients were included and the median NLR value in IMV group was significantly higher than that of other groups (P < 0.001). NLR was significantly associated with the requirement of IMV in ARDS patients (OR, 1.042; 95% CI, 1.025-1.060; P < 0.001), other independent risk factors included PaO2/FiO2, Hb, lactate, and use of vasoactive drugs (all P < 0.05). Moreover, we found that the duration of IMV was longer in patients with high NLR (8[IQR, 3-13], 10[IQR, 6-16], respectively, P=0.025). Conclusions: Our results revealed that high baseline NLR level was significantly correlated with an increased risk of IMV in patients with ARDS. Furthermore, higher NLR was associated with prolonged duration of IMV in patients with ARDS.

Intranasal immunization with avian paramyxovirus type 3 expressing SARS-CoV-2 spike protein protects hamsters against SARS-CoV-2.

Current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are administered parenterally and appear to be more protective in the lower versus the upper respiratory tract. Vaccines are needed that directly stimulate immunity in the respiratory tract, as well as systemic immunity. We used avian paramyxovirus type 3 (APMV3) as an intranasal vaccine vector to express the SARS-CoV-2 spike (S) protein. A lack of pre-existing immunity in humans and attenuation by host-range restriction make APMV3 a vector of interest. The SARS-CoV-2 S protein was stabilized in its prefusion conformation by six proline substitutions (S-6P) rather than the two that are used in most vaccine candidates, providing increased stability. APMV3 expressing S-6P (APMV3/S-6P) replicated to high titers in embryonated chicken eggs and was genetically stable, whereas APMV3 expressing non-stabilized S or S-2P were unstable. In hamsters, a single intranasal dose of APMV3/S-6P induced strong serum IgG and IgA responses to the S protein and its receptor-binding domain, and strong serum neutralizing antibody responses to SARS-CoV-2 isolate WA1/2020 (lineage A). Sera from APMV3/S-6P-immunized hamsters also efficiently neutralized Alpha and Beta variants of concern. Immunized hamsters challenged with WA1/2020 did not exhibit the weight loss and lung inflammation observed in empty-vector-immunized controls; SARS-CoV-2 replication in the upper and lower respiratory tract of immunized animals was low or undetectable compared to the substantial replication in controls. Thus, a single intranasal dose of APMV3/S-6P was highly immunogenic and protective against SARS-CoV-2 challenge, suggesting that APMV3/S-6P is suitable for clinical development.

Prone positioning in extubated patients with hypoxemic respiratory failure after cardiac surgery: A retrospective study.

BACKGROUND: Hypoxemic respiratory failure is a serious complication that can occur at any stage after cardiac surgery. Prone positioning (PP) is safe and effective for patients receiving invasive ventilation after hypoxemic respiratory failure; however, few related studies have focused on its use with extubated cardiac surgery patients. Researchers recently reported beneficial effects of PP for hypoxemic patients with COVID-19 and those with moderate ARDS (acute respiratory distress syndrome,ARDS). PP may also improve oxygenation in extubated cardiac surgery patients. OBJECTIVE: In this study, we aimed to assess the safety and effectiveness of PP in extubated cardiac surgery patients to determine whether PP can improve oxygenation and respiratory status or reduce secondary intubation. METHODS: We reviewed our institutional database between August 2018 and August 2020 and identified 22 cardiac surgery patients who had undergone PP for hypoxemic respiratory failure after extubation. From the medical and nursing records, we extracted the following data recorded before PP, during PP, and after PP for each patient, arterial blood gas analyses, hemodynamic records, laboratory reports, and respiratory function training records. RESULTS: Twenty-two extubated patients underwent 74 PP. Each patient underwent a median of 3.5 (2-5) procedures, and the median duration of each PP was 10 h. PP was implemented on the 4.5th postoperative day (median). All patients were discharged from the hospital, and none died. No complications were observed. PP improved the P/F ratio (182.65 ± 60.17, 301.53 ± 61.31, and 246.76 ± 65.68, before PP, during PP, and after PP, respectively, p < 0.001). Additionally, the respiratory rate, Forced Vital Capacity (FVC) and PaCO2 also improved, and hemodynamics showed no significant change. CONCLUSION: PP may be effective and safe for treating patients who are extubated following cardiac surgery with hypoxemic respiratory failure. For these patients, PP is associated with oxygenation and respiratory condition improvements and low secondary intubation rates.

A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters.

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2-neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P-immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.

Monocyte-to-lymphocyte ratio is associated with 28-day mortality in patients with acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). Neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW)/albumin ratio have been reported to be predictive prognostic biomarkers in ARDS patients. However, the role of monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in a variety of diseases is rarely mentioned in ARDS. In this study, we explored the relationship between MLR and disease severity in ARDS patients and compared it with other indicators associated with 28-day mortality in patients with ARDS. METHODS: We retrospectively included 268 patients who fulfilled the Berlin definition of ARDS and were admitted to a single institute from 2016 to 2020. Clinical characteristics and experimental test data were collected from medical records within 24 h after the ARDS diagnosis. MLR, NLR, and RDW/albumin ratio levels were calculated. The primary clinical outcome was 28-day mortality. Logistic regression analysis was used to illustrate the relationship between indicators and 28-day mortality. Receiver operating characteristic (ROC) curve was used to evaluate the area under the curve (AUC), and propensity score matching (PSM) was employed to validate our findings. RESULTS: The median MLR values were higher for non-survivors than for survivors before and after matching (P<0.001, P=0.001, respectively). MLR values were significantly associated with 28-day mortality (OR 2.956; 95% CI 1.873-4.665; P<0.001). MLR and NLR indicators were combined for predictive efficacy analysis, and its AUC reached 0.750. There was a significant increase in 28-day mortality depending on the increasing MLR level: low MLR group 38 (20.4%), high MLR group 47 (57.3%) (P<0.001). CONCLUSIONS: Higher MLR values were associated with 28-day mortality in patients with ARDS. Further investigation is required to verify this relationship with prospectively collected data.

Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China.

BACKGROUND: Liver injury is common and also can be fatal, particularly in severe or critical patients with coronavirus disease 2019 (COVID-19). AIM: To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk. METHODS: A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9, 2020 at Tongji Hospital, Wuhan, China. Data on clinical features, laboratory parameters, medications, and prognosis were collected. RESULTS: COVID-19-associated liver injury more frequently occurred in patients aged ≥ 65 years, female patients, or those with other comorbidities, decreased lymphocyte count, or elevated D-dimer or serum ferritin (P < 0.05). The disease severity of COVID-19 was an independent risk factor for liver injury (severe patients: Odds ratio [OR] = 2.86, 95% confidence interval [CI]: 1.78-4.59; critical patients: OR = 13.44, 95%CI: 7.21-25.97). The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk (P < 0.001). Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury. Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury. CONCLUSION: More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients, especially patients aged ≥ 65 years, female patients, or those with other comorbidities. Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.