ABSTRACT
BackgroundSARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARS-CoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated. MethodsWe collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patients convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile. FindingsAmong the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile. InterpretationReceipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicron BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals. FundingThis research is supported by Changping Laboratory (CPL-1233) and the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), sponsored by the Ministry of Science and Technology of the Peoples Republic of China. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies (many of which have not been peer-reviewed) have reported inconsistent findings regarding the effect of inactivated vaccines against the Omicron variant. On Mar 6, 2022, we searched PubMed with the query "(SARS-CoV-2) AND ((Neutralisation) OR (Neutralisation)) AND ((Omicron) OR (BA.1)) AND (inactivated vaccine)", without date or language restrictions. This search identified 18 articles, of which 13 were directly relevant. Notably, the participants in many of these studies have received only one or two doses of inactivated vaccine with heterologous booster vaccination; other studies have a limited number of participants receiving inactivated vaccines. Added value of this studyTo date, this is the first study to report on the protective effect of inactivated vaccines against the severe disease caused by the Omicron variant. We examine and compare the disease profile of adults and children. Furthermore, we estimate the effect of post-vaccination omicron infection on plasma neutralization titers against Omicron and other SARS-COV-2 variants. Specifically, the disease profile of Omicron convalescents who had received two-dose primary series of inactivated vaccines with or without a booster dose prior to infection is compared with unvaccinated patients. We also analyzed the effect of infection on neutralizing activity by comparing vaccinated convalescents with vaccinated healthy individuals with matched vaccination profiles. Implications of all the available evidenceCompared with adults, child patients infected with Omicron tend to present with less severe disease and are less likely to turn re-positive on nucleic acid tests. Receipt of two-dose primary series or three doses of inactivated vaccine is a protective factor against severe disease, ICU admission, re-positive PCR and longer hospitalization. The protection afforded by a booster dose is stronger than two-dose primary series alone. Besides vaccination, infection with Omicron is also a key factor for elevated neutralizing antibody titers, enabling cross-neutralization against Omicron, wildtype (WT) and the Beta variant.
ABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists. However, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques require the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. Therefore, the aim of this study is to explore the effectiveness and safety of combining active cycle of breathing technique and phonophoresis in treating COPD patients. METHODS AND ANALYSIS: We propose a single-blind randomized controlled trial using 75 hospitalized patients diagnosed with COPD with excessive sputum production. The patients will be divided into three groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The two comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of cooperation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week's intervention. Analysis of variance will be used to investigate differences between the groups, and a p-value of less than 0.05 (two-tailed) will be considered statistically significant. DISCUSSION: This study introduces a combination of active cycle of breathing techniques and phonophoresis to explore the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD. TRIAL REGISTRATION: The trial was registered prospectively on the Chinese Clinical Trial Registry on 24 December 2019.ClinicalTrials.gov ChiCTR1900028506 . Registered on December 2019.
Subject(s)
Phonophoresis , Pulmonary Disease, Chronic Obstructive , Dyspnea , Humans , Lung , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Randomized Controlled Trials as Topic , Single-Blind MethodABSTRACT
BACKGROUND: While active cycle of breathing technique for chronic obstructive pulmonary disease patients with more sputum can improve clinic outcomes, less is known about sputum viscosity and sputum production of the intervention. OBJECTIVE: The purpose of our study was to explore the effect of active cycle of breathing technique on sputum viscosity and production among patients with chronic obstructive pulmonary disease. DESIGN: This was a two-arms, parallel, randomized clinical trial. SETTING: Study enrollment, randomization and implementation were conducted in the department of respiratory medicine inpatient at the Medical Center in Changchun, China. PARTICIPANTS: Hospitalized patients due to chronic obstructive pulmonary disease who met additional eligibility criteria were randomized to active cycle of breathing technique (n = 50) or usual care group (n = 50). METHODS: Patients in the intervention group received a week-long intervention from an experienced physical therapist. Patients in the usual care group received usual care as well as information and advice in the light of their health plan from respiratory medicine. The primary outcome was the changes on sputum viscosity and production. RESULTS: Among one hundred patients who were randomized (mean [SD] age, 54.89 [12.06] years; females, 58%), ninety-six participants completed the study. No significant differences were found between two groups on the changes of sputum viscosity (t = 0.277, P = 0.782). And there were insignificant differences between groups in the average amount of sputum among 1 h (Z=-1.848, P = 0.065) and significant differences in the average amount of sputum among 24 h (Z=-2.236, P = 0.025). From admission to one week recovery, the changes in ratio of forced expiratory volume in 1 s to forced vital capacity (Z=-4.511, P<0.0001) and arterial oxygen saturation (Z=-2.997, P = 0.003) were better in active cycle breathing technique group. Total Chronic Obstructive Pulmonary Disease Assessment Test scale were similar among two groups (Z=-1.818, P = 0.069). No adverse events occurred during the study. CONCLUSION: For patients with chronic obstructive pulmonary disease, active cycle of breathing technique can significantly result in sputum production and respiratory function, especially those of Global Initiative for Chronic Obstructive Lung Disease classification level 3, but did not result in the short-term improvement of sputum viscosity, quality of life and cost effectiveness. Registration number: ChiCTR2000033068.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Quality of Life , China , Female , Hospitalization , Humans , Middle Aged , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Function TestsABSTRACT
In this study we investigated whether mycophenolate mofetil (MMF), a new immunosuppressant, and its metabolite mycophenolic acid (MPA) influence the activity of liver resident natural killer (NK) cells, resulting in increased susceptibility to hepatitis B virus (HBV) infection. We isolated the hepatic NK cells of C57BL/6 and C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice administered MMF in the presence or absence of interleukin (IL)-15, or incubated isolated hepatic NK cells in the presence or absence of MPA and used RT-PCR, immunolabeling to assess the expression of NK receptors Ly49A, NKG2A and NKG2D, and cytokine ELISA and [(3)H]-TdR-release assay to assess the activation and cytotoxic capacity of NK cells. After treatment of MMF in the presence or absence of IL-15, HBsAg titer was also measured in C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice. After both MPA and MMF treatments, NK cytotoxicity was reduced, NKG2D and Ly49A expression was down-regulated, but NKG2A was up-regulated. Down-regulation of NKG2D could be ameliorated by IL-15, and in HBV-transgenic mice, MMF treatment impaired NK cell activity, but did not influence virus replication, whereas IL-15 treatment depressed HBsAg titer. MPA and MMF mediate down-regulation of NKG2D in vitro and vivo, restricting the cytotoxic capacity of NK cells. Regulation of NKG2D may be important in the effect of immunosuppressant on NK cell activity and involved in HBV infection.