SARS-CoV-2-specific CD4+ T cells are associated with long-term persistence of neutralizing antibodies.

Understanding the decay and maintenance of long-term SARS-CoV-2 neutralizing antibodies in infected or vaccinated people and how vaccines protect against other SARS-CoV-2 variants is critical for assessing public vaccination plans. Here, we measured different plasm antibody levels 2 and 12 months after disease onset, including anti-RBD, anti-N, total neutralizing antibodies, and two neutralizing-antibody clusters. We found that total neutralizing antibodies declined more slowly than total anti-RBD and anti-N IgG, and the two neutralizing-antibody clusters decayed even more slowly than total neutralizing antibodies. Interestingly, the level of neutralizing antibodies at 12 months after disease onset was significantly lower than that at 2 months but more broadly neutralized SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Lambda (C.37). Significant immune escape by the Omicron variant (B.1.1.529) was also observed 2 months post-recovery. Furthermore, we revealed that a high percentage of virus-specific CD4+ T cells and cTfh1 were associated with a slower decline in humoral immunity, accompanied by higher levels of CXCR3 ligands such as CXCL9 and CXCL10, higher frequency of cTfh1, and lower levels of cTfh2 and cTfh17. Our data highlight the importance of coordinating T-cell and humoral immunity to achieve long-term protective immunity.

Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection.

T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+ and CD8+ T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.

High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China.

INTRODUCTION: The presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD. METHOD AND ANALYSIS: A randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40-80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV1), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis. DISCUSSION: Currently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I-II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IIR-17012604 . Registered on 07 September 2017.