Search

BackgroundLittle is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19.MethodsWe prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively.ResultsAnti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19.ConclusionsSevere breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Table S1. Clinical characteristics of patients with community-onset Clostridium difficile infection. Table S2. Possible offending antibiotic agents in patients with community-onset Clostridium difficile infection. Figure S1. Incidence of C. difficile infection from 2008 through 2015 (DOCX 183 kb)

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

BackgroundDespite the fact of ongoing worldwide vaccination programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding longevity, breadth, and type of immune response to coronavirus disease-19 (COVID-19) is still important to optimize the vaccination strategy and estimate the risk of reinfection. Therefore, we performed thorough immunological assessments 1 year post-COVID-19 with different severity.MethodsWe analyzed peripheral blood mononuclear cells and plasma samples at 1 year post-COVID-19 in patients who experienced asymptomatic, mild, and severe illness to assess titers of various isotypes of antibodies (Abs) against SARS-CoV-2 antigens, phagocytic capability, and memory B- and T-cell responses.FindingsA total of 24 patients (7, 9, and 8 asymptomatic, mild, and severe patients, respectively) and eight healthy volunteers were included in this study. We firstly showed that disease severity is correlated with parameters of immune responses at 1 year post-COVID-19 that play an important role in protecting against reinfection with SARS-CoV-2, namely, the phagocytic capacity of Abs and memory B-cell responses.InterpretationVarious immune responses at 1 year post-COVID-19, particularly the phagocytic capacity and memory B-cell responses, were dependent on the severity of the prior COVID-19. Our data could provide a clue for a tailored vaccination strategy after natural infection according to the severity of COVID-19.

Additional file 5: Figure S4. Cytokine-producing T cells against wild-type SARS-CoV-2 and the Delta variant according to vaccination status after COVID-19. a CD4+ T-cell populations producing specific cytokines. b CD8+ T-cell populations producing specific cytokines. NS, not significant; IFN-γ, interferon- γ; IL, interleukin; TNF-α, tumor necrosis factor-α.

Additional file 2: Figure S2. Representative gating strategy for the SARS-CoV-2-specific activated and cytokine-producing T cells.

Additional file 3: Table S1. Detailed clinical information of each group in the present study

Additional file 1: Figure S1. Purification of recombinant RBD proteins of SARS-CoV-2 variants. The purity of the purified recombinant protein was determined by non-reducing (left) and reducing (right) 14% SDS-PAGE gels. M, protein ladder. 1. RBD wild-type; 2. RBD Alpha (B.1.1.7, with N501Y mutation); 3. RBD Beta (B.1.351, with K417N, E484K, and N501Y); 4. RBD Gamma (P.1, with K417T, E484K, and N501Y mutations); 5. RBD Delta (B.1.617.2, with L452R and T478K mutations); 6. RBD Omicron (B. 1.1.529, with G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, and Y505H).

Additional file 4: Figure S3. Comparisons of humoral and cellular immune responses against different strains of SARS-CoV-2 in individuals who recovered and then received one dose of an mRNA vaccine 18 months later. a IgG-binding activities measured using an enzyme-linked immunosorbent assay. b Neutralization activities measured using a focus reduction neutralization test. c Proportions of activation-induced marker+ T cells measured by flow cytometric analysis. For simplicity, in Figure S3a, statistical significance is shown by the lines. * P < 0.05, ** P < 0.005 NS, not significant; FRNT, focus reduction neutralizing test.

Table S1. Clinical characteristics of patients with community-onset Clostridium difficile infection. Table S2. Possible offending antibiotic agents in patients with community-onset Clostridium difficile infection. Figure S1. Incidence of C. difficile infection from 2008 through 2015 (DOCX 183 kb)

We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged ≥ 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease., Graphical Abstract

Antibiotic stewardship is a key strategy for limiting antibiotic resistance. Over the last decade the South Korean government has implemented a series of healthcare policies directed to this end, consisting of legislative separation of drug prescribing and dispensing, antibiotic utilization reviews, healthcare quality assessment, and public reporting. As a result, the proportion of antibiotic prescriptions for acute upper respiratory tract infections in primary healthcare facilities decreased from 72.9% in 2002 to 42.7% in 2013. However, no significant decrease in antibiotic resistance occurred over the same period in clinically important bacteria such as Streptococcus pneumoniae. These government-driven policies played a pivotal role in improving antibiotic use for outpatients and surgical patients in South Korea. However, to achieve long-lasting successful outcomes, coordinated efforts and communications among the stakeholders, including physicians and medical societies, are needed.