Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

Specific dynamic variations in the peripheral blood lymphocyte subsets in COVID-19 and severe influenza A patients: a retrospective observational study.

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.

Clinical Characteristics and Risk Factors of Acute Respiratory Distress Syndrome (ARDS) in COVID-19 Patients in Beijing, China: A Retrospective Study.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a new infectious disease, and acute respiratory syndrome (ARDS) plays an important role in the process of disease aggravation. The detailed clinical course and risk factors of ARDS have not been well described. MATERIAL AND METHODS We retrospectively investigated the demographic, clinical, and laboratory data of adult confirmed cases of COVID-19 in Beijing Ditan Hospital from Jan 20 to Feb 29, 2020 and compared the differences between ARDS cases and non-ARDS cases. Univariate and multivariate logistic regression methods were employed to explore the risk factors associated with ARDS. RESULTS Of the 130 adult patients enrolled in this study, the median age was 46.5 (34-62) years and 76 (58.5%) were male. ARDS developed in 26 (20.0%) and 1 (0.8%) death occurred. Fever occurred in 114 patients, with a median highest temperature of 38.5 (38-39)°C and median fever duration of 8 (3-11) days. The median time from illness onset to ARDS was 10 (6-13) days, the median time to chest CT improvement was 17 (14-21) days, and median time to negative nucleic acid test result was 27 (17-33) days. Multivariate regression analysis showed increasing odds of ARDS associated with age older than 65 years (OR=4.75, 95% CL1.26-17.89, P=0.021), lymphocyte counts [0.5-1×109/L (OR=8.80, 95% CL 2.22-34.99, P=0.002); <0.5×109/L(OR=36.23, 95% CL 4.63-2083.48, P=0.001)], and temperature peak ≥39.1°C (OR=5.35, 95% CL 1.38-20.76, P=0.015). CONCLUSIONS ARDS tended to occur in the second week of the disease course. Potential risk factors for ARDS were older age (>65 years), lymphopenia (≤1.0×109/L), and temperature peak (≥39.1°C). These findings could help clinicians to predict which patients will have a poor prognosis at an early stage.