CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis.

COVID-19 patients can develop clinical and histopathological features associated with fibrosis, but the pathogenesis of fibrosis remains poorly understood. CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants, which could initiate COVID-19-related cytokine storm. Here, we systemically analyzed lung pathogenesis in SARS-CoV-2- and its delta variant-infected humanized CD147 transgenic mice. Histopathology and Transmission Electron Microscopy revealed inflammation, fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs. Consistently, RNA-sequencing identified a set of fibrosis signature genes. Furthermore, we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2. We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts, decreasing susceptibility to bleomycin-induced pulmonary fibrosis. Meplazumab, a CD147 antibody, was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins, thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2. In conclusion, we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Large pulmonary cavity in COVID-19 cured patient case report.

Coronavirus Disease 2019 (COVID-19) is a pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak began in Wuhan, China, and spread rapidly, with many cases confirmed in multiple countries. Usually, after viral pneumonia were clinical cured, the pulmonary lesions of majority patients will gradually be absorbed to complete dissipation, very few severe patients may retain pulmonary interstitial inflammation and fibrosis. In this case, we described one unique COVID-19 patient, the symptoms were: dry cough, fatigue, poor appetite and subjective fever, moreover, the patient was a non-smoker, had no pulmonary bullous, no history of tuberculosis, and also no hypertension or diabetes. The patient received antiviral therapy, antibacterial therapy, recombinant human interferon-α2a, vitamin C and oxygen inhalation. After two weeks of treatment and observation, the patient was clinical cured and discharged. However, two days later, the patient had a sudden chest stuffiness, CT images indicted: his lung didn't heal like others, but developed a large pulmonary cavity in the lower lobe of right lung. In hospital, the patient showed no symptoms of infection for another 14 days, and the pulmonary cavity remain unchanged. This case suggested: it is important to follow convalescent COVID-19 patients, especially their lung CT images, to make sure a fully recovery.