Summary: Background: SARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia. Methods: All patients received recommended strategy from Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatments released by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245. Findings: 17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.005) and case severity (p=0.021) in patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.045, HR=0.374, 95%CI[0.143-0.978]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients. Interpretation: Meplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia. Funding: National Science and Technology Major Project.

Hemorrhagic fever with renal syndrome (HFRS) has become an important public health concern because of the high incidence and mortality rates, and limited treatment and vaccination. Until now, clinical studies on characteristics and outcomes in critical patients with HFRS have been limited. The aim of this study was to observe the clinical characteristics and cumulative proportions surviving and explore the predictive effects and risk factors for prognosis.

Background: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation. Methods: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed. Results: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death). Conclusions: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Orthohantaviruses (also known as hantaviruses) are pathogens that cause two distinct, yet related forms of severe human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases pose a significant threat to global public health due to their high case fatality rates, which can range from 1% to 50%. In recent years, an increasing number of countries and regions have reported human cases, underscoring the urgent need for improved understanding, prevention, and treatment strategies. Given the severity of these diseases and the lack of specific post-exposure antiviral treatments, preventive measures are critical. For several decades, substantial efforts have been dedicated to developing orthohantavirus vaccines, leading to significant advancements. The first large-scale deployment involved inactivated vaccines, which played a crucial role in reducing HFRS incidence in South Korea and China. Subunit vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines have also been extensively researched. Nucleic acid vaccines, including both mRNA and DNA vaccines, hold the greatest potential for future development due to their rapid design and production cycles, ability to elicit robust immune responses, ease of storage and transportation, and adaptable production platforms. Ongoing advancements in computer technology and artificial intelligence promise to further enhance the development of more effective orthohantavirus vaccines.

Until now, there is non-specific treatment, and exploring early and novel biomarkers to determine the disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS) would be of importance for clinician to take systematic and timely intervention. This study observed the expression of plasma sCD138, a soluble component shedding from the glycocalyx (GCX) to the circulating blood, and evaluated its predictive value on disease severity and prognosis of HFRS. One hundred and seventy-six patients with HFRS who were treated at our center between January 2011 and December 2013 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group and a critical-type group according to the HFRS criteria for clinical classification. Thirty-five blood samples from healthy subjects were obtained as the controls. The concentrations of sCD138 were detected using enzyme linked immunosorbent assay (ELISA). The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cells (WBC), platelets (PLT), glucose (GLU), blood urea nitrogen (BUN) and serum creatinine (Scr) in the samples were routinely tested. The levels of sCD138 among the different types were compared; the correlation among sCD138 and the laboratory parameters mentioned above were analyzed. The predictive effectiveness for prognosis of sCD138 was evaluated using the receiver operating characteristic (ROC) curve analysis. Except for the mild-type, the levels of sCD138 in the moderate-, severe- and critical-type patients during the acute stage were significantly higher than that of the convalescent stage and the control (P0.05). sCD138 was negatively correlated with Fib, PLT and ALB, and was positively correlated with WBC and AST (P<0.05). sCD138 demonstrated predictive effectiveness for prognosis with the area under the curve (AUC) of 0.778 (P<0.001). Dynamic detection of plasma sCD138 might be benefit to evaluating the disease severity and prognosis of the patients with HFRS.