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.

Type-Ⅰ interferons (IFN-Ⅰ) are a widely expressed family that could promote anti-virus immunity in the process of pathogens invasion. In a human immunodeficiency virus 1 (HIV-1) infected individual, the production of IFN-Ⅰ can be detected as early as the acute phase and will persist throughout the course of infection. However, sustained stimulation of immune system by IFN-Ⅰ also contributes greatly to host-mediated immunopathology and diseases progression. Although the protective effects of IFN-Ⅰ in the acute phase of HIV-1 infection has been observed, more studies recently focus on their detrimental role in the chronic stage. Inhibition of IFN-Ⅰ signaling may reverse HIV-1-induced immune hyperactivation and furthermore reduce HIV-1 reservoirs, which suggest this strategy may provide a potential way to enhance the therapeutic effect of antiretroviral therapy. Therefore, we review the role of IFN-Ⅰ in HIV-1 progression, their effects on different immunocytes, and therapeutic prospects targeting the IFN-Ⅰ system.

Co-infection with hepatitis C (HCV) is very common in human immunodeficiency virus 1 (HIV-1) infected patients. Although HIV co-infection clearly accelerates progression of HCV-related fibrosis and liver disease, controversy remains as to the impact of HCV on HIV disease progression in co-infected patients. HIV can cause immune dysfunction, in which the regulatory function of T helper (Th) cells is very essential. Moreover, cytokines derived from Th cells play a prominent role in viral infection. Investigating the functional changes of Th1 and Th2 cells in cytokine level can improve the understanding of the effect of co-infected HCV on HIV infection.

Regulatory T cell (Treg) is a subset of CD4⁺ T cells that play a critical role in regulating the immune responses. Human immunodeficiency virus (HIV) infection is associated with T cell abnormalities and alters effector T cell function. There are a large number of patients coinfected with HIV and hepatitis C virus (HCV). Here, we evaluated the proportion of CD4⁺ Treg cells expressing CD25 and FOXP3, and the status of immune activation of CD8⁺ T cells in 60 Chinese patients chronically infected with HIV and/or HCV. Furthermore, we investigated the influence of highly active antiretroviral therapy (HAART) on the level of Treg cells and immune activated CD8⁺ T cells. We observed that the Treg level was upregulated in HIV infection and HCV infection could not enhance this kind of upregulation significantly. The level of Treg cells was negatively correlated with CD4⁺ T cell counts and positively correlated with HIV viral loads. We observed considerably elevated CD38 and HLA-DR expression in CD8⁺ T cells in HIV-infected subjects but not in HCV-infected patients in comparison to that in healthy controls. There is no significant difference concerning the proportion of CD8⁺ T cells expressing CD38 or HLA-DR between HIV-1-monoinfected and HIV/HCV-coinfected patients. After 12-week HAART, the proportion of Treg cells dropped, but still more than the level in healthy controls. HAART could reverse the abnormal immune activation of CD8⁺ T cells. The decrease of Tregs did not alter the downregulation of HIV-1-specific CTL responses in these HIV-infected patients after HAART therapy. The level of HIV virus might be the key point for the decline of CTL responses.

Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections. A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated. On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection. A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar.

Background: SARS-CoV-2 Omicron (BA.2) has stronger infectivity and more vaccine breakthrough capability than previous variants. Few studies have examined the impact of inactivated vaccines on the decrease of viral RNA levels in individuals with the Omicron variant, based on individuals' continuous daily cycle threshold (Ct) values and associated medical information from the infection to hospital discharge on a large population.Methods: We extracted 39,811 individuals from 174,371 Omicron-infected individuals according to data inclusion and exclusion criteria. We performed the survival data analysis and Generalized Estimating Equation to calculate the adjusted relative risk (aRR) to assess the effect of inactivated vaccines on the decrease of viral RNA levels.Results: Negative conversion was achieved in 54.7 and 94.3% of all infected individuals after one and 2 weeks, respectively. aRRs were shown weak effects on turning negative associated with vaccinations in asymptomatic infections and a little effect in mild diseases. Vaccinations had a protective effect on persistent positivity over 2 and 3 weeks. aRRs, attributed to full and booster vaccinations, were both around 0.7 and had no statistical significance in asymptomatic infections, but were both around 0.6 with statistical significance in mild diseases, respectively. Trends of viral RNA levels among vaccination groups were not significant in asymptomatic infections, but were significant between unvaccinated group and three vaccination groups in mild diseases.Conclusion: Inactivated vaccines accelerate the decrease of viral RNA levels in asymptomatic and mild Omicron-infected individuals. Vaccinated individuals have lower viral RNA levels, faster negative conversion, and fewer persisting positive proportions than unvaccinated individuals. The effects are more evident and significant in mild diseases than in asymptomatic infections.