Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in COVID-19-convalescent individuals.

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-3 and individuals with COVID-19 have symptoms that can be asymptomatic, mild, moderate or severe4,5. In the early phase of infection, T- and B-cell counts are substantially decreased6,7; however, IgM8-11 and IgG12-14 are detectable within 14 d after symptom onset. In COVID-19-convalescent individuals, spike-specific neutralizing antibodies are variable3,15,16. No specific drug or vaccine is available for COVID-19 at the time of writing; however, patients benefit from treatment with serum from COVID-19-convalescent individuals17,18. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in COVID-19-convalescent individuals are largely unknown. Here, we show that the majority of COVID-19-convalescent individuals maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus, and that some of the antibodies cross-neutralized SARS-CoV, Middle East respiratory syndrome coronavirus or both pseudotyped viruses. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titres, a faster increase in lymphocyte counts and a higher frequency of CXCR3+ T follicular help (TFH) cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating TFH cells were spike specific and functional, and the frequencies of CXCR3+ TFH cells were positively associated with neutralizing antibody titres in COVID-19-convalescent individuals. No individuals had detectable autoantibodies. These findings provide insights into neutralizing antibody responses in COVID-19-convalescent individuals and facilitate the treatment and vaccine development for SARS-CoV-2 infection.

Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population.

BACKGROUND AND AIM: Hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are known to be prevalent in injection drug users (IDUs); however, the relationship between the molecular epidemiologic features of hepatitis virus infection in high-risk individuals and the general population has not yet been established. METHODS: In total, 1049 IDUs and 672 individuals who underwent physical examinations at Chenzhou hospital, Hunan Province, China, were enrolled. HBV, HCV, and HDV infections were screened with serologic tests in both populations. HBsAg-positive, anti-HCV IgG-positive, and anti-HDV IgG-positive samples were further confirmed by polymerase chain reaction, quantitative polymerase chain reaction, and DNA sequencing. RESULTS: Significantly higher HBV (21.54 vs 16.52%, P = 0.01), HCV (45.95% vs 1.34%, P < 0.001), and HDV (5.62% vs 0.30%, P < 0.001) infections were detected in IDUs compared with the general population. The dual infection of HBV/HCV or HBV/HDV was also significantly higher in IDUs than in the general population. HBV genotype B and HDV genotype II were dominants in both populations. HCV infection showed genotype 6a (49.52%) dominant in IDUs, but genotype 1b accounted for 50% infection, which was followed by genotype 6a (33.33%) in the general population. Higher viral loads were associated with HBV genotype B and HCV genotype 6a compared with non-dominant genotypic infections. CONCLUSIONS: HBV and HDV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations. Our results suggest different molecular epidemiologic characteristics of HBV, HCV, and HDV infection in two populations.

HBV/HCV dual infection impacts viral load, antibody response, and cytokine expression differently from HBV or HCV single infection.

Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common among high-risk individuals. To characterize the virological and immunological features of patients with HBV/HCV dual infection, we enrolled 1,049 individuals who have been identified as injection drug users. Patients were divided into single and dual infection groups according to the serological markers. We found the average HCV RNA level was significantly lower; however, HBV viral load was significantly higher in HBV/HCV dual-infected patients (n = 42) comparing HCV single infection (n = 340) or HBV single infection (n = 136). The level of anti-HBs in patients who experienced spontaneous HBV clearance was higher than that in HCV single-infected patients with HBV spontaneous clearance. The level of anti-HCV E2 in HBV/HCV dual infection was lower than that detected in HCV single infection. Serum levels of IL-6, IL-8, and TNF-α were significantly lower in HBV/HCV dual-infected patients than in patients infected with HBV or HCV alone. Taken together, two viral replications are imbalanced in dual infected patients. The anti-HBs and anti-HCV E2 antibody production were impaired and proinflammatory IL-6, IL-8, and TNF-α also downregulated due to dual infection. These findings will help further understanding the pathogenesis of HBV/HCV dual infection.