Characterization of oral bacterial and fungal microbiome in recovered COVID-19 patients.

COVID-19 has emerged as a global pandemic, challenging the world's economic and health systems. Human oral microbiota comprises the second largest microbial community after the gut microbiota and is closely related to respiratory tract infections; however, oral microbiomes of patients who have recovered from COVID-19 have not yet been thoroughly studied. Herein, we compared the oral bacterial and fungal microbiota after clearance of SARS-CoV-2 in 23 COVID-19 recovered patients to those of 29 healthy individuals. Our results showed that both bacterial and fungal diversity were nearly normalized in recovered patients. The relative abundance of some specific bacteria and fungi, primarily opportunistic pathogens, decreased in recovered patients (RPs), while the abundance of butyrate-producing organisms increased in these patients. Moreover, these differences were still present for some organisms at 12 months after recovery, indicating the need for long-term monitoring of COVID-19 patients after virus clearance.

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China.

BACKGROUND: Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient's serum to establish a solid pathogen diagnosis. CASE PRESENTATION: We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient's abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient's serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. CONCLUSION: The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.

Kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19: a descriptive study.

BACKGROUND: To explore the kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19. METHODS: This observational study enrolled 20 patients with COVID-19, who were hospitalized between January 20-April 6, 2020, in the two COVID-19 designated hospitals of Zhoushan, Zhejiang and Rushan, Shandong, China, The laboratory findings, imaging, serum response to viral infection, and viral RNA level in the throat and stool samples were assessed from onset to recovery phase in patients with COVID-19. RESULTS: SARS-COV-2 RNA was positive as early as day four. It remained positive until day 55 post-onset in the sputum-throat swabs and became negative in most cases (55%) within 14 days after onset. Lymphocytopenia occurred in 40% (8/20) of patients during the peak infection period and returned to normal at week five. The most severe inflammation in the lungs appeared in week 2 or 3 after onset, and this was completely absorbed between week 6 and 8 in 85.7% of patients. All patients had detectable antibodies to the receptor binding domain (RBD), and 95% of these patients had IgG to viral N proteins. The antibody titer peaked at week four. Anti-S IgM was positive in 7 of 20 patients after week three. CONCLUSIONS: All COVID-19 patients in this study were self-limiting and recovered well though it may take as long as 6-8 weeks. Our findings on the kinetic changes in imaging, serum response to viral infection and viral RNA level may help understand pathogenesis and define clinical course of COVID-19.

Systematic profiling of antigen bias in humoral response against SARS-CoV-2.

We know little about the antigen bias in SARS-CoV-2 humoral response and the epitopes of spike recognized by the immune system in asymptomatic (AS) patients and symptomatic (S) patients. Here, we used a microarray to evaluate the humoral immune response in the sera collected from 33 COVID-19-recovered patients up to 1 year. We found that the levels of IgG and IgM induced by the 23 proteins differed significantly in the same patients, and were able to distinguish AS and S patients. The N- and S-specific antibodies were detected even at 12 months after onset. Five epitopes were identified to be associated with the clinical adverse events, and three peptides located in RBD. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses between AS and S recovered patients and provide insights to promote precise development of SARS-CoV-2 vaccines.

[Clinical significance of serum differential protein examination in chronic hepatitis B related liver fibrosis].

OBJECTIVE: To investigate the clinical significance of the expression of serum differential protein in patients with chronic hepatitis B (CHB) related liver fibrosis. METHODS: One hundred and ten CHB patients confirmed by liver biopsies were enrolled, 83 for modeling and 27 for verification. According to Ishak staging, 55 patients in the modeling group were with significant liver fibrosis ( F is more than or equal to 3 ) and 28 patients with normal/mild liver fibrosis ( F0-F2 ). While that in the verification group were 15 ( F is more than or equal to 3 ) and 12 ( F0-F2 ), respectively. MALDI-TOF-MS/MS was used to detect serum proteins and the spectrum for each sample was analyzed in FlexAnalysis3.0 to produce the spectrum of differential proteins. The results were compared with clinicopathologic diagnosis and the diagnosis model based on genetic algorithm was established and evaluated. RESULTS: There were 15 proteins differentially expressed in significant liver fibrosis group and normal/mild fibrosis group ( P value is less than 0.01), in which the differences on proteins 2081.73 m/z and 1944.41 m/z were the most significant. Based on these two proteins, the coordinate system was set up and the diagnosis model based on genetic algorithm was established by six characteristic peaks. After detecting 12 cases of normal/mild liver fibrosis and 15 cases of significant liver fibrosis, the results showed that the diagnostic model could identify significant fibrosis ( F is more than or equal to 3 ) and normal/mild liver fibrosis ( F0-F2 ) at 100% recognition, 94.14% prediction and 100% accuracy. CONCLUSION: Serum differential proteins examination can be used for early prediction of CHB related fibrosis. The study provides the basis for non-invasive diagnosis of hepatic fibrosis according to identifying the potential differences of the serum samples from patients with HBV related fibrosis.

Sporadic case infected by severe fever with thrombocytopenia syndrome bunyavirus in a non-epidemic region of China.

We report here a clinical and molecular study on a case suffer from severe fever with thrombocytopenia syndrome (SFTS) due to a new type of bunyavirus, named SFTS bunyavirus (SFTSV), in Zhejiang Province China. The key clinical features of this patient include fever, lymphocytopenia and thrombocytopenia. We carried out a serological and molecular investigation in the indicated case and on relatives with close contact. The SFTSV infection was confirmed through amplification of viral genetic material using the polymerase chain reaction (PCR) from the patient's serum, but not relatives with close contact. Subsequently direct sequence of PCR product demonstrated a homology of 94-96% in the nucleotide sequence compared to a reference sequence previously reported, in which the majority of patients originated from an epidemic area of Central and Northeast China. Our results suggest that SFTSV can occur in a non-epidemic area due to a similar strain of SFTSV that apparently affect the blood system, implying the importance of dissecting the pathogenesis of SFTS as well as mode of infection.