Ligand/Receptor-mediated Cell Communication Alteration Causes the Lung Inflammation Microenvironment and the Redistribution of Inter-tissue Immune Cells in COVID-19 Patients (preprint)

How SARS-CoV-2 causes disturbances of the lung microenvironment and systemic immune response remains a mystery. Here, we first analyze detailedly paired single-cell transcriptome data of the lungs, blood and bone marrow of two patients who died of COVID-19. Second, our results demonstrate that SARS-CoV-2 infection significantly increases the cellular communication frequency between AT1/AT2 cells and highly inflammatory myeloid cells, and induces the pulmonary inflammation microenvironment, and drives the disorder of fibroblasts, club and ciliated cells, thereby causing the increase of pulmonary fibrosis and mucus accumulation. Third, our works reveal that the increase of the lung T cell infiltration is mainly recruited by myeloid cells through certain ligands/receptors (ANXA1/FPR1, C5AR1/RPS19 and CCL5/CCR1), rather than AT1/AT2. Fourth, we find that some ligands and receptors such as ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1, are significantly activated and shared among patients’ lungs, blood and bone marrow, implying that dysregulated ligands and receptors may cause the migration, redistribution and the inflammatory storm of immune cells in different tissues. Overall, our study reveals a latent mechanism by which the disorders of ligands and receptors caused by SARS-CoV-2 infection drive cell communication alteration, the pulmonary inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

Aspergillus But Not Candida: Fatal Fungus Infection in COVID-19 Critical Patients (preprint)

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups.Design: Single center retrospective studyPatients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases.Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group.Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented.Funding Statement: This study was financially supported by grants Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research& Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Medical Ethical Committee of Wuhan Huoshenshan Hospital (No. HSSLL011). Written informed consent was obtained from each patient.

The Dynamic Changes of Antibodies against SARS-CoV-2 during the Infection and Recovery of COVID-19 (preprint)

Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P<0.01). The decrease of these IgG levels indicates the poor outcome of severe/critical patients. The RBD- and S-specific IgG levels are 2-fold higher in virus-free patients (P<0.05). Notably, we found that the patients who got re-infected had a low level of protective antibody on discharge. Therefore, our evidence proves that the dynamic changes of antibodies could provide an important reference for diagnosis, monitoring, and treatment, and shed new light on the precise management of COVID-19.