3044 Cases reveal important prognosis signatures of COVID-19 patients.

Critical patients and intensive care unit (ICU) patients are the main population of COVID-19 deaths. Therefore, establishing a reliable method is necessary for COVID-19 patients to distinguish patients who may have critical symptoms from other patients. In this retrospective study, we firstly evaluated the effects of 54 laboratory indicators on critical illness and death in 3044 COVID-19 patients from the Huoshenshan hospital in Wuhan, China. Secondly, we identify the eight most important prognostic indicators (neutrophil percentage, procalcitonin, neutrophil absolute value, C-reactive protein, albumin, interleukin-6, lymphocyte absolute value and myoglobin) by using the random forest algorithm, and find that dynamic changes of the eight prognostic indicators present significantly distinct within differently clinical severities. Thirdly, our study reveals that a model containing age and these eight prognostic indicators can accurately predict which patients may develop serious illness or death. Fourthly, our results demonstrate that different genders have different critical illness rates compared with different ages, in particular the mortality is more likely to be attributed to some key genes (e.g. ACE2, TMPRSS2 and FURIN) by combining the analysis of public lung single cells and bulk transcriptome data. Taken together, we urge that the prognostic model and first-hand clinical trial data generated in this study have important clinical practical significance for predicting and exploring the disease progression of COVID-19 patients.

Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated. METHODS: The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients. RESULTS: In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases. CONCLUSION: A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1ß, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment.

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.

Evolution of COVID-19 in patients with autoimmune rheumatic diseases.

The characteristics of COVID-19 patients with autoimmune rheumatic diseases (AIRD) have rarely been reported. Patients with AIRD have suppressed immune defense function, which may increase their susceptibility to COVID-19. However, the immunosuppressive agents AIRD patients routinely used may be beneficial for protecting the cytokine storm caused by SARS-CoV-2. In this retrospective study, we included all confirmed cases in Huoshenshan Hospital from February 4 to April 9. Data were extracted from electronic medical records and were analyzed for clinical and laboratory features using SPSS (version 25.0). Of 3059 patients, 21 had the comorbidities with systematic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA), including 5 with SLE, 15 with RA, and 1 with Rhupus. The proportion was 57.1% for severe cases, 61.9% for either severe or critical cases, and 4.8% for critical cases. The main manifestations, ARDS and ICU admission rate, as well as the mortality and length of hospital stay of COVID-19 in AIRD patients were similar to COVID-19 patients in the general population. Our preliminary experience shows that patients with AIRD tend to have a higher risk of SARS-CoV-2 infection, and may be at risk for a severe but less likely critical disease course. Further investigation is needed to understand the immunological features of these diseases.

Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19.

Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.

Successful recovery of COVID-19-associated recurrent diarrhea and gastrointestinal hemorrhage using convalescent plasma.

BACKGROUND: Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. CASE PRESENTATION: We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. CONCLUSION: When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.