Immune response induced by novel coronavirus infection.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has been prominent around the world since it was first discovered, affecting more than 100 million people. Although the symptoms of most infected patients are not serious, there is still a considerable proportion of patients who need hospitalization and even develop fatal symptoms such as cytokine storms, acute respiratory distress syndrome and so on. Cytokine storm is usually described as a collection of clinical manifestations caused by overactivation of the immune system, which plays an important role in tissue injury and multiorgan failure. The immune system of healthy individuals is composed of two interrelated parts, the innate immune system and the adaptive immune system. Innate immunity is the body's first line of defense against viruses; it can quickly perceive viruses through pattern recognition receptors and activate related inflammatory pathways to clear pathogens. The adaptive immune system is activated by specific antigens and is mainly composed of CD4+ T cells, CD8+ T cells and B cells, which play different roles in viral infection. Here, we discuss the immune response after SARS-CoV-2 infection. In-depth study of the recognition of and response of innate immunity and adaptive immunity to SARS-CoV-2 will help to prevent the development of critical cases and aid the exploration of more targeted treatments.

Development of a model by LASSO to predict hospital length of stay (LOS) in patients with the SARS-Cov-2 omicron variant.

The length of stay (LOS) in hospital varied considerably in different patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The study aimed to explore the clinical characteristics of Omicron patients, identify prognostic factors, and develop a prognostic model to predict the LOS of Omicron patients. This was a single center retrospective study in a secondary medical institution in China. A total of 384 Omicron patients in China were enrolled. According to the analyzed data, we employed LASSO to select the primitive predictors. The predictive model was constructed by fitting a linear regression model using the predictors selected by LASSO. Bootstrap validation was used to test performance and eventually we obtained the actual model. Among these patients, 222 (57.8%) were female, the median age of patients was 18 years and 349 (90.9%) completed two doses of vaccination. Patients on admission diagnosed as mild were 363 (94.5%). Five variables were selected by LASSO and a linear model, and those with P < 0.05 were integrated into the analysis. It shows that if Omicron patients receive immunotherapy or heparin, the LOS increases by 36% or 16.1%. If Omicron patients developed rhinorrhea or occur familial cluster, the LOS increased by 10.4% or 12.3%, respectively. Moreover, if Omicron patients' APTT increased by one unit, the LOS increased by 0.38%. Five variables were identified, including immunotherapy, heparin, familial cluster, rhinorrhea, and APTT. A simple model was developed and evaluated to predict the LOS of Omicron patients. The formula is as follows: Predictive LOS = exp(1*2.66263 + 0.30778*Immunotherapy + 0.1158*Familiar cluster + 0.1496*Heparin + 0.0989*Rhinorrhea + 0.0036*APTT).

Comparison of clinical characteristics between SARS-CoV-2 Omicron variant and Delta variant infections in China.

Background: The continued 'evolution' of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of the Omicron variant after the Delta variant, resulting in a significant increase in the number of people with COVID-19. This increase in the number of cases continues to have a significant impact on lives. Therefore, a more detailed understanding of the clinical characteristics of Omicron infection is essential. Methods: Using medical charts, we extracted clinical information for 384 patients infected with the Omicron variant in Anyang City, Henan Province, China. Epidemiology and clinical characteristics were compared with a cohort of people infected with the Delta variant in Zhengzhou in 2021. Findings: Common initial symptoms at onset of illness were cough [240 (63%)], expectoration [112 (29%)], fever [96 (25%)], nasal congestion [96 (25%)] and myalgia or fatigue [30 (6%)]. In patients with the Omicron variant, levels of total cholesterol, low-density lipoprotein and creatinine increased in 52 (14%), 36 (9%) and 58 (15%) patients, respectively, compared with patients with the Delta variant [one (1%), one (1%) and two (2%)]. Levels of triglyceride and high-density lipoprotein also increased. In patients with the Omicron variant, the levels of specific gravity and the erythrocyte sedimentation rate were increased in 115 (30%) and 81 (21%) patients, and serum levels of complement 3 decreased in 93 (41%). Results: Compared with patients infected with Delta, no major differences in initial clinical symptoms were identified in patients infected with Omicron. However, dyslipidemia and kidney injury were much more severe in patients with the Omicron variant, and the erythrocyte sedimentation rate was increased. Due to decreased levels of complement 3, the immunity of patients with the Omicron variant was weak.

Comparison of clinical characteristics between SARS-CoV-2 Omicron variant and Delta variant infections in China

Background The continued ‘evolution’ of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of the Omicron variant after the Delta variant, resulting in a significant increase in the number of people with COVID-19. This increase in the number of cases continues to have a significant impact on lives. Therefore, a more detailed understanding of the clinical characteristics of Omicron infection is essential. Methods Using medical charts, we extracted clinical information for 384 patients infected with the Omicron variant in Anyang City, Henan Province, China. Epidemiology and clinical characteristics were compared with a cohort of people infected with the Delta variant in Zhengzhou in 2021. Findings Common initial symptoms at onset of illness were cough [240 (63%)], expectoration [112 (29%)], fever [96 (25%)], nasal congestion [96 (25%)] and myalgia or fatigue [30 (6%)]. In patients with the Omicron variant, levels of total cholesterol, low-density lipoprotein and creatinine increased in 52 (14%), 36 (9%) and 58 (15%) patients, respectively, compared with patients with the Delta variant [one (1%), one (1%) and two (2%)]. Levels of triglyceride and high-density lipoprotein also increased. In patients with the Omicron variant, the levels of specific gravity and the erythrocyte sedimentation rate were increased in 115 (30%) and 81 (21%) patients, and serum levels of complement 3 decreased in 93 (41%). Results Compared with patients infected with Delta, no major differences in initial clinical symptoms were identified in patients infected with Omicron. However, dyslipidemia and kidney injury were much more severe in patients with the Omicron variant, and the erythrocyte sedimentation rate was increased. Due to decreased levels of complement 3, the immunity of patients with the Omicron variant was weak.

Clinical Characteristics of Omicron SARS-CoV-2 Variant Infection After Non-mRNA-Based Vaccination in China.

Introduction: To date, little is known about the real-world protective role of Chinese inactivated and recombinant coronavirus disease 2019 (COVID-19) vaccines under the background of the long-term "Dynamic Zero COVID-19 Case" (i.e., no infection source) in China, especially when facing the widespread Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection. Methods: In this prospective, single-center cohort study, the clinical characteristics of post-vaccination Omicron SARS-CoV-2 variant infection were investigated in the initial largest outbreak of Omicron SARS-CoV-2 variant infection that occurred between the 8 January, 2022 and 29 January, 2022 in Anyang City, Henan Province, China. The primary endpoints were the rates of severe and critical diseases or death. The secondary endpoints were the SARS-CoV-2 shedding duration and length of hospitalization. Results: A total of 380 post-vaccination patients infected with the Omicron SARS-CoV-2 variant were enrolled. The median age was 18 (interquartile range [IQR] 17-35) years, 219 (57.6%) cases were female, and 247 (65.0%) cases were students. Before confirmation of Omicron SARS-CoV-2 variant infection, patients had 3 (IQR 2-4) days of dry cough (40.3%), nasal congestion (26.3%), and sore throat (26.3%). On admission, 294 (77.4%) cases had normal chest computerized tomography (CT) imaging. Additionally, only 5 (1.3%), 30 (7.9%), 4 (4/342, 1.2%), and 7 (7/379, 0.2%) patients had lymphocyte counts <800 per mm3, C-reactive protein levels >10 mg/L, lactate dehydrogenase levels ≥250 U/L, and D-dimer levels ≥0.5 mg/L on admission, respectively. During hospitalization, 308 (81.1%) and 72 (18.9%) were identified as mild and moderate cases, respectively, and no one progressed to severe and critical types, with a SARS-CoV-2 shedding period and length of hospital stay of 17 (IQR 12-22) and 19 (IQR 15-24) days, respectively. Conclusion: The current study found that approximately 80% of individuals infected with the Omicron SARS-CoV-2 variant were mild, approximately 20% of patients were moderate, and no severe, critical, or fatal cases were identified in a prospective cohort including 380 participants vaccinated with non-mRNA-based vaccines. Discussion: This study supports the consideration of policy adjustments and changes to prevent and control the Omicron-predominant COVID-19 in China and other regions with high SARS-CoV-2 vaccination rates.

Characterization of oral and gut microbiome and plasma metabolomics in COVID-19 patients after 1-year follow-up.

BACKGROUND: Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery. METHODS: We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing. RESULTS: The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later. CONCLUSIONS: This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare.

Clinical Characteristics of Omicron SARS-CoV-2 Variant Infection After Non-mRNA-Based Vaccination in China

Introduction To date, little is known about the real-world protective role of Chinese inactivated and recombinant coronavirus disease 2019 (COVID-19) vaccines under the background of the long-term “Dynamic Zero COVID-19 Case” (i.e., no infection source) in China, especially when facing the widespread Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection. Methods In this prospective, single-center cohort study, the clinical characteristics of post-vaccination Omicron SARS-CoV-2 variant infection were investigated in the initial largest outbreak of Omicron SARS-CoV-2 variant infection that occurred between the 8 January, 2022 and 29 January, 2022 in Anyang City, Henan Province, China. The primary endpoints were the rates of severe and critical diseases or death. The secondary endpoints were the SARS-CoV-2 shedding duration and length of hospitalization. Results A total of 380 post-vaccination patients infected with the Omicron SARS-CoV-2 variant were enrolled. The median age was 18 (interquartile range [IQR] 17–35) years, 219 (57.6%) cases were female, and 247 (65.0%) cases were students. Before confirmation of Omicron SARS-CoV-2 variant infection, patients had 3 (IQR 2–4) days of dry cough (40.3%), nasal congestion (26.3%), and sore throat (26.3%). On admission, 294 (77.4%) cases had normal chest computerized tomography (CT) imaging. Additionally, only 5 (1.3%), 30 (7.9%), 4 (4/342, 1.2%), and 7 (7/379, 0.2%) patients had lymphocyte counts <800 per mm3, C-reactive protein levels >10 mg/L, lactate dehydrogenase levels ≥250 U/L, and D-dimer levels ≥0.5 mg/L on admission, respectively. During hospitalization, 308 (81.1%) and 72 (18.9%) were identified as mild and moderate cases, respectively, and no one progressed to severe and critical types, with a SARS-CoV-2 shedding period and length of hospital stay of 17 (IQR 12–22) and 19 (IQR 15–24) days, respectively. Conclusion The current study found that approximately 80% of individuals infected with the Omicron SARS-CoV-2 variant were mild, approximately 20% of patients were moderate, and no severe, critical, or fatal cases were identified in a prospective cohort including 380 participants vaccinated with non-mRNA-based vaccines. Discussion This study supports the consideration of policy adjustments and changes to prevent and control the Omicron-predominant COVID-19 in China and other regions with high SARS-CoV-2 vaccination rates.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

Alterations in the human oral and gut microbiomes and lipidomics in COVID-19.

OBJECTIVE: To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile. DESIGN: We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity. RESULTS: Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery. CONCLUSION: This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.

Characteristic of 523 COVID-19 in Henan Province and a Death Prediction Model.

Certain high-risk factors related to the death of COVID-19 have been reported, however, there were few studies on a death prediction model. This study was conducted to delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) of different degree and establish a death prediction model. In this multi-centered, retrospective, observational study, we enrolled 523 COVID-19 cases discharged before February 20, 2020 in Henan Province, China, compared clinical data, screened for high-risk fatal factors, built a death prediction model and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan. Out of the 523 cases, 429 were mild, 78 severe survivors, 16 non-survivors. The non-survivors with median age 71 were older and had more comorbidities than the mild and severe survivors. Non-survivors had a relatively delay in hospitalization, with higher white blood cell count, neutrophil percentage, D-dimer, LDH, BNP, and PCT levels and lower proportion of eosinophils, lymphocytes and albumin. Discriminative models were constructed by using random forest with 16 non-survivors and 78 severe survivors. Age was the leading risk factors for poor prognosis, with AUC of 0.907 (95% CI 0.831-0.983). Mixed model constructed with combination of age, demographics, symptoms, and laboratory findings at admission had better performance (p = 0.021) with a generalized AUC of 0.9852 (95% CI 0.961-1). We chose 0.441 as death prediction threshold (with 0.85 sensitivity and 0.987 specificity) and validated the model in 429 mild cases, six fatal cases discharged after February 16, 2020 from Henan and 14 cases from Wuhan successfully. Mixed model can accurately predict clinical outcomes of COVID-19 patients.

A Randomized, Open-Label, Controlled Clinical Trial of Azvudine Tablets in the Treatment of Mild and Common COVID-19, a Pilot Study.

Coronavirus disease 2019 (COVID-19) has spread worldwide. To date, no specific drug for COVID-19 has been developed. Thus, this randomized, open-label, controlled clinical trial (ChiCTR2000029853) was performed in China. A total of 20 mild and common COVID-19 patients were enrolled and randomly assigned to receive azvudine and symptomatic treatment (FNC group), or standard antiviral and symptomatic treatment (control group). The mean times of the first nucleic acid negative conversion (NANC) of ten patients in the FNC group and ten patients in the control group are 2.60 (SD 0.97; range 1-4) d and 5.60 (SD 3.06; range 2-13) d, respectively (p = 0.008). The mean times of the first NANC of four newly diagnosed subjects in the FNC group and ten subjects in the control group are 2.50 (SD 1.00; range 2-4) d and 9.80 (SD 4.73; range 3-19) d, respectively (starting from the initial treatment) (p = 0.01). No adverse events occur in the FNC group, while three adverse events occur in the control group (p = 0.06). The preliminary results show that FNC treatment in the mild and common COVID-19 may shorten the NANC time versus standard antiviral treatment. Therefore, clinical trials of FNC treating COVID-19 with larger sample size are warranted.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.