Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings.

The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key laboratory tests in patients with COVID-19, and identify independent prognostic factors by examining the associations between laboratory findings and outcomes of patients. This multicenter study included 56 patients with COVID-19 treated in Jilin Province, China, from January 21, 2020 to March 5, 2020. The laboratory findings, epidemiological characteristics and demographic data were extracted from electronic medical records. The average value of eosinophils and carbon dioxide combining power continued to significantly increase, while the average value of cardiac troponin I and mean platelet volume decreased throughout the course of the disease. The average value of lymphocytes approached the lower limit of the reference interval for the first 5 days and then rose slowly thereafter. The average value of thrombocytocrit peaked on day 7 and slowly declined thereafter. The average value of mean corpuscular volume and serum sodium showed an upward trend from day 8 and day 15, respectively. Age, sex, lactate dehydrogenase, platelet count and globulin level were included in the final model to predict the probability of recovery. The above parameters were verified in 24 patients with COVID-19 in another area of Jilin Province. The risk stratification and management of patients with COVID-19 could be improved according to the temporal trajectories of laboratory tests.

Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.

The relationship between nutritional status and the prognosis of COVID-19: A retrospective analysis of 63 patients.

ABSTRACT: It is important for patients to maintain a good nutritional status as a health promotion strategy to improve the immune function and thus the prognosis of coronavirus disease 2019 (COVID-19).The objective of this retrospective study is to analyze the relationships of nutritional status with inflammation levels, protein reserves, baseline immune status, severity, length of hospital stay, and prognosis of COVID-19 patients.A total of 63 COVID-19 patients hospitalized in the People's Hospital and the Traditional Chinese Medicine Hospital of the Xinzhou District, Wuhan, China, from January 29, 2020 to March 17, 2020. Sixty-three patients were divided into 3 groups according to the guidelines, moderate (n = 22), severe (n = 14), and critical (n = 25), respectively. The differences in the total nutrition risk screening (NRS) score, inflammation level, protein reserve, baseline immune status, length of hospital stay, and prognosis were compared among patients with moderate, severe, and critical COVID-19.Patients with higher NRS scores tend to have more severe COVID-19, higher C-reactive protein and serum procalcitonin levels, higher white blood cell counts, lower lymphocyte counts, and higher mortality rates (P < .05).Nutritional status may be an indirect factor of the severity and prognosis of COVID-19.

Characteristics of laboratory findings of COVID-19 patients with comorbid diabetes mellitus.

AIMS: Coronavirus disease (COVID-19), also referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is instigated by a novel coronavirus. The disease was initially reported in Wuhan, China, in December 2019. Diabetes is a risk factor associated with adverse outcomes. Herein, our objective was to investigate the characteristics of laboratory findings of type 2 diabetes mellitus (T2DM) patients infected with SARS-CoV-2. METHODS: This was a retrospective study and included 80 T2DM patients of Jinling Hospital from 2010 to 2020, as well as 76 COVID-19 patients without T2DM and 55 COVID-19 patients with T2DM who were treated at Huoshen hill Hospital from February 11 to March 18, 2020. We then compared the differences in laboratory test results between the three groups. RESULTS: The levels of lymphocytes, uric acid (UA), and globulin in the T2DM group were significantly higher. In contrast, C-reactive protein (CRP), creatinine, and lactic dehydrogenase (LDH)levels were lower than those in the COVID-19 (p < 0.05) and COVID-19 + T2DM groups (p < 0.05). No considerable difference was observed regarding the levels of alanine aminotransferase (ALT), white blood cell (WBC), aspartate aminotransferase (AST), globulin, and blood urea nitrogen (BUN) in the three groups (p > 0.05). CONCLUSION: T2DM patients infected with SARS-CoV-2 showed decreased levels of body mass index (BMI), lymphocytes, UA, and albumin, and increased CRP levels. The decreased BMI, UA, and albumin levels may be associated with oxidative stress response and nutritional consumption. The decreased lymphocyte counts and increased CRP levels may be related to the infection.

Immune-related factors associated with pneumonia in 127 children with coronavirus disease 2019 in Wuhan.

OBJECTIVE: Information regarding the association of immune-related factors with pneumonia in children with coronavirus disease 2019 (COVID-19) is scarce. This study aims to summarize the immune-related factors and their association with pneumonia in children with COVID-19. METHODS: Children with COVID-19 at Wuhan Children's Hospital from 28 January to 12 March 2020 were enrolled. Pneumonia due to causes other than COVID-19 were excluded. The clinical and laboratory information including routine blood tests, blood biochemistry, lymphocyte subsets, immunoglobulins, cytokines, and inflammatory factors were analyzed retrospectively in 127 patients. Normal ranges and mean values of laboratory markers were applied as parameters for logistic regression analyses of their association with pneumonia. RESULTS: In nonintensive care unit patients, 48.8% and 22.4% of patients had increased levels of procalcitonin and hypersensitive C-reactive protein (hs-CRP) respectively. A total 12.6% and 18.1% of patients had decreased levels of immunoglobulin A (IgA) and interleukin 10 (IL-10), respectively. Approximately 65.8% of patients had pneumonia. These patients had decreased levels of globulin (odds ratio [OR], 3.13; 95% confidence interval [CI] 1.41-6.93; P = .005), IgA (OR, 4.00; 95% CI, 1.13-14.18; P = .032), and increased levels of hs-CRP (OR, 3.14; 95% CI, 1.34-7.36; P = .008), procalcitonin (OR, 3.83; 95% CI, 2.03-7.24; P < .001), IL-10 (OR, 7.0; 95% CI, 1.59-30.80; P = .010), and CD4+ CD25+ T lymphocyte less than 5.0% (OR, 1.93; 95% CI, 1.04-3.61; P = 0.038). CONCLUSION: Decreased IgA and CD4+ CD25+ T lymphocyte percentage, and increased hs-CRP, procalcitonin, and IL-10 were associated with pneumonia, suggesting that the immune-related factors may participate in the pathogenesis of pneumonia in children with COVID-19.