BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Aged ; Antibodies, Viral ; COVID-19/therapy* ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; Immunization, Passive ; Recombinant Fusion Proteins ; SARS-CoV-2

Novel coronavirus disease 2019 (COVID-19) has started to erupt in Wuhan since December 2019, and then the cases of COVID-19 increased rapidly, the epidemic situation spreaded to most area of China. Owing to the lack of specific drugs at present, convalescent plasma therapy becomes an alternative treatment. However, the choice of the donor, suitable patients, timing of treatment, administrate dose, the advantages and disadvantages of the treatment are not clear. This article reviews the clinical studies and case reports of convalescent plasma therapy in several previous viral infectious diseases in order to provide clues for the treatment of COVID-19.
Blood Component Transfusion ; COVID-19/therapy* ; China ; Communicable Diseases ; Humans ; Immunization, Passive ; Plasma ; SARS-CoV-2

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.
Amino Acid Motifs ; Animals ; Antiviral Agents ; Betacoronavirus ; genetics ; China ; epidemiology ; Communicable Disease Control ; methods ; Coronavirus Infections ; diagnosis ; epidemiology ; physiopathology ; prevention & control ; therapy ; Humans ; Immunization, Passive ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; diagnosis ; epidemiology ; physiopathology ; therapy ; Protein Domains ; Spike Glycoprotein, Coronavirus ; chemistry ; Viral Vaccines

OBJECTIVES: To evaluate curative effects of coronavirus disease 2019 (COVID-19) patients by the transfusion of other convalescent plasma. METHODS: Retrospective analysis of the clinical data of 18 patients with severe and critical COVID-19, who were hospitalized in the ICU of Xianghu Branch of the First Affiliated Hospital of Nanchang University from February 1 to March 15, 2020. Patients were subdivided into an experimental group (=6, who had transfused the plasma) and an observation group (=12, who had no plasma transfusion). Basic clinical data and prognosis indexes of these two groups were compared. Moreover, for the experimental group, the dynamic changes of blood oxygen saturation before and after the transfusion, the changes of lymphocyte absolute value 48 hours after the transfusion, and the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid were analyzed. RESULTS: There were no significant differences in age, gender, blood type and other basic clinical data between the two groups (all >0.05).There were no significant differences in ventilator machine weaning time, extracorporeal membrane oxygenation (ECMO) weaning time, body temperature recovery to normal time, and hospitalization days between these two groups (all >0.05). For the experimental group, before, during and after the convalescent plasma transfusion, the blood oxygen saturation of all 6 patients at all time (1, 6, 8, 12, 24, 36, and 48 h) was more than 90%, and there was no significant fluctuation. There were 3 patients whose absolute value of lymphocyte was increased 48 hours after the transfusion, and the remaining was decreased. There were 5 patients whose SARS-CoV-2 nucleic acid detection turned negative 48 hours after the transfusion, accounting for 83.3%. CONCLUSIONS Transfusion of convalescent plasma will not affect outcomesof COVID-19 patients, which can neutralize SARS-CoV-2 in patients and reduce the loading capacity of SARS-CoV-2.
Betacoronavirus ; Blood Component Transfusion ; China ; Coronavirus Infections ; therapy ; Humans ; Immunization, Passive ; Pandemics ; Plasma ; Pneumonia, Viral ; therapy ; Retrospective Studies

OBJECTIVES: To explore the influential factors and titer trend of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgG antibody in convalescent patients with coronavirus disease 2019 (COVID-19), and to provide theoretical basis for the feasibility of clinical treatment of convalescent plasma. METHODS: Colloidal gold immunochromatography assay was used to detect the SARS-CoV-2 specific IgG antibody and its titer in 113 convalescent patients with COVID-19 who were followed up from February 19, 2020 to April 6, 2020. The basic characteristics and treatment factors of patients in the high titer group (antibody titer≥1꞉160, RESULTS: The difference in the clinical type of COVID-19, onset time, first admission C-reactive protein, absolute value of lymphocyte, absolute value of CD19 CONCLUSIONS Male COVID-19 patients might be more likely to produce high titer SARS-CoV-2 specific IgG antibodies than female. The peak level of SARS-CoV-2 specific IgG antibody in convalescent patients is maintained for a short period. Using plasma from convalescent COVID-19 patients for treatment should be within 28 d after discharge.
Antibodies, Viral ; Betacoronavirus ; COVID-19/therapy* ; Female ; Humans ; Immunization, Passive ; Immunoglobulin G ; Male ; Pandemics ; Pneumonia, Viral/epidemiology* ; SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first affected humans in China on December 31, 2019 (Shi et al., 2020). Coronaviruses generally cause mild, self-limiting upper respiratory tract infections in humans, such as the common cold, pneumonia, and gastroenteritis (To et al., 2013; Berry et al., 2015; Chan et al., 2015). According to the Report of the World Health Organization (WHO)-China Joint Mission on COVID-19 (WHO, 2020), the case fatality rate of COVID-19 increases with age, while the rate among males is higher than that among females (4.7% and 2.8%, respectively). Since an effective vaccine and specific anti-viral drugs are still under development, passive immunization using the convalescent plasma (CP) of recovered COVID-19 donors may offer a suitable therapeutic strategy for severely ill patients in the meantime. So far, several studies have shown therapeutic efficacy of CP transfusion in treating COVID-19 cases. A pilot study first reported that transfusion of CP with neutralizing antibody titers above 1:640 was well tolerated and could potentially improve clinical outcomes through neutralizing viremia in severe COVID-19 cases (Chen et al., 2020). Immunoglobulin G (IgG) and IgM are the most abundant and important antibodies in protecting the human body from viral attack (Arabi et al., 2015; Marano et al., 2016). Our study aimed to understand the aspects of plasma antibody titer levels in convalescent patients, as well as assessing the clinical characteristics of normal, severely ill, and critically ill patients, and thus provide a basis for guiding CP therapy. We also hoped to find indicators which could serve as a reference in predicting the progression of the disease.
Adult ; Aged ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; COVID-19/therapy* ; China ; Female ; Humans ; Immunization, Passive ; Immunoglobulin G/blood* ; Immunoglobulin M/blood* ; Male ; Middle Aged

Kawasaki disease is a form of vasculitis, mainly in small and medium arteries of unknown origin, occurring frequently in childhood. It is the leading form of childhood-onset acquired heart disease in developed countries and leads to complications of coronary artery aneurysms in approximately 25% of cases if left untreated. Although more than half a century has passed since Professor Tomisaku Kawasaki's first report in 1957, the cause is not yet clear. Currently, intravenous immunoglobulin therapy has been established as the standard treatment for Kawasaki disease. Various treatment strategies are still being studied under the slogan, “Ending powerful inflammation in the acute phase as early as possible and minimizing the incidence of coronary artery lesions,” as the goal of acute phase treatments for Kawasaki disease. Currently, in addition to immunoglobulin therapy, steroid therapy, therapy using infliximab, biological products, suppression of elastase secretion inside and outside the neutrophils, inactivated ulinastatin therapy and cyclosporine therapy, plasma exchange, etc. are performed. This chapter outlines the history and transition of the acute phase treatment for Kawasaki disease.
Aneurysm ; Arteries ; Biological Products ; Coronary Vessels ; Cyclosporine ; Developed Countries ; Heart Diseases ; Immunization, Passive ; Incidence ; Inflammation ; Infliximab ; Mucocutaneous Lymph Node Syndrome ; Neutrophils ; Pancreatic Elastase ; Plasma Exchange ; Prednisolone ; Vasculitis

Varicella-zoster virus (VZV) causes a highly contagious and generally benign, self-limited disease. However, in high-risk populations including immunocompromised patients, pregnant women, and neonates, VZV infection can be associated with significant morbidity and mortality. Healthcare-associated transmission of VZV occurs among healthcare workers (HCWs) and patients by airborne transmission or by direct contact with the index case. To minimize the risk of transmission in healthcare settings, all VZV-susceptible HCWs should be encouraged strongly to be immunized with the varicella vaccine. For post-exposure management, active immunization (varicella vaccine), passive immunization (varicella-zoster immune globulin) and/or antiviral agents, and isolation could be used in specific situations. To prevent the transmission of VZV infection in the hospital settings, the development and implementation of hospital policies for appropriate infection control is also warranted. This article reviews the general information and healthcare-associated transmission of VZV and summarizes the recommendations for the pre- and post-exposure management of HCWs and patients, in hospital settings.
Antiviral Agents ; Chickenpox Vaccine ; Delivery of Health Care* ; Female ; Herpesvirus 3, Human* ; Hospitals, Isolation ; Humans ; Immunization, Passive ; Immunocompromised Host ; Infant, Newborn ; Infection Control ; Mortality ; Occupational Exposure ; Pregnant Women ; Vaccination

A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m²×4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.
Adult ; Allografts ; Azotemia ; Biopsy ; BK Virus ; Bortezomib* ; Fathers ; Follow-Up Studies ; Glomerulonephritis* ; Glomerulonephritis, Membranoproliferative ; Graft Rejection ; Humans ; Immunization, Passive ; Immunoglobulins ; Kidney ; Kidney Transplantation ; Living Donors ; Plasmapheresis ; Recurrence ; Renal Dialysis ; Rituximab ; Transplants ; Viremia

Disseminated adenovirus infection can result in high mortality and morbidity in immunocompromised patients. Here, we report the case of a 10-year-old renal allograft recipient who presented with hematuria and dysuria. Adenovirus was isolated from his urine. His urinary symptoms decreased after intravenous hydration and reduction of immunosuppressants. However, 2 weeks later he presented with general weakness and laboratory tests indicated renal failure necessitating emergency hemodialysis. Adenovirus was detected in his sputum; therefore, intravenous ganciclovir and immunoglobulin therapy were initiated. Renal biopsy revealed diffuse necrotizing granulomatous tubulointerstitial nephritis compatible with renal involvement of the viral infection. Adenovirus was detected in his serum. Despite cidofovir administration for 2 weeks, adenovirus was also detected in the cerebrospinal fluid, resulting in generalized tonic-clonic seizure. The patient died 7 weeks after the onset of urinary symptoms. Adenovirus should be considered in screening tests for post-renal transplantation patients who present with hemorrhagic cystitis.
Adenoviridae Infections* ; Adenoviridae* ; Allografts* ; Biopsy ; Cerebrospinal Fluid ; Child* ; Cystitis ; Dysuria ; Emergencies ; Ganciclovir ; Hematuria ; Humans ; Immunization, Passive ; Immunocompromised Host ; Immunosuppressive Agents ; Kidney Transplantation ; Mass Screening ; Mortality ; Nephritis, Interstitial ; Opportunistic Infections ; Pediatrics ; Renal Dialysis ; Renal Insufficiency ; Seizures ; Sputum