Performance and correlation of ten commercial immunoassays for the detection of SARS-CoV-2 antibodies.

Accurate immunoassays with a good correlation to neutralizing antibodies are required to support SARS-CoV-2 diagnosis, management, vaccine deployment, and epidemiological investigation. We conducted a study to evaluate the performance and correlation of the surrogate virus neutralization test (sVNT) and other commercial immunoassays. We tested 107 sera of COVID-19 confirmed cases from three different time points, 58 confirmed non-COVID-19 sera, and 52 sera collected before the pandemic with two sVNTs, seven chemiluminescent assays, and one fluorescein assay. All assays achieved excellent sensitivity (95%-100%, ≥15 days after onset of illness), specificity (95.5%-100%), and showed moderate to high correlation with GenScript sVNT (r = 0.58 to r = 0.98), except Roche total antibodies (r = 0.48). Vazyme sVNT and Siemens total antibodies showed the highest correlation with GenScript sVNT (r = 0.98 and 0.88, respectively). Median indexes that may be used to estimate sera with the highest ability to inhibit SARS-CoV-2 and ACE-2 receptor attachment (GenScript sVNT inhibition 90%-100%) were 6.9 S/C (Abbott IgG), 161.9 COI (FREND™ IgG), 16.8 AU/ml (Snibe IgG), 40.1 S/CO (Beckman IgG), 281.9 U/ml (Mindray IgG), 712.2 U/ml (Mindray total antibodies), >10 index (Siemens total antibodies), and 95.3% inhibition (Vazyme sVNT). All ten commercial COVID-19 serology assays, with different targeting antigens, demonstrated a reliable performance, supporting the utility of those assays in clinical and research settings. However, further studies using more samples are needed to refine the results of evaluating the performances of these marketed serological assays. Reliable serological assays would be useful for clinicians, researchers and epidemiologists in confirming SARS-CoV-2 infections, observing SARS-CoV-2 transmission, and immune response post infection and vaccination, leading to better management and control of the disease.

Mild reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant: First case report from Indonesia.

Background: Reinfection with SARS-CoV-2 has been well documented, yet little is known about the degree of protection a previous infection provides against reinfection, especially against Variants of Concern (VOC). Case presentation: Here we describe a case of an unvaccinated 49-year-old man who experienced two sequential SARS-CoV-2 infections with two different variants, as evidenced by genomic sequencing. The first episode was caused by the Pango lineage B.1.466.2 and resulted in severe COVID-19 with 5 days in an intensive care unit (ICU). The second episode occurred approximately 6 months later, during the Delta surge in Indonesia. Genomic analysis showed that the second infection was caused by the Delta variant (Pango lineage B.1.617.2) and resulted in mild disease that did not require hospitalization. No SARS-CoV-2 nucleic acid was detected between the two episodes, but both binding and neutralizing antibodies to SARS-CoV-2 were detected prior to the reinfection, with the second infection leading to an increase in the levels of antibody. Conclusion: We confirmed that the patient experienced a reinfection instead of persistent viral shedding from the first infection based on epidemiological, clinical, serological, and genomic analyses. Our case supports the hypothesis that SARS-CoV-2 reinfection may occur once antibody titers decrease or following the emergence of a new variant. The milder presentation in the patient's second infection deserves further investigation to provide a clear picture of the role of post-infection immunity in altering the course of subsequent disease.

Design of an observational multi-country cohort study to assess immunogenicity of multiple vaccine platforms (InVITE).

In response to the COVID-19 pandemic, COVID-19 vaccines have been developed, and the World Health Oraganization (WHO) has granted emergency use listing to multiple vaccines. Studies of vaccine immunogenicity data from implementing COVID-19 vaccines by national immunization programs in single studies spanning multiple countries and continents are limited but critically needed to answer public health questions on vaccines, such as comparing immune responses to different vaccines and among different populations.

Mild reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant: First case report from Indonesia

Background Reinfection with SARS-CoV-2 has been well documented, yet little is known about the degree of protection a previous infection provides against reinfection, especially against Variants of Concern (VOC). Case presentation Here we describe a case of an unvaccinated 49-year-old man who experienced two sequential SARS-CoV-2 infections with two different variants, as evidenced by genomic sequencing. The first episode was caused by the Pango lineage B.1.466.2 and resulted in severe COVID-19 with 5 days in an intensive care unit (ICU). The second episode occurred approximately 6 months later, during the Delta surge in Indonesia. Genomic analysis showed that the second infection was caused by the Delta variant (Pango lineage B.1.617.2) and resulted in mild disease that did not require hospitalization. No SARS-CoV-2 nucleic acid was detected between the two episodes, but both binding and neutralizing antibodies to SARS-CoV-2 were detected prior to the reinfection, with the second infection leading to an increase in the levels of antibody. Conclusion We confirmed that the patient experienced a reinfection instead of persistent viral shedding from the first infection based on epidemiological, clinical, serological, and genomic analyses. Our case supports the hypothesis that SARS-CoV-2 reinfection may occur once antibody titers decrease or following the emergence of a new variant. The milder presentation in the patient’s second infection deserves further investigation to provide a clear picture of the role of post-infection immunity in altering the course of subsequent disease.

Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection. METHODS: This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period. RESULTS: There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups. CONCLUSIONS: Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856.

Diagnosis of COVID-19 in a Dengue-Endemic Area.

Emergence of SARS-CoV-2 in dengue virus (DENV)-endemic areas complicates the diagnosis of both infections. COVID-19 cases may be misdiagnosed as dengue, particularly when relying on DENV IgM, which can remain positive months after infection. To estimate the extent of this problem, we evaluated sera from 42 confirmed COVID-19 patients for evidence of DENV infection. No cases of SARS-CoV-2 and DENV coinfection were identified. However, recent DENV infection, indicated by the presence of DENV IgM and/or high level of IgG antibodies, was found in seven patients. Dengue virus IgM and/or high IgG titer should not exclude COVID-19. SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing is appropriate when dengue nonstructural protein 1 (NS1) or RT-PCR is negative. Given the possibility of coinfection, testing for both DENV and SARS-CoV-2 is merited in the setting of the current pandemic.