Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

Analysis of Nucleic Acid and Antibody Detection Results for SARS-CoV-2 Infection.

BACKGROUND: Real-time polymerase chain reaction (RT-PCR) of virus nucleic acid test (NAT) has become the standard method to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are still many limitations, especially the problem of the high false negative rate. Therefore, the aim of this study was to investigate the positive rate of SARS-CoV-2 NAT and evaluate the diagnostic performance of SARS-CoV-2 IgM and IgG antibody detection in novel coronavirus infection. METHODS: A total of 10309 suspected or high-risk cases of infection with SARS-CoV-2 in Wuhan Hubei, China, were tested for virus NAT by RT-PCR. Among those cases, 762 COVID-19 patients and 143 patients with non-COVID-19 who were tested for SARS-CoV-2 IgM and IgG during the NAT period were screened. The difference between the two test methods was analyzed using the chi-square test. RESULTS: The positive rate of 10309 cases was about 36% (95% CI: 33.39%-39.67%). SARS-CoV-2 was present in various types of specimens, and alveolar lavage fluid had the highest positive rate [52.38% (95% CI: 31.02-73.74)]. The clinical sensitivity of serum SARS-CoV-2 IgM and IgG was 77.17% (588/762) and 94.88% (723/762), respectively, and the clinical specificity was 93.71% (134/143) and 90.21% (129/143). The area under the curve (AUC) of SARS-CoV-2 IgG and combination of IgG with IgM were equally larger than IgM [0.973 (95% CI: 0.964-0.983) vs 0.930 (95% CI: 0.910-0.949)]. IgG antibody had the highest specificity [100.0% (95% CI: 100.00%-100.00%)] and sensitivity [94.0% (95% CI: 92.45%-95.55%)] when detected alone or in combination with IgM antibody. The total coincidence rate of SARS-CoV-2 antibodies detection and SARS-CoV-2 NAT for the diagnosis of SARS-CoV-2 infection was 92.04% (833/905). Among the 34 SARS-CoV-2 NAT-negative patients with clinical symptoms and CT imaging features, 29 (85.29%) patients were positive for SARS-CoV-2 IgM, and 31 (91.76%) were positive for IgG. CONCLUSION: SARS-CoV-2 NAT should be considered for many types of specimens, and the combined test of SARS-CoV-2 IgM and IgG can make up for the problem of missed NAT in COVID-19 patients.

Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients.

Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.

Time-dependent changes in the clinical characteristics and prognosis of hospitalized COVID-19 patients in Wuhan, China: A retrospective study.

Cases of coronavirus disease 2019 (COVID-19) have been breaking out around the world recently. However, the dynamic changes in the clinical symptoms and prognosis of COVID-19 patients remain unknown. According to the onset time of initial clinical symptoms, 843 COVID-19 patients admitted between Jan 22 and Feb 14, 2020 were divided into three groups: group A (Jan 21 to Jan 25, n = 324), group B (Jan 26 to Jan 31, n = 358) and group C (Feb 1 to Feb 10, n = 161). Data on the demographics, symptoms, first laboratory results, treatments and outcomes (within 12 days of hospitalization) were collected. The results showed that the median duration from symptom onset to admission shortened over time (13, 10 and 5 days, respectively, p < 0.05). Fewer patients had fever symptoms and bilateral pneumonia in group C than in the group A and B. Laboratory results showed that white blood cell, neutrophil, and platelet counts, lactic acid and D-dimer levels were lower, while lymphocyte, CD3, and CD8 counts were higher in group C. In addition, group C had more mild-moderate cases and fewer severe cases than the other two groups. More importantly, the incidence of complications (18.5%, 14.2% and 11.2%, respectively, p < 0.05) and all-cause mortality (11.7%, 8.4%, and 5.6%, respectively, p < 0.05) decreased over time. The clinical characteristics and prognosis of COVID-19 patients changed over time. Improved prognosis was found at a later stage.

Development and multicenter performance evaluation of fully automated SARS-CoV-2 IgM and IgG immunoassays.

Objectives: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread globally. The laboratory diagnosis of SARS-CoV-2 infection has relied on nucleic acid testing; however, it has some limitations, such as low throughput and high rates of false negatives. Tests of higher sensitivity are needed to effectively identify infected patients. Methods: This study has developed fully automated chemiluminescent immunoassays to determine IgM and IgG antibodies to SARS-CoV-2 in human serum. The assay performance has been evaluated at 10 hospitals. Clinical specificity was evaluated by measuring 972 hospitalized patients and 586 donors of a normal population. Clinical sensitivity was assessed on 513 confirmed cases of SARS-CoV-2 by RT-PCR. Results: The assays demonstrated satisfied assay precision with coefficient of variation of less than 4.45%. Inactivation of specimen did not affect assay measurement. SARS-CoV-2 IgM showed clinical specificity of 97.33 and 99.49% for hospitalized patients and the normal population respectively, and SARS-CoV-2 IgG showed clinical specificity of 97.43 and 99.15% respectively. SARS-CoV-2 IgM showed clinical sensitivity of 82.54, 92.93, and 84.62% before 7 days, 7-14 days, and after 14 days respectively, since onset of symptoms, and SARS-CoV-2 IgG showed clinical sensitivity of 80.95, 97.98, and 99.15% respectively at the same time points above. Conclusions: We have developed fully automated immunoassays for detecting SARS-CoV-2 IgM and IgG antibodies in human serum. The assays demonstrated high clinical specificity and sensitivity, and add great value to nucleic acid testing in fighting against the global pandemic of the SARS-CoV-2 infection.

Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages.

BACKGROUND: Information about the clinical characteristics and mortality of patients with coronavirus disease 2019 at different ages is limited. RESULTS: The older group had more patients with dyspnea and fewer patients with fever and muscle pain. Older patients had more underlying diseases, secondary infection, myocardial injury, renal dysfunction, coagulation dysfunction, and immune dysfunction on admission. More older patients received immunoglobulin therapy and mechanical ventilation. The proportions of patients with multiple organ injuries, critically ill patients and death increased significantly with age. The older groups had higher cumulative death risk than the younger group. Hypertension, cerebrovascular disease, comorbidities, acute cardiac injury, shock and complications are independent predictors of death. CONCLUSIONS: The symptoms of the elderly patients were more atypical, with more comorbidities, secondary infection, organ injuries, immune dysfunction and a higher risk of critical illness. Older age was an important risk factor for mortality. METHODS: 1000 patients diagnosed with coronavirus disease 2019 from January 1, 2020 to February 14, 2020 were enrolled. According to age, patients were divided into group 1 (<60 years old), group 2 (60-74 years old) and group 3 (≥75 years old). The clinical symptoms, first laboratory results, CT findings, organ injuries, disease severity and mortality were analyzed.

Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors.

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.