https://backend.orbit.dtu.dk/ws/files/238108460/1_s2.0_S0092867420310084_main.pdf

Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years.

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Immunological considerations for COVID-19 vaccine strategies.

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every corner of the globe, causing societal instability. The resultant coronavirus disease 2019 (COVID-19) leads to fever, sore throat, cough, chest and muscle pain, dyspnoea, confusion, anosmia, ageusia and headache. These can progress to life-threatening respiratory insufficiency, also affecting the heart, kidney, liver and nervous systems. The diagnosis of SARS-CoV-2 infection is often confused with that of influenza and seasonal upper respiratory tract viral infections. Due to available treatment strategies and required containments, rapid diagnosis is mandated. This Review brings clarity to the rapidly growing body of available and in-development diagnostic tests, including nanomaterial-based tools. It serves as a resource guide for scientists, physicians, students and the public at large.

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Diagnostics for SARS-CoV-2 infections.

Currently, detecting SARS-CoV-2 RNAs is a standard approach for COVID-19 diagnosis. However, there is an urgent need for reliable and rapid serological diagnostic methods to screen SARS-CoV-2infected people including those who do not have overt symptoms. Most emerging studies described serological tests based on detection of SARS-CoV-2-specific IgM and IgG. Although detection of SARS-CoV-2-specific IgA in serum has been reported in few papers, analyses of IgA levels in a larger number of COVID-19 patients are still lacking. This study enrolled a total of 87 confirmed COVID-19 patients (Supplementary Table 1) who were admitted to the First Affiliated Hospital of USTC Hospital or the First Affiliated Hospital of Anhui Medical University between January 26, and Mar 5, 2020. Their blood samples were collected during routine clinical testing. All enrolled cases were confirmed with SARS-CoV-2 infection by use of a standard RT-qPCR assay on throat swab samples from the respiratory tract. For all of the enrolled patients, the date of illness onset, clinical classifications of severity, RNA testing results during the hospitalization period, and the personal demographic information were obtained from the clinical records. Highly purified receptor-binding domain (RBD) of the SARSCoV-2 spike protein (Supplementary Fig. 1) was expressed in human 293F cells and used to make a set of chemical luminescence kits for detecting the presence of RBD-specific IgA, IgM, and IgG, respectively. To evaluate the diagnostic power of the these kits, 216 sera from 87 SARS-CoV-2-infected patients and a total of 483 control sera including 330 healthy sera, 138 “interfering” sera of other-type patients and 15 sera from oncesuspected pneumonia cases were tested. The detected signals relative light units (RLU), for each of isotype of the RBD-specific antibodies, were plotted (Fig. 1a–c). The RBD-specific IgA, IgM, and IgG kits showed diagnostic sensitivities of 98.6%, 96.8%, and 96.8%, and specificities of 98.1%, 92.3%, and 99.8%, respectively (Supplementary Fig. 2a–c). The sensitivities, specificities, and overall agreements of the RBD-specific IgA, IgM, or IgG kit and their combinations are also summarized in Supplementary Table 2. When combining the RBD IgA and IgG kits, the sensitivity, specificity, and overall agreement elevated to 99.1%, 100%, and 99.7%, respectively. This is better than those when IgM and IgG kits are combined using our data or the previous data shown by others. In order to investigate the seroconversion during COVID-19 pathogenesis, all the data from 216 sera samples were divided into six groups according to the time windows of collection after illness onset (Fig. 1d). At 4–10 days after symptom onset, the IgA kit exhibited the highest positive diagnostic rate as 88.2% (15/17), while IgM and IgG kit showed detection rates of 76.4% (13/17) and 64.7% (11/17), respectively. The 2 sera diagnosed as negative in the 4–10 days group by IgA kit were collected at the 4th day after illness onset, all other sera includes 2 at the 6th day, 3 at the 7th day, 1 at the 8th day, 6 at the 9th day, and 3 at 10th day after illness onset were tested as positive. In the group of 11–41 days after symptom onset, both RBD IgA and IgG kit showed the same positive diagnostic rate of 99.5% (198/199). In contrast, IgM kit somehow showed a relatively lower positive diagnostic rate as 98.5% (196/199). These results suggest that including IgA in a test provides better diagnostic outcome in early stages. Overall, the medium seroconversion time for IgA, IgM, and IgG are 4–6, 4–6, and 5–10 days post symptom onset, respectively, if tested with the RBD-kits described in this study. While it generally follows a typical seroconversion and immunoglobulin class switching time course, our kits provides an early diagnosis solution due to high sensitivities. To better understand the trends of antibody levels in all of the 87 COVID-19 patients (some of them contributed multiple samples), we plotted the median RLU reading according the time windows when sera were collected (Fig. 1e). IgA detection shows the highest sensitivity during about 4–25 days after illness onset. The median RLU of RBD-specific IgA reached the peak during 16–20 days after illness onset, and then began to decline but remained at relatively high reading until 31–41 days. The median RLU of RBD-specific IgG was the lowest in early disease stages but raised at 15 days post illness onset, the IgG reached its peak during 21–25 days after illness onset, and stayed at a relatively high reading until 31–41 days, suggesting that IgG is powerful for diagnostics at later stages. Although IgM reached its peak at early stages, the RLU reading was lower than that of IgA or IgG.

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Serum IgA, IgM, and IgG responses in COVID-19.

IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study.

Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity.

Diagnostic performances and thresholds: The key to harmonization in serological SARS-CoV-2 assays?

Background Reliable high-throughput serological assays for SARS-CoV-2 antibodies (Abs) are urgently needed for the effective containment of the COVID-19 pandemic, as it is of crucial importance to understand the strength and duration of immunity after infection, and to make informed decisions concerning the activation or discontinuation of physical distancing restrictions. Methods In 184 serum samples from 130 COVID-19 patients and 54 SARS-CoV-2 negative subjects, the analytical and clinical performances of four commercially available chemiluminescent assays (Abbott SARS-Cov-2 IgG, Roche Elecsys anti-SARS-CoV-2, Ortho SARS-CoV-2 total and IgG) and one enzyme-linked immunosorbent assay (Diesse ENZY-WELL SARS-CoV-2 IgG) were evaluated and compared with the neutralization activity achieved using the plaque reduction neutralization test (PRNT). Findings Precision results ranged from 0.9% to 11.8% for all assays. Elecsys anti-SARS-CoV-2 demonstrated linearity of results at concentrations within the cut-off value. Overall, sensitivity ranged from 78.5 to 87.8%, and specificity, from 97.6 to 100%. On limiting the analysis to samples collected 12 days after onset of symptoms, the sensitivity of all assays increased, the highest value (95.2%) being obtained with VITRO Anti-SARS-CoV-2 Total and Architect SARS-CoV-2 IgG. The strongest PRNT50 correlation with antibody levels was obtained with ENZY-Well SARS-CoV-2 IgG (rho = 0.541, p Interpretation The results confirmed that all immunoassays had an excellent specificity, whereas sensitivity varied across immunoassays, depending strongly on the time interval between symptoms onset and sample collection. Further studies should be conducted to achieve a stronger correlation between antibody measurement and PRNT50 in order to obtain useful information for providing effective passive antibody therapy, and developing a vaccine against the SARS-CoV-2 virus.

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Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity

Abstract Objectives Coronavirus disease 2019 (COVID-19) is a life-threatening infectious disorder characterized by a sustained prothrombotic state. Since homocysteine is a potential biomarker of thrombotic diseases, the aim of this article is to provide an updated overview on the possible role played by hyperhomocysteinemia in influencing an unfavorable COVID-19 progression. Methods We carried out an electronic search in Medline (PubMed interface) using the keywords (“COVID-19” OR “SARS-CoV-2”) AND “homocysteine”, between 2019 and the present time, with no language restrictions, to identify all articles which explored the concentration of homocysteine in COVID-19 patients with or without unfavorable disease progression. Results Three studies, totaling 694 hospitalized COVID-19 patients, were included in our systematic review. Overall, the differences between the mean homocysteine values in non-severe vs. severe COVID-19 patients were always positive (i.e., 15.1%, 24.1% and 22.8%, generating a positive weight mean difference of 1.75 μmol/L (95%CI, 1.26–2.25 μmol/L; p=0.011), which translates into a cumulative difference of approximately ∼1.2 μmol/L. Conclusions Despite the limited evidence that has been garnered so far, increased homocysteine levels may be a potentially useful marker for predicting the risk of unfavorable progression in patients with COVID-19.

Davide Negrini

Papers

IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study.

Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity.

Diagnostic performances and thresholds: The key to harmonization in serological SARS-CoV-2 assays?

Analytical and clinical performances of five immunoassays for the detection of SARS-CoV-2 antibodies in comparison with neutralization activity

Homocysteine in coronavirus disease (COVID-19): a systematic literature review