Comparison of the approaches to evaluation the virus-neutralizing activity of sera from COVID-19 recovered individuals

Background: Serum virus-neutralization (VNT)capacity is an important parameter of immunological response in COVID-19 recovered individuals and it can also be used to predict the effectiveness of therapy with COVID-19 convalescent plasma. The most commonly used tests to assess virus-neutralization are those that use native SARS-CoV- 2 (cVNT), SARS-CoV- 2 spike pseudotyped lentivirus-like particles (pVNT), and also inhibition of recombinant RBD binding to ACE2 receptor in vitro (surrogate VNT, sVNT). The aim of this study was to determine the interchangeability of different approaches in the evaluation of the virus-neutralization activity of convalescent serum samples. Method(s): Serum samples (n = 111) were collected 10-36 days after recovery between May and September 2020. The SARS-CoV- 2 strain PMVL-12/ 2020 was used in cVNT at 100 doses of TCID50. In pVNT SARS-CoV- 2 pseudotyped HIV-1 based virus-like particles with GFP reporter gene were used. sVNT was performed with a kit from Xema Co., Russia. Result(s): A very strong correlation was observed between cVNT and pVNT results (Spearman's r = 0.841). The correlation of cVNT and pVNT with the sVNT was only moderate (r = 0.674 and 0.696, respectively). This is consistent with the fact that sVNT detects only RBD blocking antibodies, which are the main but not the only inhibitors of viral infection. Serum samples were also tested for RBD-specific IgG, IgM, IgA antibodies by ELISA. A good correlation was found between the cVNT, pVNT, sVNT results and the RBD-specific IgG (r = 0.669, 0.620, and 0.643, respectively), that confirms a crucial role of specific IgG antibodies in virus-neutralization. RBD-specific IgA showed a moderate correlation with the neutralization capacity of sera from recovered individuals (r = 0.563, 0.583, 0.544). Correlation of approximately the same level was observed between cVNT, pVNT, and RBD-specific IgM (r = 0.663, 0.615), but not sVNT and RBD-specific IgM (r = 0.395). Conclusion(s): This study demonstrated the possibility of using the safe and relatively simple pseudotyped virus-neutralization test instead of cVNT to assess the sera virus-neutralizing capacity. sVNT may be efficiently used in screening studies.

An Overview of the Treatment Contributions Measured Globally for the COVID-19 Outbreak

Background: SARS CoV2 is a newly emerged animal beta coronavirus that causes respiratory illness. This infection has affected 212 countries to date and has been declared a pandemic by the World Health Organization. Due to the high transmission rate and lack of availability of any approved anti-viral drug, the formulation of a specific anti-viral therapy has now become a global emergency. Genomic studies have revealed a 79% identity of SARS CoV2 with SARS CoV and 50% identity with MERS CoV, which has given a clue point to test the drugs that were efficient against previously encoun-tered beta coronaviruses. For this purpose, several clinical trials based on the knowledge of existing drugs are moving ahead. These therapies include chloroquine and hydroxychloroquine, remdesivir, cor-ticosteroids therapy, favipiravir, ribavirin, lopinavir/ritonavir, anti-cytokine therapy, and convalescent sera. Aim of the study: The purpose of this review is to give a pointer of contributions conducted globally, including strategies utilized for treatments, the pattern of dosage, adverse reactions, and effective outcomes from different drugs. Methodology: Literature has been retrieved from PubMed, PubMed Central, ResearchGate, ScienceDi-rect, and Google Scholar, using a combination of keywords for extensive information. Conclusion(s): Among all the drug options, Remdesivir and the use of Convalescent Sera have been con-sidered as the safest options for treatment against COVID-19. Data from the ongoing clinical trials will be required for the formulation of a specific and approved anti-viral drug,.Copyright © 2021 Bentham Science Publishers.

Characterisation and analysis of linear epitopes corresponding to SARS-CoV-2 outbreak in Jilin Province, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants have caused hundreds of thousands of deaths and shown serious social influence worldwide. Jilin Province, China, experienced the first wave of the outbreak from December 2020 to February 2021. Here, we analysed the genomic characteristics of the SARS-CoV-2 outbreak in Jilin province using a phylogeographic tree and found that clinical isolates belonged to the B.1 lineage, which was considered to be the ancestral lineage. Several dominant SARS-CoV-2 specific linear B cell epitopes that reacted with the convalescent sera were also analysed and identified using a peptide microarray composed of S, M, and E proteins. Moreover, the serum of convalescent patients infected with SARS-CoV-2 showed neutralising activity against four widely spreading SARS-CoV-2 variants; however, significant differences were observed in neutralising activities against different SARS-CoV-2 variants. These data provide important information on genomic characteristics, linear epitopes, and neutralising activity of SARS-CoV-2 outbreak in Jilin Province, China, which may aid in understanding disease patterns and regional aspects of the pandemic. This article is protected by copyright. All rights reserved.

Nanoparticles: Efficient, safe and affordable platforms for developing vaccines against coronaviruses

Introduction: Vaccines need to be rationally designed to be delivered to the immune system for maximizing induction of dynamic immune responses. Virus-like nanoparticles (VLPs) are ideal platforms for such 3D vaccines. Coronaviruses have recently gained a lot of attention, due to the ongoing pandemic caused by SARS-CoV-2 and previous endemics by MERS-CoV. Methods: We have provided proof of concepts in murine models for effective development of VLP-based vaccines against MERS-CoV and SASR-CoV-2. We have used chemical conjugation or genetic fusion techniques to display receptor-binding domain or motif on our immunologically optimized (CuMVTT -VLPs). These VLPs incorporate a tetanus toxin epitope and ssRNA, TLR7/8 ligands. The vaccines were tested in murine models. Results: The vaccines are stable for more than a year at 4°C and highly scalable. Vaccination using subcutaneous or intranasal routes are feasible with nanoparticles. We demonstrated that these vaccines are highly immunogenic in mice as well as rabbits and can induce high avidity antibodies compared to convalescent human sera. Furthermore, the induced antibodies are cross-reactive with different VoCs (in case of SARS-CoV-2). The longevity of the induced immune response lasted longer than 120 days. Conclusion: Collectively, we show that VLP-based vaccines can efficiently induce high specific anti-RBD and spike antibodies that effectively neutralize different Coronaviruses and their VoCs. As Coronaviruses represent a continuous global threat to human health, it seems rational to further develop these vaccines.

Variation of SARS-CoV-2 spike protein and its effects on neutralization sensitivity

The COVID-19 epidemic that occurred at the end of 2019 spreads rapidly to all parts of the world, putting the global public health system to a severe test. With the continuation of the epidemic, SARS-CoV-2 variants are constantly emerging. In particular, the mutation of the spike protein can cause changes in the infectivity and antigenicity of the virus, resulting in an increase in the infectivity and a decline in the protective efficacy of existing vaccines, and even the replacement of epidemic strains. This is also one of the reasons why the epidemic has not been effectively controlled so far. Nowadays, the main circulating variants have changed their characteristics to a certain extent, and the neutralization sensitivity of some variants to neutralizing monoclonal antibodies, immune sera and convalescent sera has decreased to a certain extent compared with the original strains. The emergence of variants is not only related to the characteristics of the virus itself, but also to the changes of transmission host and the chronic infection in people with deficient immunity. The emerging variants should be closely monitored, and their functional characteristics should be systematically studied so as to provide data for vaccine research and development and the designation of immunization strategies.

IMMUNE RESPONSES after ChAdOx1 or BNT162b2 BOOSTERS in PRIMARY CORONAVAC VACCINATION

Background: Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programmes. However, an immune response of CoronaVac significantly declined after 3 months, our study, thus, aimed to explore the immune response against COVID-19 following the booster dose by assessing both B-cell and T-cell activities compared to the convalescent samples. Methods: In this prospective cohort study, 98 healthcare workers with a 2-dose CoronaVac vaccination with a subsequent booster dose of ChAdOx1 nCoV-19 (n=56) or BNT162b2 (n=42) were included during March and October 2021. Immune responses were evaluated by surrogated viral neutralization test (sVNT, cPass™), anti-SARS-CoV-2 RBD total antibodies (Elecsys®) and the ELISPOT with spike (S1) peptide pools. The samples were analyzed at baseline, 4 and 12 weeks after the second CoronaVac and 4 weeks after a booster dose. In addition, convalescent sera and peripheral blood mononuclear cells (PBMCs) of the COVID-19 patients were collected at 4 weeks after diagnosis. Results: Median (interquartile range, IQR) age was 40 (31-52) years old with female predominant (80%). The median (IQR) interval after the second CoronaVac was 88 (74-92) days for ChAdOx1 nCoV-19 and 113 (112-115) days for BNT162b2. There was a significant decrease in neutralizing antibodies at the 12th week after primary CoronaVac vaccination (Figure 1). At 4 weeks after the ChAdOx1 nCoV-19 booster, median (IQR) level of sVNT and anti-RBD total antibody levels were 98.1% (97.9-98.2%) and 7768 (5349-11142), respectively, which were significantly different from the BNT162b2 booster, 98.5% (98.5-98.6%) and 25129 (17531-39434) BAU/mL, respectively (p<0.001 both). The antibody levels of the booster vaccine group were significantly higher than in the COVID-19 patients, which median (IQR) of sVNT was 80.8% (61.7-94.2%) in the mild COVID-19 and 93.8% (85.4-95.6%) in COVID-19 pneumonia, while anti-RBD total antibody levels were 94 (22-207) and 222 (130-378) BAU/mL, respectively. Using the ELISPOT with S1 peptide pools, median (IQR) of T cell response was 106 (24-256) and 196 (60-244) Spot Forming Unit (SFU)/millions of PBMCs for ChAdOx1 nCoV-19 and BNT162b2, respectively (p 0.49) which were comparable to the COVID-19 cases. Conclusion: A 2-dose CoronaVac followed by ChAdOx1 nCoV-19 or BNT162b2 effectively boosted a significantly higher antibody response than the natural COVID-19 infection. In addition, BNT162b2 booster induced significantly higher antibody levels than ChAdOx1 nCoV-19.

Convalescent serum-derived exosomes: Attractive niche as COVID-19 diagnostic tool and vehicle for mRNA delivery.

The spread of SARS-CoV-2 over the entire world is more commonly known as COVID-19. COVID-19 has impacted society in every aspect of routine life. SARS-CoV-2 infection is often misdiagnosed as influenza or seasonal upper respiratory tract viral infections. General diagnostic tools can detect the viral antigen or isotypes of antibodies. However, inter- and intraindividual variations in antibody levels can cause false negatives in antibody immunoassays. On the contrary, the false-positive test results can also occur due to either cross-reactivity of the viral antigens or some other patient-related autoimmune factors. There is need for a cogent diagnostic tool with more specificity, selectivity, and reliability. Here, we have described the potential of convalescent serum-derived exosome as a diagnostic tool for the detection of SARS-CoV-2, even in asymptomatic patients, which is a limitation for currently practiced diagnostic tests throughout the globe. In addition, its potential as a vehicle for messenger RNA (mRNA) delivery is also emphasized.

Longitudinal antibody dynamics in children infected with SARS-CoV-2 through 6 months post-infection

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits antibodies (Abs) that bind several viral proteins such as the spike entry protein and the abundant nucleocapsid (N) protein. We examined convalescent sera collected through 6 months (~24wks) post-SARS-CoV-2 infection in children to evaluate changes in neutralization potency and N-binding. Methods. Outpatient, hospitalized, and community recruited volunteers < 18 years with COVID-19 were enrolled in a longitudinal study at Seattle Children's Hospital. Analysis includes symptomatic and asymptomatic children with laboratory-confirmed SARS-CoV-2 infection who provided blood samples at approximately 4wks (range: 2-18wks, IQR:4-8wks) and 24 wks (range: 23-35wks, IQR:25-27wks) after diagnosis. We measured neutralizing Ab using an in-house pseudoneutralization assay and anti-N binding Ab using the Abbott Architect assay. Results. Of 32 children enrolled between April 2020 and January 2021, 27 had no underlying immunocompromised state and 25 of these 27 children had symptomatic disease. Ten of 27 had a > 2-fold decrease neutralization titers between 4 and 24wks (most were < 10-fold);12 had < 2-fold change;and 5 had neutralization titers that increased > 2-fold over time (Fig. 1A). All but one of these 27 children had detectable neutralizing activity at 24wks. Anti-N Abs were assessed for 25 children at 4wks and 17 children at 24wks (data pending for 14 samples);all children with paired samples had a > 1.75-fold Abbott index reduction at 24wks, and 5 children had no detectable anti-N Abs by 24wks (Fig. 2A). An additional 5 children with symptomatic disease had complicating immunosuppression or multiple blood transfusions;2 had decreasing neutralizing titers, 2 increased, and 1 had no change (Fig. 1B). Anti-N Abs were undetectable for one child by 24wks (data pending for 4 samples) (Fig. 2B). No participants received COVID-19 vaccine. Conclusion. We show neutralizing Abs wane to a small degree over 24wks post-SARS-CoV-2 infection and remain detectable in most children. In contrast, anti-N Abs decreased, becoming undetectable in some children by 24wks. These findings add to understanding of the natural history of SARS-CoV-2 immunity in children.

Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift.

Variants of SARS-CoV-2 continue to emerge, posing great challenges in outbreak prevention and control. It is important to understand in advance the impact of possible variants of concern (VOCs) on infectivity and antigenicity. Here, we constructed one or more of the 15 high-frequency naturally occurring amino acid changes in the receptor-binding domain (RBD) of Alpha, Beta, and Gamma variants. A single mutant of A520S, V367F, and S494P in the above three VOCs enhanced infectivity in ACE2-overexpressing 293T cells of different species, LLC-MK2 and Vero cells. Aggregation of multiple RBD mutations significantly reduces the infectivity of the possible three VOCs. Regarding neutralization, it is noteworthy that E484K, N501Y, K417N, and N439K predispose to monoclonal antibodies (mAbs) protection failure in the 15 high-frequency mutations. Most importantly, almost all possible VOCs (single RBD mutation or aggregation of multiple mutations) showed no more than a fourfold decrease in neutralizing activity with convalescent sera, vaccine sera, and immune sera of guinea pigs with different immunogens, and no significant antigenic drift was formed. In conclusion, our pseudovirus results could reduce the concern that the aggregation of multiple high-frequency mutations in the RBD of the spike protein of the three VOCs would lead to severe antigenic drift, and this would provide value for vaccine development strategies.

Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis.

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

Reduced sensitivity of the SARS-CoV-2 Lambda variant to monoclonal antibodies and neutralizing antibodies induced by infection and vaccination.

Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3-2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.

Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study.

PURPOSE: Racial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19. METHODS: We leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in COVID-19 clinical trials, mortality, need for renal replacement therapy, and need for mechanical ventilation. RESULTS: Compared to non-Black patients, Black patients had a higher prevalence of COVID-19 risk factors including obesity, hypertension, and diabetes mellitus and were more likely to require renal replacement therapy (15.8% vs 7.1%, P < .001) and mechanical ventilation (37.2% vs 26.6%, P < .001) during their hospitalization. Mortality was similar between both groups (15.5% for Blacks vs 14.0% for non-Blacks, P = .49). Black patients were less likely to receive corticosteroids (44.9% vs 63.8%, P< .001) or remdesivir (23.8% vs 57.8%, P < .001) and were less likely to be enrolled in COVID-19 clinical trials (15.3% vs 28.2%, P < .001). In adjusted analyses, Black race was associated with lower levels of C-reactive protein and soluble urokinase receptor and higher odds of death, mechanical ventilation, and renal replacement therapy. Differences in outcomes were not significant after adjusting for use of remdesivir and corticosteroids. CONCLUSIONS: Racial differences in outcomes of patients with COVID-19 may be related to differences in inflammatory response and differential use of therapies.

Antibodies for COVID-19 - which, when and how long?

Infection with SARS-CoV2 leads to COVID-19, the severity of which derives from the host's immune response, especially the release of a storm of pro-inflammatory cytokines. This coronavirus infects by first binding to the ectoenzyme Angiotensin Converting Enzyme 2 (ACE2), a serine protease acting as the receptor, while another serine protease is necessary for priming the viral spike "S" protein required for entering the cells. Repurposing existing drugs for potential anti-coronavirus activity have failed. As a result, there were intense efforts to rapidly produce ways of providing prophylactic active immunization (vaccines) or abortive passive (convalescent plasma or monoclonal antibodies) neutralizing antibodies. The availability of vaccines for COVID-19 have been largely successful, but many questions still remain unanswered. In spite of the original enthusiasm, clinical studies using convalescent serum or monoclonal antibodies have shown limited benefit. Moreover, the emergence of Long-COVID syndrome in most infected patients necessitates the development of treatment approaches that may prevent viral entry by blocking both serine proteases involved, as with a liposomal blend of the natural flavonoids luteolin and quercetin.

Use of convalescent serum reduces severity of COVID-19 in nonhuman primates.

Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently being used to treat patients with coronavirus disease 2019 where clinical efficacy trials are ongoing. Here, we assess therapeutic passive transfer in groups of SARS-CoV-2-infected African green monkeys with convalescent sera containing either high or low anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and pathology are minimal between monkeys that receive the lower titer convalescent sera and untreated controls. However, lower levels of SARS-CoV-2 in respiratory compartments, reduced severity of virus-associated lung pathology, and reductions in coagulopathy and inflammatory processes are observed in monkeys that receive high titer sera versus untreated controls. Our data indicate that convalescent plasma therapy in humans may be an effective strategy provided that donor sera contain high anti-SARS-CoV-2 neutralizing titers given in early stages of the disease.

Review of Current Advances in Serologic Testing for COVID-19.

OBJECTIVES: To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. RESULTS: The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. CONCLUSIONS: The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation.

Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.

The phenotypic and functional dichotomy between IRF8+ type 1 and IRF4+ type 2 conventional dendritic cells (cDC1s and cDC2s, respectively) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen-presenting cells (APCs). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of the Fc receptor CD64 shared with MCs and of IRF8 shared with cDC1s. These inflammatory cDC2s (inf-cDC2s) were superior in inducing CD4+ T helper (Th) cell polarization while simultaneously presenting antigen to CD8+ T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2s matured in response to cell-intrinsic Toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module, and acquired antigens via convalescent serum and Fc receptors. Because hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.

Perspectives of Immune Therapy in Coronavirus Disease 2019.

The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.