Assessment of S-Specific IgG and IgM Positive Rates in Healthy Hospital Staff Members Vaccinated with the Inactivated SARS-CoV-2 Vaccine.

Widespread vaccination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine makes the assessment of antibodies' positive rates essential. In this study, a total of 378 hospital staff members vaccinated with the vaccine were selected as research subjects. Serum-specific IgG and IgM against the SARS-CoV-2 spike protein (S) were detected, and S-specific IgG and IgM positive rates were analyzed in different age and sex groups, as was the serological pattern of IgG/IgM. The positive rates of IgG and IgM were 92.06% and 44.44%, respectively. The percentage of both IgG and IgM positive (IgG+IgM+) was 43.92%. A total of 182 vaccinees (46.90%) were IgG positive and IgM negative (IgG+IgM-), and 28 vaccinees (7.41%) were negative for both IgG and IgM (IgG-IgM-); 2 participants were positive for IgM alone (IgG-IgM+). In sex subgroups, the rate of IgM positivity was significantly higher in the male group than in the female group (p = 0.027). In different age subgroups, positive rates for IgG in the young group were significantly higher than those in the other group (p = 0.035). Furthermore, ratios of sample values to cutoff values (S/CO values) for IgG in vaccinees who were S-specific IgG positive were compared, and the S/CO values of IgG were significantly higher in the younger group than in the other group (p < 0.001). When comparing the influence of sex on two specific serological patterns (IgG+IgM- and IgG+IgM+), a significant difference in positivity rates was detected (p = 0.011). Male vaccinees were more likely than females to have an IgG+IgM+ pattern.

Potential 3-chymotrypsin-like cysteine protease cleavage sites in the coronavirus polyproteins pp1a and pp1ab and their possible relevance to COVID-19 vaccine and drug development.

Coronavirus (CoV) 3-chymotrypsin (C)-like cysteine protease (3CLpro ) is a target for anti-CoV drug development and drug repurposing because along with papain-like protease, it cleaves CoV-encoded polyproteins (pp1a and pp1ab) into nonstructural proteins (nsps) for viral replication. However, the cleavage sites of 3CLpro and their relevant nsps remain unclear, which is the subject of this perspective. Here, we address the subject from three standpoints. First, we explore the inconsistency in the cleavage sites and relevant nsps across CoVs, and investigate the function of nsp11. Second, we consider the nsp16 mRNA overlapping of the spike protein mRNA, and analyze the effect of this overlapping on mRNA vaccines. Finally, we study nsp12, whose existence depends on ribosomal frameshifting, and investigate whether 3CLpro requires a large number of inhibitors to achieve full inhibition. This perspective helps us to clarify viral replication and is useful for developing anti-CoV drugs with 3CLpro as a target in the current coronavirus disease 2019 (COVID-19) pandemic.

Is lymphopenia different between SARS and COVID-19 patients?

Lymphopenia is commonly observed in SARS and COVID-19 patients although the lymphocyte count is not always below 0.8 × 109 /L in all the patients. It is suggested that lymphopenia serves as a useful predictor for prognosis in the patients. It is also hypothesized that lymphopenia is related to glucocorticoids and apoptosis. However, the ordering between lymphopenia and apoptosis appears different between SARS and COVID-19 patients, ie, lymphopenia is prior to apoptosis in SARS patients whereas apoptosis is prior to lymphopenia in COVID-19 patients. This paper attempts to figure out this contradiction through three players, lymphopenia, glucocorticoids, and apoptosis. Although the literature does not provide a solid explanation, the level of glucocorticoids could determine the ordering between lymphopenia and apoptosis because the administration of high doses of glucocorticoids could lead to lymphopenia whereas low doses of glucocorticoids could benefit patients. In the meantime, this paper raises several questions, which need to be answered in order to better understand the whole course of COVID-19.

Spatial and temporal roles of SARS-CoV PLpro -A snapshot.

SARS-CoV and SARS-CoV-2 encode four structural and accessory proteins (spike, envelope, membrane and nucleocapsid proteins) and two polyproteins (pp1a and pp1ab). The polyproteins are further cleaved by 3C-like cysteine protease (3CLpro ) and papain-like protease (PLpro ) into 16 nonstructural proteins (nsps). PLpro is released from nsp3 through autocleavage, and then it cleaves the sites between nsp1/2, between nsp2/3 and between nsp3/4 with recognition motif of LXGG, and the sites in the C-terminus of ubiquitin and of protein interferon-stimulated gene 15 (ISG15) with recognition motif of RLRGG. Alone or together with SARS unique domain (SUD), PLpro can stabilize an E3 ubiquitin ligase, the ring-finger, and CHY zinc-finger domain-containing 1 (RCHY1), through domain interaction, and thus, promote RCHY1 to ubiquitinate its target proteins including p53. However, a dilemma appears in terms of PLpro roles. On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state. This mini-review analyzes the dilemma and provides a snapshot on how the viral PLpro smartly manages its roles to avoid its simultaneously contradictory actions, which could shed lights on possible strategies to deal with SARS-CoV-2 infections.