Broad cross-neutralizing antibodies against animal-associated sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans (preprint)

The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that both SARS-CoV-2 infection and vaccination elicited broad cross-nAbs against multiple sarbecoviruses, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL, indicating its potential for combating new sarbecovirus outbreaks. Collectively, our findings suggest that both SARS-CoV-2 infection and current vaccination schemes elicit broad cross-neutralizing antibodies against diverse sarbecoviruses, enforcing prevention and therapeutic strategies for future sarbecovirus spillover events.

LS-MolGen: Ligand-and-Structure Dual-driven Deep Reinforcement Learning for Target-specific Molecular Generation Improves Binding Affinity and Novelty (preprint)

Molecule generative models based on deep learning have attracted significant attention in de novo drug design. However, most current generative approaches are either only ligand-based or only structure-based, which do not leverage the complementary knowledge from ligands and the structure of binding target. In this work, we proposed a new ligand and structure combined molecular generative model, LS-MolGen, that integrates representation learning, transfer learning, and reinforcement learning. Focus knowledge from transfer learning and special explore strategy in reinforcement learning enables LS-MolGen to generate novel and active molecules efficiently. The results of evaluation using EGFR and case study of inhibitor design for SARS-CoV-2 Mpro showed that LS-MolGen outperformed other state-of-the-art ligand-based or structure-based generative models and was capable of de novo designing promising compounds with novel scaffold and high binding affinity. Thus, we recommend that this proof-of-concept ligand-and-structure-based generative model will provide a promising new tool for target-specific molecular generation and drug design.

Identification of key genes related to immune cells in patients with COVID-19 via Integrated Bioinformatics-Based Analysis (preprint)

Background COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis.Methods The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms.Results There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signalling pathway. As much as 358 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signalling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI: 0.920–0.988), 0.941(95% CI: 0.892 − 0.980), and 0.929(95% CI: 0.880 − 0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells.Conclusions Our study discovered that CDC25A, PDCD6 and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19.

Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Physical condition, psychological status, and posttraumatic stress disorder among recovered COVID-19 subjects: A mediation analysis

The physical condition of individuals who contracted COVID-19 had a profound influence on mitigating the physical and psychological impact of the disease and the symptoms of posttraumatic stress disorder (PTSD). Little attention has been focused on the influence of physical condition on PTSD among recovered COVID-19 subjects. This study explored the relationship between physical and psychological status and PTSD and the potential mechanisms. Questionnaires were completed by 73 (50.7%, 73/144) COVID-19 recovered subjects who were diagnosed in Taizhou, Zhejiang, China. We conducted a face-to-face survey from January 17 to March 10, 2020. The mediation analysis approach was applied in this research. Our data show that recovered COVID-19 subjects who were in better physical condition exhibited fewer psychological problems [B (95%CI), (−1.65 −3.04, −0.26)] and lower PTSD [B (95%CI), −6.13 (−9.43, −2.83)]. In addition, the worse the psychological status of recovered COVID-19 subjects was, the stronger the PTSD (B [95%CI], 0.58 [0.02, 1.14]). Moreover, psychological status could significantly mediate the impact of physical condition on PTSD (β1θ2 = −0.87). Together, COVID-19 recovered subjects who have better physical condition could decrease their PTSD, and the worse the physical condition of COVID-19 recovered subjects would increase their psychological problems. Our finding about psychological status could significantly mediate the impact of the physical condition on PTSD might be useful for medical institutions and the government seeking to help with the follow-up rehabilitation training of recovered COVID-19 subjects.

Spike-specific CXCR3+ TFH cells play a dominant functional role in supporting antibody responses in SARS-CoV-2 infection and vaccination (preprint)

CD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3- TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3- TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3- TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory.

An Exploration of Students’ Attitudes Toward Employment Services in Private Schools: The Case of the Sanya Institute of Technology

Providing long-term career coaching or counseling has become an increasingly important part of university life as the coronavirus pandemic rapidly sweeps across the world. Career coaching has become one of the most important drivers of revenue and enrollment growth in nongovernmental schools. However, little research has been carried out to evaluate the effectiveness of these long-term career coaching or counseling services. Accordingly, this study aims to use a mixed method approach to track and measure students? satisfaction from private higher vocational colleges to identify opportunities for improving employment services. Students were asked how satisfied they were with employment services provided by this private vocational school. The results obtained lead us to suggest that private higher vocational colleges could strengthen the employability of graduates by providing a wide variety of enrichment activities and establishing a regular monitoring mechanism to evaluate perceptions of their engagement and educational experiences in the current coronavirus crisis.

Human metapneumovirus in hospitalized children with acute respiratory tract infections in Beijing, China (preprint)

Background: This study aims to described the epidemiology and genotypic diversity of Human metapneumovirus (HMPV) and the impact of SARS-CoV-2 on the prevalence of HMPV in hospitalized children with Acute respiratory tract infections (ARTIs) in Beijing, China. Methods From April 2018 to March 2019 and from September 2020 to August 2021, nasopharyngeal aspirates (NPAs) from hospitalized children with ARTIs in Beijing were collected and subjected to real-time polymerase chain reaction tests for HMPV. Then genotyping, detection of 15 common respiratory viruses and clinical characteristics were analyzed on HMPV positive samples. Results 7.9% (124/1572) enrolled paediatric patients were identified as having HMPV infection, and the majority of children under the age of 5 (78.2%, 92/124), From April 2018 to March 2019. The detection rate of HMPV in spring and winter is significantly higher than that in summer and autumn. The co-infection rate were 37.1% (46/124), the most common co-infected virus were parainfluenza virus type 3 (HPIV-3). The main diagnosis of HMPV infection was pneumonia (92.7%,115/124), most patient have cough and fever. Of 78 HMPV-positive specimens, A2b (82.1%,64/78) were the main epidemic subtypes. .During the COVID-19 outbreak, Among 232 samples, only 4 cases were HMPV-positive. After statistical test, the detection rate of HMPV during the COVID-19 pandemic has decreased significantly compared with that before the epidemic (p=0.001). Conclusions HMPV is an important cause of ARTIs in children under 5 years old. Under the prevention and control of the COVID-19 pandemic, the HMPV infection of hospitalized children with ARTIs has decreased significantly.

Difference and Cluster Analysis on the Carbon Dioxide Emissions in China During COVID-19 Lockdown via a Complex Network Model

The continuous increase of carbon emissions is a serious challenge all over the world, and many countries are striving to solve this problem. Since 2020, a widespread lockdown in the country to prevent the spread of COVID-19 escalated, severely restricting the movement of people and unnecessary economic activities, which unexpectedly reduced carbon emissions. This paper aims to analyze the carbon emissions data of 30 provinces in the 2020 and provide references for reducing emissions with epidemic lockdown measures. Based on the method of time series visualization, we transform the time series data into complex networks to find out the hidden information in these data. We found that the lockdown would bring about a short-term decrease in carbon emissions, and most provinces have a short time point of impact, which is closely related to the level of economic development and industrial structure. The current results provide some insights into the evolution of carbon emissions under COVID-19 blockade measures and valuable insights into energy conservation and response to the energy crisis in the post-epidemic era.

ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells (preprint)

Currently, the COVID-19 pandemic, caused by SARS-CoV-2 infection, represents a serious public health problem worldwide. Although it has been shown that ACE2 serves as the main receptor for SARS-CoV-2 entry into host cells, studies have shown that ACE2 is expressed at extremely low levels in various tissues, especially in some organs where virus particles have been found, such as the heart and liver. Therefore, these organs potentially express additional SARS-CoV-2 receptors that have not yet been discovered. Here, by a genome-wide CRISPR-Cas9 activation library screening, we found that ASGR1 promoted SARS-CoV-2 infection of 293T cells. In Huh-7 and HepG2 cell lines, simultaneous knock out of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary liver parenchymal cells, both of which hardly express ACE2, SARS-CoV-2 could successfully establish an infection. After treatment with ASGR1 antibody, the infection rate significantly reduced. This suggests that SARS-CoV-2 infects liver cells mainly through an ASGR1-dependent mechanism. Finally, we also found that the soluble ASGR1 could not only prevent the SARS-CoV-2 pseudovirus, which binds to the ASGR1 receptors, from infecting host liver cells, but also had a protective effect on those expressing ACE2, indicating that administration of soluble ASGR1 protein may represent a new treatment approach. CONCLUSIONS: Colletively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells.

A Real-World Study on Myopia Control 6 Months After Withdrawal of 1% Atropine Eye Gel (preprint)

Purpose: This study aimed to observe the changes in spherical equivalent and ocular axial length 6 months after withdrawal of 1% atropine eye gel. Methods: Due to COVID-19, the follow-up of patients in our optometric clinic who were undergoing myopia control treatment with a dropwise 1% atropine “5+3” regimen was interrupted. No return visit was made after the 3 months of at-home treatment, and follow-ups resumed 6 months after treatment withdrawal. The contralateral eye was not treated over the 9-month period. A total of 16 patients aged 11.5 years (average) were enrolled from November 2019 to March 2021 during the COVID-19 pandemic. The treated eyes formed a treatment group (16 eyes) and the contralateral eyes formed a control group (16 eyes). The changes in spherical equivalent, ocular axial length, and intraocular pressure (IOP) were compared between groups. Results: After 9 months, the changes in spherical equivalent were significantly less in the treatment group (0.00 ± 0.20 [D]) compared to the control group (-0.67 ± 0.25 [D]) (P<0.05). The ocular axial length changes were significantly less in the treatment group (0.00 ± 0.06 mm) compared to the control group (0.25 ± 0.11 mm) (P<0.05). There was no significant difference between the two groups for changes in IOP. Conclusions: Despite treatment withdrawal after 3 months, treatment with 1% atropine eye gel successfully controlled myopia progression in the 6 months after withdrawal, as evidence by no rebound increase in myopic spherical equivalent after the withdrawal.

Angiotensin-converting enzyme 2 SNPs as the common genetic loci and optimal early identification genetic markers for COVID-19 (preprint)

Background: Angiotensin-converting enzyme 2 (ACE2) is implicated as a host cell receptor that causes infection in the pathogenesis of Coronavirus disease 2019 (COVID-19), and its genetic polymorphisms in the ACE2 gene may promote cardiovascular disease and systemic inflammatory injury in COVID-19. Hence, genetic background may potentially explain the broad inter-individual variation of disease susceptibility and/or severity. Methods The genetic susceptibility to COVID-19 by examining single-nucleotide polymorphisms (SNPs) of ACE2 was analyzed in 196 patients with COVID-19 and 210 normal controls using TaqMan genotyping assay. Results We demonstrated that ACE2 SNP rs4646142, rs6632677, and rs2074192 were associated with COVID-19 (all P < 0.05), and the differences of ACE2 SNPs rs4646142 and rs6632677 were correlated with COVID-19 related systemic inflammatory injury and cardiovascular risk. Specially, rs4646142 was associated with high-sensitive C-reactive protein (hs-CRP), prealbumin (PAB), apolipoprotein A (APOA), high-density lipoprotein (HDL), and acid glycoprotein (AGP). Rs6632677 was also associated with elevated CRP and haptoglobin (HPT). Conclusions Our results suggest that early identification of these individuals can provide a possible strategy for preventing the spread of the COVID-19, and ACE2 SNPs rs4646142 and rs6632677 may be a common genetic loci and optimal early identification genetic marker for COVID-19 with cardiovascular risks.

Usage of Compromised Lung Volume in Monitoring Steroid Therapy on Severe COVID-19 (preprint)

Background: Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19)and for monitoringits progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19. Methods: Between February 7 and February 17, 2020, 300 chest CT scans from 72 patients with severe COVID-19 were retrospectively collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lungaccording to different Hounsfield unit (HU) intervals. The primary outcomeswerechanges in percentage of compromised lung volume (%CL, –500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders. Results: Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (-3.27% [95%CI, -5.86 to -0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P <0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P <0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group ( P <0.05), but not inthe low CL group. Conclusions: Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process. Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247

Ventilation and Air Conditioning Design of the Ward Protection Unit in the COVID-19 Emergency Hospital

Ward protection unit is the basic isolation unit of infectious disease hospital, and it is the basic element of physical isolation. The isolation of airflow depends on the reasonable setting of ventilation and air conditioning system. For the COVID-19 emergency hospital, the design of ventilation and air conditioning system in its ward protection unit is very important and is an important means to control the air transmission route. Based on the design of Wuhan Huoshenshan hospital, starting from the principles and objectives of protection unit design, this paper focuses on the analysis of system division and air distribution, protection unit pressure difference control, ventilation calculation, filter and outdoor fan setting, etc., and discusses the ventilation and air conditioning design of each area in the protection unit item by item. Finally, the differences between the COVID-19 emergency hospital and the conventional infectious disease hospital in ventilation and air conditioning design are compared, and the design method and technical requirements are summarized, hoping to provide reference for similar engineering design.

Research progress of mechanisms of spike protein in SARS-CoV-2 infection

Human ACE2 receptors on cells binding to Spike(S) protein on the surface of SARS-CoV-2 may be the main cause of the viruses entering into human cells. In this article, the current situation of the research on the S protein related SARS-CoV-2 infection and its mechanisms were summarized. We focused on the effect of structure of S protein on the infection, the binding sites of S proteins on ACE2 receptors in various tissues and other proteins which may regulate the process of binding, in order to elucidate the mechanisms of the infection of SARS-CoV-2. The variation of the gene of S protein can affect the transmission and virulence of SARS-CoV-2, which may give some useful references to the comprehensive understanding of the new virus of SARS-CoV-2.

Needs, gaps and opportunities for standard and e-mental health care among at-risk populations in the Asia Pacific in the context of COVID-19: A rapid scoping review. (preprint)

Background: The COVID-19 pandemic is expected to have profound mental health impact, including in the Asia Pacific Economic Cooperation (APEC) region. Some populations might be at higher risk of experiencing negative mental health impacts and may encounter increased barriers to accessing mental health care. The pandemic and related restrictions have led to changes in care delivery, including a rapid shift to the use of e-mental health and digital technologies. It is therefore essential to consider needs and opportunities for equitable mental health care delivery to the most at-risk populations. This rapid scoping review: 1) identifies populations in the APEC region that are at higher risk of the negative mental health impacts of COVID-19, 2) identifies needs and gaps in access to standard and e-mental health care among these populations, and 3) explores the potential of e-mental health to address these needs.Methods: We conducted a rapid scoping review following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). We searched Medline, Embase and PsychInfo databases and Google Scholar using a search strategy developed in consultation with a biomedical librarian. We included records related to mental health or psychosocial risk factors and COVID-19 among at-risk groups; that referred to one or more APEC member economies or had a global, thus generalizable, scope; English language papers, and papers with full text available.Results: A total of 132 records published between December 2019 and August 2020 were included in the final analysis. Several priority as-risk populations, risk factors, challenges and recommendations for standard and e-mental health care were identified. Results demonstrate that e-mental health care can be a viable option for care delivery but that specific accessibility and acceptability considerations must be considered. Options for in-person, hybrid or “low-tech” care must also remain available.Conclusions: The COVID-19 pandemic has highlighted the urgent need for equitable standard and e-mental health care. It has also highlighted the persistent social and structural inequities that contribute to poor mental health. The APEC region is vast and diverse; findings from the region can guide policy and practice in the delivery of equitable mental health care in the region and beyond.

Sewage Treatment Project Design of Wuhan Huoshenshan and Leishenshan Hospitals

The Huoshenshan hospital and Leishenshan hospital are special infectious diseases hospitals that were designed to focus on the treatment of patients infected by new Coronavirus pneumonia( COVID-19). The design of sewage treatment system was "pre-disinfection contact tank + septic tank + lifting pump station( including crushed grille) + regulating tank + MBBR biochemical tank +coagulation sedimentation tank + contact disinfection tank ". MBBR process could achieve efficient removal of pollutants in sewage at low temperature. Two-stage disinfection process guaranteed 100% virus elimination. At the same time,HDPE membrane was laid under the sewage station according to the landfill standard to ensure the full collection,disinfection and discharge of rainwater and sewage. The sludge was collected and transported as hazardous waste after disinfection and dehydration. The waste gas was collected,deodorized and disinfected in a unified way,so as to realize the full collection and treatment of rainwater,sewage,sludge and waste gas. At present,the operations of the sewage stations of Huoshenshan and Leishenshan hospitals had kept stable,and the relevant effluent indexes met the design requirements. COD concentration was stable below 50 mg/L,ammonia nitrogen was stable below 2 mg/L,residual chlorine was stable near 13 mg/L. Therefore,the pollutant removal and disinfection effect were stable during the whole operation.

Performance Evaluation of the Serological Test and Dynamic Changes of Anti-2019-nCoV Antibodies Among COVID‐19 Patients (preprint)

BackgroundSerological tests for anti-2019-nCoV antibodies have been developed, however, validation with clinical samples was insufficient and mixed. MethodsA total of 197 patients with COVID-19 hospitalized in the Wuhan Pulmonary Hospital and 114 healthy people were enrolled in this study. The IgM/IgG was measured by chemiluminescence detection kit and the performance of IgM/IgG was assessed through diagnostic test. A smooth spline function was used to fit a possible dynamic changes of antibody content.ResultsThe sensitivity and specificity to diagnose COVID-19 were 96.95% and 92.98% for IgG, and 65.99% and 98.25% for IgM, respectively. The period with the highest IgM positive rate (93.75%) was 11 to 13 days after the onset, while the IgG positive rate was almost 100% in the patients whose serum was collected 7 days after onset. Small differences were found in IgM content among mild/regular, severe and critical patients. IgG content in critical patients were highest in the 2-week post-symptom onset group, while the IgG in the severe patients were highest in the 15-28 days and more than 28 days post-symptom onset.ConclusionsSerological testing performed well in the diagnosis for COVID-19, and the positive rate and variance of IgG are higher than those of IgM.