Elevated INR in a COVID-19 patient after concomitant administration of azvudine and anticoagulants.

Background: Azvudine (FNC) is a promising treatment candidate for managing coronavirus disease 2019 (COVID-19). However, drug interactions with azvudine have been poorly studied, especially with no reported cases of azvudine with anticoagulants such as warfarin and rivaroxaban. Case summary: The patient was diagnosed with lower limb venous thrombosis and took warfarin regularly. The international normalized ratio (INR) was stable (2.0-3.0). However, the INR increased to 7.52 after administering azvudine. The patient had no other factors justifying this change. This increase in INR occurred again with the administration of azvudine in combination with rivaroxaban, and the INR increased to 18.91. After azvudine administration was stopped, the INR did not increase when rivaroxaban was used alone. Conclusion: Azvudine, warfarin, and rivaroxaban might have previously unidentified drug interactions that increased the INR. Therefore, the INR must be closely monitored when they are concomitantly administered in COVID-19 patients.

Mapping current status and emerging trends in NETosis: A bibliometric study.

BACKGROUND: NETosis is a critical innate immune mechanism of neutrophils that contributes to the accelerated progression of autoimmune diseases, thrombosis, cancer, and coronavirus disease 2019 (COVID-19). This study qualitatively and quantitatively analyzed the relevant literature by bibliometric methods in order to provide a more comprehensive and objective view of the knowledge dynamics in the field. METHODS: The literature on NETosis was downloaded from the Web of Science Core Collection, analyzed with VOSviewer, CiteSpace, and Microsoft for co-authorship, co-occurrence, and co-citation analysis. RESULTS: In the field of NETosis, the United States was the most influential countries. Harvard University was the most active institutions. Mariana J. Kaplan and Brinkmann V were, respectively, the most prolific and most co-cited authors. Frontiers in Immunology, Journal of Immunology, Plos One, Blood, Science, Journal of Cell Biology, and Nature Medicine were the most influential journals. The top 15 keywords are associated with immunological and NETosis formation mechanisms. The keywords with the strongest burst detection were mainly related to COVID-19 (coronavirus, ACE2, SARS coronavirus, cytokine storm, pneumonia, neutrophil to lymphocyte ratio), and cancer (circulating tumor cell). CONCLUSION: Research on NETosis is currently booming. The mechanism of NETosis and its role in innate immunity, autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis, and thrombosis are the focus of research in the field of NETosis. A future study will concentrate on the function of NETosis in COVID-19 and recurrent metastasis of cancer.

Comparison of requirements for clinical study of SARS-CoV-2 antigen test kits in China, the USA and Europe.

Aims: This study was designed to analyze the requirements for clinical trials of SARS-CoV-2 antigen testing to explore the rationality and scientific rigor of clinical trials. Methods: The guidelines for the listing of SARS-CoV-2 antigen tests were compared and the requirements for clinical trials were analyzed to find similarities and differences between China, the USA and Europe. Results: The requirements for clinical trials of SARS-CoV-2 antigen tests in China, the USA and Europe were consistent in terms of methods. However, differences were found in the requirements for protocol design. Conclusion: The differences in clinical trial requirements stem from regulations and the actual conditions across regions, but all clinical trials are designed to obtain valid clinical performance of products.

Long-Term Cross Immune Response in Mice following Heterologous Prime-Boost COVID-19 Vaccination with Full-Length Spike mRNA and Recombinant S1 Protein.

(1) Background: As the COVID-19 pandemic enters its fourth year, it continues to cause significant morbidity and mortality worldwide. Although various vaccines have been approved and the use of homologous or heterologous boost doses is widely promoted, the impact of vaccine antigen basis, forms, dosages, and administration routes on the duration and spectrum of vaccine-induced immunity against variants remains incompletely understood. (2) Methods: In this study, we investigated the effects of combining a full-length spike mRNA vaccine with a recombinant S1 protein vaccine, using intradermal/intramuscular, homologous/heterologous, and high/low dosage immunization strategies. (3) Results: Over a period of seven months, vaccination with a mutant recombinant S1 protein vaccine based on the full-length spike mRNA vaccine maintained a broadly stable humoral immunity against the wild-type strain, a partially attenuated but broader-spectrum immunity against variant strains, and a comparable level of cellular immunity across all tested strains. Furthermore, intradermal vaccination enhanced the heterologous boosting of the protein vaccine based on the mRNA vaccine. (4) Conclusions: This study provides valuable insights into optimizing vaccination strategies to address the ongoing challenges posed by emerging SARS-CoV-2 variants.

Do governmental policy interventions help urban economic recovery? Experimental evidence from China's provinces governance amid the COVID-19 pandemic.

By examining China's province-level data, this paper uses governmental intervention theory to investigate the extent to which governmental policy interventions alleviate the impact of the COVID-19 pandemic on local economic growth. Results suggest that stronger government intervention during COVID-19 pandemic boost the economic recovery, and the effectiveness of governmental policy interventions is contingent on pandemic severity and local economic endowment. Specifically, facilitating effect of government intervention on economic growth is effective in all provinces, and the impact of government intervention is more pronounced in the province with more diagnosed cases, a high level of marketization and fiscal income.

Changes in air pollution, land surface temperature, and urban heat islands during the COVID-19 lockdown in three Chinese urban agglomerations.

COVID-19 has notably impacted the world economy and human activities. However, the strict urban lockdown policies implemented in various countries appear to have positively affected pollution and the thermal environment. In this study, Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) and aerosol optical depth (AOD) data were selected, combined with Sentinel-5P images and meteorological elements, to analyze the changes and associations among air pollution, LST, and urban heat islands (UHIs) in three urban agglomerations in mainland China during the COVID-19 lockdown. The results showed that during the COVID-19 lockdown period (February 2020), the levels of the AOD and atmospheric pollutants (fine particles (PM2.5), NO2, and CO) significantly decreased. Among them, PM2.5 and NO2 decreased the most in all urban agglomerations, by >14 %. Notably, the continued improvement in air pollution attributed to China's strict control policies could lead to overestimation of the enhanced air quality during the lockdown. The surface temperature in all three urban agglomerations increased by >1 °C during the lockdown, which was mainly due to climate factors, but we also showed that the lockdown constrained positive LST anomalies. The decrease in the nighttime urban heat island intensity (UHIInight) in the three urban agglomerations was greater than that in the daytime quantity by >25 %. The reduction in surface UHIs at night was mainly due to the reduced human activities and air pollutant emissions. Although strict restrictions on human activities positively affected air pollution and UHIs, these changes were quickly reverted when lockdown policies were relaxed. Moreover, small-scale lockdowns contributed little to environmental improvement. Our results have implications for assessing the environmental benefits of city-scale lockdowns.

Symptom Burden among Older COVID-19 Survivors Two Years after Hospital Discharge.

To study the long-term symptom burden among older COVID-19 survivors 2 years after hospital discharge and identify associated risk factors. The current cohort study included COVID-19 survivors aged 60 years and above, who were discharged between February 12 and April 10, 2020, from two designated hospitals in Wuhan, China. All patients were contacted via telephone and completed a standardized questionnaire assessing self-reported symptoms, the Checklist Individual Strength (CIS)-fatigue subscale, and two subscales of the Hospital Anxiety and Depression Scale (HADS). Of the 1,212 patients surveyed, the median (IQR) age was 68.0 (64.0-72.0), and 586 (48.3%) were male. At the two-year follow-up, 259 patients (21.4%) still reported at least one symptom. The most frequently self-reported symptoms were fatigue, anxiety, and dyspnea. Fatigue or myalgia, which was the most common symptom cluster (11.8%; 143/1212), often co-occurred with anxiety and chest symptoms. A total of 89 patients (7.7%) had CIS-fatigue scores ≥ 27, with older age (odds ratio [OR], 1.08; 95% CI: 1.05-1.11, P < 0.001) and oxygen therapy (OR, 2.19; 95% CI: 1.06-4.50, P= 0.03) being risk factors. A total of 43 patients (3.8%) had HADS-Anxiety scores ≥ 8, and 130 patients (11.5%) had HADS-Depression scores ≥ 8. For the 59 patients (5.2%) who had HADS total scores ≥ 16, older age, serious illness during hospitalization and coexisting cerebrovascular diseases were risk factors. Cooccurring fatigue, anxiety, and chest symptoms, as well as depression, were mainly responsible for long-term symptom burden among older COVID-19 survivors 2 years after discharge.

Residential mobility predicts COVID-19 and seasonal flu vaccination behaviors in the United States.

Aim: Vaccination is one of the most effective strategies to contain the transmission of infectious diseases; however, people's intentions and behavior for vaccination vary across different regions and countries around the world. It is not clear how socioecological factors such as residential mobility influence people's vaccination behaviors for infectious diseases. Methods: We analyzed public data on residential mobility and vaccination rates for COVID-19 and seasonal flu in the United States and explored how residential mobility in the previous year influenced vaccination rates for COVID-19 and seasonal flu (2011-2018) across 50 states of the US. The data were accessed and analyzed in 2021. Results: Study 1 demonstrated that collective-level residential mobility predicted COVID-19 vaccination rates across the United States (B = -168.162, 95% CI [-307.097, -29.227], adjusted R 2 = 0.091, p = 0.019). Study 2 corroborated this finding by documenting that collective-level residential mobility predicted vaccination rates for seasonal flu from 2011 to 2018 across the United States (B = -0.789, 95% CI = [-1.018, -0.56], adjusted R 2 = 0.222, p < 0.001). The link between residential mobility and vaccination behavior was robust after controlling relevant variables, including collectivism, cultural tightness-looseness, and sociodemographic variables. Conclusions: Our research demonstrated that residential mobility is an important socioecological factor that influences people's vaccination behaviors for COVID-19 and seasonal flu. The results enrich our understanding of the socioecological factors that influence vaccination behaviors and have implications for developing tailored interventions to promote vaccination during pandemics of infectious diseases.

CDetection.v2: One-pot assay for the detection of SARS-CoV-2.

Introduction: The ongoing 2019 coronavirus disease pandemic (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants, is a global public health threat. Early diagnosis and identification of SARS-CoV-2 and its variants plays a critical role in COVID-19 prevention and control. Currently, the most widely used technique to detect SARS-CoV-2 is quantitative reverse transcription real-time quantitative PCR (RT-qPCR), which takes nearly 1 hour and should be performed by experienced personnel to ensure the accuracy of results. Therefore, the development of a nucleic acid detection kit with higher sensitivity, faster detection and greater accuracy is important. Methods: Here, we optimized the system components and reaction conditions of our previous detection approach by using RT-RAA and Cas12b. Results: We developed a Cas12b-assisted one-pot detection platform (CDetection.v2) that allows rapid detection of SARS-CoV-2 in 30 minutes. This platform was able to detect up to 5,000 copies/ml of SARS-CoV-2 without cross-reactivity with other viruses. Moreover, the sensitivity of this CRISPR system was comparable to that of RT-qPCR when tested on 120 clinical samples. Discussion: The CDetection.v2 provides a novel one-pot detection approach based on the integration of RT-RAA and CRISPR/Cas12b for detecting SARS-CoV-2 and screening of large-scale clinical samples, offering a more efficient strategy for detecting various types of viruses.

Chinese Canadians' Experiences of the Dual Pandemics of COVID-19 and Racism: Implications for Identity, Negative Emotion, and Anti-Racism Incident Reporting

De nombreux Canadiens d'origine chinoise ont connu un plus grand nombre d' incidents de racisme et de xénophobie depuis le début de la pandémie de coronavirus (COVID-19). La présente étude porte sur cette discrimination accrue a l'égard des Chinois et en quoi celleci et les menaces liées a la pandémie elle-meme nuisent au bien-etre des Canadiens d' origine chinoise ainsi qu' a leur identité chinoise et canadienne. Nous avons interrogé 874 adultes d'origine chinoise de partout au Canada - M?ge = 42,09;47,7 % de femmes;628 nés a l'étranger, de premiere génération (G1), et 246 nés au Canada, de deuxieme génération (G2) au moins. Les taux rapportés d'expériences discriminatoires sont alarmants : plus de la moitié des répondants ont dit avoir été traités avec moins de respect en raison deleurethnie (G1: 60,6 %;G2: 56,8 %), et plus du tiers ont dit avoir été personnellement menacés ou avoir été victimes d' intimidation (G1 : 35,2%;G2 : 39,8%). Le statut générationnel influait sur les expériences des Canadiens d' origine chinoise durant la pandémie : les membres de la G1 ont ressenti davantage de menaces pour leur santé, leur situation financiere et leur culture durant la pandémie, et les membres de la G2 ont témoigné d'une plus grande discrimination personnelle et a l'égard de leur groupe. La discrimination perçue était associée a l'affect négatif, meme apres avoir tenu compte des menaces liées a la pandémie. Le type de discrimination a des répercussions différentes pour les identités culturelles patrimoniale et dominante. Au sein des deux groupes, la discrimination personnelle était négativement associée a l' identité canadienne, et la discrimination de groupe était positivement associée a l'identité chinoise. Environ 10 % seulement des Canadiens d'origine chinoise qui ont été victimes de harcelement ont rapporté leurs expériences aux autorités ou dans les médias sociaux;leur propre perception d'etre, aux yeux d'autrui, de perpétuels étrangers les a empechés de rapporter le harcelement. Les auteurs discutent des répercussions du signalement du harcelement sur l'acculturation, l'identité, les stratégies antiracistes et la responsabilisation personnelle.Alternate :Many Chinese Canadians (CCs) have experienced increased racism and xenophobia since the beginning of the Coronavirus disease (COVID-19) pandemic. This study focused on how this rise of anti-Chinese discrimination, in addition to the threats posed by the pandemic itself, affects not only CCs' well-being, but also their Chinese and Canadian identities. We surveyed 874 CC adults from across Canada, Mage = 42.09;47.7% females;628 foreign-born, first-generation (G1) and 246 Canadian-born, second or later generation (G2). The reported rates of discriminatory experiences were alarming: More than half of the respondents reported that they had been treated with less respect because of their ethnicity (G1: 60.6%;G2: 56.8%), and over a third reported that they had been personally threatened or intimidated (G1: 35.2%;G2: 39.8%). Generational status moderated CCs' pandemic experiences, such that G1 CCs perceived more health, financial, and cultural threats due to the pandemic, but G2 CCs reported more personal and group discrimination. Perceived discrimination was associated with CCs' negative affect even after controlling for pandemic threats. The type of discrimination had different implications for heritage and mainstream cultural identities. For both groups, personal discrimination was negatively associated with Canadian identity, whereas group discrimination was positively associated with Chinese identity. Only about 10% of CCs who experienced harassment reported their encounters to authorities or on social media;CCs' perceptions that others saw them as perpetual foreigners undermined their reporting of harassment. The findings' implications for acculturation, identity, anti-racism strategies, and empowerment in reporting harassment are discussed.

Clinical research of pre-hospital emergency care, nursing, infection prevention and control for senile osteoporotic vertebral compression fracture during epidemic period

Background: Novel coronavirus pneumonia (NCP) and osteoporotic vertebral compression fractures (OVCF) are the high incidences of diseases in the elderly. During the epidemic period, if not treated in time, the complications are high and the mortality is high. If we do not pay attention to infection prevention and control in pre-hospital emergency care, it will lead to the first time infection of medical staff and in-hospital cross infection in emergency outpatient receiving area. The correct consideration of both and the establishment of perfect pre-hospital emergency treatment and infection prevention and control synchronous strategy is an important premise to ensure the stable, orderly and safe medical treatment. Background: To explore the effect of synchronous implementation of pre-hospital emergency care, nursing and infection pre-vention and control for senile OVCF during the epidemic. In order to improve the efficiency of pre-hospital emergency care and prevent the spread of infection. Method: A total of 92 elderly patients with OVCF who received pre-hospital treatment in 18 hospitals in Zhangjiakou City during the epidemic prevention and control period from January 2020 to November 2022 and met the inclusion criteria were selected as research objects, including 24 males and 68 females, aged 65 - 82 (74.2 +or- 2.2) years. All patients were associated with concomitant injuries and underlying diseases. All patients in this group underwent predictive pre-hospital rescue and infection prevention and control procedures. Results: All the 92 elderly patients with OVCF received timely pre-hospital treatment during the epidemic period, and no aggravation occurred of the 92 patients, 35 were in the high risk area, 10 were in the medium risk area, and 47 were in the low risk area. Exclude OVCF for NCP Patients were treated according to the conventional diagnosis and treatment principles. Suspected and confirmed cases are transferred to designated surgical hospitals for treatment. All patients were followed up 3 months, 6 months and 12 months after treatment. There was no death rate, high satisfaction of pre-hospital first aid, high diagnostic accuracy, and good curative effect. None of the rescue personnel had any infection rate, and no hospital infection transmission and nosocomial cross infection occurred. Conclusion: It is the first step to safely treat patients and prevent cross infection to establish a perfect synchronous strategy of pre-hospital first aid and infection prevention and control.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

The relationship between leisure activities and the mental health of college students during the COVID-19 pandemic

Despite the benefits of leisure activities for mental health, very little is known about the link between leisure activities and mental health of college students during the COVID-19 pandemic. To fill this knowledge gap, this study sought to examine the relationship between leisure activities and mental health during the COVID-19 pandemic and lockdown. A cross-sectional online survey of 30 Chinese provinces was conducted from March 9 to 25. The Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale were conducted to measure mental health, while the duration of leisure activities was used to evaluate leisure. Results of logistic regression showed the impact of leisure activities on self-rated mental health depends on types of leisure activities. Reading and calligraphy are beneficial to self-rated mental health while online activities are not. Self-rated mental health is associated with leisure activities. More college students with self-reported anxiety symptoms like to participate in hobbies and outdoor physical activities, while college students who reported depression are reluctant to participate in most leisure activities. Females, postgraduates incline to participate in more types of leisure activities, and students living in urban areas are reluctant to join outdoor physical activities. Besides, these groups are more likely to have self-reported mental illness symptoms.

Preparation of equine anti-SARS-CoV-2 immunoglobulin special IgG and special F (ab')2

After immunizing healthy horses with SARS-CoV-2 virus-like particles (VLPs) as immunogens, immunized horse serum was collected. The total IgG in the serum was separated by affinity chromatography, and then digested with pepsin to obtain immunoglobulin F(ab')2, the IgG and F(ab')2 using an immunochro-matographic column that binds to the RBD protein to obtain a highly specific horse Anti-SARS-CoV-2 IgG and F(ab')2. It's concentration of IgG and F(ab')2 is 2.36 mg/mL and 1.05 mg/mL, whi le the recovery rates were 11% and 4.89%, and the purities of prepared IgG and F(ab')2 were 91% and 96%. Semi-inhibited concentrations of pseudovirus (IC50) were 1.406 g/mL and 0.862 g/mL. These results show that a high purity, specificity, activity of specific IgG and F(ab')2 against SARS-CoV-2 was prepared successfully, which laid a foundation for preparing safe and efficient anti-SARS-CoV-2 therapeutic antibody drugs.

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation.

Messenger RNA (mRNA) has become a key focus in the development of therapeutic agents, showing significant potential in preventing and treating a wide range of diseases. The COVID-19 pandemic in 2020 has accelerated the development of mRNA nucleic therapeutics and attracted significant investment from global biopharmaceutical companies. These therapeutics deliver genetic information into cells without altering the host genome, making them a promising treatment option. However, their clinical applications have been limited by issues such as instability, inefficient in vivo delivery, and low translational efficiency. Recent advances in molecular design and nanotechnology have helped overcome these challenges, and several mRNA formulations have demonstrated promising results in both animal and human testing against infectious diseases and cancer. This review provides an overview of the latest research progress in structural optimization strategies and delivery systems, and discusses key considerations for their future clinical use.

Effect of vitamin D supplementation on COVID-19 patients: A systematic review and meta-analysis.

Objective: To systematically evaluate the impact of vitamin D supplementation on mortality, ICU admission, and the rates of mechanical ventilation or intubation among COVID-19 patients. Data sources and study selection: The PubMed, Embase, Cochrane Library, CBM, CNKI, VIP, and WanFang databases were searched from 1 December 2019 to 31 December 2022. The authors sought to identify randomized controlled trials and cohort studies that examined the relationship between vitamin D supplementation and mortality, ICU admission, and mechanical ventilation or intubation rates among COVID-19 patients. Data extraction and synthesis: Two investigators independently searched the literature, extracted the data, and assessed the quality of the included studies. The Grading of Recommendation, Assessment, Development, and Evaluation approach was used to evaluate the quality of the evidence. Meta-analysis was conducted using RevMan 5.3, STATA 15.1, and R 4.1.3 software. Results: Eight randomized controlled trials (RCTs) and eight cohort studies were included, involving 3359 COVID-19 patients. The pooled analysis of randomized controlled trials showed that vitamin D supplementation did not have a significant effect on reducing mortality (Relative Risk, RR = 0.94, 95% CI 0.69-1.29, P = 0.7), while the results of cohort studies indicated that vitamin D supplementation had a positive impact on reducing mortality among COVID-19 patients (RR = 0.33, 95% CI 0.23-0.47, P < 0.001). There was no statistically significant difference in the rates of ICU admission (RCTs: RR = 0.64, 95%CI 0.38-1.08, P = 0.10; cohort studies: RR = 0.32, 95% CI 0.08-1.29, P = 0.109) or rates of mechanical ventilation or intubation (RCTs: RR = 0.77, 95% CI 0.58-1.02, P = 0.07; cohort studies: RR = 0.93, 95% CI 0.55-1.58, P = 0.789). Conclusion: The results of this systematic review and meta-analysis suggest that vitamin D supplementation does not have a significant impact on reducing mortality, ICU admission, and the rates of mechanical ventilation or intubation among COVID-19 patients. However, due to the limited number and quality of the studies included, further high-quality studies are needed to confirm these findings. Systematic review registration: www.crd.york.ac.uk, identifier CRD42021299521.

Study of the Effects of Several SARS-CoV-2 Structural Proteins on Antiviral Immunity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein is a critical viral antigenic protein that enables the production of neutralizing antibodies, while other structural proteins, including the membrane (M), nucleocapsid (N) and envelope (E) proteins, have unclear roles in antiviral immunity. In this study, S1, S2, M, N and E proteins were expressed in 16HBE cells to explore the characteristics of the resultant innate immune response. Furthermore, peripheral blood mononuclear cells (PBMCs) from mice immunized with two doses of inactivated SARS-CoV-2 vaccine or two doses of mRNA vaccine were isolated and stimulated by these five proteins to evaluate the corresponding specific T-cell immune response. In addition, the levels of humoral immunity induced by two-dose inactivated vaccine priming followed by mRNA vaccine boosting, two homologous inactivated vaccine doses and two homologous mRNA vaccine doses in immunized mice were compared. Our results suggested that viral structural proteins can activate the innate immune response and elicit a specific T-cell response in mice immunized with the inactivated vaccine. However, the existence of the specific T-cell response against M, N and E is seemingly insufficient to improve the level of humoral immunity.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques.

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Therapeutic equine hyperimmune antibodies with high and broad-spectrum neutralizing activity protect rodents against SARS-CoV-2 infection.

The emergence of SARS-CoV-2 variants stresses the continued need for broad-spectrum therapeutic antibodies. Several therapeutic monoclonal antibodies or cocktails have been introduced for clinical use. However, unremitting emerging SARS-CoV-2 variants showed reduced neutralizing efficacy by vaccine induced polyclonal antibodies or therapeutic monoclonal antibodies. In our study, polyclonal antibodies and F(ab')2 fragments with strong affinity produced after equine immunization with RBD proteins produced strong affinity. Notably, specific equine IgG and F(ab')2 have broad and high neutralizing activity against parental virus, all SARS-CoV-2 variants of concern (VOCs), including B.1.1,7, B.1.351, B.1.617.2, P.1, B.1.1.529 and BA.2, and all variants of interest (VOIs) including B.1.429, P.2, B.1.525, P.3, B.1.526, B.1.617.1, C.37 and B.1.621. Although some variants weaken the neutralizing ability of equine IgG and F(ab')2 fragments, they still exhibited superior neutralization ability against mutants compared to some reported monoclonal antibodies. Furthermore, we tested the pre-exposure and post-exposure protective efficacy of the equine immunoglobulin IgG and F(ab')2 fragments in lethal mouse and susceptible golden hamster models. Equine immunoglobulin IgG and F(ab')2 fragments effectively neutralized SARS-CoV-2 in vitro, fully protected BALB/c mice from the lethal challenge, and reduced golden hamster's lung pathological change. Therefore, equine pAbs are an adequate, broad coverage, affordable and scalable potential clinical immunotherapy for COVID-19, particularly for SARS-CoV-2 VOCs or VOIs.

Dynamics of disease characteristics and viral RNA decay in patients with asymptomatic and mild infections during the Omicron wave in Shanghai, China: A retrospective cohort study.

OBJECTIVES: Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections. METHODS: A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated. RESULTS: On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection. CONCLUSION: A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar.