Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants.

The highly contagious SARS-CoV-2 Omicron subvariants severely attenuated the effectiveness of currently licensed SARS-CoV-2 vaccines based on ancestral strains administered via intramuscular injection. In this study, we generated a recombinant, replication-incompetent human adenovirus type 5, Ad5-S-Omicron, that expresses Omicron BA.1 spike. Intranasal, but not intramuscular vaccination, elicited spike-specific respiratory mucosal IgA and residential T cell immune responses, in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron subvariants. We tested intranasal Ad5-S-Omicron as a heterologous booster in mice that previously received intramuscular injection of inactivated ancestral vaccine. In addition to inducing serum broadly neutralizing antibodies, there was a significant induction of respiratory mucosal IgA and neutralizing activities against Omicron subvariants BA.1, BA.2, BA.5, BA.2.75, BF.7 as well as pre-Omicron strains Wildtype, Beta, and Delta. Serum and mucosal neutralizing activities against recently emerged XBB, BQ.1, and BQ.1.1 could also be detected but were much lower. Nasal lavage fluids from intranasal vaccination contained multimeric IgA that can bind to at least 10 spike proteins, including Omicron subvariants and pre-Omicron strains, and possessed broadly neutralizing activities. Intranasal vaccination using Ad5-S-Omicron or instillation of intranasal vaccinee's nasal lavage fluids in mouse nostrils protected mice against Omicron challenge. Taken together, intranasal Ad5-S-Omicron booster on the basis of ancestral vaccines can establish effective mucosal and systemic immunity against Omicron subvariants and multiple SARS-CoV-2 variants. This candidate vaccine warrants further development as a safe, effective, and user-friendly infection and transmission-blocking vaccine.

Booster vaccination is required to elicit and maintain COVID-19 vaccine-induced immunity in SIV-infected macaques.

Prolonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated. Herein, we report that the magnitude and persistence of antibody and cell-mediated immunity (CMI) elicited by an Ad5-vectored COVID-19 vaccine are impaired in SIV-infected macaques with high viral loads (> 105 genome copies per ml plasma, SIVhi) but not in macaques with low viral loads (< 105, SIVlow). After a second vaccination, the immune responses are robustly enhanced in all uninfected and SIVlow macaques. These responses also show a moderate increase in 70% SIVhi macaques but decline sharply soon after. Further analysis reveals that decreased antibody and CMI responses are associated with reduced circulating follicular helper T cell (TFH) counts and aberrant CD4/CD8 ratios, respectively, indicating that dysregulation of CD4+ T cells by SIV infection impairs the COVID-19 vaccine-induced immunity. Ad5-vectored COVID-19 vaccine shows no impact on SIV loads or SIV-specific CMI responses. Our study underscores the necessity of frequent booster vaccinations in HIV-infected patients and provides indicative biomarkers for predicting vaccination effectiveness in these patients.

Dynamics of COVID-19 progression and the long-term influences of measures on pandemic outcomes.

The pandemic progression is a dynamic process, in which measures yield outcomes, and outcomes in turn influence subsequent measures and outcomes. Due to the dynamics of pandemic progression, it is challenging to analyse the long-term influence of an individual measure in the sequence on pandemic outcomes. To demonstrate the problem and find solutions, in this article, we study the first wave of the pandemic-probably the most dynamic period-in the Nordic countries and analyse the influences of the Swedish measures relative to the measures adopted by its neighbouring countries on COVID-19 mortality, general mortality, COVID-19 incidence, and unemployment. The design is a longitudinal observational study. The linear regressions based on the Poisson distribution or the binomial distribution are employed for the analysis. To show that analysis can be timely conducted, we use table data available during the first wave. We found that the early Swedish measure had a long-term and significant causal effect on public health outcomes and a certain degree of long-term mitigating causal effect on unemployment during the first wave, where the effect was measured by an increase of these outcomes under the Swedish measures relative to the measures adopted by the other Nordic countries. This information from the first wave has not been provided by available analyses but could have played an important role in combating the second wave. In conclusion, analysis based on table data may provide timely information about the dynamic progression of a pandemic and the long-term influence of an individual measure in the sequence on pandemic outcomes.

Information propagation on cyber, relational and physical spaces about covid-19 vaccine: Using social media and splatial framework.

With the advent of social media, human dynamics studied in purely physical space have been extended to that of a cyber and relational context. However, connections and interactions between these hybrid spaces have not been sufficiently investigated. The "space-place (Splatial)" framework proposed in recent years allows capturing human activities in the hybrid of spaces. This study applies the Splatial framework to examine the information propagation between cyber, relational, and physical spaces through a case study of Covid-19 vaccine debates in New York State (NYS). Whereby the physical space represents the regional boundaries and locations of social media (i.e., Twitter) users in NYS, the relational space indicates the social networks of these NYS users, and the cyber space captures the larger conversational context of the vaccination debate. Our results suggest that the Covid-19 vaccine debate is not polarized across all three spaces as compared to that of other vaccines. However, the rate of users with a pro-vaccine stance decreases from physical to relational and cyber spaces. We also found that while users from different spaces interact with each other, they also engage in local communications with users from the same region or same space, and distance-based and boundary-confined clusters exist in cyber and relational space communities. These results based on the Splatial framework not only shed light on the vaccination debates but also help to define and elucidate the relationships between the three spaces. The intense interactions between spaces suggest incorporating people's relational network and cyber presence in physical place-making.

COVID-19 pandemic unmasking cardiovascular risk factors and non-communicable diseases among migrant workers: a cross-sectional study in Singapore.

OBJECTIVES: This study aims to report the prevalence of cardiovascular risk factors (CVRFs) and other non-communicable diseases among migrant workers in Singapore admitted for COVID-19 infection, to highlight disease burden and the need for changes in health screening and healthcare delivery in this unique population. SETTING: The study was conducted in the largest tertiary hospital in Singapore. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: 883 migrant workers who had mild or asymptomatic COVID-19 infection admitted to three isolation wards between 6 April 2020 and 31 May 2020 were included in this study. OUTCOME MEASURES: The outcome measures were the prevalence of pre-existing and newly diagnosed comorbid conditions and the prevalence of CVRFs-diabetes mellitus, hypertension and hyperlipidaemia-and non-communicable diseases at the time of discharge. The OR of having specific CVRFs depending on country of origin was generated via multivariate logistic regression analysis. RESULTS: The median age of our study population was 45 years. 17.0% had pre-existing conditions and 25.9% received new diagnoses. Of the new diagnoses, 15.7% were acute medical conditions and 84.3% chronic medical conditions. The prevalence of CVRFs was higher in Southeast Asian and South Asian migrant workers compared with Chinese. The prevalence of non-communicable diseases on discharge was highest among Southeast Asians (49.4%). CONCLUSIONS: The COVID-19 outbreak in a large number of migrant workers in Singapore unmasked a significant disease burden among them, increasing stakeholders' interests in their welfare. Moving forward, system-level changes are necessary to deliver healthcare sustainably and effect improvements in migrant workers' health.

Translational Control of COVID-19 and Its Therapeutic Implication

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, which has broken out worldwide for more than two years. However, due to limited treatment, new cases of infection are still rising. Therefore, there is an urgent need to understand the basic molecular biology of SARS-CoV-2 to control this virus. SARS-CoV-2 replication and spread depend on the recruitment of host ribosomes to translate viral messenger RNA (mRNA). To ensure the translation of their own mRNAs, the SARS-CoV-2 has developed multiple strategies to globally inhibit the translation of host mRNAs and block the cellular innate immune response. This review provides a comprehensive picture of recent advancements in our understanding of the molecular basis and complexity of SARS-CoV-2 protein translation. Specifically, we summarize how this viral infection inhibits host mRNA translation to better utilize translation elements for translation of its own mRNA. Finally, we discuss the potential of translational components as targets for therapeutic interventions.

The statistical evidence missing from the Swedish decision-making of COVID-19 strategy during the early period: A longitudinal observational analysis.

A controversy about the Swedish strategy of dealing with COVID-19 during the early period is how decision-making was based on evidence, which refers to data and data analysis. During the earliest period of the pandemic, the Swedish decision-making was based on subjective perspective. However, when more data became available, the decision-making stood on mathematical and descriptive analyses. The mathematical analysis aimed to model the condition for herd immunity while the descriptive analysis compared different measures without adjustment of population differences and updating pandemic situations. Due to the dubious interpretations of these analyses, a mild measure was adopted in Sweden upon the arrival of the second wave, leading to a surge of poor public health outcomes compared to the other Nordic countries (Denmark, Norway, and Finland). In this article, using data available during the first wave, we conduct longitudinal analysis to investigate the consequence of the shred of evidence in the Swedish decision-making for the first wave, where the study period is between January 2020 and August 2020. The design is longitudinal observational study. The linear regressions based on the Poisson distribution and the binomial distribution are employed for the analysis. We found that the early Swedish measure had a long-term and significant effect on general mortality and COVID-19 mortality and a certain mitigating effect on unemployment in Sweden during the first wave; here, the effect was measured by an increase of general deaths, COVID-19 deaths or unemployed persons under Swedish measure relative to the measures adopted by the other Nordic countries. These pieces of statistical evidence were not studied in the mathematical and descriptive analyses but could play an important role in the decision-making at the second wave. In conclusion, a timely longitudinal analysis should be part of the decision-making process for containing the current pandemic or a future one.

All-in-One Metal-Oxide Heterojunction Artificial Synapses for Visual Sensory and Neuromorphic Computing Systems

An all-in-one artificial synapse integrating central nervous and sensory nervous functions utilizing low-dimensional metal-oxide heterojunction is demonstrated in this work. With an ion-electrolyte gate, synaptic emulations modulated by electrical and photonic stimulus have been integrated into one high-performance three-terminal artificial synapse. Various long-term and short-term synaptic plasticity functions have been achieved by altering the electrolyte-gate stimulus amplitude/width/frequency/number. The linear potentiation behavior and maintained states enable artificial synapses for neuromorphic computing. Simulated artificial neural network based on the artificial synapses achieved Covid-19 chest image recognition (>85%). The photo-sensing metal-oxide heterojunction enables the synaptic functions mimicking the biological visual sensory functions responding to optical and UV stimulus. Photonic synaptic plasticity modulations responding to photonic stimulus wavelength/power/width/number are investigated, and short-term/long-term synaptic plasticity transition was achieved. Dual-mode modulation combining photonic stimulus and gate stimulus was examined, along with a ‘AND Gate’ demonstration with electrical and photonic inputs. Finally, an artificial neural network was demonstrated based on the synapses with dual-mode synaptic weight modulation, indicating the potential of the artificial synapse for compact artificial intelligence systems combing neuromorphic computing and visual sensory nervous functions.

Novel Evidence Showing the Possible Effect of Environmental Variables on COVID‐19 Spread

Coronavirus disease (COVID‐19) remains a serious issue, and the role played by meteorological indicators in the process of virus spread has been a topic of academic discussion. Previous studies reached different conclusions due to inconsistent methods, disparate meteorological indicators, and specific time periods or regions. This manuscript is based on seven daily meteorological indicators in the NCEP reanalysis data set and COVID‐19 data repository of Johns Hopkins University from 22 January 2020 to 1 June 2021. Results showed that worldwide average temperature and precipitable water (PW) had the strongest correlation (ρ > 0.9, p < 0.001) with the confirmed COVID‐19 cases per day from 22 January to 31 August 2020. From 22 January to 31 August 2020, positive correlations were observed between the temperature/PW and confirmed COVID‐19 cases/deaths in the northern hemisphere, whereas negative correlations were recorded in the southern hemisphere. From 1 September to 31 December 2020, the opposite results were observed. Correlations were weak throughout the near full year, and weak negative correlations were detected worldwide (;ρ;< 0.4, p ≤ 0.05);the lag time had no obvious effect. As the latitude increased, the temperature and PW of the maximum confirmed COVID‐19 cases/deaths per day generally showed a decreasing trend;the 2020‐year fitting functions of the response latitude pattern were verified by the 2021 data. Meteorological indicators, although not a decisive factor, may influence the virus spread by affecting the virus survival rates and enthusiasm of human activities. The temperature or PW threshold suitable for the spread of COVID‐19 may increase as the latitude decreases. Key Points A more than yearlong and global scale analysis showed environmental variables having a possible influence on coronavirus disease (COVID‐19) spread Temperature and precipitable water had the strongest correlations with COVID‐19 (ρ > 0.9, p < 0.001) than common meteorological indicators The latitude pattern of COVID‐19 may be a key point in the prediction of the next round of its outbreak

Novel Evidence Showing the Possible Effect of Environmental Variables on COVID-19 Spread.

Coronavirus disease (COVID-19) remains a serious issue, and the role played by meteorological indicators in the process of virus spread has been a topic of academic discussion. Previous studies reached different conclusions due to inconsistent methods, disparate meteorological indicators, and specific time periods or regions. This manuscript is based on seven daily meteorological indicators in the NCEP reanalysis data set and COVID-19 data repository of Johns Hopkins University from 22 January 2020 to 1 June 2021. Results showed that worldwide average temperature and precipitable water (PW) had the strongest correlation (ρ > 0.9, p < 0.001) with the confirmed COVID-19 cases per day from 22 January to 31 August 2020. From 22 January to 31 August 2020, positive correlations were observed between the temperature/PW and confirmed COVID-19 cases/deaths in the northern hemisphere, whereas negative correlations were recorded in the southern hemisphere. From 1 September to 31 December 2020, the opposite results were observed. Correlations were weak throughout the near full year, and weak negative correlations were detected worldwide (|ρ| < 0.4, p ≤ 0.05); the lag time had no obvious effect. As the latitude increased, the temperature and PW of the maximum confirmed COVID-19 cases/deaths per day generally showed a decreasing trend; the 2020-year fitting functions of the response latitude pattern were verified by the 2021 data. Meteorological indicators, although not a decisive factor, may influence the virus spread by affecting the virus survival rates and enthusiasm of human activities. The temperature or PW threshold suitable for the spread of COVID-19 may increase as the latitude decreases.

Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.

The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine. Most monoclonal antibodies that are directed against the receptor-binding motif lost in vitro neutralizing activity against Omicron, with only 3 out of 29 monoclonal antibodies retaining unaltered potency, including the ACE2-mimicking S2K146 antibody1. Furthermore, a fraction of broadly neutralizing sarbecovirus monoclonal antibodies neutralized Omicron through recognition of antigenic sites outside the receptor-binding motif, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major antigenic shift in SARS-CoV-2. Broadly neutralizing monoclonal antibodies that recognize RBD epitopes that are conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

Safety of Pfizer-BioNtech COVID-19 Vaccine in Healthcare Workers, Singapore

Background On 14 December 2020, the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine was granted emergency use authorization in Singapore. Healthcare workers (HCW) were prioritized to receive the vaccine. We aim to investigate the side effects and risk factors for allergic reactions in our institution. Methods All HCW vaccinations were recorded in an electronic centralized database. All reactions occurring within a 30-minute observation period post vaccination were recorded. Staff were required to report any vaccine-related medical consult including hospitalization occurring within 14 days after vaccination. Moderate/severe reactions were assessed by a medical team and determined if the reactions were probable allergic reactions with consultation with an Allergist. We extracted data from 8 Jan 2021 to 30 April 2021. Results 5030 and 159 HCW completed 2 doses and 1 dose of the vaccine respectively. There were 1056 HCWs (20.3%) with self-reported pre-existing allergy. There were 114 (1.1%) reactions occurring without the 30-minute observation period, and 64 (56.1%) were related to first dose of vaccine. The most common side effect experienced was aches or pain on any part of the body (n=46, 40.4%) followed by fatigue and/or giddiness (n=45, 39.5%), palpitations and/or shortness of breath (n=22, 19.3%), systemic rash and/or angioedema (n=12, 10.5%) and nausea and/or vomiting (n=12, 10.5%). A total of 23 HCWs complained of systemic rash and/or angioedema that occurred anytime post vaccination. Fifteen HCWs (0.29% of the cohort) were considered to have probable allergic reaction to the vaccine. None of the reactions were classified as anaphylaxis or severe reactions, but 4 HCWs required short hospitalization stay for observation. HCWs with pre-existing allergy had 2.6 times the risk of having probable vaccine-related allergic reaction than HCWs without pre-existing allergy (RR 2.6, 95% CI 0.9 to 7.3, p=0.068) but this was not statistically significant. Conclusion No anaphylaxis or severe reactions were observed in our institution. Acute side effects in our cohort were in line with published trial reports. We noted a raised relative risk of 2.6 of pre-existing allergy with probable vaccine-related allergic reaction but this was not statistically significant. Disclosures All Authors: No reported disclosures

The clinical implications of sinus tachycardia in mild COVID-19 infection: A retrospective cohort study.

OBJECTIVES: This study aims to estimate the prevalence of sinus tachycardia in hospitalized patients with mild COVID-19 infection and to identify the clinical, radiological, and biological characteristics associated with sinus tachycardia. METHODS: A retrospective cohort study was conducted on patients with mild COVID-19 infection and sinus tachycardia during hospitalization. Outcomes measured included incidences of venous thromboembolism, high-dependency/intensive care unit admission, laboratory parameters, and radiological findings. RESULTS: A total of 236 COVID-19 positive patients admitted to Singapore General Hospital isolation general wards from 1 June 2020 to 30 June 2020 were included in this study. Ninety-seven (41.1%) patients had sinus tachycardia on or during their admission. All patients were monitored in general wards and discharged to community quarantine facilities. None required oxygen support or high-dependency/intensive care unit admission. Sinus tachycardia was associated with increased C-reactive protein level (odds ratio = 1.033, 95% confidence interval = 1.002-1.066), abnormal chest X-ray findings (odds ratio = 3.142, 95% confidence interval = 1.390-7.104), and longer hospitalization (odds ratio = 1.117, 95% confidence interval = 1.010-1.236). There was no significant statistical association between sinus tachycardia and incidences of venous thromboembolism. CONCLUSION: This study suggests that patients with mild COVID-19 infection and concurrent sinus tachycardia are more likely to have higher inflammatory marker levels, abnormal imaging, and prolonged hospitalization. However, no significant association between sinus tachycardia and thromboembolism is identified in mild COVID-19 infection.

Increased occurrence of PTSD symptoms in adolescents with major depressive disorder soon after the start of the COVID-19 outbreak in China: a cross-sectional survey.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic continues to threaten the physical and mental health of people across the world. This study aimed to understand the psychological impact of this disease on adolescents with major depressive disorder (MDD) at 1 month after the start of the outbreak in China. METHODS: Using the Children's Impact of Event Scale (CRIES-13) questionnaire, we investigated the occurrence of posttraumatic stress disorder (PTSD) in two groups of adolescents: MDD patients who were in continuous antidepressant therapy and healthy controls. Total scores and factor subscores were compared between the two groups and subgroups stratified by sex and school grade. Logistic regression was used to identify variables associated with high total CRIES-13 scores. RESULTS: Compared to controls (n = 107), the MDD group (n = 90) had higher total CRIES-13 scores and a higher proportion with a total score ≥ 30. They also had a lower intrusion subscore and a higher arousal subscore. In the MDD group, males and females did not differ significantly in total CRIES-13 scores or factor subscores, but junior high school students had higher avoidance subscores than senior high school students. Logistic regression showed high total CRIES-13 scores to be associated with MDD and the experience of "flashbacks" or avoidance of traumatic memories associated with COVID-19. CONCLUSIONS: It is crucial to understand the psychological impact of COVID-19 on adolescents with MDD in China, especially females and junior high school students. Long-term monitoring of adolescents with a history of mental illness is required to further understand these impacts. TRIAL REGISTRATION: ChiCTR, ChiCTR2000033402 , Registered 31 May 2020.

Antibodies Can Last for More Than 1 Year After SARS-CoV-2 Infection: A Follow-Up Study From Survivors of COVID-19.

Background: COVID-19 is a global pandemic. The prevention of SARS-CoV-2 infection and the rehabilitation of survivors are currently the most urgent tasks. However, after patients with COVID-19 are discharged from the hospital, how long the antibodies persist, whether the lung lesions can be completely absorbed, and whether cardiopulmonary abnormalities exist remain unclear. Methods: A total of 56 COVID-19 survivors were followed up for 12 months, with examinations including serum virus-specific antibodies, chest CT, and cardiopulmonary exercise testing. Results: The IgG titer of the COVID-19 survivors decreased gradually, especially in the first 6 months after discharge. At 6 and 12 months after discharge, the IgG titer decreased by 68.9 and 86.0%, respectively. The IgG titer in patients with severe disease was higher than that in patients with non-severe disease at each time point, but the difference did not reach statistical significance. Among the patients, 11.8% were IgG negative up to 12 months after discharge. Chest CT scans showed that at 3 and 10 months after discharge, the lung opacity had decreased by 91.9 and 95.5%, respectively, as compared with that at admission. 10 months after discharge, 12.5% of the patients had an opacity percentage >1%, and 18.8% of patients had pulmonary fibrosis (38.5% in the severe group and 5.3% in the non-severe group, P < 0.001). Cardiopulmonary exercise testing showed that 22.9% of patients had FEV1/FVC%Pred <92%, 17.1% of patients had FEV1%Pred <80%, 20.0% of patients had a VO2 AT <14 mlO2/kg/min, and 22.9% of patients had a VE/VCO2 slope >30%. Conclusions: IgG antibodies in most patients with COVID-19 can last for at least 12 months after discharge. The IgG titers decreased significantly in the first 6 months and remained stable in the following 6 months. The lung lesions of most patients with COVID-19 can be absorbed without sequelae, and a few patients in severe condition are more likely to develop pulmonary fibrosis. Approximately one-fifth of the patients had cardiopulmonary dysfunction 6 months after discharge.

Increased symptoms of post-traumatic stress in school students soon after the start of the COVID-19 outbreak in China.

BACKGROUND: The outbreak of Coronavirus Disease 2019(COVID-19) caused psychological stress in Chinese adults population. But we are unaware of whether the pandemic causes psychological stress on children. METHODS: We used the Children's Impact of Event Scale questionnaire (CRIES-13) to investigate the degree of Post-traumatic Stress (PTSD) symptoms caused by the pandemic in students selected from schools in Sichuan, Jiangsu, Henan, Yunnan, and Chongqing provinces of China. RESULTS: A total of 7769 students(3692 male and 4077 female), aged 8-18 years, were enrolled in the study, comprising 1214 in primary schools, 2799 in junior high schools and 3756 in senior high schools. A total of 1639 students (21.1%) had severe psychological stress reactions. A large proportion of senior high school students (23.3%) experienced severe psychological stress, and they had the highest median total CRIES-13 score. Female students were more likely to experience severe psychological stress and had higher median CRIES-13 total scores than males. CONCLUSION: COVID-19 has placed psychological stresses on primary and secondary school students in China. These stresses are more likely to reach severe levels among female students and senior high school students.

AN Analysis of COVID-19 Clinical Research Based on Trials & Publications in 2020

The global pandemic of COVID-19 has brought huge public health challenges to the world. To meet the challenge, researchers worldwide have carried out a series of clinical studies. This article aims to analyze the progress of COVID-19, and explore the development and main research directions in 2020. The clinical trials focus on the design of the trial plan, which can be registered on the platform after the design is completed. The purpose of clinical publications is to publish trial results, focusing on in vitro tests, drug screening and so on. Based on these characteristics, this paper analyzes both clinical publications and clinical trials, and explores the development of global clinical research in 2020 from countries, intervention methods and trial designs. The experimental results show that the United States and China have published the most publications and carried out the most clinical trials. The maximum intervention methods in clinical trials & publications are focused on the drugs.

COVID-19 and male reproduction: Current research and unknown factors.

BACKGROUND: The testes are suspected target organs of SARS-CoV-2. However, the results of studies on the effect of COVID-19 on male reproduction are controversial. OBJECTIVE: To summarize current research on the effects of COVID-19 on male reproduction. METHODS: A systematic review of English literature was performed using PubMed and Ovid Embase up to 18 August 2020. Research articles on the presence of SARS-CoV-2 in semen, the effects of the virus on semen parameters and any pathological changes in the testes were evaluated. RESULTS: Fourteen studies were included in this review. Six of 176 survivors (3.4%) and 1 of 13 decedents (7.7%) in 2 of 12 studies were positive for viral RNA in semen and testicular tissue, respectively. After stratification of patient groups, we found that the virus was detected in the relatively early stage of infection, 6-16 days after disease onset, in semen from survivors. Two of 3 studies reported that some participants had substandard semen quality after COVID-19, and 1 study found that COVID-19 may impair semen quality in a severity-related manner. Pathological analyses showed that injuries to the seminiferous tubule occurred in all decedents (N = 11). Another study found that orchitic and testis fibrin microthrombi occurred in patients with fatal disease (100%, N = 2). Scrotal discomfort of orchiepididymitis or spermatic cord inflammation has also been reported in COVID-19 patients. CONCLUSION: Current studies suggest that semen is rarely considered a carrier of SARS-CoV-2 genetic material during the infection period but not in the semen of recovered patients. Fatal COVID-19 may cause testicular structure damage without the presence of virus.