The Impact of Post Embryo Transfer SARS-CoV-2 Infection on Pregnancy in In Vitro Fertilization: A Prospective Cohort Study (preprint)

ImportanceLimited knowledge exists on the effects of SARS-CoV-2 infection after embryo transfer, despite an increasing number of studies exploring the impact of previous SARS-CoV-2 infection on IVF outcomes. ObjectiveThis prospective cohort study aimed to assess the influence of SARS-CoV-2 infection at various time stages after embryo transfer on pregnancy outcomes in patients undergoing conventional in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI) treatment. DesignThe study was conducted at a single public IVF center in China. SettingThis was a population-based prospective cohort study. ParticipantsFemale patients aged 20 to 39 years, with a body mass index (BMI) between 18 and 30 kg/m2, undergoing IVF/ICSI treatment, were enrolled from September 2022 to December 2022, with follow-up until March 2023. ExposureThe pregnancy outcome of patients was compared between those SARS-CoV-2-infected after embryo transfer and those noninfected during the follow-up period. Main Outcomes and MeasuresThe pregnancy outcomes included biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. ResultsA total of 857 female patients undergoing IVF/ICSI treatment were included in the analysis. We observed the incidence of SARS-CoV-2 infection within 10 weeks after embryo transfer. The biochemical pregnancy rate and implantation rate were lower in the infected group than the uninfected group (58.1% vs 65.9%; 36.6% vs 44.0%, respectively), but no statistically significant. Although, the clinical pregnancy rate was significant lower in the infection group when compared with the uninfected group (49.1%vs 58.2%, p < 0.05), after adjustment for confounders, this increased risk was no longer significant between the two groups (adjusted OR, 0.736, 95% CI, 0.518-1.046). With continued follow-up, a slightly higher risk of early miscarriage in the infected group compared to the uninfected group (9.3% vs 8.8%), but it was not significant (adjusted OR, 0.907, 95% CI, 0.414-1.986). Conclusions and RelevanceThe studys findings suggested that SARS-CoV-2 infection within 10 weeks after embryo transfer may have not significantly affect pregnancy outcomes. This evidence allays concerns and provides valuable insights for assisted reproduction practices. Key pointsO_ST_ABSQuestionC_ST_ABSDid the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after embryo transfer affect pregnancy outcomes? FindingsIn this prospective cohort study involving 857 patients, we made a pioneering discovery that SARS-CoV-2 infection following embryo transfer did not exhibit adverse impact on the biochemical pregnancy rate, embryo implantation rate, clinical pregnancy rate, and early miscarriage rate. MeaningThe evidence from this study alleviates existing concerns and offers new insights into the actual risk of SARS-CoV-2 infection after embryo transfer in assisted reproduction.

Protein sensors combining both on-and-off model for antibody homogeneous assay.

Protein sensors based on allosteric enzymes responding to target binding with rapid changes in enzymatic activity are potential tools for homogeneous assays. However, a high signal-to-noise ratio (S/N) is difficult to achieve in their construction. A high S/N is critical to discriminate signals from the background, a phenomenon that might largely vary among serum samples from different individuals. Herein, based on the modularized luciferase NanoLuc, we designed a novel biosensor called NanoSwitch. This sensor allows direct detection of antibodies in 1 µl serum in 45 min without washing steps. In the detection of Flag and HA antibodies, NanoSwitches respond to antibodies with S/N ratios of 33-fold and 42-fold, respectively. Further, we constructed a NanoSwitch for detecting SARS-CoV-2-specific antibodies, which showed over 200-fold S/N in serum samples. High S/N was achieved by a new working model, combining the turn-off of the sensor with human serum albumin and turn-on with a specific antibody. Also, we constructed NanoSwitches for detecting antibodies against the core protein of hepatitis C virus (HCV) and gp41 of the human immunodeficiency virus (HIV). Interestingly, these sensors demonstrated a high S/N and good performance in the assays of clinical samples; this was partly attributed to the combination of off-and-on models. In summary, we provide a novel type of protein sensor and a working model that potentially guides new sensor design with better performance.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Some characteristics of clinical sequelae of COVID-19 survivors from Wuhan, China: A multi-center longitudinal study.

BACKGROUND: The pandemic of COVID-19 has a persistent impact on global health, yet its sequelae need to be addressed at a wide scale around the globe. This study aims to investigate the characteristics, prevalence, and risk factors for mid-term (>6 months) clinical sequelae in a cohort of COVID-19 survivors. METHODS: Totally 715 COVID-19 survivors discharged before April 1, 2020, from three medical centers in Wuhan, China, were included. The longitudinal study was conducted by telephone interviews based on a questionnaire including the clinical sequelae of general, respiratory, and cardiovascular systems. Demographics and some characteristics of clinical sequelae of the survivors were recorded and analyzed. Multivariate logistic regression analysis was applied to explore the risk factors for the sequelae. RESULTS: The median time interval from discharge to telephone interview was 225.0 days. The COVID-19 survivors' median ages were 69 years, and 51.3% were male. Among them, 29.9% had at least one clinical sequela. There were 19.2%, 22.7%, and 5.0% of the survivors reporting fatigue, respiratory symptoms, and cardiovascular symptoms, respectively. Comorbidities, disease severity, the application of mechanical ventilation and high-flow oxygen therapy, and the history of re-admission were associated with the presence of clinical sequelae. CONCLUSIONS: Our study provides further evidence for the prevalence and characteristics of clinical sequelae of COVID-19 survivors, suggesting long-term monitoring and management is needed for their full recovery.

Coronavirus Disease 2019 (COVID-19) Learning Online: A Flipped Classroom Based on Micro-Learning Combined with Case-Based Learning in Undergraduate Medical Students.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, medical colleges in China had to use online teaching. This study explored the effect of COVID-19 knowledge learning online in a flipped classroom based on micro-learning combined with case-based learning (CBL). METHODS: There were 74 undergraduate medical students who were randomly grouped to an observation group and a control group with 37 participants in each virtual classroom on the Network Teaching Platform. Students learning in the control group utilized face-to-face lecture with PowerPoint pre-provided, while students learning in the observation group were conducted in a flipped classroom based on micro-learning combined with CBL. We compared the effect of both formats of COVID-19 knowledge learning online and the impact on clinical practice attitude in two groups. RESULTS: All 74 students (100%) responded pretest, posttest and retention test, and completed the questionnaire online. Both formats significantly improved COVID-19 knowledge acquisition at the conclusion of online COVID-19 curriculum. Students' knowledge test scores including total score and scores of five knowledge dimensions of COVID-19 were significantly higher in the observation group than those in the control group (P<0.05). Compared with students in the control group, students in the observation group performed better in retention test and had a significantly more positive clinical practice attitude (P<0.05 in all items). CONCLUSION: A flipped classroom based on micro-learning combined with CBL showed greater effectiveness in COVID-19 knowledge gain in undergraduate medical students and made their attitude toward clinical practice more positive.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Immune memory in convalescent patients with asymptomatic or mild COVID-19.

It is important to evaluate the durability of the protective immune response elicited by primary infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we systematically evaluated the SARS-CoV-2-specific memory B cell and T cell responses in healthy controls and individuals recovered from asymptomatic or symptomatic infection approximately 6 months prior. Comparatively low frequencies of memory B cells specific for the receptor-binding domain (RBD) of spike glycoprotein (S) persisted in the peripheral blood of individuals who recovered from infection (median 0.62%, interquartile range 0.48-0.69). The SARS-CoV-2 RBD-specific memory B cell response was detected in 2 of 13 individuals who recovered from asymptomatic infection and 10 of 20 individuals who recovered from symptomatic infection. T cell responses induced by S, membrane (M), and nucleocapsid (N) peptide libraries from SARS-CoV-2 were observed in individuals recovered from coronavirus disease 2019 (COVID-19), and cross-reactive T cell responses to SARS-CoV-2 were also detected in healthy controls.

SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development.

The pandemic of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing great threats to the world in many aspects. Effective therapeutic and preventive approaches including drugs and vaccines are still unavailable although they are in development. Comprehensive understandings on the life logic of SARS-CoV-2 and the interaction of the virus with hosts are fundamentally important in the fight against SARS-CoV-2. In this review, we briefly summarized the current advances in SARS-CoV-2 research, including the epidemic situation and epidemiological characteristics of the caused disease COVID-19. We further discussed the biology of SARS-CoV-2, including the origin, evolution, and receptor recognition mechanism of SARS-CoV-2. And particularly, we introduced the protein structures of SARS-CoV-2 and structure-based therapeutics development including antibodies, antiviral compounds, and vaccines, and indicated the limitations and perspectives of SARS-CoV-2 research. We wish the information provided by this review may be helpful to the global battle against SARS-CoV-2 infection.

Post-Infection Cognitive Impairments in Elderly Patients with COVID-19 (preprint)

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19.Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13; controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81; controls: 3.15±0.39, p<0.001) than the controls. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients (TICS-40: 22.98±7.12 vs. 30.46±5.53, p<0.001; IQCODE: 4.06±1.39 vs. 3.33±0.68, p<0.001) and controls (TICS-40: 22.98±7.12 vs. 30.74±5.95, p<0.001; IQCODE: 4.06±1.39 vs. 3.15±0.39, p<0.001). Severe COVID-19 patients had a higher proportion of cases with a current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients and controls. COVID-19 severity (OR: 8.142, 95% CI: 5.007-13.239) was associated with worse current cognitive function. Older age (OR: 1.024, 95% CI: 1.003 to 1.046), COVID-19 severity (OR: 2.277, 95% CI: 1.308 to 3.964), mechanical ventilation (OR: 5.388, 95% CI: 3.007 to 9.656), and hypertension (OR: 1.866, 95% CI: 1.376 to 2.531) were associated with an increased risk of longitudinal cognitive decline.Interpretation: SARS-CoV-2 infection is associated with delayed cognitive decline in elderly population. COVID-19 patients with risk factors, including severe disease, older age, mechanical ventilation, and hypertension, should be intensively monitored for delayed cognitive decline. Funding: National Natural Science Foundation of China.Conflict of Interest: We declared no conflict of interests.Ethical Approval: The study protocols were approved by the institutional review boards of the hospitals. Verbal informed consent was obtained from all participants prior to the survey.

Control of infection of medical team assisting Wuhan during COVID-19 epidemic

OBJECTIVE: To explore the control of infection in living places of medical teams assisting Wuhan during COVID-19 epidemic so as to offer help and reference for members of the medical teams. METHODS: The plans and measures for control of infection in working and living places of the medical teams were formulated based on the etiological and epidemiological characteristics of SARS-CoV-2 as well as national guidelines for diagnosis, treatment, control and prevention. RESULTS: The regulations, flow charts and plans have been formulated, involving the medical teams' responsibilities in prevention and control of infection, on-duty and off-duty flow charts and daily living management of team members, active health monitoring, emergency treatment of fever patients, and cleaning and disinfection of living places. CONCLUSION: The prevention and control of infection in the living places is one of the key links to prevent the infection in the team members and the spread of the epidemic, and the medical teams must pay great attention to and rigidly put the infection control measures into practice.

Research Progress of Peracetic Acid Inactivation of Virus in Wastewater Disinfection

Peracetic acid( PAA),a high-efficiency broad-spectrum disinfectant,is recommended by the government for the prevention and control of new coronavirus epidemics.The basic properties of PAA and its efficient ability of inactivating viruses were introduced in this review.The disinfection principle of PAA was clarified and the advantages of PAA were analyzed by comparing with other disinfection methods.Finally, the paper summarized the application methods of PAA in practical disinfection,in order to provide reference for its application in the prevention and control of new coronavirus epidemics.

Improvement of the C-glycosylation Step for the Synthesis of Remdesivir

The bulk supply of the antiviral C-nucleoside analogue remdesivir is largely hampered by a low-yielding Cglycosylation step in which the base is coupled to the pentose unit. Here, we disclose a significantly improved methodology for this critical transformation. By utilizing diisopropylamine as a cost-effective additive, the addition reaction furnishes an optimal yield of 75% of the desired ribofuranoside adduct, representing the highest yield obtained thus far for this key step. The method proved suitable for hectogram scale synthesis without column chromatographic operations.

Economic Burden of Public Health Care Was Higher Than That of Hospitalization and Treatment Associated With COVID-19 in China (preprint)

Background: During the coronavirus disease 2019 (COVID-19) pandemic, it is essential to evaluate the socioeconomic burden imposed on the Chinese health care system.Methods: We prospectively collected information from the Center for Disease Control and Prevention and the designated hospitals to determine the cost of public health care and hospitalization due to COVID-19. We estimated the resource use and direct medical costs per confirmed case and the costs associated with public health care per thousand people at the national level.Results: The average costs per case for specimen collection and nucleic acid testing (NAT) were $29.49 and $53.44, respectively, while the average cost of NAT for high-risk populations was $297.94 per capita. The average costs per thousand people for epidemiological surveys, disinfectant, health education and centralized isolation were $49.54, $247.01, $90.22 and $543.72, respectively. A single hospitalization for COVID-19 in China cost an average of $3,792.69 ($2,754.82-$5,393.76) in direct medical costs incurred only during hospitalization, while the total costs associated with hospitalization were estimated to have reached nearly $31,229.39 million in China as of 20 May 2020. The cost of public health care ($6.81 billion) was 20 times that of hospitalization.Conclusions: This study highlights the magnitude of resources needed to control the COVID-19 pandemic and treat COVID-19 cases. Public health measures implemented by the Chinese government have been valuable with regard to reducing the infection rate and may be cost-effective ways to control emerging infectious diseases.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. OBJECTIVE: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. RESULTS AND LIMITATIONS: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. CONCLUSIONS: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. PATIENT SUMMARY: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.

The clinical and immunological features of pediatric COVID-19 patients in China.

In December 2019, the corona virus disease 2019 (COVID-19) caused by novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide. Few information on clinical features and immunological profile of COVID-19 in paediatrics. The clinical features and treatment outcomes of twelve paediatric patients confirmed as COVID-19 were analyzed. The immunological features of children patients was investigated and compared with twenty adult patients. The median age was 14.5-years (range from 0.64 to 17), and six of the patients were male. The average incubation period was 8 days. Clinically, cough (9/12, 75%) and fever (7/12, 58.3%) were the most common symptoms. Four patients (33.3%) had diarrhea during the disease. As to the immune profile, children had higher amount of total T cell, CD8+ T cell and B cell but lower CRP levels than adults (P < 0.05). Ground-glass opacity (GGO) and local patchy shadowing were the typical radiological findings on chest CT scan. All patients received antiviral and symptomatic treatment and the symptom relieved in 3-4 days after admitted to hospital. The paediatric patients showed mild symptom but with longer incubation period. Children infected with SARS-CoV-2 had different immune profile with higher T cell amount and low inflammatory factors level, which might ascribed to the mild clinical symptom. We advise that nucleic acid test or examination of serum IgM/IgG antibodies against SARS-CoV-2 should be taken for children with exposure history regardless of clinical symptom.

Improved Early Recognition of Coronavirus Disease-2019 (COVID-19): Single-Center Data from a Shanghai Screening Hospital.

BACKGROUND: In December 2019, an outbreak of a novel coronavirus disease (COVID-19; previously known as 2019-nCoV) was reported in Wuhan, Hubei province, China, which has subsequently affected more than 200 countries worldwide including Europe, North America, Oceania, Africa and other places. The number of infected people is rapidly increasing, while the diagnostic method of COVID-19 is only by nucleic acid testing. OBJECTIVE: To explain the epidemiological characteristics, clinical features, imaging manifestations and to judge diagnostic value of COVID-19 by analyzing the clinical data of COVID-19 suspected and confirmed patients in a non-outbreak, Shanghai, China. To clarify the early epidemiology and clinical characteristics about COVID-19. METHODS: Cross-sectional, single-center case reports of the 86 patients screened at Zhoupu Hospital in Pudong New District, Shanghai, China, from January 23 to February 16, 2020. Epidemiology, demography, clinical, laboratory and chest CTs were collected and analyzed. The screened patients were divided into COVID-19 and non-COVID-19 based on nucleic acid test results. RESULTS: Of the 86 screened patients, 11 were confirmed (12.8%) by nucleic acid testing (mean age 40.73 ± 11.32, 5 males). No significant differences were found in clinical symptoms including fever, cough, dyspnea, sore throat, and fatigue (P > 0.05). No statistical difference was observed in plasma C-reactive protein (CRP) between the two groups (COVID-19 and non-COVID-19 ) of patients (P = 0.402), while the white blood cell count and lymphocyte count of the confirmed patients were slightly lower than those of the suspected patients (P < 0.05). Some non-COVID-19 chest CTs also showed subpleural lesions, such as ground-glass opacities (GGO) combined with bronchiectasis; or halo nodules distributed under the pleura with focal GGO; consolidation of subpleural distribution or combined with air bronchi sign and vascular bundle sign, etc. CONCLUSION: The early clinical manifestations and imaging findings of COVID-19 are not characteristic in non-outbreak areas. Etiological testing should be performed as early as possible for clinically suspected patients.

Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice (preprint)

Background We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of serocon-version for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of IgG seroconversion and [≥] 4-fold increase in the IgG titers in sequential samples together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or [≥] 4-fold increase in the IgG titer is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.