A real-world data validation of the value of early-stage SIR modelling to public health.

Performance of Susceptible-Infected-Recovered (SIR) model in the early stage of a novel epidemic may be hindered by data availability. Additionally, the traditional SIR model may oversimplify the disease progress, and knowledge about the virus and transmission is limited early in the epidemic, resulting in a greater uncertainty of such modelling. We aimed to investigate the impact of model inputs on the early-stage SIR projection using COVID-19 as an illustration to evaluate the application of early infection models. We constructed a modified SIR model using discrete-time Markov chain to simulate daily epidemic dynamics and estimate the number of beds needed in Wuhan in the early stage of COVID-19 epidemic. We compared eight scenarios of SIR projection to the real-world data (RWD) and used root mean square error (RMSE) to assess model performance. According to the National Health Commission, the number of beds occupied in isolation wards and ICUs due to COVID-19 in Wuhan peaked at 37,746. In our model, as the epidemic developed, we observed an increasing daily new case rate, and decreasing daily removal rate and ICU rate. This change in rates contributed to the growth in the needs of bed in both isolation wards and ICUs. Assuming a 50% diagnosis rate and 70% public health efficacy, the model based on parameters estimated using data from the day reaching 3200 to the day reaching 6400 cases returned a lowest RMSE. This model predicted 22,613 beds needed in isolation ward and ICU as on the day of RWD peak. Very early SIR model predictions based on early cumulative case data initially underestimated the number of beds needed, but the RMSEs tended to decline as more updated data were used. Very-early-stage SIR model, although simple but convenient and relatively accurate, is a useful tool to provide decisive information for the public health system and predict the trend of an epidemic of novel infectious disease in the very early stage, thus, avoiding the issue of delay-decision and extra deaths.

The social psychological impact of the COVID-19 pandemic on medical staff in China: A cross-sectional study.

BACKGROUND: The COVID-19 outbreak required the significantly increased working time and intensity for health professionals in China, which may cause stress signs. METHODS: From March 2-13 of 2020, 4,618 health professionals in China were included in an anonymous, self-rated online survey regarding their concerns on exposure to the COVID-19 outbreak. The questionnaires consisted of five parts: basic demographic information and epidemiological exposure; occupational and psychological impact; concerns during the episode; coping strategies; and the Huaxi Emotional-Distress Index (HEI). RESULTS: About 24.2% of respondents experienced high levels of anxiety or/and depressive symptoms since the COVID-19 outbreak. Respondents who worried about their physical health and those who had COVID-19 infected friends or close relatives were more likely to have high HEI levels, than those without these characteristics. Further, family relationship was found to have an independent protective effect against high HEI levels. Their main concerns were that their families would not be cared for and that they would not be able to work properly. Compared to respondents with clear emotional problems, those with somewhat hidden emotional issues adopted more positive coping measures. CONCLUSIONS: About a quarter of medical staff experienced psychological problems during the pandemic of COVID-19. The psychological impact of stressful events was related to worrying about their physical health, having close COVID-19 infected acquaintances and family relationship issues. Therefore, the psychological supprot for medical staff fighting in the COVID-19 pandemic may be needed.

Long-Term Follow-Up Study of COVID-19: Evaluation on Thin-Slice CT.

Purpose: To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge. Patients and Methods: A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher's exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0. Results: There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe-critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient's condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%). Conclusion: The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients' age and disease conditions were positively correlated with residual lesions.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

Long-Term Follow-Up Study of COVID-19: Evaluation on Thin-Slice CT

Purpose To retrospectively analyse the CT imaging during the long-term follow-up of COVID-19 patients after discharge. Patients and Methods A total of 122 patients entered the study group. All patients underwent CT examinations. The CT images, which included distribution and imaging signs, were evaluated by two chest radiologists. Laboratory examinations included routine blood work, biochemical testing, and SARS-CoV-2 antibody screening. Statistical methods include chi-square, Fisher’s exact test, one-way analysis of variance, rank sum test and logistic regression by SPSS 17.0. Results There were 22 (18.0%) patients in the mild group, 74 (60.7%) patients in the moderate group, and 26 (21.3%) patients in the severe–critical group. The median follow-up interval was 405 days (378.0 days, 462.8 days). Only monocytes, prothrombin activity, and γ-glutamyltransferase showed significant differences among the three groups. We found that the more severe the patient’s condition, the more SARS-CoV-2 IgG antibodies existed. Only 11 patients (11.0%) showed residual lesions on CT. The CT manifestations included irregular linear opacities in nine cases (9.0%), reticular patterns in six cases (6.0%), and GGOs in five cases (5.0%). Conclusion The proportion of residual lesions on CT in COVID-19 patients was significantly reduced after long-term follow-up. The patients’ age and disease conditions were positively correlated with residual lesions.

Total Chemical Synthesis of a SARS-CoV-2 Miniprotein Inhibitor LCB1.

Native chemical ligation is a widely used technique for peptide fragment condensation in aqueous solutions, which has broken through the length limitation of traditional solid-phase peptide synthesis. It can achieve high-efficient chemical synthesis of proteins containing more than 300 amino acid residues. Peptide hydrazide, as a valuable reagent equivalent to a thioester peptide, can be easily and efficiently prepared by the Fmoc-based SPPS method and has been widely used in native chemical ligation. Here we take the chemical synthesis of a SARS-CoV-2 miniprotein inhibitor LCB1 as an example to describe the detailed procedure of hydrazide-based native chemical ligation.

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics.

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.

Role of perceived family support in psychological distress for pregnant women during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused major public panic in China. Pregnant women may be more vulnerable to stress, which may cause them to have psychological problems. AIM: To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic. METHODS: A total of 2232 subjects were recruited from three cities in China. Through the online surveys, information on demographic data and health status during pregnancy were collected. Insomnia severity index, generalized anxiety disorder 7-item scale, patient health questionnaire-9, somatization subscale of the symptom check list 90 scale, and posttraumatic stress disorder checklist were used to assess the psychological distress. RESULTS: A total of 1015 (45.4%) women reported having at least one psychological distress. The women who reported having inadequate family support were more likely to suffer from multiple psychological distress (≥ 2 psychological distress) than women who received adequate family support. Among the women who reported less family support, 41.8% reported depression, 31.1% reported anxiety, 8.2% reported insomnia, 13.3% reported somatization and 8.9% reported posttraumatic stress disorder (PTSD), which were significantly higher than those who received strong family support. Perceived family support level was negatively correlated with depressive symptoms (r = -0.118, P < 0.001), anxiety symptoms (r = -0.111, P < 0.001), and PTSD symptoms (r = -0.155, P < 0.001). CONCLUSION: Family support plays an important part on pregnant women's mental health during the COVID-19 pandemic. Better family support can help improve the mental health of pregnant women.

A Comparison of Vaccine Hesitancy of COVID-19 Vaccination in China and the United States.

OBJECTIVES: To investigate the differences in vaccine hesitancy and preference of the currently available COVID-19 vaccines between two countries, namely, China and the United States (U.S.). METHOD: A cross-national survey was conducted in both China and the United States, and discrete choice experiments, as well as Likert scales, were utilized to assess vaccine preference and the underlying factors contributing to vaccination acceptance. Propensity score matching (PSM) was performed to enable a direct comparison between the two countries. RESULTS: A total of 9077 (5375 and 3702 from China and the United States, respectively) respondents completed the survey. After propensity score matching, over 82.0% of respondents from China positively accepted the COVID-19 vaccination, while 72.2% of respondents from the United States positively accepted it. Specifically, only 31.9% of Chinese respondents were recommended by a doctor to have COVID-19 vaccination, while more than half of the U.S. respondents were recommended by a doctor (50.2%), local health board (59.4%), or friends and families (64.8%). The discrete choice experiments revealed that respondents from the United States attached the greatest importance to the efficacy of COVID-19 vaccines (44.41%), followed by the cost of vaccination (29.57%), whereas those from China held a different viewpoint, that the cost of vaccination covered the largest proportion in their trade-off (30.66%), and efficacy ranked as the second most important attribute (26.34%). Additionally, respondents from China tended to be much more concerned about the adverse effect of vaccination (19.68% vs. 6.12%) and have a lower perceived severity of being infected with COVID-19. CONCLUSION: Although the overall acceptance and hesitancy of COVID-19 vaccination in both countries are high, underpinned distinctions between these countries were observed. Owing to the differences in COVID-19 incidence rates, cultural backgrounds, and the availability of specific COVID-19 vaccines in the two countries, vaccine rollout strategies should be nation-dependent.

CT appearances, patterns of progression, and follow-up of COVID-19: evaluation on thin-section CT.

BACKGROUND: To retrospectively analyze CT appearances and progression pattern of COVID-19 during hospitalization, and analyze imaging findings of follow-up on thin-section CT. METHODS: CT findings of 69 patients with COVID-19 were evaluated on initial CT, peak CT, and pre-discharge CT. CT pattern were divided into four types on CT progression. Lesion percentage of pulmonary lobe (lobe score) was graded. Correlation analysis was made between scores and intervals. 53 patients were followed up by CT. RESULTS: Among 69 patients, 33.3% exhibited improvement pattern, 65.2% peak pattern, 1.5% deterioration pattern, and 0% fluctuation pattern. The lobe scores were positively correlated with most of intervals. It was more common to observe consolidation, pleural thickening and pleural effusion on the peak CT, and irregular line and reticulation on pre-discharge CT. The peak-initial interval were shortened when the initial CT with consolidation and pleural thickening. The intervals were extended when the irregular lines appeared on peak CT and reticulation on pre-discharge CT. Among 53 follow-up patients, 37.7% showed normal chest CT, and 62.3% showed viral pneumonia remained that mainly included GGO (100.0%) and irregular lines (33.3%). CONCLUSIONS: COVID-19 displayed different appearances on CT as progressing. The peak pattern was the most common progression pattern. The CT appearances showed closely related to the intervals. The COVID-19 pneumonia can be remained or completely absorbed on CT with follow-up.

Could the ambient higher temperature decrease the transmissibility of COVID-19 in China?

BACKGROUND: Existing literatures demonstrated that meteorological factors could be of importance in affecting the spread patterns of the respiratory infectious diseases. However, how ambient temperature may influence the transmissibility of COVID-19 remains unclear. OBJECTIVES: We explore the association between ambient temperature and transmissibility of COVID-19 in different regions across China. METHODS: The surveillance data on COVID-19 and meteorological factors were collected from 28 provincial level regions in China, and estimated the instantaneous reproductive number (Rt). The generalized additive model was used to assess the relationship between mean temperature and Rt. RESULTS: There were 12,745 COVID-19 cases collected in the study areas. We report the associated effect of temperature on Rt is likely to be negative but not of statistical significance, which holds for most Chinese regions. CONCLUSIONS: We found little statistical evidence for that the higher temperature may reduce the transmissibility of COVID-19. Since intensive control measures against the COVID-19 epidemics were implemented in China, we acknowledge this may impact the underlying effect size estimation, and thus cautiousness should be taken when interpreting our findings.

RAPPID: a platform of ratiometric bioluminescent sensors for homogeneous immunoassays (preprint)

Heterogeneous immunoassays such as ELISA have become indispensable in modern bioanalysis, yet translation into easy-to-use point-of-care assays is hindered by their dependence on external calibration and multiple washing and incubation steps. Here, we introduce RAPPID (Ratiometric Plug-and-Play Immunodiagnostics), a "mix-and-measure" homogeneous immunoassay platform that combines highly specific antibody-based detection with a ratiometric bioluminescent readout that can be detected using a basic digital camera. The concept entails analyte-induced complementation of split NanoLuc luciferase fragments, photoconjugated to an antibody sandwich pair via protein G adapters. We also introduce the use of a calibrator luciferase that provides a robust ratiometric signal, allowing direct in-sample calibration and quantitative measurements in complex media such as blood plasma. We developed RAPPID sensors that allow low-picomolar detection of several protein biomarkers, anti-drug antibodies, therapeutic antibodies, and both SARS-CoV-2 spike protein and anti-SARS-CoV-2 antibodies. RAPPID combines ratiometric bioluminescent detection with antibody-based target recognition into an easy-to-implement standardized workflow, and therefore represents an attractive, fast, and low-cost alternative to traditional immunoassays, both in an academic setting and in clinical laboratories for point-of-care applications.

Transmission patterns of COVID-19 in the mainland of China and the efficacy of different control strategies: a data- and model-driven study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has seriously endangered the health and lives of Chinese people. In this study, we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of China. METHODS: According to the COVID-19 epidemic status, we constructed a compartmental model. Based on reported data from the National Health Commission of People's Republic of China during January 10-February 17, 2020, we estimated the model parameters. We then predicted the epidemic trend and transmission risk of COVID-19. Using a sensitivity analysis method, we estimated the efficacy of several intervention strategies. RESULTS: The cumulative number of confirmed cases in the mainland of China will be 86 763 (95% CI: 86 067-87 460) on May 2, 2020. Up until March 15, 2020, the case fatality rate increased to 6.42% (95% CI: 6.16-6.68%). On February 23, 2020, the existing confirmed cases reached its peak, with 60 890 cases (95% CI: 60 350-61 431). On January 23, 2020, the effective reproduction number was 2.620 (95% CI: 2.567-2.676) and had dropped below 1.0 since February 5, 2020. Due to governmental intervention, the total number of confirmed cases was reduced by 99.85% on May 2, 2020. Had the isolation been relaxed from February 24, 2020, there might have been a second peak of infection. However, relaxing the isolation after March 16, 2020 greatly reduced the number of existing confirmed cases and deaths. The total number of confirmed cases and deaths would increase by 8.72 and 9.44%, respectively, due to a 1-day delayed diagnosis in non-isolated infected patients. Moreover, if the coverage of close contact tracing was increased to 100%, the cumulative number of confirmed cases would be decreased by 88.26% on May 2, 2020. CONCLUSIONS: The quarantine measures adopted by the Chinese government since January 23, 2020 were necessary and effective. Postponing the relaxation of isolation, early diagnosis, patient isolation, broad close-contact tracing, and strict monitoring of infected persons could effectively control the COVID-19 epidemic. April 1, 2020 would be a reasonable date to lift quarantine in Hubei and Wuhan.

A new method to calculate the instant case fatality rate of COVID-19 in Wuhan and Hubei of China (preprint)

The worst-hit area of coronavirus disease 2019 (COVID-19) in China was Wuhan City and its affiliated Hubei Province, where the outbreak has been well controlled. The case fatality rate (CFR) is the most direct indicator to evaluate the hazards of an infectious disease. However, most reported CFR on COVID-19 represent a large deviation from reality. We aimed to establish a more accurate way to estimate the CFR of COVID-19 in Wuhan and Hubei and compare it to the reality. The daily case notification data of COVID-19 from December 8, 2019, to May 1, 2020, in Wuhan and Hubei were collected from the bulletin of the Chinese authorities. The instant CFR of COVID-19 was calculated from the numbers of deaths and the number of cured cases, the two numbers occurred on the same estimated diagnosis dates. The instant CFR of COVID-19 was 1.3%-9.4% in Wuhan and 1.2%-7.4% in Hubei from January 1 to May 1, 2020. It has stabilized at 7.69% in Wuhan and 6.62% in Hubei since early April. The cure rate was between 90.1% and 98.8% and finally stabilized at 92.3% in Wuhan and stabilized at 93.5% in Hubei. The mortality rates were 34.5/100 000 in Wuhan and 7.61/100 000 in Hubei. In conclusion, this approach reveals a way to accurately calculate the CFR, which may provide a basis for the prevention and control of infectious diseases.

Estimating the instant case fatality rate of COVID-19 in China.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) in China has been basically controlled. However, the global epidemic of COVID-19 is worsening. We established a method to estimate the instant case fatality rate (CFR) and cure rate of COVID-19 in China. METHODS: A total of 82 735 confirmed cases released officially by the Chinese authorities from December 8, 2019 to April 18, 2020 were collected. The estimated diagnosis dates of deaths and cured cases were calculated based on the median cure time or median death time of individual cases. Following this, the instant CFR was calculated according to the number of deaths and cured cases on the same estimated diagnosis date. RESULTS: In China, the instant CFR of COVID-19 was 3.8-14.6% from January 1 to January 17; it then declined gradually and stabilized at 5.7% in April. The average CFR in China was 6.1±2.9%, while the CFR was 1.0±0.4% in China except Hubei Province. The cure rate of COVID-19 was 93.9±2.9% in China, and stabilized at 94.3%, while it was 99.0±0.4% in China except Hubei Province. CONCLUSIONS: The instant CFR of COVID-19 in China overall was much higher than that in China except Hubei Province. The CFR of COVID-19 in China was underestimated.

Effects of media reporting on mitigating spread of COVID-19 in the early phase of the outbreak.

The 2019 novel coronavirus disease (COVID-19) is running rampantly in China and is swiftly spreading to other countries in the world, which causes a great concern on the global public health. The absence of specific therapeutic treatment or effective vaccine against COVID-19 call for other avenues of the prevention and control measures. Media reporting is thought to be effective to curb the spreading of an emergency disease in the early stage. Cross-correlation analysis based on our collected data demonstrated a strong correlation between media data and the infection case data. Thus we proposed a deterministic dynamical model to examine the interaction of the disease progression and the media reports and to investigate the effectiveness of media reporting on mitigating the spread of COVID-19. The basic reproduction number was estimated as 5.3167 through parameterization of the model with the number of cumulative confirmed cases, the number of cumulative deaths and the daily number of media items. Sensitivity analysis suggested that, during the early phase of the COVID-19 outbreak, enhancing the response rate of the media reporting to the severity of COVID-19, and enhancing the response rate of the public awareness to the media reports, both can bring forward the peak time and reduce the peak size of the infection significantly. These findings suggested that besides improving the medical levels, media coverage can be considered as an effective way to mitigate the disease spreading during the initial stage of an outbreak.

Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT.

RATIONALE AND OBJECTIVES: To retrospectively analyze the chest imaging findings in patients with coronavirus disease 2019 (COVID-19) on thin-section CT. MATERIALS AND METHODS: Fifty-three patients with confirmed COVID-19 infection underwent thin-section CT examination. Two chest radiologists independently evaluated the imaging in terms of distribution, ground-glass opacity (GGO), consolidation, air bronchogram, stripe, enlarged mediastinal lymph node, and pleural effusion. RESULTS: Fourty-seven cases (88.7%) had findings of COVID-19 infection, and the other six (11.3%) were normal. Among the 47 cases, 78.7% involved both lungs, and 93.6% had peripheral infiltrates distributed along the subpleural area. All cases showed GGO, 59.6% of which were round and 40.4% patchy. Other imaging features included "crazy-paving pattern" (89.4%), consolidation (63.8%), and air bronchogram (76.6%). Air bronchograms were observed within GGO (61.7%) and consolidation (70.3%). Neither enlarged mediastinal lymph nodes nor pleural effusion were present. Thirty-three patients (62.3%) were followed an average interval of 6.2 ± 2.9 days. The lesions increased in 75.8% and resorbed in 24.2% of patients. CONCLUSION: COVID-19 showed the pulmonary lesions in patients infected with COVID-19 were predominantly distributed peripherally in the subpleural area.

Estimation of instant case fatality rate of COVID-19 in Wuhan and Hubei based on daily case notification data (preprint)

Background The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Mar 10, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Results From Jan 1, 2020 to Feb 22, 2020 in Wuhan City, the instant case fatality rate of COVID-19 was 3.4%19.5% and the instant cured rate was 80.0%96.6%. The average fatality rate reached 11.4% while the average cure rate was 88.6%. During the same period in Hubei Province, the instant case fatality rate was 3.8%16.6% and the instant cured rate was 83.4%96.6%. The average fatality rate and the average cure rate were 9.2% and 91.8%, respectively. Conclusions The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did.