Global analysis of lysine acetylation in the brain cortex of K18-hACE2 mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected hundreds of millions of people all over the world and thus threatens human life. Clinical evidence shows that SARS-CoV-2 infection can cause several neurological consequences, but the existing antiviral drugs and vaccines have failed to stop its spread. Therefore, an understanding of the response to SARS-CoV-2 infection of hosts is vital to find a resultful therapy. Here, we employed a K18-hACE2 mouse infection model and LC-MS/MS to systematically evaluate the acetylomes of brain cortexes in the presence and absence of SARS-CoV-2 infection. Using a label-free strategy, 3829 lysine acetylation (Kac) sites in 1735 histone and nonhistone proteins were identified. Bioinformatics analyses indicated that SARS-CoV-2 infection might lead to neurological consequences via acetylation or deacetylation of important proteins. According to a previous study, we found 26 SARS-CoV-2 proteins interacted with 61 differentially expressed acetylated proteins with high confidence and identified one acetylated SARS-CoV-2 protein nucleocapsid phosphoprotein. We greatly expanded the known set of acetylated proteins and provide the first report of the brain cortex acetylome in this model and thus a theoretical basis for future research on the pathological mechanisms and therapies of neurological consequences after SARS-CoV-2 infection.

Early-stage predictors of deterioration among 3145 nonsevere SARS-CoV-2-infected people community-isolated in Wuhan, China: A combination of machine learning algorithms and competing risk survival analyses.

OBJECTIVE: To determine which early-stage variables best predicted the deterioration of coronavirus disease 2019 (COVID-19) among community-isolated people infected with severe acute respiratory syndrome coronavirus 2 and to test the performance of prediction using only inexpensive-to-measure variables. METHODS: Medical records of 3145 people isolated in two Fangcang shelter hospitals (large-scale community isolation centers) from February to March 2020 were accessed. Two complementary methods-machine learning algorithms and competing risk survival analyses-were used to test potential predictors, including age, gender, severity upon admission, symptoms (general symptoms, respiratory symptoms, and gastrointestinal symptoms), computed tomography (CT) signs, and comorbid chronic diseases. All variables were measured upon (or shortly after) admission. The outcome was deterioration versus recovery of COVID-19. RESULTS: More than a quarter of the 3145 people did not present any symptoms, while one-third ended isolation due to deterioration. Machine learning models identified moderate severity upon admission, old age, and CT ground-glass opacity as the most important predictors of deterioration. Removing CT signs did not degrade the performance of models. Competing risk models identified age ≥ 35 years, male gender, moderate severity upon admission, cough, expectoration, CT patchy opacity, CT consolidation, comorbid diabetes, and comorbid cardiovascular or cerebrovascular diseases as significant predictors of deterioration, while a stuffy or runny nose as a predictor of recovery. CONCLUSIONS: Early-stage prediction of COVID-19 deterioration can be made with inexpensive-to-measure variables, such as demographic characteristics, severity upon admission, observable symptoms, and self-reported comorbid diseases, among asymptomatic people and mildly to moderately symptomatic patients.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice

Background Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex;however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding This study was supported by grants from the 10.13039/501100005150Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the 10.13039/501100001809National Natural Science Foundation of China, and the 10.13039/501100004826Natural Science Foundation of Beijing.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Long-term outcomes in COVID-19 patients who recovered from the first wave of the pandemic.

This cross-sectional study evaluated the long-term health effects of coronavirus disease 2019 (COVID-19) in Jianghan District (Wuhan, China). The results showed that 61.4% of COVID-19 patients reported at least one symptom and 8.8% had depressive symptoms at the 17-month follow-up. The proportion of patients with chest radiographic abnormalities in Fangcang shelter hospitals and designated COVID-19 hospitals was 31.6% and 41.1%, respectively, and the proportion of patients with impaired pulmonary diffusion capacity in these hospitals was 52.8% and 60.9%, respectively. Female sex (odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.16-1.88), severe disease (OR = 1.46, 95% CI: 1.01-2.10) and a higher number of initial symptoms (OR = 1.31, 95% CI: 1.23-1.40) were associated with the development of sequelae symptoms at 17 months. This study involving community-dwelling COVID-19 adults may help determine the long-term effects of COVID-19 during the first pandemic wave. Nonetheless, larger follow-up studies are needed to characterize the post-COVID-19 condition.

Animated, video entertainment-education to improve vaccine confidence globally during the COVID-19 pandemic: an online randomized controlled experiment with 24,000 participants.

BACKGROUND: Science-driven storytelling and entertainment-education (E-E) media demonstrate potential for promoting improved attitudes and behavioral intent towards health-related practices. Months after the outbreak of coronavirus disease 2019 (COVID-19), emerging research highlights the essential role of interventions to improve public confidence in the COVID-19 vaccine. To improve vaccine confidence, we designed three short, animated videos employing three research-informed pedagogical strategies. These can be distributed globally through social media platforms, because of their wordless and culturally accessible design. However, the effectiveness of short, animated storytelling videos, deploying various pedagogic strategies, needs to be explored across different global regions. METHODS/DESIGN: The present study is a multi-site, parallel group, randomized controlled trial (RCT) comparing the effectiveness of (i) a storytelling-instructional-humor approach, (ii) a storytelling-analogy approach, (iii) a storytelling-emotion-focused approach, and (iv) no video. For our primary outcomes, we will measure vaccine hesitancy, and for secondary outcomes, we will measure behavioral intent to seek vaccination and hope. Using online platforms, we will recruit 12,000 participants (aged 18-59 years) from the USA and China, respectively, yielding a total sample size of 24,000. DISCUSSION: This trial uses innovative online technology, reliable randomization algorithms, validated survey instruments, and list experiments to establish the effectiveness of three short, animated videos employing various research-informed pedagogical strategies. Results will be used to scientifically support the broader distribution of these short, animated video as well as informing the design of future videos for rapid, global public health communication. TRIAL REGISTRATION: German Clinical Trials Register DRKS #00023650 . Date of registration: 2021/02/09.

Attitudes Toward the Global Allocation of Chinese COVID-19 Vaccines: Cross-sectional Online Survey of Adults Living in China.

BACKGROUND: COVID-19 vaccines are in short supply worldwide. China was among the first countries to pledge supplies of the COVID-19 vaccine as a global public product, and to date, the country has provided more than 600 million vaccines to more than 200 countries and regions with low COVID-19 vaccination rates. Understanding the public's attitude in China toward the global distribution of COVID-19 vaccines could inform global and national decisions, policies, and debates. OBJECTIVE: The aim of this study was to determine the attitudes of adults living in China regarding the global allocation of COVID-19 vaccines developed in China and how these attitudes vary across provinces and by sociodemographic characteristics. METHODS: We conducted a cross-sectional online survey among adults registered with the survey company KuRunData. The survey asked participants 31 questions about their attitudes regarding the global allocation of COVID-19 vaccines developed in China. We disaggregated responses by province and sociodemographic characteristics. All analyses used survey sampling weights. RESULTS: A total of 10,000 participants completed the questionnaire. Participants generally favored providing COVID-19 vaccines to foreign countries before fulfilling domestic needs (75.6%, 95% CI 74.6%-76.5%). Women (3778/4921, 76.8%; odds ratio 1.18, 95% CI 1.07-1.32; P=.002) and those living in rural areas (3123/4065, 76.8%; odds ratio 1.13, 95% CI 1.01-1.27; P=.03) were especially likely to hold this opinion. Most respondents preferred providing financial support through international platforms rather than directly offering support to individual countries (72.1%, 95% CI 71%-73.1%), while for vaccine products they preferred direct provision to relevant countries instead of via a delivery platform such as COVAX (77.3%, 95% CI 76.3%-78.2%). CONCLUSIONS: Among our survey sample, we found that adults are generally supportive of the international distribution of COVID-19 vaccines, which may encourage policy makers to support and implement the distribution of COVID-19 vaccines developed in China worldwide. Conducting similar surveys in other countries could help align policy makers' actions on COVID-19 vaccine distribution with the preferences of their constituencies.

SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.

Prevalence of depression in China during the early stage of the COVID-19 pandemic: a cross-sectional study in an online survey sample.

OBJECTIVES: We aimed to determine (1) the prevalence of depression during the COVID-19 pandemic among Chinese adults and (2) how depression prevalence varied by province and sociodemographic characteristics. DESIGN: Cross-sectional study. SETTING: National online survey in China. PARTICIPANTS: We conducted a cross-sectional online survey among adults registered with the survey company KuRunData from 8 May 2020 to 8 June 2020. We aimed to recruit 300-360 adults per province (n=14 493), with a similar distribution by sex and rural-urban residency as the general population within each of these provinces. PRIMARY OUTCOME: Participants completed the Patient Health Questionaire-9 (PHQ-9). We calculated the prevalence of depression (defined as a PHQ-9 score ≥10) nationally and separately for each province. ANALYSIS: Covariate-unadjusted and covariate-adjusted logistic regression models were used to examine how the prevalence of depression varied by adults' sociodemographic characteristics. All analyses used survey sampling weights. RESULTS: The survey was initiated by 14 493 participants, with 10 000 completing all survey questions and included in the analysis. The prevalence of depression in the national sample was 6.3% (95% CI 5.7% to 6.8%). A higher odds of depression was associated with living in an urban area (OR 1.50; 95% CI 1.18 to 1.90) and working as a nurse (OR 3.06; 95% CI 1.41 to 6.66). A lower odds of depression was associated with participants who had accurate knowledge of COVID-19 transmission prevention actions (OR 0.71; 95% CI 0.51 to 0.98), the knowledge that saliva is a main transmission route (OR 0.80; 95% CI 0.64 to 0.99) and awareness of COVID-19 symptoms (OR, 0.82; 95% CI 0.68 to 1.00). CONCLUSION: Around one in 20 adults in our online survey sample had a PHQ-9 score suggestive of depression. Interventions and policies to prevent and treat depression during the COVID-19 pandemic in China may be particularly needed for nurses and those living in urban areas.

Factors Predicting Progression to Severe COVID-19: A Competing Risk Survival Analysis of 1753 Patients in Community Isolation in Wuhan, China.

Most studies of coronavirus disease 2019 (COVID-19) progression have focused on the transfer of patients within secondary or tertiary care hospitals from regular wards to intensive care units. Little is known about the risk factors predicting the progression to severe COVID-19 among patients in community isolation, who are either asymptomatic or suffer from only mild to moderate symptoms. Using a multivariable competing risk survival analysis, we identify several important predictors of progression to severe COVID-19-rather than to recovery-among patients in the largest community isolation center in Wuhan, China from 6 February 2020 (when the center opened) to 9 March 2020 (when it closed). All patients in community isolation in Wuhan were either asymptomatic or suffered from mild to moderate COVID-19 symptoms. We performed competing risk survival analysis on time-to-event data from a cohort study of all COVID-19 patients (n = 1753) in the isolation center. The potential predictors we investigated were the routine patient data collected upon admission to the isolation center: age, sex, respiratory symptoms, gastrointestinal symptoms, general symptoms, and computed tomography (CT) scan signs. The main outcomes were time to severe COVID-19 or recovery. The factors predicting progression to severe COVID-19 were: male sex (hazard ratio (HR) = 1.29, 95% confidence interval (CI) 1.04-1.58, p = 0.018), young and old age, dyspnea (HR = 1.58, 95% CI 1.24-2.01, p < 0.001), and CT signs of ground-glass opacity (HR = 1.39, 95% CI 1.04-1.86, p = 0.024) and infiltrating shadows (HR = 1.84, 95% CI 1.22-2.78, p = 0.004). The risk of progression was found to be lower among patients with nausea or vomiting (HR = 0.53, 95% CI 0.30-0.96, p = 0.036) and headaches (HR = 0.54, 95% CI 0.29-0.99, p = 0.046). Our results suggest that several factors that can be easily measured even in resource-poor settings (dyspnea, sex, and age) can be used to identify mild COVID-19 patients who are at increased risk of disease progression. Looking for CT signs of ground-glass opacity and infiltrating shadows may be an affordable option to support triage decisions in resource-rich settings. Common and unspecific symptoms (headaches, nausea, and vomiting) are likely to have led to the identification and subsequent community isolation of COVID-19 patients who were relatively unlikely to deteriorate. Future public health and clinical guidelines should build on this evidence to improve the screening, triage, and monitoring of COVID-19 patients who are asymtomatic or suffer from mild to moderate symptoms.

Knowledge About COVID-19 Among Adults in China: Cross-sectional Online Survey.

BACKGROUND: A detailed understanding of the public's knowledge and perceptions of COVID-19 could inform governments' public health actions in response to the pandemic. OBJECTIVE: The aim of this study was to determine the knowledge and perceptions of COVID-19 among adults in China and its variation among provinces and by sociodemographic characteristics. METHODS: Between May 8 and June 8, 2020, we conducted a cross-sectional online survey among adults in China who were registered with the private survey company KuRunData. We set a target sample size of 10,000 adults, aiming to sample 300-360 adults from each province in China. Participants were asked 25 questions that tested their knowledge about COVID-19, including measures to prevent infection, common symptoms, and recommended care-seeking behavior. We disaggregated responses by age; sex; education; province; household income; rural-urban residency; and whether or not a participant had a family member, friend, or acquaintance who they know to have been infected with SARS-CoV-2. All analyses used survey sampling weights. RESULTS: There were 5079 men and 4921 women who completed the questionnaire and were included in the analysis. Out of 25 knowledge questions, participants answered a mean and median of 21.4 (95% CI 21.3-21.4) and 22 (IQR 20-23) questions correctly, respectively. A total of 83.4% (95% CI 82.7%-84.1%) of participants answered four-fifths or more of the questions correctly. For at least one of four ineffective prevention measures (using a hand dryer, regular nasal irrigation, gargling mouthwash, and taking antibiotics), 68.9% (95% CI 68.0%-69.8%) of participants answered that it was an effective method to prevent a SARS-CoV-2 infection. Although knowledge overall was similar across provinces, the percent of participants who answered the question on recommended care-seeking behavior correctly varied from 47.0% (95% CI 41.4%-52.7%) in Tibet to 87.5% (95% CI 84.1%-91.0%) in Beijing. Within provinces, participants who were male, were middle-aged, were residing in urban areas, and had higher household income tended to answer a higher proportion of the knowledge questions correctly. CONCLUSIONS: This online study of individuals across China suggests that the majority of the population has good knowledge of COVID-19. However, a substantial proportion still holds misconceptions or incorrect beliefs about prevention methods and recommended health care-seeking behaviors, especially in rural areas and some less wealthy provinces in Western China. This study can inform the development of tailored public health policies and promotion campaigns by identifying knowledge areas for which misconceptions are comparatively common and provinces that have relatively low knowledge.

Correction: Knowledge About COVID-19 Among Adults in China: Cross-sectional Online Survey.

[This corrects the article DOI: 10.2196/26940.].

Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.

BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Clinical utility of a computed tomography-based receiver operating characteristic curve model for the diagnosis of COVID-19.

BACKGROUND: The outbreak of COVID-19 poses a major and urgent threat to global public health. CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. This study aimed to retrospectively analyze abnormal lung changes following initial computed tomography (CT) among patients with coronavirus disease 2019 (COVID-19) in Yunnan, and to evaluate the effectiveness of a chest CT-based model for the diagnosis of COVID-19. METHODS: One hundred and nine patients with COVID-19 pneumonia confirmed with the positive new coronavirus nucleic acid antibody who exhibited abnormal findings on initial CT were retrospectively analyzed. Thereafter, changes in the number, distribution, shape, and density of the lesions were observed. Further, the epidemiological, clinical, and CT imaging findings (+/-) were correlated. Following univariate and multivariate logistic regression analysis, receiver operating characteristic (ROC) curves were generated for significant factors, and models were established to evaluate the diagnostic ability of CT for COVID-19. RESULTS: Our results showed significant differences between patients with COVID-19 in epidemiological history (first, second, and third generation), clinical type (moderate, severe, and critical), and abnormal CT imaging characteristics (+/-) (P<0.05). Moreover, significant differences in abnormal CT imaging characteristics, including region, extent, and focus, were observed between the first generation and the other generations (P<0.05). For the diagnosis of COVID-19, the areas under the ROC curves for logistic regression models 1, 2, and 3 were 0.8016 (95% CI: 0.6759-0.9274), 0.9132 (95% CI: 0.8571-0.9693), and 0.9758 (95% CI: 0.9466-1), respectively. CONCLUSIONS: The ROC curve regression model based on chest CT signs displayed a high diagnostic value for COVID-19.

Curbing the COVID-19 pandemic with facility-based isolation of mild cases: a mathematical modeling study.

BACKGROUND: In many countries, patients with mild coronavirus disease 2019 (COVID-19) are told to self-isolate at home, but imperfect compliance and shared living space with uninfected people limit the effectiveness of home-based isolation. We examine the impact of facility-based isolation compared to self-isolation at home on the continuing epidemic in the USA. METHODS: We developed a compartment model to simulate the dynamic transmission of COVID-19 and calibrated it to key epidemic measures in the USA from March to September 2020. We simulated facility-based isolation strategies with various capacities and starting times under different diagnosis rates. Our primary model outcomes are new infections and deaths over 2 months from October 2020 onwards. In addition to national-level estimations, we explored the effects of facility-based isolation under different epidemic burdens in major US Census Regions. We performed sensitivity analyses by varying key model assumptions and parameters. RESULTS: We find that facility-based isolation with moderate capacity of 5 beds per 10 000 total population could avert 4.17 (95% credible interval 1.65-7.11) million new infections and 16 000 (8000-23 000) deaths in 2 months compared with home-based isolation. These results are equivalent to relative reductions of 57% (44-61%) in new infections and 37% (27-40%) in deaths. Facility-based isolation with high capacity of 10 beds per 10 000 population could achieve reductions of 76% (62-84%) in new infections and 52% (37-64%) in deaths when supported by expanded testing with an additional 20% daily diagnosis rate. Delays in implementation would substantially reduce the impact of facility-based isolation. The effective capacity and the impact of facility-based isolation varied by epidemic stage across regions. CONCLUSION: Timely facility-based isolation for mild COVID-19 cases could substantially reduce the number of new infections and effectively curb the continuing epidemic in the USA. Local epidemic burdens should determine the scale of facility-based isolation strategies.

Dynamic analysis of pulmonary computed tomography (CT) characteristics in cured coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: To retrospectively analyze the pulmonary computed tomography (CT) characteristics and dynamic changes in the lungs of cured coronavirus disease 2019 (COVID-19) patients at discharge and reexamination. METHODS: A total of 155 cured COVID-19 patients admitted to designated hospitals in Yunnan Province, China, from February 1, 2020, to March 20, 2020, were included. All patients underwent pulmonary CT at discharge and at 2 weeks after discharge (during reexamination at hospital). A retrospective analysis was performed using these two pulmonary CT scans of the cured patients to observe changes in the number, distribution, morphology, and density of lesions. RESULTS: At discharge, the lung CT images of 15 cured patients showed no obvious lesions, while those of the remaining 140 patients showed different degrees of residual lesions. Patients with moderate disease mostly had multiple pulmonary lesions, mainly in the lower lobes of both lungs. At reexamination, the lung lesions in the patients with moderate disease had significantly improved (P<0.05), and the lung lesions in the patients with severe disease had partially improved, especially in patients with multi-lobe involvement (χ 2 =3.956, P<0.05). At reexamination, the lung lesions of patients with severe disease did not show significant changes (P>0.05). CONCLUSIONS: The pulmonary CT manifestations of cured COVID-19 patients had certain characteristics and variation patterns, providing a reference for the clinical evaluation of treatment efficacy and prognosis of patients.

Buying Time for an Effective Epidemic Response: The Impact of a Public Holiday for Outbreak Control on COVID-19 Epidemic Spread.

Rapid responses in the early stage of a new epidemic are crucial in outbreak control. Public holidays for outbreak control could provide a critical time window for a rapid rollout of social distancing and other control measures at a large population scale. The objective of our study was to explore the impact of the timing and duration of outbreak-control holidays on the coronavirus disease 2019 (COVID-19) epidemic spread during the early stage in China. We developed a compartment model to simulate the dynamic transmission of COVID-19 in China starting from January 2020. We projected and compared epidemic trajectories with and without an outbreak-control holiday that started during the Chinese Lunar New Year. We considered multiple scenarios of the outbreak-control holiday with different durations and starting times, and under different assumptions about viral transmission rates. We estimated the delays in days to reach certain thresholds of infections under different scenarios. Our results show that the outbreak-control holiday in China likely stalled the spread of COVID-19 for several days. The base case outbreak-control holiday (21 d for Hubei Province and 10 d for all other provinces) delayed the time to reach 100 000 confirmed infections by 7.54 d. A longer outbreak-control holiday would have had stronger effects. A nationwide outbreak-control holiday of 21 d would have delayed the time to 100 000 confirmed infections by nearly 10 d. Furthermore, we find that outbreak-control holidays that start earlier in the course of a new epidemic are more effective in stalling epidemic spread than later holidays and that additional control measures during the holidays can boost the holiday effect. In conclusion, an outbreak-control holiday can likely effectively delay the transmission of epidemics that spread through social contacts. The temporary delay in the epidemic trajectory buys time, which scientists can use to discover transmission routes and identify effective public health interventions and which governments can use to build physical infrastructure, organize medical supplies, and deploy human resources for long-term epidemic mitigation and control efforts.

Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation.

BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.