Impacts of the COVID-19 pandemic on pediatric and adult patients with haemophilia (preprint)

Background:The COVID-19-associated mortality rate of haemophilia patients is similar to that of the general population, but the risk of hospitalization and bleeding is higher. However, the specific impact of this infection on haemophilia patients has not been reported yet. In this study, we aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the infection susceptibility, symptoms, drug use, and social intercourse of patients with haemophilia. Methods: A survey was distributed to a total of 265 patients with haemophilia [adult (n = 185) and pediatric patients (n = 80)] in the Fujian haemophilia therapeutic center (Fuzhou City, China) during the COVID-19 pandemic, and data were collected between January 2022 and January 2023. The impacts of SARS-CoV-2 infection on haemophilia symptoms, drug use, and social intercourse of these patients were investigated, and the association between the recovery time and disease conditions was explored in infected patients. Results: During the COVID-19 pandemic, compared with adult patients, pediatric patients had reduced social intercourse and outdoor activities because of the fear of contracting COVID-19 (85.0% vs. 66.5%; P = 0.002). Bleeding events were also significantly fewer in children than in adults (61.2% vs. 81.1%; P = 0.001). The SARS-CoV-2 infection rate was significantly higher in patients living in urban areas than in those living in rural areas (74.3% vs. 53.6%; P < 0.001). The duration of achieving symptomatic recovery from COVID-19 was not significantly associated with hemorrhage, type and classification of haemophilia, presence of inhibitors, complications, and vaccination status. Conclusion: Having COVID-19 infection did not significantly influence the symptoms and treatments in patients with haemophilia. Compared with adults, pediatric patients had significantly fewer bleeding events.

The Mental Health Status and Associated Factors Among Medical Students Engaged in Online Learning at Home During the Pandemic: A Cross-Sectional Study From China

Background: The purpose of this study was to assess the mental health status of medical students engaged in online learning at home during the pandemic, and explore the potential risk factors of mental health. Methods: A cross-sectional study was conducted via an online survey among 5,100 medical students from Wannan Medical College in China. The Depression, Anxiety and Stress scale (DASS-21) was used to measure self-reported symptoms of depression, anxiety, and stress among medical students during online learning in the pandemic. Results: In total, 4,115 participants were included in the study. The prevalence symptoms of depression, anxiety, and stress were 31.9, 32.9, and 14.6%, respectively. Depression was associated with gender, grade, length of schooling, relationship with father, students' daily online learning time, and students' satisfaction with online learning effects. Anxiety was associated with gender, length of schooling, relationship with father, relationship between parents, students' daily online learning time, and students' satisfaction with online learning effects. Stress was associated with grade, relationship with father, relationship between parents, students' daily online learning time, and students' satisfaction with online learning effects. Conclusions: Nearly one-third of medical students survived with varying degrees of depression, anxiety, and stress symptoms during online learning of the COVID-19 pandemic. Gender, grade, length of schooling, family environment, and online learning environment play vital roles in medical students' mental health. Families and schools should provide targeted psychological counseling to high-risk students (male, second-year and third-year, four-year program). The findings of this study can provide reference for educators to cope with the psychological problems and formulate the mental health curriculum construction among medical students during online learning.

Perinatal depression and anxiety among Chinese women during the outbreak of the COVID-19 Delta variant (preprint)

Background: This study aimed to assess the COVID-19 Delta variant impact on the incidence of depressive and anxiety symptoms in pregnant women in Guangdong Province, China, as well as to identify related risk factors.Methods: A three-week, multisite, cross-sectional study was conducted from June to July 2021 to evaluate the mental health status of pregnant women by the Edinburgh Postnatal Depression Scale. Approximately 1,450 women from 25 Guangdong hospitals were included in the study. We employed the Edinburgh Postnatal Depression Scale to assess symptoms of maternal depression and anxiety. Risk factors and relevance rates were analyzed.Results: Pregnant women who were determined to be underweight before pregnancy, primiparous, above 35 years of age, employed full-time, of middle income status, and had comfortable living arrangements were at higher risk of developing depression and anxiety during a COVID-19 outbreak.Conclusion: The occurrence of the COVID-19 Delta variant has increased the risk of mental disorders in pregnant women, which include thoughts of self-harm. Programs designed to address maternal stress as well as isolation such as constructive risk, communication, and providing psychological first aid may be particularly useful to avoid negative outcomes in pregnant women and their fetuses.

Potential Urinary Biomarkers of Young Adults With Short-Term Co-Exposure to Particulate Matter and Bioaerosols in a Time Course Identified by an Unbiased Metabolomic Approach With Gas/Liquid Chromatography–Mass Spectroscopy (preprint)

Background: Numerous epidemiological studies showed close relationships of outdoor air pollution with increased risk of cancer, infection, and cardiopulmonary diseases. However, a very limited number of studies investigate the potential biomarkers of the co-exposures of particle matters (PM) and bioaerosols, especially under current circumstances of the Coronavirus disease 2019 (COVID-19) pandemic. In the present study, we aimed to identify metabolic candidate biomarkers that are associated with co-exposure to PM and bioaerosols.Methods: We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites of 92 samples from young healthy individuals collected at three different time points with exposure to clean, polluted ambient, and purified air , followed by a cycling test after air re-pollution and re-purification with two additional time points. Subsequently, we compared metabolomic profiles in between two-time points via an integrated analysis, plus KEGG enriched pathway and time series analysis.Findings: We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure, respectively. The results from KEGG data and time series analysis indicated significantly enriched pathways and dynamic alterations of metabolomic profiles, respectively. 16-Dehydroprogesterone and 4-Hydroxyphenylethanol in urine might be used as biomarkers for diagnosis of PM- or bioaerosol-relevant diseases.Interpretation: The present studies revealed dynamic alterations in urinary metabolites of young healthy humans with the cycling of the clean and polluted air environment. Our findings help to investigate detrimental health effects of airborne PM and bioaerosols in a real-time manner and improve clinically diagnostic tools for PM- and bioaerosol-related diseases.Funding Information: This work was financially supported by the National Natural Science Foundation of China [NSFC Grant no. 81673958, 82074262, and 81828010]; CAMS Innovation Fund for Medical Sciences [CIFMS 2016-I2M-3-013]; The Drug Innovation Major Project of China [2018ZX09711001-007-002].Declaration of Interests: The authors declare no conflicts of interest in this work.Ethics Approval Statement: Our study was approved by the Ethical Committee of Guang'anmen Hospital. All recruited subjects provided written informed consent.

Analysis and evaluation of 670 convalescent plasma samples from patients with COVID-19 infection

Objective: To systematically analyze the 670 convalescent plasma (CP) samples from patients with coronavirus disease 2019 (COVID-19).

Treatment of COVID-19:hydroxychloroquine and other approaches

The new type of coronavirus pneumonia (COVID-19) is raging around the world, and the number of diagnoses and deaths continues to rise, and there is still no specific treatment drug. Chloroquine is a traditional medicine for the treatment of malaria and autoimmune diseases. It has shown initial efficacy in the treatment of COVID-19 and has attracted much attention. Hydroxychloroquine is a derivative of chloroquine, and its clinical drug safety is higher than that of chloroquine. It is listed by the World Health Organization as one of the 4 candidate trial drugs for the treatment of COVID-19 , Has also been included in the trial of the sixth and seventh editions of the COVID-19 treatment plan by the National Health Commission of China. However, the clinical efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19 is still very controversial, and sufficient Clinical data supports its use as a recommended drug for the treatment of COVID-19. In order to have a clearer understanding of chloroquine and hydroxychloroquine, this article briefly summarizes the pathological changes and treatment options of COVID-19, focusing on the efficacy of hydroxychloroquine in clinical trials and an in-depth analysis The potential causes and possible mechanisms of the different results of hydroxychloroquine in clinical trials, and the potential therapeutic effects of anisodamine and the antiviral drug remdesivir and psychological interventions are discussed, which are important for the rationalization of COVID-19 treatment options Reference value.

High Incidence of Venous Thromboembolism in Patients with Coronavirus Disease 2019: A Call for Improved Awareness and Prevention (preprint)

Background: An increased risk of venous thromboembolism (VTE) in patients with coronavirus disease 2019 (COVID-19) has been reported. We performed a meta-analysis to evaluate the prevalence of VTE in COVID-19 patients.Methods: The PubMed and Embase databases were searched for studies reporting VTE in COVID-19 patients up to June 27, 2020. The selected studies were predefined into the “suspected screening group” and the “routine screening group.” The VTE prevalence was calculated using random-effect models.Results: We selected 20 studies including a total of 2763 COVID-19 patients. In 2203 COVID-19 patients from the suspected screening group, the pool VTE incidence was 15.2% (95% confidence interval [CI]: 10.5–21.6%). In 560 COVID-19 patients from the routine screening group, the VTE prevalence was 40.8% (95% CI: 20.6–64.7%). Furthermore, the VTE incidence of critically ill COVID-19 patients from the two groups was 19.6% and 61.4%, respectively, which indicates that critically ill COVID-19 patients were more susceptible to VTE.Conclusions: A high incidence of VTE was observed in COVID-19 patients, especially in severe cases. The incidence of VTE in COVID-19 patients from the routine screening group was higher than that in patients from the suspected screening group. This indicates that a lower threshold of suspicion to perform VTE imaging tests may be reasonable and there is an urgent need to adapt a regular screening strategy for VTE.

Balancing Common Treatment and Epidemic Control in Medical Procurement during COVID-19: Transform-and-Divide Evolutionary Optimization (preprint)

Balancing common disease treatment and epidemic control is a key objective of medical supplies procurement in hospitals during a pandemic such as COVID-19. This problem can be formulated as a bi-objective optimization problem for simultaneously optimizing the effects of common disease treatment and epidemic control. However, due to the large number of supplies, difficulties in evaluating the effects, and the strict budget constraint, it is difficult for existing evolutionary multiobjective algorithms to efficiently approximate the Pareto front of the problem. In this paper, we present an approach that first transforms the original high-dimensional, constrained multiobjective optimization problem to a low-dimensional, unconstrained multiobjective optimization problem, and then evaluates each solution to the transformed problem by solving a set of simple single-objective optimization subproblems, such that the problem can be efficiently solved by existing evolutionary multiobjective algorithms. We applied the transform-and-divide evolutionary optimization approach to six hospitals in Zhejiang Province, China, during the peak of COVID-19. Results showed that the proposed approach exhibits significantly better performance than that of directly solving the original problem. Our study has also shown that transform-and-divide evolutionary optimization based on problem-specific knowledge can be an efficient solution approach to many other complex problems and, therefore, enlarge the application field of evolutionary algorithms.

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.

COVID-19: Abnormal liver function tests.

BACKGROUND & AIMS: Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results. METHODS: Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis. RESULTS: Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01). CONCLUSION: Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently. LAY SUMMARY: Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.

A rare symptom of ofactory dysfunction in coronavirus disease 2019: report of three cases (preprint)

Three patients of coronavirus disease (COVID-19) showed the symptoms of olfactory dysfunction. Clinical characteristics and treatment were retrospective analyzed. Olfactory disorders are uncommon symptoms of COVID-19. Early diagnosis and intervention are key to the recovery of olfactory disorders. Particular attention should be devoted to rare symptoms of COVID-19. 

COVID-19 in a designated infectious diseases hospital outside Hubei Province, China.

BACKGROUND: The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei Province are less understood. METHODS: We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen City, China, from January 11, 2020, to February 6, 2020, and followed until March 6, 2020. RESULTS: Among the 298 confirmed cases, 233 (81.5%) had been to Hubei, while 42 (14%) did not have a clear travel history. Only 218 (73.15%) cases had a fever as the initial symptom. Compared with the nonsevere cases, severe cases were associated with older age, those with underlying diseases, and higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS: In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild, and there are sufficient medical resources to care and treat the disease.

Characterization of a big family cluster infection associated with SARS-Cov-2 in Nanjing district (preprint)

Background: Outbreak of COVID-19 has brought catastrophe to huge numbers of families. However, even though numerous tragedies occurred, there were few reports about family cluster infection in the academic journals. Methods: The electronic medical records of 10 COVID-19 patients in a big family were retrospectively reviewed and analyzed.Results: These 10 patients, 4 males and 6 females, were infected through two successive family feasts during Spring Festival. The infection source was a family member at asymptomatic state, who lived in Hubei but travelled to Nanjing. The median age of these 10 patients was 61.5, with the oldest 95 and youngest 38. The incubation period varied from 3 to 17 days, with the median of 5.5. Of them, 2 patients were asymptomatic. The most common symptoms at onset were fever (6/10) and dry cough (6/10). All of them displayed lesions on the chest CT. 40% of them had leukopenia, neutropenia and lymphopenia. After anti-virus treatment, all the patients significantly improved and were discharged. Conclusions: SARS-Cov-2 was highly contagious and so crafty that a varied incubation period did exist. Part of patients might be asymptomatic, which was the potential source of transmission. More measures for protection or quarantine should be taken at home if family member had travel history nearby the epidemic area. 

Characterization of a big family cluster infection associated with SARS-Cov-2 in Nanjing district (preprint)

Background: Outbreak of COVID-19 has brought catastrophe to huge numbers of families. However, even though numerous tragedies occurred, there were few reports about family cluster infection in the academic journals. Methods: The electronic medical records of 10 COVID-19 patients in a big family were retrospectively reviewed and analyzed. Results: These 10 patients, 4 males and 6 females, were infected through two successive family feasts during Spring Festival. The infection source was a family member at asymptomatic state, who lived in Hubei but travelled to Nanjing. The median age of these 10 patients was 61.5, with the oldest 95 and youngest 38. The incubation period varied from 3 to 17 days, with the median of 5.5. Of them, 2 patients were asymptomatic. The most common symptoms at onset were fever (6/10) and dry cough (6/10). All of them displayed lesions on the chest CT. 40% of them had leukopenia, neutropenia and lymphopenia. After anti-virus treatment, all the patients significantly improved and were discharged. Conclusions: SARS-Cov-2 was highly contagious and so crafty that a varied incubation period did exist. Part of patients might be asymptomatic, which was the potential source of transmission. More measures for protection or quarantine should be taken at home if family member had travel history nearby the epidemic area. Keywords: COVID-19, SARS-Cov-2, family cluster, asymptomatic, incubation period.

Epidemiological and clinical characteristics of COVID-19 patients in Nanjing (preprint)

Background: Since December 2019, the outbreak of COVID-19 has spread quickly and thumped many countries and regions. The epidemic of central China was under the spotlight and attracted much more attentions. However, there are few reports describing COVID-19 patients in the regions outside of Wuhan, which are undergoing the change from sporadic imported cases to community-acquired transmission.Methods: The electronic medical records of 74 laboratory-confirmed patients of COVID-19 were retrospectively reviewed and analyzed. Their epidemiological, demographic, clinical and radiological characteristics were systematically summarized. The difference between severe patients and non-severe patients were also analyzed statistically.Results: The 74 COVID-19 patients were composed of 4 (5.4%) mild patients, 56 (75.7%) common patients, 13 (17.6%) severe patients and 1 (1.4%) critical patient. 43 were male, and 31 were female, with the average age 48.1±17.5. No significant difference of susceptibility was observed between genders, and almost people with all age were susceptible to SARS-CoV-2 infection. Before Jan 26, only imported sporadic cases were observed. However, from that day onward, family cluster infection cases increased dramatically, up to 70.3% (52/74), which were mainly from 15 family. The incubation period spanned from 0 to 19 days, with the median 5, and 81.4% had symptom onset within 7 days. At admission, 31.1% of patients had underlying diseases and the most common underlying diseases were hypertension (13.5%) and diabetes (5.4%). The most common symptoms were fever (90.5%), cough (75.7%), fatigue (36.5%) and chest distress (32.4%). 36.5% and 16.2% of patients had leukopenia and lymphocytopenia. 43.2% of patients had increased C reactive protein (CRP), and 40.5% had higher erythrocyte sedimentation rate (ESR) and 21.6% had higher calcitonin. 74.3% of patients had obvious lesions in both lung lobes and 56.8% of lesions manifested as ground glass opacity. Compared with non-severe group, the severe/critical group were significantly older and had more underlying diseases. After treatment, all patients improved and were discharged. No medical professional infection and death case were reported.Conclusion: The epidemic of COVID-19 in Nanjing were mainly caused by family cluster infection. The entire prevalence and illness were much milder than those of Wuhan. The disease of COVID-19 could be controlled and cured.  

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.

Comparative study of the lymphocyte change between COVID-19 and non-COVID-19 pneumonia cases suggesting uncontrolled inflammation might not be the main reason of tissue injury (preprint)

Background: The corona virus disease 2019 (COVID-19) shows unusually high transmission rate and unique clinical characteristics, with key pathological mechanism remaining unclear. Here, we analysed the laboratory data based on clinical samples from COVID-19 patients, in parallel comparison with non-COVID-19 pneumonia cases, in an attempt to elucidate the key pathological features of COVID-19 during its infection of the human body. Methods: We analysed biochemical indices and lymphocyte subpopulation in COVID-19 patients, and compare these data from non-COVID-19 pneumonia cases. Correlation analysis was performed between leukocyte subgroups count and biochemical indexes in COVID-19 patients. Results: The study enrolled 110 patients, comprising 88 COVID-19 patients and 22 non-COVID-19 pneumonia cases. We observed significant differences, including abnormal biochemical indices (CRP, LDH, AST, eGFR, and sodium ion concentration) and reduced lymphocyte subsets count, between the COVID-19 patients and non-COVID-19-caused pneumonia cases. Correlation analysis indicates that the count for lymphocyte subsets-but not that for neutrophils and monocytes-exhibits a significant negative correlation with biochemical indices relating to organ injury, in the COVID-19 infected patients. Conclusions: The study indicates significantly different clinical features between 2019 novel coronavirus (2019-nCoV)-caused and non-2019-nCoV-caused pneumonia, especially in terms of lymphocytopenia and organ injury. Notably, correlation analysis demonstrates that tissue damage in COVID-19 patients is attributed to virus infection itself rather than uncontrolled inflammatory responses ("cytokine storm"). These findings provide new insights for developing efficient therapeutic strategies against COVID-19 infection.

[Instructions for clinical research of oral diseases under the first level response to public health emergencies]

Corona virus disease 2019(COVID-19) has swept across our country and local governments have successively initiated first level response to public health emergencies. The outbreak of COVID-19 poses a huge challenge to the implementation of various clinical researches including oral diseases. In view of the specialty of oral diseases, it is particularly necessary to protect the health and rights of the participators and related practitioners, and to standardize the implementation of clinical trials. Based on the normative standards issued by the National Health Commission of China, consensus on clinical trial management formulated by the organization of clinical research, and regulations for the diagnosis and treatment of oral diseases during public health emergencies by Chinese Stomatological Association, we drafted the guideline for clinical research of oral diseases, with a view to provide reference for the clinical studies of oral diseases under the first level response to major public health emergencies.