Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.

Changes in Serum Neutralizing Antibodies Levels During Convalescence of COVID-19 Patients.

Detection of serum-specific SARS-CoV-2 antibody has become a complementary means for the identification of coronavirus disease 2019 (COVID-19). As we already know, the neutralizing antibody titers in patients with COVID-19 decrease during the course of time after convalescence, whereas the duration of antibody responses in the convalescent patients has not been defined clearly. In the current study, we collected 148 serum samples from 37 confirmed COVID-19 cases with different disease severities. The neutralizing antibodies (Nabs), IgM and IgG against COVID-19 were determined by CLIA Microparticle and microneutralization assay, respectively. The time duration of serum titers of SARS-CoV-2 antibodies were recorded. Our results indicate that IgG (94.44%) and Nabs (89.19%) can be detected at low levels within 190-266 days of disease onset. The findings can advance knowledge regarding the antibody detection results for COVID-19 patients and provide a method for evaluating the immune response after vaccination.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown (preprint)

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs.We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8–16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown.A total of 3,327 participants were included in the COVID-19 survey, including 2,098 (63.1%) reported having NCDs at baseline and 1,457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9–13.5%, and poor sleepers from 23.9–15.3%, while low physical activity increased from 13.4–25.2%, among participants with NCDs. Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI, 1.05–1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI, 1.15–2.02).Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown, which is highly likely to happen in the near future.

Predicting the Molecular Mechanism of Shenling Baizhu San in Treating Convalescent Patients With COVID-19 Based on Network Pharmacology and Molecular Docking

Objective: Shenling Baizhu San (SBS) was selected as the regimen for the treatment of COVID-19 in Guangdong Province. It is mainly used for the convalescent treatment of COVID-19 patients with deficiency of both lung and spleen. In this study, we aimed to explore the mechanism of SBS in the treatment of COVID-19 through network pharmacology combined with molecular docking. Methods: The targets of active components of SBS were collected through Traditional Chinese Medicine Systems Pharmacology (TCMSP) and ETCM databases. Using the Genecards, TTD, OMIM and other databases, the targets of COVID-19 were determined. The next step was to use a string database to build a protein?protein interactions (PPI) network between proteins, and use David database to perform gene ontology (GO) function enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on core targets. Then we used Cytoscape software to construct the active ingredients-core target-signaling pathway network, and finally the active ingredients of SBS were molecularly docked with the core targets to predict the mechanism of SBS in the treatment of COVID-19. Results: A total of 177 active compounds, 43 core targets and 58 signaling pathways were selected. Molecular docking results showed that the binding energies of the top six active components and the targets were all less than ?5?kcal/MOL. Conclusion: The potential mechanism of action of SBS in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with IL6, DPP4, PTGS2, PTGS1 and TNF.

Changes in Lifestyles and Depressive Symptom Among Patients with Chronic Diseases During COVID-19 Lockdown (preprint)

Background: During the COVID-19 pandemic, patients with non-communicable diseases (NCDs), even without symptoms or a diagnosis of COVID-19, may be affected more than the general population due to the lockdown and healthcare service redistribution. This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs.Methods: We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown.Findings: A total of 3,327 participants were included in the COVID-19 survey, including 2,098 (63.1%) reported having NCDs at baseline and 1,457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9% to 13.5%, and poor sleepers from 23.9% to 15.3%, while low physical activity increased from 13.4% to 25.2%, among participants with NCDs. Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI, 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI, 1.15-2.02).Interpretation: Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown, which is highly likely to happen in the near future.Funding: Initial foundational funding for the Stanford Wellness Living laboratory (WELL) was provided by Amway via an unrestricted gift through the Nutrilite Health Institute Wellness Fund to Stanford University. Through Zhejiang University, the Cyrus Tang Foundation and Zhejiang University Education Foundation also provided important financial support for the study. The follow-up survey was supported by Hsun K. Chou Fund of Zhejiang University Education Foundation.Declaration of Interest: The authors declare no conflict of interest.Ethical Approval: The WELL-China project was approved by the ethics review board at both Zhejiang University (No. ZGL201507-3) in China and Stanford University (IRB- 35020) in USA. All participants provided written informed consent. The follow-up telephone interview was further approved by the ethics review board at Zhejiang University (No. ZGL202004-01).

Risk of pre-term births and major birth defects resulting from paternal intake of COVID-19 medications prior to conception (preprint)

Objective: . With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the three months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone. Results: . For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (<300 offspring). Our evidence suggests that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. For the other drugs investigated larger exposures are needed for conclusive statements.

Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications (preprint)

IMPORTANCE How to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVE To characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTS A cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURES Polymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Univariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS 16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCE This case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches.

Household Secondary Attack Rate of COVID-19 and Associated Determinants (preprint)

Background: As of April 2, 2020, the global reported number of COVID-19 cases has crossed over 1 million with more than 55,000 deaths. The household transmissibility of SARS-CoV-2, the causative pathogen, remains elusive. Methods: Based on a comprehensive contact-tracing dataset from Guangzhou, we estimated both the population-level effective reproductive number and individual-level secondary attack rate (SAR) in the household setting. We assessed age effects on transmissibility and the infectivity of COVID-19 cases during their incubation period. Results: A total of 195 unrelated clusters with 212 primary cases, 137 nonprimary (secondary or tertiary) cases and 1938 uninfected close contacts were traced. We estimated the household SAR to be 13.8% (95% CI: 11.1-17.0%) if household contacts are defined as all close relatives and 19.3% (95% CI: 15.5-23.9%) if household contacts only include those at the same residential address as the cases, assuming a mean incubation period of 4 days and a maximum infectious period of 13 days. The odds of infection among children (<20 years old) was only 0.26 (95% CI: 0.13-0.54) times of that among the elderly ([≥]60 years old). There was no gender difference in the risk of infection. COVID-19 cases were at least as infectious during their incubation period as during their illness. On average, a COVID-19 case infected 0.48 (95% CI: 0.39-0.58) close contacts. Had isolation not been implemented, this number increases to 0.62 (95% CI: 0.51-0.75). The effective reproductive number in Guangzhou dropped from above 1 to below 0.5 in about 1 week. Conclusion: SARS-CoV-2 is more transmissible in households than SARS-CoV and MERS-CoV, and the elderly [≥]60 years old are the most vulnerable to household transmission. Case finding and isolation alone may be inadequate to contain the pandemic and need to be used in conjunction with heightened restriction of human movement as implemented in Guangzhou.

Strategy of nursing care on the face skin injuries caused by wearing medical-grade protective equipment / 中华烧伤杂志

For effective resistance to virus attack and infection, reducing virus transmission chance, it is extremely important for the medical staff and related workers to have their own safe protection. This paper summarizes the development causes, common locations, and prevention ways about the device related pressure injuries on the face resulted from wearing medical-grade protective equipment for a long working time. The paper proposes the nursing strategy for device related pressure injuries and other nursing strategy is proposed to take care efficiently the device related pressure injuries. Meantime, a corresponding nursing strategy is also suggested to deal with the correlative skin diseases during the application of medical-grade protective equipment. These paper aims to provide reference for the prevention of device related pressure injuries and the care of skin-related diseases for clinical working staff, especially to the respectable personnel in front line of fighting against Corona virus disease 2019.

Correlation between the migration scale index and the number of new confirmed Novel Coronavirus Pneumonia cases in China (preprint)

Background: In late December, 2019, patients of atypical pneumonia due to an unidentified microbial agent were reported in Wuhan, Hubei Province, China. Subsequently, a novel coronavirus was identified as the causative pathogen which was named 2019 novel coronavirus (2019-nCoV). As of Feb 12, 2020, more than 44,000 cases of 2019-nCoV infection have been confirmed in China and continue to expand. Provinces, municipalities and autonomous regions of China have launched first-level response to major public health emergencies one after another from Jan 23.2020, which means restricting movement of people among provinces, municipalities and autonomous regions. The aim of this study was to explore the correlation between the migration scale index and the number of confirmed Novel Coronavirus Pneumonia (NCP) cases and to depict the effect of restricting population movement. Methods: Excel 2010 was used to demonstrate the temporal distribution at the day level and SPSS 23.0 was used to analyze the correlation between the migration scale index and the number of confirmed NCP cases. Results: Since January 23, 2020, Wuhan migration scale index has dropped significantly and since January 26, 2020, Hubei province migration scale index has dropped significantly. New confirmed NCP cases per day in China except Wuhan gradually increased since January 24, 2020, and showed a downward trend from February 6, 2020. New confirmed NCP cases per day in China except Hubei province gradually increased since January 24, 2020, and maintained at a high level from January 24, 2020 to February 4, 2020, then showed a downward trend. Wuhan emigration scale index from January 9 to January 22, January 10 to January 23 and January 11 to January 24 was correlated with the number of new confirmed NCP cases per day in China except Wuhan from January 22 to February 4. Hubei province emigration scale index from January 10 to January 23 and January 11 to January 24 was correlated with the number of new confirmed NCP cases per day in China except Hubei province from January 22 to February 4.Conclusions: People who left Wuhan from January 9 to January 22 may lead to the outbreak in China except Wuhan and people who left Hubei province from January 10 to January 24 may lead to the outbreak in China except Hubei province. “Wuhan lockdown” and Hubei province launching first-level response to major public health emergencies may have had a good effect the control NCP epidemic. Because there were still new confirmed NCP cases in China except Wuhan and in China except Hubei province and this may indicate that the occurrence of second-generation cases.