Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis

Background Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242;95% confidence interval [CI], 0.802 to 34.246;P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327;95% CI, 1.702 to 6.501;P < 0.001), lower lymphocyte count (OR, 0.076;95% CI, 0.012 to 0.461;P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008;95% CI, 1.003 to 1.013;P = 0.002), and anticoagulation therapy (OR, 11.187;95% CI, 2.459 to 50.900;P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081;95% CI, −1.012 to 3.657;P = 0.265) or discharge (β Value 0.114;95% CI, −0.723 to 6.408;P = 0.117). d-dimer (β Value, 0.144;95% CI, 0.012 to 0.817;P = 0.044), LDH (β Value 0.260;95% CI, 0.010 to 0.034;P < 0.001), and antiviral therapy (β Value 0.220;95% CI, 1.373 to 6.263;P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value −0.206;95% CI, −6.248 to −1.197;P = 0.004), LDH (β Value 0.231;95% CI, 0.012 to 0.048;P = 0.001), antiviral therapy (β Value 0.143;95% CI, 0.058 to 7.497;P = 0.047), and antibacterial therapy (β Value 0.152;95% CI, 0.133 to 8.154;P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=−2.362, P = 0.018;Z=−2.010, P = 0.044) and a shorter hospital stay (Z=−2.735, P = 0.006;Z=−3.858, P < 0.001). Conclusions In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

Background: Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods: This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results: Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (ß Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (ß Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (ß Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (ß Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (ß Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (ß Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (ß Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (ß Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (ß Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions: In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Global research trends in the COVID-19 and digestive disease: A review of visualization and bibliometric study.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) has attracted worldwide attention. There were also reported gastrointestinal symptoms in patients with COVID-19. This work aims to analyze the global research trends in COVID-19 and digestive disease. METHODS: The related papers on COVID-19 and digestive disease were identified with Pubmed and web of science core collection on September 3, 2021. Bibliometric visualization was conducted through VOSviewer and CiteSpace. RESULTS: The analytic research was based on original articles and reviews. There were 997 articles found, with citations ranging from 0 to 878. These articles were distributed among 86 countries and 355 journals. The USA mainly contributed (288 articles), where 3 of the top 10 institutions were located. Followed by China (215 articles) and Italy (160 articles). The highest level of scientific collaboration has been formed between the USA to China. The World Journal of Gastroenterology (39 papers) published the most significant number of articles. Concerning the research topic, the colon/small bowel had the largest number of articles, followed by the liver and pancreaticobiliary. "Liver injury," "inflammatory bowel disease," "management," and "endoscopy" were the hotspot keywords. The largest cluster of liver transplantation had offered hints regarding research frontiers. CONCLUSION: The analytic results showed that the liver, especially liver transplantation, and inflammatory bowel disease were the 2 most influential research topics in COVID-19 and digestive disease.

Assessing the medical resources in COVID-19 based on evolutionary game.

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (ß < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (ß > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality.

Effects of short-term quarantine on growth and development of children aged 1-36 months during the Omicron outbreak.

Consequences of epidemic quarantine on children's well-being are not clear and there are scarce data about the short-term impact of epidemic quarantine on children's growth and development. The study aimed to explore and analyze the potential impacts of the Omicron outbreak on children's growth and development during the lockdown in Shanghai, China. Totally, 4565 children aged 1-36 months who had a routine physical examination in the child health departments of hospitals before (June 1, 2021, to July 6, 2021) and after (June 1, 2022, to July 6, 2022) Shanghai's lockdown were included in this study. A population-based cross-sectional study was conducted by using the Infant Toddler Growth Development Screening Test (ITGDST). The children's growth and development in these two periods were compared with a propensity score matching (PSM) approach. After 1:1 matching, a total of 2462 children aged 1-36 months were analyzed. After PSM, there was no significant difference in terms of overall development, gross motor, fine motor, and language development for children before and after the Omicron lockdown. However, statistically significant decrease of wasting was observed for children after the lockdown (p < 0.05). Further interaction analysis indicated older age group (OR = 0.26, 95% CI 0.11-0.59) and the group of second parity (OR = 0.30, 95% CI 0.11-0.83) were favorable to language development during the lockdown.  Conclusion: Short-term quarantine had no significant adverse, but rather beneficial, effects on growth and development of children aged 1-36 months during the Omicron epidemic in Shanghai, China. What is Known: • Consequences of epidemic quarantine on children's well-being are not clear. Long-term psychological effects of coronavirus disease 2019 pandemic on children have been reported. However, there are scarce data about the short-term impact of epidemic quarantine on children's growth and development. What is New: • Short-term quarantine had no significant adverse, but rather beneficial, effects on growth and development of children aged 1-36 months during the Omicron epidemic in Shanghai, China.

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.

Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.

Corrigendum: Prevalence of post-traumatic stress disorder status among healthcare workers and its impact on their mental health during the crisis of COVID-19: A cross-sectional study.

[This corrects the article DOI: 10.3389/fpubh.2022.904550.].

Comprehensive Subcellular Localization of Swine Acute Diarrhea Syndrome Coronavirus Proteins.

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV was first identified in diarrheal piglets in 2017. As a novel alphacoronavirus, SADS-CoV shares ~95% identity with bat alphacoronavirus HKU2. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Thus far, no effective antiviral drugs or vaccines are available to treat infections with SADS-CoV. Therefore, knowledge of the protein-coding gene set and a subcellular localization map of SADS-CoV proteins are fundamental first steps in this endeavor. Here, all SADS-CoV genes were cloned separately into Flag-tagged plasmids, and the subcellular localizations of viral proteins, with the exception of nsp11, were detected using confocal microscopy techniques. As a result, nsp1, nsp3-N, nsp4, nsp5, nsp7, nsp8, nsp9, nsp10, nsp14, and nsp15 were localized in the cytoplasm and nuclear spaces, and these viral proteins may perform specific functions in the nucleus. All structural and accessory proteins were mainly localized in the cytoplasm. NS7a and membrane protein M colocalized with the Golgi compartment, and they may regulate the assembly of SADS-CoV virions. Maturation of SADS-CoV may occur in the late endosomes, during which envelope protein E is involved in the assembly and release of the virus. In summary, the present study demonstrates for the first time the location of all the viral proteins of SADS-CoV. These fundamental studies of SADS-CoV will promote studies of basic virology of SADS-CoV and support preventive strategies for animals with infection of SADS-CoV. IMPORTANCE SADS-CoV is the first documented spillover of a bat coronavirus that causes severe diseases in domestic animals. Our study is an in-depth annotation of the newly discovered swine coronavirus SADS-CoV genome and viral protein expression. Systematic subcellular localization of SADS-CoV proteins can have dramatic significance in revealing viral protein biological functions in the subcellular locations. Furthermore, our study promote understanding the fundamental science behind the novel swine coronavirus to pave the way for treatments and cures.

A comprehensive evaluation of the potential binding poses of fentanyl and its analogs at the µ-opioid receptor.

Fentanyl and its analogs are selective agonists of the µ-opioid receptor (MOR). Among novel synthetic opioids (NSOs), they dominate the recreational drug market and are the main culprits for the opioid crisis, which has been exacerbated by the COVID-19 pandemic. By taking advantage of the crystal structures of the MOR, several groups have investigated the binding mechanism of fentanyl, but have not reached a consensus, in terms of both the binding orientation and the fentanyl conformation. Thus, the binding mechanism of fentanyl at the MOR remains an unsolved and challenging question. Here, we carried out a systematic computational study to investigate the preferred fentanyl conformations, and how these conformations are being accommodated in the MOR binding pocket. We characterized the free energy landscape of fentanyl conformations with metadynamics simulations, and compared and evaluated several possible fentanyl binding conditions in the MOR with long-timescale molecular dynamics simulations. Our results indicate that the most preferred binding pose in the MOR binding pocket corresponds well with the global minimum on the energy landscape of fentanyl in the absence of the receptor, while the energy landscape can be reconfigured by modifying the fentanyl scaffold. The interactions with the receptor may stabilize a slightly unfavored fentanyl conformation in an alternative binding pose. By extending similar investigations to fentanyl analogs, our findings establish a structure-activity relationship of fentanyl binding at the MOR. In addition to providing a structural basis to understand the potential toxicity of the emerging NSOs, such insights will contribute to developing new, safer analgesics.

Long non-coding RNAs in virus-related cancers.

Some viral infections lead to tumourigenesis explained by a variety of underlying molecular mechanisms. Long non-coding RNAs (lncRNAs) have the potential to be added to this list due to their diverse mechanisms in biological functions and disease processes via gene alternation, transcriptional regulation, protein modification, microRNA sponging and interaction with RNA/DNA/proteins. In this review, we summarise the dysregulation and mechanism of lncRNAs in virus-related cancers focussing on Hepatitis B virus, Epstein-Barr virus, Human Papillomavirus. We will also discuss the potential implications of lncRNAs in COVID-19.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized 129Xe MRI.

The recovery process of COVID-19 patients is unclear. Some recovered patients complain of continued shortness of breath. Vasculopathy has been reported in COVID-19, stressing the importance of probing pulmonary microstructure and function at the alveolar-capillary interface. While computed tomography (CT) detects structural abnormalities, little is known about the impact of disease on lung function. 129Xe magnetic resonance imaging (MRI) is a technique uniquely capable of assessing ventilation, microstructure, and gas exchange. Using 129Xe MRI, we found that COVID-19 patients show a higher rate of ventilation defects (5.9% versus 3.7%), unchanged microstructure, and longer gas-blood exchange time (43.5 ms versus 32.5 ms) compared with healthy individuals. These findings suggest that regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished. This study establishes the feasibility of localized lung function measurements in COVID-19 patients and their potential usefulness as a supplement to structural imaging.

Prevalence and Risk Factors Associated With Self-reported Psychological Distress Among Children and Adolescents During the COVID-19 Pandemic in China.

Importance: Schools have been suspended nationwide in 188 countries, and classes have shifted to home-based distance learning models to control the spread of the coronavirus disease 2019 (COVID-19) pandemic. Additional information is needed to determine mental health status among school-aged children and adolescents during this public health crisis and the risk factors associated with psychological distress during the pandemic. Objective: To assess self-reported psychological distress among school-aged children and adolescents associated with the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study using data from a survey on the mental health of school-aged children and adolescents in Guangdong province, China, conducted by using a stratified cluster random sampling method between March 8 to 30, 2020. To estimate outcomes associated with location of districts, only data from students with internet protocol addresses and current addresses in Guangdong were included. Data were analyzed from April 5 to July 20, 2020. Exposure: Home-based distance learning during the COVID-19 pandemic. Main Outcome and Measures: The main outcome was self-reported psychological distress, measured using the total score on the 12-item General Health Questionnaire of 3 or greater. Multivariate logistic regression was used to analyze risk factors associated with mental health status. Odds ratios (ORs) were used to analyze the associations of factors with psychological distress. Results: Among 1 310 600 students who completed the survey, 1 199 320 students (mean [SD] age, 12.04 [3.01] years; 619 144 [51.6%] boys) were included in the final analysis. A total of 126 355 students (10.5%) self-reported psychological distress. Compared with students in primary school, high school students had increased risk of psychological distress (OR, 1.19 [95% CI, 1.15-1.23]). Compared with students who wore a face mask frequently, students who never wore a face mask had increased risk of psychological distress (OR, 2.59 [95% CI, 2.41-2.79]). Additionally, students who spent less than 0.5 hours exercising had increased odds of self-reported psychological distress compared with students who spent more than 1 hour exercising (OR, 1.64 [95% CI, 1.61-1.67]). Conclusions and Relevance: These findings suggest that the prevalence of self-reported psychological distress among students during the COVID-19 pandemic was relatively high. Frequency of wearing a face mask and time spent exercising were factors associated with mental health. Therefore, it may be necessary for governments, schools, and families to pay attention to the mental health of school-aged children and adolescents during the COVID-19 pandemic and take corresponding countermeasures to reduce the impact of the COVID-19 pandemic on students' mental health.

Suicidal and self-harm ideation among Chinese hospital staff during the COVID-19 pandemic: Prevalence and correlates.

The COVID-19 pandemic put global medical systems under massive pressure for its uncertainty, severity, and persistence. For detecting the prevalence of suicidal and self-harm ideation (SSI) and its related risk factors among hospital staff during the COVID-19 pandemic, this cross-sectional study collected the sociodemographic data, epidemic-related information, the psychological status and need, and perceived stress and support from 11507 staff in 46 hospitals by an online survey from February 14 to March 2, 2020. The prevalence of SSI was 6.47%. Hospital staff with SSI had high family members or relatives infected number and the self-rated probability of infection. Additionally, they had more perceived stress, psychological need, and psychological impact. On the contrary, hospital staff without SSI reported high self-rated health, willingness to work in a COVID-19 ward, confidence in defeating COVID-19, and perceived support. Furthermore, they reported better marital or family relationship, longer sleep hours, and shorter work hours. The infection of family members or relatives, poor marital status, poor self-rated health, the current need for psychological intervention, perceived high stress, perceived low support, depression, and anxiety were independent factors to SSI. A systematic psychological intervention strategy during a public health crisis was needed for the hospital staff's mental well-being.

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Preliminary investigation of relationship between clinical indicators and CT manifestation patterns of COVID-19 pneumonia improvement.

BACKGROUND: To retrospectively evaluate several clinical indicators related to the improvement of COVID-19 pneumonia on CT. METHODS: A total of 62 patients with COVID-19 pneumonia were included. The CT scores based on lesion patterns and distributions in serial CT were investigated. The improvement and deterioration of pneumonia was assessed based on the changes of CT scores. Grouped by using the temperature, serum lymphocytes and high sensitivity CRP (hs-CRP) on admission respectively, the CT scores on admission, at peak time and at discharge were evaluated. Correlation analysis was carried out between the time to onset of pneumonia resolution on CT images and the recovery time of temperature, negative conversion of viral nucleic acid, serum lymphocytes and hs-CRP. RESULTS: The CT scores of the fever group and lymphopenia group were significantly higher than those of normal group on admission, at peak time and at discharge; and the CT scores of normal hs-CRP group were significantly lower than those of the elevated hs-CRP group at peak time and at discharge (P all<0.05). The time to onset of pneumonia resolution on CT image was moderately correlated with negative conversion duration of viral nucleic acid (r =0.501, P<0.05) and the recovery time of hs-CPR (r =0.496, P<0.05). CONCLUSIONS: COVID-19 pneumonia patients with no fever, normal lymphocytes and hs-CRP had mild lesions on admission, and presented with more absorption and fewer pulmonary lesions on discharge. The negative conversion duration of viral nucleic acid and the recovery time of hs-CPR may be the indicator of the pneumonia resolution.

Quarantine at home may not enough!-from the epidemiological data in Shaanxi Province of China.

OBJECTIVES: A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. RESULTS: 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

Identifying the Risk of SARS-CoV-2 Infection and Environmental Monitoring in Airborne Infectious Isolation Rooms (AIIRs).

Healthcare workers (HCWs) are at high risk of occupational exposure to the new pandemic human coronavirus, SARS-CoV-2, and are a source of nosocomial transmission in airborne infectious isolation rooms (AIIRs). Here, we performed comprehensive environmental contamination surveillance to evaluate the risk of viral transmission in AIIRs with 115 rooms in three buildings at the Shanghai Public Health Clinical Center, Shanghai, during the treatment of 334 patients infected with SARS-CoV-2. The results showed that the risk of airborne transmission of SARS-CoV-2 in AIIRs was low (1.62%, 25/1544) due to the directional airflow and strong environmental hygiene procedures. However, we detected viral RNA on the surface of foot-operated openers and bathroom sinks in AIIRs (viral load: 55.00-3154.50 copies/mL). This might be a source of contamination to connecting corridors and object surfaces through the footwear and gloves used by HCWs. The risk of infection was eliminated by the use of disposable footwear covers and the application of more effective environmental and personal hygiene measures. With the help of effective infection control procedures, none of 290 HCWs was infected when working in the AIIRs at this hospital. This study has provided information pertinent for infection control in AIIRs during the treatment of COVID-19 patients.

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.

BACKGROUND: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. OBJECTIVES: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. METHODS: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. MEASUREMENTS AND MAIN RESULTS: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. CONCLUSIONS: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.