Characterization of severe and critical COVID-19 infected individuals outside of Wuhan, China (preprint)

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible among people，and the critical cases are still tough to treat, even leading to death. METHODS We retrospectively collected the clinical data of all the critical patients admitted to the Three Gorges Hospital(Chongqing, China) from Jan 20, 2020 to Feb 16, 2020 , whom were divided into improved group and worsen group. At last, we analyzed and compared the differences in laboratory indexes and length of hospital stay of the two groups. RESULT 46 cases were enrolled in the study. Comorbid conditions were present in 25 cases (54.3%). Most cases had symptoms, such as fever, cough, sputum, shortness of breath and dyspnea. The worsen group had a higher APACHE II score of 14(range from 5 to 23) than improved group(5, range from 3 to 7)(p<0.05). 32(69.6%) cases had low level lymphocyte counts (<1.0×109/L), including 8(66.7%) worsen group patients and 24(70.6%) improved group patients. The worsen group was 14.3(range from 8.21 to 18) with the ratio of neutrophil counts to lymphocyte counts, higher than that in improved group((7.33, range from 4.71 to 14.35)(p<0.05). There were faster respiratory frequencies in worsen group(23, range from 20 to 24.75) (p<0.05). And the worsen group had a lower OI(156.5, range from 74.25 to 233) than the other group(206, range from 177.5 to 242.75)(p<0.05). CONCLUSIONS Initial lower lymphocytes and higher APACHE II scores might be relative to the poor prognosis. And most of severe or critical patients had underlying diseases.

Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial (preprint)

Background: High flow nasal oxygen (HFNO) therapy is a leading treatment technique for acute hypoxemic respiratory failure (AHRF), but its treatment failure rate remains high. The awake prone position（APP） has been proven to inease oxygenation and reduce the endotracheal intubation rate in patients with COVID-19-induced AHRF. However, because the APP is poorly tolerated in patients, its performance in improving prognoses is controversial. The lateral position has a similar mechanism and effect to the prone position, but it is more tolerable than the prone position. Thus, it is worth exploring whether the lateral position is better for awake patients with acute respiratory failure. Methods: This is a protocol for a three-arm parallel group multicentre randomised controlled open-label exploratory trial. A total of 220 patients from two teaching hospitals in Chongqing, China, will be randomised to take the semirecumbent position, lateral position, or prone position at a ratio of 1:1:1. Patients are all diagnosed with AHRF secondary to non-COVID-19-related pneumonia or lung infection and receiving HFNO therapy. The primary outcome is 28-day all-cause mortality. The secondary outcomes are the 28-day intubation rate, total position change time, the incidence of adverse events, number of days using HFNO therapy, length of hospital and intensive care unit (ICU) stay, and others. We will conduct subgroup analyses on the arterial partial pressure of oxygen to the fraction of inspiration oxygen（PaO2/FiO2）ratio (>200 mmHg or ≤200 mmHg), time from hospitalisation to implementation (<24 h or ≥24 h), position changing time, and different diagnoses. Discussion: Thistrial will explore the prognostic effects of the APP with that of the lateral position in awake patients with non-COVID-19 induced AHRF, and compare the differences between them. To provide evidence for clinical decision-making and further research on position management. Trial registration: This trial was registered in the Chinese Clinical Trial Registry. The registration number is ChiCTR2200055822. Registered on January 20, 2022 ，https://www.chictr.org.cn/showproj.aspx?proj=130563

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

Booster of mRNA-1273 Vaccine Reduces SARS-CoV-2 Omicron Escape from Neutralizing Antibodies (preprint)

Data obtained on SARS-CoV-2 variant Omicron suggest that Omicron poses an increased risk of symptomatic breakthrough infections in people who receive only 2 doses of mRNA-1273. Administration of a booster mRNA vaccine may substantially reduce this risk.

Rapid immunoassay and clinical evaluation of the SARS-CoV-2 antibody assay on the real express-6 analyzer.

We developed a rapid and simple magnetic chemiluminescence enzyme immunoassay on the Real Express-6 analyzer, which could simultaneously detect immunoglobulin G and immunoglobulin M antibodies against SARS-CoV-2 virus in human blood within 18 min, and which could be used to detect clinical studies to verify its clinical efficacy. We selected blood samples from 185 COVID-19 patients confirmed by polymerase chain reaction and 271 negative patients to determine the clinical detection sensitivity, specificity, stability, and precision of this method. Meanwhile, we also surveyed the dynamic variance of viral antibodies during SARS-CoV-2 infection. This rapid immunoassay test has huge potential benefits for rapid screening of SARS-CoV-2 infection and may help clinical drug and vaccine development.

The Global Landscape of SARS-CoV-2 Genomes, Variants, and Haplotypes in 2019nCoVR.

On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, haplotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.

Effects of Early Physical and Pulmonary Rehabilitation for Severely and Critically ill COVID-19 Patients: A Retrospective, Cohort, and Multicenter Study (preprint)

BackgroundEffects of early rehabilitation therapy in severe and critical COVID-19 patients remains to be elucidated. MethodsWe recruited 80 severely and critically ill COVID-19 patients in Chongqing from January 21 to March 15, 2020, who had received rehabilitation therapies or standard treatments within 72 h of intensive care unit (ICU) admission. We analyzed mortality rates, length of stay in the ICU and hospital, ventilator-free days, and adverse events during hospitalization. Respiratory function, independent functional status, muscle strength, exercise capacity and life quality were measured at hospital discharge and during a three-month follow-up. ResultsWe found no significant differences between the intervention and control groups in terms of ICU, hospital, and 28-day mortality rates, and lengths of stay in the ICU and hospital. Additionally, early rehabilitation enhanced the duration of ventilator-free days, with no increased adverse events and complications. Total lung capacity and carbon monoxide diffusion capacity, Barthel index, and functional independence measure for patients in the intervention group were all higher than those in the control group at hospital discharge and one month after discharge. Compared to the control group, patients in the intervention group had significantly higher Medical Research Council scores and greater walking distance capacities within 6 min at hospital discharge, as well as one month and three months after discharge. The St. George's Respiratory Questionnaire score was lower in the intervention group than in the control group at one month and three months after hospital discharge.ConclusionsEarly physical and pulmonary rehabilitation is safe and effective for severely and critically ill COVID-19 patients to promote their functional, physical, and psychological recovery.

Epidemiological and clinical features of 2019-nCoV acute respiratory disease cases in Chongqing municipality, China: a retrospective, descriptive, multiple-center study (preprint)

BackgroundIn January 19, 2020, first case of 2019 novel coronavirus (2019-nCoV) pneumonia (COVID-19) was confirmed in Chongqing municipality, China. MethodsIn this retrospective, descriptive, multiple-center study, total of 267 patients with COVID-19 confirmed by real-time RT-PCR in Chongqing from Jan 19 to Feb 16, 2020 were recruited. Epidemiological, demographic, clinical, radiological characteristics, laboratory examinations, and treatment regimens were collected on admission. Clinical outcomes were followed up until Feb 16, 2020. Results267 laboratory-confirmed COVID-19 patients admitted to 3 designated-hospitals in Chongqing provincial municipality from January 19 to February 16, 2020 were enrolled and categorized on admission. 217 (81.27%) and 50 (18.73%) patients were categorized into non-severe and severe subgroups, respectively. The median age of patients was 48.0 years (IQR, 35.0-65.0), with 129 (48.3%) of the patients were more than 50 years of age. 149 (55.8%) patients were men. Severe patients were significantly older (median age, 71.5 years [IQR, 65.8-77.0] vs 43.0 years [IQR, 32.5-57.0]) and more likely to be male (110 [50.7%] vs 39 [78.0%]) and have coexisting disorders (15 [30.0%] vs 26 [12.0%]). 41 (15.4%) patients had a recent travel to Hubei province, and 139 (52.1%) patients had a history of contact with patients from Hubei. On admission, the most common symptoms of COVID-19 were fever 225(84.3%), fatigue (208 [77.9%]), dry cough (189 [70.8%]), myalgia or arthralgia (136 [50.9%]). Severe patients were more likely to present dyspnea (17 [34.0%] vs 26 [12.0%]) and confusion (10 [20.0%] vs 15 [6.9%]). Rales (32 [12.0%]) and wheezes (20 [7.5%]) are not common noted for COVID-19 patients, especially for the non-severe (11 [5.1%], 10 [4.6%]). 118 (44.2%). Most severe patients demonstrated more laboratory abnormalities. 231 (86.5%), 61 (22.8%) patients had lymphopenia, leukopenia and thrombocytopenia, respectively. CD4+T cell counts decrease was observed in 77.1 % of cases, especially in the severe patients (45, 100%). 53.1% patients had decreased CD+3 T cell counts, count of CD8+T cells was lower than the normal range in part of patients (34.4%). More severe patients had lower level of CD4+ T cells and CD+3 T cells (45 [100.0%] vs 29[56.9%], 31 [68.9%] vs 20 [39.2%]). Most patients had normal level of IL-2, IL-4, TNF- and INF-{gamma}, while high level of IL-6 and IL-17A was common in COVID-19 patients (47 [70.1%], 35 [52.2%]). Level of IL-6, IL-17A and TNF- was remarkably elevated in severe patients (32 [84.2%] vs 15 [51.7%], 25 [65.8%] vs 10 [34.5%], 17 [44.7%] vs 5 [17.2%]). All patients received antiviral therapy (267, 100%). A portion of severe patients (38, 76.0%) received systemic corticosteroid therapy. Invasive mechanical ventilation in prone position, non-invasive mechanical ventilation, high-flow nasal cannula oxygen therapy was adopted only in severe patients with respiratory failure (5[10.0%], 35[70.0%], 12[24.0%]). Traditional Chinese medicine was adopted to most of severe patients (43,86.0%). Conclusion:Our study firstly demonstrated the regional disparity of COVID-19 in Chongqing municipality and further thoroughly compared the differences between severe and non-severe patients. The 28-day mortality of COVID-19 patients from 3 designed hospitals of Chongqing is 1.5%, lower than that of Hubei province and mainland China including Hubei province. However, the 28-mortality of severe patients was relatively high, with much higher when complications occurred. Notably, the 28-mortality of critically severe patients complicated with severe ARDS is considerably as high as 44.4%. Therefore, early diagnosis and intensive care of critically severe COVID-19 cases, especially those combined with ARDS, will be considerably essential to reduce mortality.