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Background: To explore the impact of diabetes on the clinical features and prognosis of COVID-19 and assess the influence of glucocorticoid use on the prognosis of patients with COVID-19 and diabetes., Methods: This retrospective multicenter cohort study included patients admitted between December 2022 and January 2023. The patients were grouped according to diabetes and glucocorticoid use. The primary outcome was in-hospital mortality., Results: Among 400 patients with glucocorticoid data, 109 (27.3%) had diabetes. The inflammatory cytokines were higher in patients with diabetes, manifested by higher IL-6 (25.33 vs. 11.29 ng/L, p = 0.011), CRP (26.55 vs. 8.62 mg/L, p = 0.003), and PCT (0.07 vs. 0.04 ng/ml, p = 0.010), while CD4 + (319 vs. 506 /mL, p = 0.004) and CD8 + (141 vs. 261 /mL, p < 0.001) T lymphocytes were lower. The overall mortality rate of hospitalized COVID-19 patients with diabetes was 13.46%. The diabetic patients who received glucocorticoids vs. those who did not receive glucocorticoids had a similar mortality (15.00% vs. 11.39%, p = 0.591)., Conclusions: Patients with COVID-19 and diabetes are more likely to experience hyperinflammatory response and T cell reduction, especially those with severe/critical disease. Glucocorticoid use was not associated with the prognosis of COVID-19 in patients with diabetes. Still, glucocorticoids should be used cautiously in diabetic patients with severe/critical COVID-19., (© 2024. The Author(s).)

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19., (© 2023. The Author(s).)

Background: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients., Methods: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information., Results: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%., Conclusions: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.

Background: The global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic., Methods: We collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2., Result: Transmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins., Conclusions: These results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs., Competing Interests: Authors YC, YFL, WL, JL, NC, JX and DW are employed by Shenzhen SecreTech Co. Ltd. Author DW was employed by Vesicode AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Cai, Zhou, Bai, Zhu, Kong, Sun, Li, Liu, Liao, Liu, Cui, Xiang, Li, Zhao, Wu and Ran.)

Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses., (© 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course., Methods: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models., Results: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available., Interpretation: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization., Key Points: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration., (© 2021. European Society of Radiology.)

Background: Gastrointestinal symptoms have been reported in patients with COVID-19. Several clinical investigations suggested that gastrointestinal symptoms were associated with disease severity of COVID-19. However, the relevance of gastrointestinal symptoms and mortality of COVID-19 remains largely unknown. We aim to investigate the relationship between gastrointestinal symptoms and COVID-19 mortality., Methods: We searched the PubMed, Embase, Web of science and Cochrane for studies published between Dec 1, 2019 and May 1, 2021, that had data on gastrointestinal symptoms in COVID-19 patients. Additional literatures were obtained by screening the citations of included studies and recent reviews. Only studies that reported the mortality of COVID-19 patients with/without gastrointestinal symptoms were included. Raw data were pooled to calculate OR (Odds Ratio). The mortality was compared between patients with and without gastrointestinal symptoms, as well as between patients with and without individual symptoms (diarrhea, nausea/vomiting, abdominal pain)., Results: Fifty-three literatures with 55,245 COVID-19 patients (4955 non-survivors and 50,290 survivors) were included. The presence of GI symptoms was not associated with the mortality of COVID-19 patients (OR=0.88; 95% CI 0.71-1.09; P=0.23). As for individual symptoms, diarrhea (OR=1.01; 95% CI 0.72-1.41; P=0.96), nausea/vomiting (OR=1.16; 95% CI 0.78-1.71; P=0.46) and abdominal pain (OR=1.55; 95% CI 0.68-3.54; P=0.3) also showed non-relevance with the death of COVID-19 patients., Conclusions: Gastrointestinal symptoms are not associated with higher mortality of COVID-19 patients. The prognostic value of gastrointestinal symptoms in COVID-19 requires further investigation., (© 2022. The Author(s).)

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval,  0.088 to 0.739; P  = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis -expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6 / IL-6-AS1 locus by the polymorphisms. The protective rs2066992- T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1 , which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T , represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G - C - G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19., Competing Interests: YL is an editor of Frontiers in Immunology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xu, Huang, Zhou, Deng, He, Liu, Li, Zhong and Sang.)

Background: Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear., Methods: We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed., Results: Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13 days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28-day survival rate., Conclusions: In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.

Objective: To evaluate the effect of Xuebijing injection on the improvement of pneumonia severity index (PSI) and prognosis in patients with severe coronavirus disease 2019 (COVID-19)., Methods: A multicenter prospective cohort study was designed. Adult patients with COVID-19 admitted to the intensive care unit (ICU) of 28 designated COVID-19 hospitals in 15 provinces and cities of China from January to March 2020 were enrolled. All patients were treated according to the standard treatment plan of COVID-19 issued by the National Health Commission of the People's Republic of China. They were divided into Xuebijing group and standard treatment group according to whether they received Xuebijing injection or not. In the standard treatment group, routine medical care measures such as antiviral, respiratory support, circulatory support and symptomatic treatment were taken. In the Xuebijing group, on the basis of standard treatment, Xuebijing was used within 12 hours of admission to the ICU, 100 mL each time, twice daily. The minimum duration of Xuebijing administration was 1 day. The improvement rate of PSI risk rating on the 8th day and clinical outcome on the 28th day were recorded., Results: A total of 276 COVID-19 patients were screened continuously, and the data of 144 severe patients who met PSI risk rating III-V were analyzed. Seventy-two cases were involved each in standard treatment group and Xuebijing group. The average age of the standard treatment group and Xuebijing group were (65.7±7.9) years old and (63.5±10.9) years old, and male accounted for 75.0% (54/72) and 70.8% (51/72), respectively. There were no significant differences in general conditions, comorbidities, PSI risk rating and score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO 2 /FiO 2 ), respiratory support mode and other baseline indicators between the two groups. Compared with the standard treatment group, the improvement rate of PSI risk rating in Xuebijing group on the 8th day after admission was significantly improved [56.9% (41/72) vs. 20.8% (15/72), between-group difference and 95% confidence interval (95%CI) was 36.1% (21.3% to 50.9%), P < 0.01], PSI score, SOFA score and PaO 2 /FiO 2 were significantly improved [PSI score: 83.7±34.8 vs. 108.2±25.6, between-group difference (95%CI) was -24.5 (-34.9 to -14.1); SOFA score: 2.0 (1.0, 4.0) vs. 7.0 (4.0, 10.0), between-group difference (95%CI) was -3.5 (-5.0 to -2.0); PaO 2 /FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 289.4±111.6 vs. 188.5±98.1, between-group difference (95%CI) was 100.9 (65.3 to 136.5); all P < 0.01]. The 28-day discharge rate of Xuebijing group was 44.5% higher than that of standard treatment group [66.7% (48/72) vs. 22.2% (16/72), P < 0.01], and the 28-day survival rate was 9.8% [91.7% (66/72) vs. 81.9% (59/72), P < 0.01]. There was no significant difference in the combination of antiviral drugs, antibiotics, anticoagulants and vasopressor drugs between the two groups. There was no significant difference in the incidence of adverse events between the Xuebijing group and standard treatment group [41.7% (30/72) vs. 43.1% (31/72), P > 0.05], and no serious adverse events and adverse reactions of Xuebijing were reported., Conclusions: Standard treatment combined with Xuebijing injection can significantly improve the PSI risk score and clinical prognosis of patients with severe COVID-19 without increasing drug safety risk.

Background: Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown., Methods: Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT)., Results: The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks., Conclusions: Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.

In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was confirmed in Wuhan, China, and spread rapidly beyond Wuhan and around the world. By 7 May 2020, a total of 84,409 patients were infected in mainland China, with 4,643 deaths, according to a Chinese Center for Disease Control and Prevention report. Recent studies reported that critically ill patients were presented with high mortality. However, the clinical experiences of patients with coronavirus disease 2019 (COVID-19) have not been described in Guangdong Province, where by 7 May 2020, 1,589 people had been confirmed as having COVID-19 but with a very low mortality of 8 death (0.5%). Here, we describe the experience of critical care response to the outbreak of SARS-CoV-2 in Guangdong Province in the following points: Early intervention by the government, Establishment of a Multidisciplinary Working Group, Prompt intensive care interventions, Adequate ICU beds and Human resource in ICU, Infection control practices., (Copyright © 2020 Liu, Xu, Xu, Xu, He, Huang, Zhong, Qin and Li.)

Background: Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary., Methods: We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate., Results: A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51-2·23; P = 0.87; I 2  = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias., Conclusions: The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.

Since the coronavirus disease 2019 (COVID‐19) was identified in 2019, it has caused more than 664 million confirmed cases and more than 6.7 million deaths globally by January 20, 2023. So far, the novel coronavirus has undergone mutations from the original, Alpha, Delta, and Omicron strains. Omicron was first detected in South Africa in November 2021 and has since spread rapidly to more than 100 countries around the world, leading the World Health Organization (WHO) to classify it as a "variant of concern" for COVID‐19. Due to its stronger infectivity, faster transmission, and higher reinfection rate, it is more likely to cause immune evasion and infection breakthrough in the vaccinated population. Omicron has replaced Delta strain as the main epidemic strain imported from overseas and in China. People with immunodeficiency are more susceptible to the novel coronavirus due to abnormal immune function, and viral infections tend to be more lasting and severe. In addition, due to the existence of underlying diseases, most people with immunodeficiency have been taking immunosuppressants and other related drugs for a long time, and there are different degrees of interaction between novel coronavirus treatment drugs and original drugs, which brings great challenges to the diagnosis and treatment of people with immunodeficiency after infection with novel coronavirus. According to the Novel Coronavirus Infection Diagnosis and Treatment Protocol (Trial 10th Edition) issued by the National Health Commission, which emphasizes "strengthening the protection of key groups," people with immune deficiency belong to the high‐risk groups of severe or critical disease. Based on the evidence of evidence‐based medicine and after many discussions by experts from multiple disciplines (Department of Respiratory and Critical Care, Department of Organ Transplantation, Department of Rheumatology, Department of Hematology, Department of Infection, Department of Critical Care Medicine, etc.), 13 recommendations are summarized to provide theoretical and practical reference for the diagnosis and treatment strategy of this special population. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic has spread all over the world resulting in high mortality, yet no specific antiviral treatment has been recommended. Methods: A retrospective descriptive study was conducted involving 19 consecutive critically ill patients during January 27, 2020 to April 18, 2020. Ribavirin was given at 0.15g q8h orally upon ICU admission for 7 to 21 days. Here, 28-day mortality, lower respiratory tract specimens (ETA), and ribavirin side effect on the day of ICU admission (Day 1), Day 7, Day 14 and Day 21 were analyzed. Results: All the nineteen critically ill COVID-19 patients (14 males and 5 females, median age 56yr) survived through to the 28th day of observations with 6 patients (31.58%) being discharged from the ICU. The SARS-CoV-2 viral positivity in sputum/ETA was 100% (19/19) on Day 1, 73.68% (14/19) on Day 7, 57.89% (11/19) on Day 14 and 36.84% (7/19) on Day 21. Ribavirin side effect was not observed in these patients. Conclusion: Ribavirin is well tolerated in critically ill patients with COVID-19 and may benefit COVID-19 patients through increasing the virus clearance. [ABSTRACT FROM AUTHOR]

Introduction: Close contacts of individuals with COVID-19 may directly gain immunity against SARS-CoV-2 despite lacking a detectable infection. This study examined SARS-CoV-2-specific antibodies levels based on gender, age, and exposure source in close contacts of individuals with COVID-19 and compared antibody levels to patients with an asymptomatic or symptomatic COVID-19 infection. Methods: Two patients had confirmed COVID-19 infections at a community hospital in Qiongzhong, Hainan province. Contact tracing identified all individuals in the community who had been exposed to the two patients during the 14 days before their diagnoses. Close contacts quarantined for 14 days, underwent two SARS-CoV-2 tests, and were screened for SARS-CoV-2-specific antibodies at 7 and 12 weeks after the end of quarantine. SARS-CoV-2-specific antibody levels for the close contacts were compared to those for patients with an asymptomatic or symptomatic COVID-19 infection at 7 and 12 weeks after their diagnoses. Results: Contact tracing identified 10,573 individuals in the community, including 360 (3.4%) close contacts. At 7 weeks, 30 (8.33%) close contacts were positive for SARS-CoV-2-specific antibodies (IgG, n = 26 [7.22%]; IgM, n = 4 [1.11%]), which were lower than the proportion of patients with an asymptomatic (IgG, 100% [12/12]) or symptomatic (IgG, 93.6% [44/47]) COVID-19 infection. SARS-CoV-2-specific IgM antibody levels were significantly higher in close contacts who were exposed through a relative compared to a doctor–patient relationship (P = 0.032). SARS-CoV-2-specific IgG antibody levels were significantly higher in close contacts aged < 18 years vs 18– 64 years (P = 0.014). At 12 weeks, SARS-CoV-2-specific IgG antibody levels among close contacts were significantly lower than among patients with an asymptomatic (P = 0.004) or symptomatic COVID-19 infection (P < 0.001). Conclusion: Immune protection conferred by close contact is short term and unlikely to contribute to herd immunity. There remains an unmet public health need for mass vaccination of populations to increase levels of protective antibodies and achieve and maintain herd immunity. [ABSTRACT FROM AUTHOR]

To inform seroepidemiological studies, we characterized the IgG‐ responses in COVID‐19 patients against the two major SARS‐CoV‐2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID‐19 sera collected up to 85 days post‐symptom onset and 230 non‐COVID‐19 sera, including 27 SARS sera from 2003. Although the average SARS‐CoV‐2 S and N‐IgG titers were comparable, N‐responses were more variable among individuals. S‐ and N‐assay specificity tested with non‐COVID‐19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross‐reactive potential and its' more consistent frequency of detection compared to N. [ABSTRACT FROM AUTHOR]

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19. [ABSTRACT FROM AUTHOR]

Background: Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. Methods: We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. Results: Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. Conclusions: While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19. [ABSTRACT FROM AUTHOR]

The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern. It is imperative to identify these patients early. We show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission. We develop this model using a cohort of 1590 patients from 575 medical centers, with internal validation performance of concordance index 0.894 We further validate the model on three separate cohorts from Wuhan, Hubei and Guangdong provinces consisting of 1393 patients with concordance indexes of 0.890, 0.852 and 0.967 respectively. This model is used to create an online calculation tool designed for patient triage at admission to identify patients at risk of severe illness, ensuring that patients at greatest risk of severe illness receive appropriate care as early as possible and allow for effective allocation of health resources. The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern and early assessment would be vital. Here, the authors show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission. [ABSTRACT FROM AUTHOR]

A novel infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in Wuhan, China, in December 2019. SARS-CoV-2 and severe acute respiratory syndrome coronavirus (SARS-CoV) use ACE2 receptor to... SARS-CoV-2 has been sequenced [[3]]. Further analysis even suggested that SARS-CoV-2 recognizes human ACE2 more efficiently than SARS-CoV increasing the ability of SARS-CoV-2 to transmit from person to person [[4]]. SARS-CoV and likely SARS-CoV-2 lead to downregulation of the ACE2 receptor, but not ACE, through binding of the spike protein with ACE2. [Extracted from the article]

The article focuses on case series highlighting ventilatory ratio in hypercapnic mechanically ventilated patients with COVID-19–associated acute respiratory distress syndrome (ARDS) and their individualized ventilation strategies. It mentions hypercapnia was common in patients with COVID-19–related ARDS with low VT ventilation. It also mentions increased pulmonary dead space reflects the inefficiency of the lungs to eliminate carbon dioxide which may lead to hypercapnia.

Objective: To provide clinical management guidelines for novel coronavirus (COVID-19) in pregnancy.Methods: On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed.Results: Ten key recommendations were provided for the management of COVID-19 infections in pregnancy.Conclusion: Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status. [ABSTRACT FROM AUTHOR]