Outbreak dynamics of COVID-19 in China and the United States

Biomechanics and Modeling in Mechanobiology - On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective...     

Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19 Patients at Early Stage of Outbreak

Virologica Sinica - The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has spread around the world with high mortality. To diagnose promptly and accurately is the vital step to...     

Proteomics Investigation of Diverse Serological Patterns in COVID-19

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.     

Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak

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SARS-CoV-2污染的进口冷链产品导致的一起大连本土新冠疫情

2020年12月15日,大连市报告了4名码头冷链货物搬运工人SARS-CoV-2核酸检测呈阳性,在此之前,大连市已经连续136天没有报告本土病例.在这次大连COVID-19疫情(简称"大连新冠疫情")中,我们收集了2020年12月15日至2021年1月8日期间大连新冠疫情中全部感染者(83)及部分接触的轮船货物样本,其中确诊病例占61.45％(51/83),无症状感染者占38.55％(32/83).通过高通量测序,共获得76条SARS-CoV-2全基因组序列,其中72条(86.75％,72/83)来自临床样本,4条来自R国籍A货船上的冷链食品外包装样本.基因组分析数据显示,与武汉参考株(NC_045512)相比,76条全基因组分别存在12～16个核苷酸突变位点,共享12个核苷酸突变位点,符合B.1.1进化分支突变特征.结合病毒基因组学和现场流行病学调查结果综合分析表明,大连新冠疫情是一起由SARS-CoV-2污染的进口冷链产品感染码头工人导致的本土疫情,在传播过程中至少形成了3个病毒代际和3个相对独立的传播链.     

Correction to: Dynamic Changes of Antibodies to SARS-CoV-2 in COVID-19 Patients at Early Stage of Outbreak

Virologica Sinica - Due to type-setting error, the affiliation of author Huaqing Shu and Shuzhen Wang was mislabeled.     

A Prognostic Model to Predict Recovery of COVID-19 Patients Based on Longitudinal Laboratory Findings

Virologica Sinica - The temporal change patterns of laboratory data may provide insightful clues into the whole course of COVID-19. This study aimed to evaluate longitudinal change patterns of key...     

Patients with COVID-19: in the dark-NETs of neutrophils

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.Subject terms: Immunological disorders, Infectious diseases, Respiratory tract diseases     

Opportunistic Candida Infections in Critical COVID-19 Patients

The frequency of opportunistic fungal infections in critically ill patients whose intensive care unit stays are prolonged due to coronavirus disease 2019 (COVID-19) is higher than in the period before COVID-19. We planned this study to improve the management of Candida infections by defining the Candida species, the etiology of infections caused by Candida species, and the antifungal susceptibility of the species. This retrospective study included patients older than 18 hospitalized in the intensive care unit (ICU) with a definitive diagnosis of COVID-19 for seven months (from March 2021 to September 2021). All study data that we recorded in a standard study form were analyzed with TURCOSA (Turcosa Analytics Ltd. Co., Turkey, www.turcosa.com.tr) statistical software. The patients were evaluated in four groups as group 1 (candidemia patients, n = 78), group 2 (candiduria patients, n = 189), group 3 (control patients, n = 57), and group 4 (patients with candidemia in urine cultures taken before Candida was detected in blood culture, n = 42). Candida species were identified using both conventional and VITEK® 2 (BioMérieux, France) methods. The antifungal susceptibility of fungi was determined using the E test method. Of the 5,583 COVID-19 patients followed during the study period, 78 developed candidemia, and 189 developed candiduria. The incidence of candidemia (per 1,000 admissions) was determined to be 1.6. As a result of statistical analysis, we found that Candida albicans was the dominant strain in candidemia and candiduria, and there was no antifungal resistance except for naturally resistant strains. Candida strains grown in blood and urine were the same in 40 of 42 patients. Mortality was 69.2% for group 1, 60.4% for group 2, and 57.8% for group 3. Antifungals were used in 34 (43.5%) patients from group 1, and 95 (50.2%) from group 2. In the candidemia group without antifungal use, mortality was quite high (77.2%). Antifungal use reduced mortality in the group 2 (p < 0.05). Length of ICU stays, comorbidity, broad-spectrum antibiotics, and corticosteroids are independent risk factors for candidemia in critically ill COVID-19 patients. Our study contributes to the knowledge of risk factors for developing COVID-19-related candida infections. The effect of candiduria on the development of candidemia in critically ill COVID-19 patients should be supported by new studies.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients

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Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients

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Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.     

新型冠状病毒感染相关嗅觉障碍的流行现状、机制和康复

新型冠状病毒感染（coronavirus disease 2019,COVID-19）,下简称“新冠”,是由严重急性呼吸系统综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）引发的全球流行传染病。鉴于嗅觉障碍是其主要神经症状,明确相关流行现状、机制和康复对促进公共健康非常重要。文献报道的新冠相关嗅觉障碍的发生率存在差异,与评估工具、人群以及变异毒株3个因素有关。其中,不同毒株之间嗅觉障碍发生率的差异可能源于刺突糖蛋白和侵入方式的变异。在外周嗅觉系统,SARS-CoV-2主要引发嗅裂炎症、支持细胞死亡和宿主免疫反应,而关于SARS-CoV-2入侵中枢的途径和机制仍存争议。部分“长新冠”患者存在持续的嗅觉障碍,SARS-CoV-2诱发慢性炎症反应和对嗅上皮再生的破坏是其潜在的病理基础。根据嗅觉媒介假说,SARS-CoV-2可能借由嗅觉系统影响中枢功能并最终诱发神经退行性变。嗅觉训练、药物等方法可帮助新冠相关嗅觉障碍的康复。     

Different Laboratory Abnormalities in COVID-19 Patients with Hypertension or Diabetes

We reported recently that hypertension is a risk factor for severe cases of COVID-19, independent of age and other variables (Liu et al. 2020a). An important question is why patients with hypertension and diabetes yield poorer clinical outcomes than those without. Human pathogenic coronavirus SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for viral cell entry. Since the levels of ACE2 are substantially increased in patients with hypertension or diabetes, who are treated with ACE inhibitors (ACEIs) and angiotensin Ⅱ type-Ⅰ receptor blockers (ARBs) (Ferrario et al. 2005), Fang and colleagues hypothesized that ACE2-stimulating drugs could potentially increase the risk of developing severe COVID-19 (Fang et al. 2020). This was not supported by a recent study led by Dr. Reynolds (Reynolds et al. 2020), whose analysis showed no positive association for ACEIs or ARBs for either the risk of SARS-CoV-2 infection or severe illness (Reynolds et al. 2020). What else might explain the poorer clinical outcomes of COVID-19 patients with hypertension or diabetes?To explore this question, we re-analysed the same cohort of 99 COVID-19 patients discharged from the general wards of Renmin Hospital of Wuhan University between 5 February 2020 and 14 March 2020 (Ethics approval No: WDRY2020-K124) (Liu et al. 2020a, b).     

Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

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Beta-Adrenergic Blockers as a Potential Treatment for COVID-19 Patients

More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the “ARAS loop”) is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo .