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1.
Bioactive Materials ; 21:531-546, 2023.
Article in English | ScienceDirect | ID: covidwho-2041591

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction. Inspired by macrophage membranes harbor the receptors with special high affinity for proinflammation cytokines, lipopolysaccharide (LPS)-stimulated macrophage membrane-coated nanoparticles (LMNP) were developed to show strong sponge ability to both IFN-γ and IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo. Besides, LMNP also efficiently alleviated HLH-related symptoms including cytopenia, hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models. Furthermore, its sponge effect also worked well for five human HLH samples in vitro. Altogether, it's firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation, which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.

2.
Preprint in English | bioRxiv | ID: ppbiorxiv-491301

ABSTRACT

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-488075

ABSTRACT

The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies reveal that the Omicron BA.2 spike trimer have 11-fold and 2-fold higher potency to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to have efficient inhibition of Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants from human-cat-mouse-human circle, which could have important implications in establishing an effective strategy in combating viral infection.

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-483948

ABSTRACT

Severe injuries following viral infection cause lung epithelial destruction with the presence of ectopic basal progenitor cells (EBCs), although the exact function of EBCs remains controversial. We and others previously showed the presence of ectopic tuft cells in the disrupted alveolar region following severe influenza infection. Here, we further revealed that the ectopic tuft cells are derived from EBCs. This process is amplified by Wnt signaling inhibition but suppressed by Notch inhibition. Further analysis revealed that p63-CreER labeled population de novo arising during regeneration includes alveolar epithelial cells when Tamoxifen was administrated after viral infection. The generation of the p63-CreER labeled alveolar cells is independent of tuft cells, demonstrating segregated differentiation paths of EBCs in lung repair. EBCs and ectopic tuft cells can also be found in the lung parenchyma post SARS-CoV-2 infection, suggesting a similar response to severe injuries in humans.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324514

ABSTRACT

Background: The potentially devastating impact of novel coronavirus disease 2019 (COVID-19) has led to wide-spread concern about how individuals’ mental health will be affected. Evidence suggests that mental health in the general population has worsened due to enforced isolation during this pandemic, but it remains unknown how lockdown measures have specifically affected the wellbeing of children and adolescents.Methods: This longitudinal study investigated the psychological impact and mental health status of 1349 adolescents before, during and after the Chinese lockdown from 21 January 2020 to 13 April 2020 and identified risk and protective factors.Outcomes: Counter to our expectations, during the lockdown, school closures had a beneficial effect by reducing depression and anxiety symptoms, whereas the lockdown itself, online learning, and tracking of health information worsened these outcomes as expected. Compared with before the pandemic, unexpectedly, an overall decrease in depressive and anxiety symptoms, state anhedonia, and bullying victimization were found before, during and after lockdown. Protective factors included positive attributional style, whereas COVID-19-related stressors, anhedonia, negative attributional style, bullying, bullying victimization and schizotypal personality traits were potential risk factors.Interpretation: The decrease in emotional and behavioural problems relative to previous trends indicated that school closures may have improved the mental health of adolescents in China overall. The results investigated risk and protective factors related to COVID-19 that may better protect children and adolescents. Funding: Social Science Foundation of Hunan ProvinceDeclaration of Interests: There are no conflicts of interest specifically related to this work.Ethics Approval Statement: The study was approved by the Wenzhou Medical University ethics committee (2020-131).

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309023

ABSTRACT

Background: The COVID-19 pandemic is a major health crisis has led to adverse mental health consequences in the general public, medical staff, and individual in self isolation. In order to stop transmission of the virus and save lives, Fangcang shelter hospitals were developed and used for the first time in China. However, there is no research on mental health problems in Fangcang shelter hospitals patients during the COVID-19 outbreak. The aim of this study was to survey the prevalence and major influencing factors of anxiety, depression among the hospitalized Coronavirus Disease 2019 (COVID-19) cases in Fangcang shelter hospital. Methods From February 23rd, 2020, to February 26th, 2020, we obtained the information of demographic data, clinical symptoms, and assessed the mental health status, sleep quality by using an online questionnaire including self-rating anxiety scale (SAS), self-rating depressive scale (SDS) and pittsburgh sleep quality index (PSQI) at Jianghan Fangcang shelter hospital. We assessed the prevalence of anxiety, depression symptoms and poor sleep quality via the scores of SAS, SDS and PSQI. We explored the influencing factors of anxiety and depression in COVID-19 patients using multivariable logistic regression models. Results We collected data from 307 COVID-19 patients in Jianghan Fangcang shelter hospital. The prevalence of anxiety, depression symptoms were 18.6% and 13.4%, respectively. Poor Sleep quality, number of current physical symptoms ≥ 2 were independent risk factors for anxiety symptoms ( P  < 0.05);female, family member confirmed COVID-19, number of current physical symptoms ≥ 2 were independent risk factors for depression symptoms ( P  < 0.05). PSQI scores were significant positively associate with SAS scores and SDS scores ( P ༜ 0.05). Conclusions Anxiety and depression are common among the COVID-19 patients in Fangcang shelter hospital. Those with more current physical symptoms, poor sleep quality are more likely to have anxiety. Females, those with their family members diagnosed with COVID-19, more current physical symptoms are more vulnerable to depression symptom. Our findings can be used to formulate targeted psychological interventions to reduce adverse psychological impacts in Fangcang shelter hospital during the outbreak of epidemic disease in the future.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316928

ABSTRACT

Background: The chest computed tomography (CT) had been used to define the diagnostic and discharge criteria for COVID-19. However, it is difficult to determine the suitability for discharge of a patient with COVID-19 based on CT features in a clinical setting. Deep learning (DL) technology has demonstrated great success in the medical imaging. Purpose: This study applied the novel deep learning (DL) on chest computed tomography (CT) of COVID-19 patients with consecutive negative respiratory pathogen nucleic acid test results at a “square cabin” hospital in Wuhan, China, with the intent to standardize criteria for discharge. Methods: : The study included 270 patients (102men, 168 women;mean age, 51.9 ± 15.6[18–65] years) who had two consecutive negative respiratory pathogen tests (sampling interval: ≥1 day) and underwent low-dose CT 1 day after the first negative test, with strict adherence to epidemic prevention standards. The chest CT of COVID-19 patients with negative nucleic acid tests were evalued by DL, and the standard for discharge was a total volume ratio of lesions to lung of less than 50% determined by DL. Results: : The average intersection over union is 0.7894. Fifty-seven (21.1%) and 213 (78.9%) patients exhibited normal lung findings and pneumonia, respectively. 54.0% (115/213) involved mild interstitial fibrosis. 18.8% (40/213) had total volume ratio of lesions to lung of more than and equal to 50% according to our severity scale and were monitored continuously in hospital, and three cases of which had a positive follow-up nucleic acid test during hospital observation. None of the 230 discharged cases later tested positive or exhibited pneumonia progression. Conclusions: : The novel DL enables the accurate management of COVID-19 patients and can help avoid cluster transmission or exacerbation due to patients with false negitive acid test.

8.
Preprint in English | bioRxiv | ID: ppbiorxiv-474273

ABSTRACT

The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7{degrees}C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.

9.
Preprint in English | bioRxiv | ID: ppbiorxiv-437123

ABSTRACT

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections. One-Sentence SummaryPrevalence and durability of SARS-CoV-2-specific IgG responses and neutralizing capacities correlate with COVID-19 symptoms.

10.
Preprint in English | medRxiv | ID: ppmedrxiv-21249417

ABSTRACT

OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (Q-14) plus standard care compared with standard care alone in adult with coronavirus disease 2019 (COVID-19). Study DESIGNSingle-center, open label, randomised controlled trial. SETTINGWuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS204 patients with laboratory confirmed COVID-19 were randomised in to treatment group and control group, which was 102 patients each group. INTERVENTIONSIn treatment group, Q-14 was administrated at 10g (granules), twice daily for 14 days and plus standard care. In control group, patients were given standard care alone for 14 days. MAIN OUTCOME MEASUREThe primary outcome was conversion time of SARS-CoV-2 viral assay. Adverse events were analyzed in the safety population. RESULTSAmong 204 patients, 195 were analyzed according to the intention to treat principle. There were 149 patients (71 vs. 78 in treatment group and control group respectively) turning to negative via SARS-CoV-2 viral assay. No statistically significance showed in conversion time between treatment group and control group (FAS: Median (IQR): 10.00 (9.00-11.00) vs. 10.00 (9.00-11.00); Mean rank: 67.92 vs. 81.44; P=0.051.). Time to recovery of fever was shorter in treatment group as compared in control group. The disappearance rate of symptom in cough, fatigue, chest discomfort was significantly higher in treatment group. In chest computed tomography (Chest CT) examinations, overall evaluation of chest CT examination after treatment compared with baseline showed more patients improved in treatment group .There were no significant differences in the other outcomes. CONCLUSIONAdministration of Q-14 on standard care for COVID-19 was useful for improvement of symptoms (such as fever, cough, fatigue and chest discomfort), while did not result in a significantly higher probability of negative conversion of SARS-CoV-2 viral assay. No serious adverse events were reported. TRIAL REGISTRATIONChiCTR2000030288

11.
Preprint in English | medRxiv | ID: ppmedrxiv-20248377

ABSTRACT

The global spread of COVID-19 seriously endangers human health and even lives. By predicting patients individualized disease development and further performing intervention in time, we may rationalize scarce medical resources and reduce mortality. Based on 1337 multi-stage ([≥]3) high-resolution chest computed tomography (CT) images of 417 infected patients from three centers in the epidemic area, we proposed a random forest + cellular automata (RF+CA) model to forecast voxel-level lesion development of patients with COVID-19. The model showed a promising prediction performance (Dice similarity coefficient [DSC] = 71.1%, Kappa coefficient = 0.612, Figure of Merit [FoM] = 0.257, positional accuracy [PA] = 3.63) on the multicenter dataset. Using this model, multiple driving factors for the development of lesions were determined, such as distance to various interstitials in the lung, distance to the pleura, etc. The driving processes of these driving factors were further dissected and explained in depth from the perspective of pathophysiology, to explore the mechanism of individualized development of COVID-19 disease. The complete codes of the forecast system are available at https://github.com/keyunj/VVForecast_covid19.

12.
Preprint in English | bioRxiv | ID: ppbiorxiv-383463

ABSTRACT

An unaddressed key question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of immunity for which specific T cell responses against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an indispensable element. Being situated in Wuhan where the pandemic initiated enables us to conduct the longest analyses of memory T cell responses against SARS-CoV-2 in COVID-19 convalescent individuals (CIs). Magnitude and breadth of SARS-CoV-2 memory CD4 and CD8 T cell responses were heterogeneous between patients but robust responses could be detected up to 9 months post disease onset in most CIs. Loss of memory CD4 and CD8 T cell responses were observed in only 16.13% and 25.81% of CIs, respectively. Thus, the overall magnitude and breadth of memory CD4 and CD8 T cell responses were quite stable and not inversely correlated with the time from disease onset. Interestingly, the only significant decrease in the response was found for memory CD4 T cells in the first 6-month post COVID-19 disease onset. Longitudinal analyses revealed that the kinetics of SARS-CoV-2 memory CD4 and CD8 T cell responses were quite heterogenous between patients. Loss of memory CD4 T cell responses was observed more frequently in asymptomatic cases than after symptomatic COVID-19. Interestingly, the few CIs in which SARS-CoV-2-specific IgG responses disappeared showed more durable memory CD4 T cell responses than CIs who remained IgG-positive for month. Collectively, we provide the first comprehensive characterization of the long-term memory T cell response in CIs, suggesting that SARS-CoV-2-specific T cell immunity is long-lasting in the majority of individuals.

13.
Preprint in English | bioRxiv | ID: ppbiorxiv-363812

ABSTRACT

SARS-CoV-2 has caused a global pandemic of COVID-19 that urgently needs an effective treatment. Nucleoside analog drugs including favipiravir have been repurposed for COVID-19 despite of unclear mechanism of their inhibition of the viral RNA polymerase (RdRp). Here we report the cryo-EM structures of the viral RdRp in complex with favipiravir and two other nucleoside inhibitor drugs ribavirin and penciclovir. Ribavirin and the ribosylated form of favipiravir share a similar ribose scaffold that is distinct from penciclovir. However, the structures reveal that all three inhibitors are covalently linked to the primer strand in a monophosphate form despite the different chemical scaffolds between favipiravir and penciclovir. Surprisingly, the base moieties of these inhibitors can form mismatched pairs with the template strand. Moreover, in view of the clinical disadvantages of remdesivir mainly associated with its prodrug form, we designed several orally-available remdesivir parent nucleoside derivatives, including VV16 that showed 5-fold more potent than remdesivir in inhibition of viral replication. Together, these results demonstrate an unexpected promiscuity of the viral RNA polymerase and provide a basis for repurpose and design of nucleotide analog drugs for COVID-19. One Sentence SummaryCryo-EM structures of the RNA polymerase of SARS-CoV-2 reveals the basis for repurposing of old nucleotide drugs to treat COVID-19.

14.
PLoS One ; 15(8): e0238416, 2020.
Article in English | MEDLINE | ID: covidwho-732991

ABSTRACT

Fangcang shelter hospitals were established in China during the coronavirus disease 2019 (COVID-19) pandemic as a countermeasure to stop the spread of the disease. To our knowledge, no research has been conducted on mental health problems among patients in Fangcang shelter hospitals. This study aimed to determine the prevalence and major influencing factors of anxiety and depressive symptoms among COVID-19 patients admitted to Fangcang shelter hospitals. From February 23, 2020, to February 26, 2020, we obtained sociodemographic and clinical characteristics information of COVID-19 patients in Jianghan Fangcang Shelter Hospital (Wuhan, China) and assessed their mental health status and sleep quality. Data were obtained with an online questionnaire. The questionnaire consisted of a set of items on demographic characteristics, a set of items on clinical characteristics, the Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Pittsburgh Sleep Quality Index. Three hundred seven COVID-19 patients who were admitted to Jianghan Fangcang Shelter Hospital participated in this study. The prevalence of anxiety and depressive symptoms were 18.6% and 13.4%, respectively. Poor sleep quality and having ≥ two current physical symptoms were independent risk factors for anxiety symptoms. Female sex, having a family member with confirmed COVID-19, and having ≥ two current physical symptoms were independent risk factors for depressive symptoms. Anxiety and depressive symptoms were found to be common among COVID-19 patients in Fangcang Shelter Hospital, with some patients being at high risk.


Subject(s)
Anxiety/epidemiology , Coronavirus Infections/psychology , Depression/epidemiology , Pneumonia, Viral/psychology , Adult , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Cross-Sectional Studies , Female , Hospitals, Special , Humans , Male , Middle Aged , Mobile Health Units , Pandemics , Pneumonia, Viral/epidemiology , Prevalence , Risk Factors , SARS-CoV-2
15.
Preprint in English | medRxiv | ID: ppmedrxiv-20179358

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.

16.
Preprint in English | bioRxiv | ID: ppbiorxiv-262329

ABSTRACT

SARS-CoV-2 infection induces a T cell response that most likely contributes to virus control in COVID-19 patients, but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B, as well as perforin within different effector CD8+ T cell subsets. PD-1 expressing CD8+ T cells also produced cytotoxic molecules during acute infection indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provides valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development. ImportanceCytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients.

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-242511

ABSTRACT

Neutralizing agents against SARS-CoV-2 are urgently needed for treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domain binders with high affinity toward neutralizing epitopes without the need for high-resolution structural information. We constructed a VH-phage library and targeted a known neutralizing site, the angiotensin-converting enzyme 2 (ACE2) binding interface of the trimeric SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified 85 unique VH binders to two non-overlapping epitopes within the ACE2 binding site on Spike-RBD. This enabled us to systematically link these VH domains into multivalent and bi-paratopic formats. These multivalent and bi-paratopic VH constructs showed a marked increase in affinity to Spike (up to 600-fold) and neutralization potency (up to 1400-fold) on pseudotyped SARS-CoV-2 virus when compared to the standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with half-minimal inhibitory concentration (IC50) of 4.0 nM (180 ng/mL). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain bound an RBD at the ACE2 binding site, explaining its increased neutralization potency and confirming our original design strategy. Our results demonstrate that targeted selection and engineering campaigns using a VH-phage library can enable rapid assembly of highly avid and potent molecules towards therapeutically important protein interfaces.

18.
World J Clin Cases ; 8(14): 2950-2958, 2020 Jul 26.
Article in English | MEDLINE | ID: covidwho-692833

ABSTRACT

BACKGROUND: A large number of pneumonia cases due to coronavirus disease 2019 (COVID-19) have been first reported in China. Meanwhile, the virus is sweeping all around the world and has infected millions of people. Fever and pulmonary symptoms have been noticed as major and early signs of infection, whereas gastrointestinal symptoms were also observed in a significant portion of patients. The clinical investigation of disease onset was underestimated, especially due to the neglection of cases presenting with gastrointestinal symptoms. AIM: To characterize the clinical features of coronavirus-infected patients with gastrointestinal symptoms as initial symptoms. METHODS: This is a retrospective, single-center case series of the general consecutive hospitalized patients with confirmed COVID-19 at Wuhan Union Hospital from February 2, 2020 to February 13, 2020. According to their initial symptoms, these patients were classified into two groups. Patients in group one presented with pulmonary symptoms (PS) as initial symptoms, and group two presented with gastrointestinal symptoms (GS). Epidemiological, demographic, clinical, laboratory, and treatment data were collected for analysis. RESULTS: Among the 50 patients recruited, no patient has been admitted to intensive care units, and no patient died during the study. The duration of hospitalization was longer in the GS group than in the PS group (12.13 ± 2.44 vs 10.00 ± 2.13, P < 0.01). All of the 50 patients exhibited decreased lymphocytes. However, lymphocytes in the GS group were significantly lower compared to those in the PS group (0.94 ± 0.06 vs 1.04 ± 0.15, P < 0.01). Procalcitonin and hs-CRP were both significantly higher in the GS group than in the PS group. Accordingly, the duration of viral shedding was significantly longer in the GS group compared to the PS group (10.22 ± 1.93 vs 8.15 ± 1.87, P < 0.01). CONCLUSION: COVID-19 patients presenting with gastrointestinal symptoms as initial symptoms need more days of viral shedding and hospitalization than the patients presenting with pulmonary symptoms.

19.
Preprint in English | medRxiv | ID: ppmedrxiv-20159178

ABSTRACT

Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected. The positivity rate and magnitude of IgM-S and IgG-N responses increased rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset were associated with virus control and IgG-S titers correlated closely with the capacity to neutralize SARS-CoV-2. While specific IgM-S/N became undetectable 12 weeks after disease onset in most patients, IgG-S/N titers showed an intermediate contraction phase, but stabilized at relatively high levels over the six months observation period. At late time points the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies was still over 70%. Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity.

20.
Preprint in English | medRxiv | ID: ppmedrxiv-20155150

ABSTRACT

System-wide molecular characteristics of COVID-19, especially in those patients without comorbidities, have not been fully investigated. We compared extensive molecular profiles of blood samples from 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Amongst the major findings, asymptomatic patients were characterized by highly activated anti-virus interferon, T/natural killer (NK) cell activation, and transcriptional upregulation of inflammatory cytokine mRNAs. However, given very abundant RNA binding proteins (RBPs), these cytokine mRNAs could be effectively destabilized hence preserving normal cytokine levels. In contrast, in critically ill patients, cytokine storm due to RBPs inhibition and tryptophan metabolites accumulation contributed to T/NK cell dysfunction. A machine-learning model was constructed which accurately stratified the COVID-19 severities based on their multi-omics features. Overall, our analysis provides insights into COVID-19 pathogenesis and identifies targets for intervening in treatment.

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