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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22268821

ABSTRACT

We estimated the probability of undetected emergence of the SARS-CoV-2 Omicron variant in 25 low and middle-income countries (LMICs) prior to December 5, 2021. In nine countries, the risk exceeds 50%; in Turkey, Pakistan and the Philippines, it exceeds 99%. Risks are generally lower in the Americas than Europe or Asia.

2.
Preprint in English | bioRxiv | ID: ppbiorxiv-474084

ABSTRACT

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21267507

ABSTRACT

Superspreading in transmission is a feature of SARS-CoV-2 transmission. We conducted a systematic review and meta-analysis on globally reported dispersion parameters of SARS-CoV-2. The pooled estimate was 0.55 (95% CI: 0.30, 0.79). The study location and method were found to be important drivers for its diversity.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21267410

ABSTRACT

Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.

5.
Preprint in English | EuropePMC | ID: ppcovidwho-292562

ABSTRACT

Background: As of April 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead in China. We aimed to understand environmental factors leading to COVID-19-related mortality in non-Hubei region.Methods:: We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level case fatality rate (CFR) of COVID-19 outside Hubei, China.Results: Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P <0.001) and humidity (r=-0.607, P =0.002), while latitude was positively correlated with the CFR (r=0.636, P =0.001). There were no statistically significant associations between CFR and the social environment factors.Conclusion: Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

7.
Preprint in English | EuropePMC | ID: ppcovidwho-292329

ABSTRACT

Background: :The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading globally. The information regarding the characteristics and prognosis of antibody non-responders with COVID-19 is scarce. Method: In this retrospective, single-center study, we included all the patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1921 patients were divided into the antibody-negative group (n=94) and antibody-positive group (n=1827), and the 1:1 propensity score matching (PSM) was used to match two groups. Results: : In the antibody negative group, 40 patients (42.6%) were male, 54 patients (57.4%) were female, and 49 patients (52.1%) were older than 65 years old. Cough was the most common symptoms in the antibody negative group. White blood cell counts (WBC) 6.6×109/L [5.0, 9.1], Neutrophils 4.3×109/L [3.1, 6.6], C-reactive protein 7.3 mg/L [1.3, 49.0], Procalcitonin (PCT) 0.1 ng/mL [0.0, 0.2], Interleukin-6 (IL-6) 64.2 [1.5, 28.7], Lactate dehydrogenase (LDH) 193.8 U/L [154.9,260.6], Creatine kinase 60.5 U/L [40.5, 103.7], Creatine kinase isoenzyme 10.3 ng/mL [8.2, 14.5], Urea nitrogen 5.3 mmol/L [4.0, 8.7] and Creatinine 77.7 μmol/L [60.6, 98.7] were significantly higher in antibody negative patients than in antibody positive group (P<0.005). The days of nucleic acid negative conversion in the antibody negative group was shorter than that in the antibody positive group (P < 0.001). Meanwhile, the hospitalization time of antibody negative patients was shorter than that of antibody positive patients (8.0 [6.0, 10.0] VS 13.0 [8.2, 23.0], P < 0.001). Conclusion: Some COVID-19 patients without specific antibodies had mild symptoms, but the inflammatory reaction caused by innate clinical immunity was more intense than those with antibodies, and the virus was cleared faster. The production of specific antibodies was unnecessary for SARS-CoV-2 clearance, and non-specific immune responses played an essential role in virus clearance.

8.
J Ultrasound Med ; 2021 Nov 05.
Article in English | MEDLINE | ID: covidwho-1499289
9.
Preprint in English | medRxiv | ID: ppmedrxiv-21264371

ABSTRACT

We recently performed 568 rapid neutralizing antibody (NAb) tests on 164 fully vaccinated individuals who received either Moderna or Pfizer COVID-19 vaccine regimens over 7 weeks. The NAb levels against the wild type (WA1/2020), Delta, and Kappa variants were measured and compared. Depending on each individuals medical condition and vaccination status, the NAb levels for most of the fully vaccinated people decreased within 2-6 months, while a small number of individuals either generated non-detectable amount of NAbs after full vaccination (e.g., immunocompromised), or had high NAb levels lasting beyond 6 months. Since the NAb levels vary significantly among different individuals and decrease over time, the deployment of a low-cost rapid test to monitor NAb levels against both the wild type and emerging variants among fully vaccinated individuals can play a very crucial role to control the current pandemic. Our study provides an example of using such a rapid NAb test to fill this currently unmet medical need.

10.
Front Immunol ; 12: 635701, 2021.
Article in English | MEDLINE | ID: covidwho-1399135

ABSTRACT

Serological testing is a powerful tool in epidemiological studies for understanding viral circulation and assessing the effectiveness of virus control measures, as is the case of SARS-CoV-2, the pathogenic agent of COVID-19. Immunoassays can quantitatively reveal the concentration of antiviral antibodies. The assessment of antiviral antibody titers may provide information on virus exposure, and changes in IgG levels are also indicative of a reduction in viral circulation. In this work, we describe a serological study for the evaluation of antiviral IgG and IgM antibodies and their correlation with antiviral activity. The serological assay for IgG detection used two SARS-CoV-2 proteins as antigens, the nucleocapsid N protein and the 3CL protease. Cross-reactivity tests in animals have shown high selectivity for detection of antiviral antibodies, using both the N and 3CL antigens. Using samples of human serum from individuals previously diagnosed by PCR for COVID-19, we observed high sensitivity of the ELISA assay. Serological results with human samples also suggest that the combination of higher titers of antiviral IgG antibodies to different antigen targets may be associated with greater neutralization activity, which can be enhanced in the presence of antiviral IgM antibodies.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/prevention & control , Immunologic Surveillance , SARS-CoV-2/immunology , Animals , Antibodies, Viral/blood , Antigens, Viral/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/standards , Cross Reactions , Dengue Virus/immunology , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Mice , Mice, Inbred BALB C , Sensitivity and Specificity , Zika Virus/immunology
11.
Preprint in English | medRxiv | ID: ppmedrxiv-21261735

ABSTRACT

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines. One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.

12.
J Ultrasound Med ; 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1359805

ABSTRACT

Coronavirus disease 2019 has become a widespread public health crisis across the globe, requiring multiple approaches to containment, treatment, and prevention. Vaccines are an important tool to prevent morbidity and mortality from this devastating virus. Ensuring direct administration of vaccines into target tissue helps provide an optimal immune response while decreasing unintended adverse effects. Point-of-care ultrasound can better assist clinicians to determine appropriate needle length and penetration level especially in special populations. Examples include patients who are obese, pregnant, or with refractory lymphedema, and those living in areas where needle supply is unstable or insufficient.

13.
Preprint in English | medRxiv | ID: ppmedrxiv-21261544

ABSTRACT

ImportanceWhether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults [≥]60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults[≥]60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses. InterventionsTwo formulations (3 g, and 6 g) were used in phase 1 trial, and an additional formulation of 1.5 g was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose. Main outcomes and measuresGeometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination. ResultsNeutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 g group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity. Conclusion and relevanceNeutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults. Trial registrationClinicalTrials.gov (NCT04383574).

14.
Natural Science ; 12(11):717-725, 2020.
Article in English | CAB Abstracts | ID: covidwho-1319796

ABSTRACT

Around the end of 2019, a new viral species caused large-scale transmissions and infections, discovered in Wuhan (WHO Emergencies Preparedness, Response, 2020) and subsequently around the world (WHO COVID-19 Disease Dashboard, 2020). Symptoms caused include coughing, shortness of breath, and fever. Around 1% to 5% (Worldometer, 2020) of confirmed infections have resulted in deaths, mainly due to severe respiratory failure (CDC, 2020). Genealogical tree studies of the new virus strains have later revealed them to be phylogenetically intimate relatives of the Severe Acute Respiratory Syndrome Coronavirus, namely (SARS-CoV), first identified in 2003 [1]. This new virus has been named SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV) (Gorbalenya et al., 2020) on February 11th, 2020.

15.
Preprint in English | medRxiv | ID: ppmedrxiv-21258114

ABSTRACT

Seroconversion to SARS-CoV-2 has been widely studied to evaluate infection spreading for epidemiological purpose, or even in studies of protective immunity in convalescent or vaccinated individuals. The viral particle has an envelope harboring the spike glycoprotein, which can be used as an antigen for assay development, to detect antiviral antibodies to SARS-CoV-2. Since several vaccines encode a spike subunit, the full length spike-based immunoassay should be a universal tool to evaluate seroconversion. In this manuscript, we propose a low-cost ELISA that can be used to detect antiviral IgG to SARS-CoV-2 in human serum.

16.
Clin Transplant ; 35(8): e14330, 2021 08.
Article in English | MEDLINE | ID: covidwho-1241002

ABSTRACT

INTRODUCTION: The COVID-19 pandemic continues, with a late hyperinflammatory phase. The immunosuppressive therapy used in heart transplant patients, in theory, could reduce inflammation, thus benefitting patients with COVID-19. So far, however, there is still very little literature on this subject. METHODS: This is a single-center retrospective study. We described laboratory parameters and clinical outcomes from 11 heart transplant patients with COVID-19 assisted at Dante Pazzanese Institute of Cardiology between March and July 2020. RESULTS: Patients with ages of between 35 and 79 years were enrolled, and heart transplantation ranged from 3 to 264 months. The main comorbidities were diabetes mellitus (9/11; 81.8%), hypertension (10/11; 90.9%), and chronic renal disease (6/11; 54.5%). Cyclosporine A was used in 10 (90.9%) patients, mycophenolate mofetil in 9 (81.8%) patients, and mTOR inhibitor in 5 (45.5%) patients. Fever and cough were observed in 8 (72.7%) patients, and dyspnea and gastrointestinal symptoms in 5 (45.5%) patients. Lymphopenia was observed in 10 (90.9%) patients and thrombocytopenia in 5 (45.5%) patients. The higher level of troponin associated with chest tomography above 50% of bilateral pulmonary infiltrates with ground-glass opacity (GGO) was observed in those with the worst outcomes. Nine patients needed intensive care, and hospital stay ranged from 4 to 21 days, with 2 (18.2%) patients requiring vasopressor drugs and mechanical ventilation, and three (27.3%) patients dying due to COVID-19 complications. CONCLUSION: Heart transplant patients had similar symptoms and outcomes as the general population; immunosuppressive therapy seems not to have protected them. Patients who presented higher levels of troponin and D-dimer, associated with greater GGO pulmonary infiltrates, had worse outcomes. More studies with larger cohorts may clarify immunosuppressive effects on COVID-19 outcomes.


Subject(s)
COVID-19 , Heart Transplantation , Brazil , Heart Transplantation/adverse effects , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
17.
European Journal of Inflammation (Sage Publications, Ltd.) ; : 1-13, 2021.
Article in English | Academic Search Complete | ID: covidwho-1136205

ABSTRACT

COVID-19 is spreading exponentially. In order to optimize medical resources allocation and reduce mortality, biomarkers are needed to differentiate between COVID-19 patients with or without severe diseases early as possible. We searched Ovid MEDLINE(R), Ovid EMBASE, CNKI, Wanfang, VIP databases, the Cochrane Library, and medRxiv for primary articles in English or Chinese up to March 30, 2020 to systematically evaluate the risk factors for severe patients in China. Mean difference or standardize mean difference and odds ratio with 95% confidence intervals were performed by random-effect or fixed models in cases of significant heterogeneity between studies. We used I 2 to evaluate the magnitude of heterogeneity. A total of 54 articles involving about 7000 patients were eligible for this meta-analysis. In total, 52 of 67 parameters between severe and non-severe cases were significantly different. Elderly male patients with comorbidities including hypertension, diabetes, chronic obstructive pulmonary disease (COPD) cardiovascular disease, cerebrovascular disease, chronic kidney disease, or cancer were more common in severe COVID-19 patients. Regarding the clinical manifestations on admission, fever, cough, expectoration, dyspnea, chest distress, fatigue, headache, chills, anorexia, or abdominal pain were more prevalent in severe COVID-19 patients. The results of the clinical examination showed that high C-reactive protein (CRP), high lactate dehydrogenase (LDH), high D-dimer, and decreased T lymphocytes cells subsets, decreased lymphocyte may help clinicians predict the progression of severe illness in patients with COVID-19. Our findings will be conducive for clinician to stratify the COVID-19 patients to reduce mortality under the relative shortage of medical resources. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

18.
Experimental & Therapeutic Medicine ; 21(4):N.PAG-N.PAG, 2021.
Article in English | Academic Search Complete | ID: covidwho-1130015

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly infectious type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly become a global pandemic. COVID-19, SARS and Middle East respiratory syndrome (MERS) are all caused by members of the Coronaviridae family. As expected, emerging genetic and clinical evidence from patients with COVID-19 has indicated that the pathway of infection is similar to that of SARS and MERS. Additionally, much like SARS and MERS, chest imaging serves an important role in the diagnosis, management and follow-up of patients with COVID-19. Although these related viruses present a similar pneumonic pathogenesis, the imaging results have distinguishable features. The current review evaluated the imaging results of patients with SARS and MERS and explored the potential similarities and differences among patients with COVID-19, SARS and MERS at early, progressive, severe and recovery stages, with the aim of improving our understanding of SARS-CoV-2 infections by comparing the features of COVID-19 images with those of SARS and MERS. The current review assessed whether imaging results had implications for the administration of corticosteroids as treatment for COVID-19. Whether corticosteroids can inhibit inflammatory cytokine storms and reduce the mortality of patients with viral pneumonia remains controversial. However, his review may help radiologists and clinicians to identify viral pneumonia and guide appropriate COVID-19 treatment. [ABSTRACT FROM AUTHOR] Copyright of Experimental & Therapeutic Medicine is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

19.
Preprint | SSRN | ID: ppcovidwho-5138

ABSTRACT

Background: Tocilizumab is reported to be able to attenuate the "cytokine storm" in COVID-19 patients. We tried to ascertain the effectiveness and safety of tocilizumab in COVID-19 and identify patients most likely to be benefit from the treatment. Methods: This was a randomized, controlled, open-label, multicenter trial at 6 hospitals in Anhui and Hubei. Patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care, or standard care alone. The first dose of tocilizumab was 400 mg, diluted in 100 ml 0.9% saline, and intravenous dripped in more than 1 h. A second dose was given if a patient remained febrile for 24 hours after the first dose. The primary endpoint was the cure rate. Primary analysis was done in the intention -to -treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: Between Feb 13, 2020, and March 13, 2020, 65 patients were enrolled and randomly assigned to a treatment group (33 to tocilizumab and 32 to the controls). One patient in the control group, who aggravated severely 3 days after randomization, was transferred to the tocilizumab group. The cure rate in tocilizumab group was higher than that in the controls but not significant (94.12% vs 87.10%, P=0.4133). Adverse events were recorded in 20 (58.82%) of 34 tocilizumab recipients versus 4 (12.90%) of 31 in the controls. No serious adverse events were reported in tocilizumab group. Interpretation: Tocilizumab treatment did not increase the cure rate of COVID-19. A large scale of study enrolling more patients is needed. However,tocilizumab can improve oxygenation without significant influence on the time virus load tunes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab should be recommended for better disease management. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (Number: ChiCTR2000029765). Funding: This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province (grant number: 202004a07020001) and the China National Center for Biotechnology Development (grant number: 2020YFC0843800).

20.
Preprint in English | medRxiv | ID: ppmedrxiv-21249384

ABSTRACT

A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in all 15 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom by December 7th.

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