A Prospective Multicenter Randomized Study State of Humoral Immunity after a New Coronavirus Infection (COVID-19) of a Mild or Asymptomatic Course

Background.The rapid spread of COVID-19 in the world, the severity of disease, high morbidity and mortality have rightly made the COVID-19 pandemic a major threat to humanity. Therefore, one of the most urgent problems for practical health care is the issue of development of immunity for COVID-19 survivors, the possibility of re-infection, and the appropriateness of vaccination. The article presents the interim results of the study was named RESPONSE devoted to assessing the immunity for 90 days from patients that survived COVID-19 in a mild or asymptomatic course. Aims to study of the dynamics of generation of SARS-CoV-2 adhesive (S) protein neutralizing antibodies (IgG) and specificities of humoral immunity from COVID-19 survivors with light and asymptomatic form of disease in depending on gender and age. Materials and methods.Joint study by the Military Medical Academy n.a. S.M. Kirov and Laboratory Service Helix is being undertaken in the period from January 06, 2020 to August 1, 2021 on the basis of Academy clinics and Helix diagnostic centers in Saint Petersburg. The study was included 1109 males and females aged 18 to 70 (average age 38.2), who received to outpatient treatment of light and asymptomatic form of New Coronavirus Infection. All patients included in the investigation were done survey of quantitative neutralizing antibodies of class IgG to S-protein SARS-CoV-2 content in venous blood in 30, 45, 60 and 90 days from the last result of positive polymerase chain reaction with reverse transcription (OT-PCR) for determining nucleic acid SARS-CoV-2 in biological material by immunochemiluminescent analysis (LIAISON XL, DiaSorin S.p.A., made in Italy). Results.The IgG class antibody to the S-protein SARS-CoV-2 were not diagnosed 30 days after the survived infection only 0.9% of young women (1844 years) and 0.8% of men in the same age bracket. In other age groups, antibodies were defined in all participants of study. Titer of IgG gradually increases to peak concentration after 45 days, its kept at this level to the 60th day, and then it has a decreasing trend after 90 days from the onset of the disease. Conclusions.The results show the timing of generation and duration of the humoral response in survived patients COVID-19 in a mild or asymptomatic form. For 45 days, antibodies were determined in all participants of the study, reflecting the development of post-infectious humoral immunity, which was maintained in patients with the mild or asymptomatic forms of COVID-19 at least 3 months.

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Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant

10.1101/2020.10.08.332544 ◽

2020 ◽

Cited By ~ 1

Author(s):

Cheryl Yi-Pin Lee ◽

Siti Naqiah Amrun ◽

Rhonda Sin-Ling Chee ◽

Yun Shan Goh ◽

Tze-Minn Mak ◽

...

Keyword(s):

Point Mutation ◽

Humoral Immunity ◽

Neutralizing Antibodies ◽

Transmission Rate ◽

Single Point ◽

Cross Protection ◽

Viral Fitness ◽

Reference Sequence ◽

Single Point Mutation ◽

S Protein

ABSTRACTThe emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions.IMPORTANCERandom mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant.

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Structure of herd immunity to SARS-COV-2 in the Krasnoyarsk region population in the COVID-19 epidemic

Acta biomedica scientifica ◽

10.29413/abs.2021-6.3.23 ◽

2021 ◽

Vol 6 (3) ◽

pp. 227-238

Author(s):

A. Yu. Popova ◽

E. B. Ezhlova ◽

A. A. Melnikova ◽

V. S. Smirnov ◽

L. V. Lyalina ◽

...

Keyword(s):

Humoral Immunity ◽

Online Survey ◽

Statistical Significance ◽

Venous Blood ◽

Herd Immunity ◽

Age Groups ◽

Rank Correlation ◽

Population Immunity ◽

Formation Of Groups

Purpose. Determination of the SARS-CoV-2 population humoral immunity among the population of the Krasnoyarsk Territory during the COVID-19 epidemic.Materials and methods. The study was carried out as a part of project for assessing population immunity to SARS-CoV-2 among the population of Russian Federation using unified methodology developed by Rospotrebnadzor, with the participation of the Research Institute for Epidemiology and Microbiology named by Pasteur, and taking into account the recommendations of the WHO. The work involved 2907 volunteers, selected by the online survey and randomization by age and territory. All volunteers were divided into 7 age groups: 1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70 and older (70+), including a total 246–449 people. Population immunity testing was carried out during the formation of groups (1st stage), and then twice more, with the interval of 6–8 weeks. Serum was obtained from venous blood samples obtained from volunteers, in which antibodies to the SARS-CoV-2 nucleocapsid were determined by the enzyme immunoassay. The results were analyzed by methods of nonparametric statistics: median, interquartile range, rank correlation coefficient were calculated in the Excel statistical package. The confidence interval to seroprevalence indicators (95% CI) was calculated using the WinPepi statistical package (version 11.65). The statistical significance of the differences was assessed with a probability level of p ≤ 0.05.Results. The seroprevalence of the population of the Krasnoyarsk Territory during the 5-month period of seromonitoring had increased 3.3 times from 12.8% (95% CI 11.3–14.4) to 41.7% (95% CI 39.4–4.0) , while the grouping by age had not revealed any peculiarities throughout the study. The trend towards a decrease in the incidence was formed on the 6th week of 2021. The seroprevalence of convalescents after COVID-19 during the initial testing was 61.5% (95% CI 40,6–79.8), among those who were in contact with patients with COVID-19 or convalescents –23.8% (95% CI 13.9–36.2) . Among the volunteers, 347 seropositive persons were identified, 324 of which were observed asymptomatic course.Conclusion. The structure of the population humoral immunity to SARS-CoV-2 of he population of the Krasnoyarsk Territory has been investigated. It was found that an increase in seroprevalence to 41.7% (95% CI 39.4–4.0) was accompanied by a decrease in morbidity.

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Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)

Kardiologiia ◽

10.18087/cardio.2020.11.n1440 ◽

2020 ◽

Vol 60 (11) ◽

pp. 4-15

Author(s):

V. Yu. Mareev ◽

Ya. A. Orlova ◽

A. G. Plisyk ◽

E. P. Pavlikova ◽

S. T. Matskeplishvili ◽

...

Keyword(s):

Thrombus Formation ◽

Clinical Status ◽

Randomized Study ◽

Lung Damage ◽

Control Group ◽

Virus Elimination ◽

Combine Endpoint ◽

Positive Polymerase Chain Reaction ◽

Number Of Patients ◽

Coronavirus Infection

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

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Prevalence of IgG and Neutralizing Antibodies againstStaphylococcus aureusAlpha-Toxin in Healthy Human Subjects and Diverse Patient Populations

Infection and Immunity ◽

10.1128/iai.00671-17 ◽

2017 ◽

Vol 86 (3) ◽

Cited By ~ 4

Author(s):

Yuling Wu ◽

Xu Liu ◽

Ahmad Akhgar ◽

Jia J. Li ◽

Hoyin Mok ◽

...

Keyword(s):

Young Children ◽

Neutralizing Antibodies ◽

Human Subjects ◽

Age Groups ◽

Surgical Site Infections ◽

Neutralizing Antibody ◽

High Morbidity ◽

Healthy Human ◽

Content Type ◽

Antibody Levels

ABSTRACTStaphylococcus aureuscauses an array of serious infections resulting in high morbidity and mortality worldwide. This study evaluated naturally occurring serum anti-alpha-toxin (anti-AT) antibody levels in human subjects from various age groups, individuals withS. aureusdialysis and surgical-site infections, andS. aureus-colonized versus noncolonized subjects. Anti-AT immunoglobulin G (IgG) and neutralizing antibody (NAb) levels in infants (aged ≤1 year) were significantly lower than those in other populations. In comparison to adolescent, adult, and elderly populations, young children (aged 2 to 10 years) had equivalent anti-AT IgG levels but significantly lower anti-AT NAb levels. Therefore, the development of anti-AT NAbs appears to occur later than that of AT-specific IgG, suggesting a maturation of the immune response to AT. Anti-AT IgG levels were slightly higher inS. aureus-colonized subjects than in noncolonized subjects. The methicillin susceptibility status of colonizing isolates had no effect on anti-AT antibody levels inS. aureus-colonized subjects. The highest anti-AT IgG and NAb levels were observed in dialysis patients with acuteS. aureusinfection. Anti-AT IgG and NAb levels were well correlated in subjects aged >10 years, regardless of colonization or infection status. These data demonstrate that AT elicits a robust IgG humoral response in infants and young children that becomes stable prior to adolescence, matures into higher levels of NAbs in healthy adolescents, and becomes elevated duringS. aureusinfection. These findings may assist in identifying subjects and patient populations that could benefit from vaccination or immunoprophylaxis with anti-AT monoclonal antibodies.

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Impact of Novel Coronavirus (COVID-19) on Pregnant Women: A Review

Coronaviruses ◽

10.2174/2666796701999201116123457 ◽

2020 ◽

Vol 01 ◽

Author(s):

Saima Habeeb ◽

Manju Chugani

Keyword(s):

Pregnant Women ◽

Vertical Transmission ◽

Respiratory Infections ◽

Age Groups ◽

Well Being ◽

Fetal Outcome ◽

Global Public Health ◽

Coronavirus Infection ◽

Novel Coronavirus ◽

The Impact

: The novel coronavirus infection (COVID‐19) is a global public health emergency.Since its outbreak in Wuhan, China in December 2019, the infection has spread at an alarming rate across the globe and humans have been locked down to their countries, cities and homes. As of now, the virus has affected over 20million people globally and has inflicted over 7 lac deaths. Nevertheless, the recovery rate is improving with each passing day and over 14 million people have recuperated so far. The statistics indicate that nobody is immune to the disease as the virus continues to spread among all age groups; newborns to the elders, and all compartmentsincluding pregnant women. However, pregnant women may be more susceptible to this infection as they are, in general, highly vulnerable to respiratory infections. There is no evidence for vertical transmission of the COVID-19 virus among pregnant women, but an increased prevalence of preterm deliveries. Besides this, the COVID-19 may alter immune response at the maternal-fetal interface and affect the well-being of mothers as well as infants. Unfortunately, there is limited evidence available in the open literature regarding coronavirus infection during pregnancy and it now appears that certain pregnant women have infected during the present 2019-nCoV pandemic. In this short communication, we study the impact of the COVID-19 infection on vertical transmission and fetal outcome among pregnant women.

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The discovery of biological subphenotypes in ARDS: a novel approach to targeted medicine?

Journal of Intensive Care ◽

10.1186/s40560-021-00528-w ◽

2021 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Karin Wildi ◽

Samantha Livingstone ◽

Chiara Palmieri ◽

Gianluigi LiBassi ◽

Jacky Suen ◽

...

Keyword(s):

Age Groups ◽

Geographical Location ◽

High Morbidity ◽

Shock State ◽

Pharmacological Agents ◽

New Approach ◽

Novel Approach ◽

Active Research ◽

Targeted Medicine ◽

Core Features

AbstractThe acute respiratory distress syndrome (ARDS) is a severe lung disorder with a high morbidity and mortality which affects all age groups. Despite active research with intense, ongoing attempts in developing pharmacological agents to treat ARDS, its mortality rate remains unaltered high and treatment is still only supportive. Over the years, there have been many attempts to identify meaningful subgroups likely to react differently to treatment among the heterogenous ARDS population, most of them unsuccessful. Only recently, analysis of large ARDS cohorts from randomized controlled trials have identified the presence of distinct biological subphenotypes among ARDS patients: a hypoinflammatory (or uninflamed; named P1) and a hyperinflammatory (or reactive; named P2) subphenotype have been proposed and corroborated with existing retrospective data. The hyperinflammatory subphenotyope was clearly associated with shock state, metabolic acidosis, and worse clinical outcomes. Core features of the respective subphenotypes were identified consistently in all assessed cohorts, independently of the studied population, the geographical location, the study design, or the analysis method. Additionally and clinically even more relevant treatment efficacies, as assessed retrospectively, appeared to be highly dependent on the respective subphenotype. This discovery launches a promising new approach to targeted medicine in ARDS. Even though it is now widely accepted that each ARDS subphenotype has distinct functional, biological, and mechanistic differences, there are crucial gaps in our knowledge, hindering the translation to bedside application. First of all, the underlying driving biological factors are still largely unknown, and secondly, there is currently no option for fast and easy identification of ARDS subphenotypes. This narrative review aims to summarize the evidence in biological subphenotyping in ARDS and tries to point out the current issues that will need addressing before translation of biological subohenotypes into clinical practice will be possible.

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A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples

Scientific Reports ◽

10.1038/s41598-021-94653-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amelia E. Sancilio ◽

Richard T. D’Aquila ◽

Elizabeth M. McNally ◽

Matthew P. Velez ◽

Michael G. Ison ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Venous Blood ◽

Host Cells ◽

Dried Blood Spot ◽

Blood Collection ◽

Widespread Application ◽

Live Virus ◽

Dilution Series ◽

Wide Range ◽

Blood Spot

AbstractThe spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose–response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

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Occupational health risk among healthcare workers during COVID-19 pandemic: actions to limit the risk

Journal of Egyptian Public Health Association ◽

10.1186/s42506-021-00076-z ◽

2021 ◽

Vol 96 (1) ◽

Author(s):

Eman Casper

Keyword(s):

Occupational Health ◽

Health Risk ◽

Healthcare Workers ◽

World Health ◽

High Morbidity ◽

Wuhan City ◽

Coronavirus Infection ◽

Health Organization ◽

Respiratory Droplets ◽

Very High

AbstractThe World Health Organization declared coronavirus infection 2019 (COVID-19) as a pandemic in March 2020. The infection with coronavirus started in Wuhan city, China, in December 2019. As of October 2020, the disease was reported in 235 countries. The coronavirus infection 2019 (COVID-19) is a disease with high morbidity and mortality. As of February 2021, the number of confirmed cases of COVID-19 globally is 102,942,987 and 2,232,233 deaths according to WHO report. This infection is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is a ribonucleic acid (RNA) β-coronavirus. The infection is mainly transmitted through respiratory droplets.Healthcare workers (HCWs) play an essential role at the front lines, providing care for patients infected with this highly transmittable disease. They are exposed to very high occupational health risk as they frequently contact the infective persons. In order to limit the number of infected cases and deaths among healthcare workers, it is crucial to have better awareness, optimistic attitude, efficient PPE, and adequate health practices about COVID-19.

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Amino Acids 1055 to 1192 in the S2 Region of Severe Acute Respiratory Syndrome Coronavirus S Protein Induce Neutralizing Antibodies: Implications for the Development of Vaccines and Antiviral Agents

Journal of Virology ◽

10.1128/jvi.79.6.3289-3296.2005 ◽

2005 ◽

Vol 79 (6) ◽

pp. 3289-3296 ◽

Cited By ~ 59

Author(s):

Choong-Tat Keng ◽

Aihua Zhang ◽

Shuo Shen ◽

Kuo-Ming Lip ◽

Burtram C. Fielding ◽

...

Keyword(s):

Amino Acids ◽

Severe Acute Respiratory Syndrome ◽

Viral Entry ◽

Neutralizing Antibodies ◽

Antiviral Agents ◽

Host Cells ◽

Heptad Repeat ◽

Antigenic Determinants ◽

Amino Acid Residues ◽

S Protein

ABSTRACT The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) interacts with cellular receptors to mediate membrane fusion, allowing viral entry into host cells; hence it is recognized as the primary target of neutralizing antibodies, and therefore knowledge of antigenic determinants that can elicit neutralizing antibodies could be beneficial for the development of a protective vaccine. Here, we expressed five different fragments of S, covering the entire ectodomain (amino acids 48 to 1192), as glutathione S-transferase fusion proteins in Escherichia coli and used the purified proteins to raise antibodies in rabbits. By Western blot analysis and immunoprecipitation experiments, we showed that all the antibodies are specific and highly sensitive to both the native and denatured forms of the full-length S protein expressed in virus-infected cells and transfected cells, respectively. Indirect immunofluorescence performed on fixed but unpermeabilized cells showed that these antibodies can recognize the mature form of S on the cell surface. All the antibodies were also able to detect the maturation of the 200-kDa form of S to the 210-kDa form by pulse-chase experiments. When the antibodies were tested for their ability to inhibit SARS-CoV propagation in Vero E6 culture, it was found that the anti-SΔ10 antibody, which was targeted to amino acid residues 1029 to 1192 of S, which include heptad repeat 2, has strong neutralizing activities, suggesting that this region of S carries neutralizing epitopes and is very important for virus entry into cells.

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