Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    SARS-CoV-2 antigens expressed in plants detect antibody SERO responses in COVID-19 patients

    Authors: Mohau S Makatsa; Marius B Tincho; Jerome M Wendoh; Sherazaan D Ismail; Rofhiwa Nesamari; Francisco Pera; Scott de Beer; Anura David; Sarika Jugwanth; Maemu P Gededzha; Nakampe Mampeule; Ian Sanne; Wendy Stevens; Lesley Scott; Jonathan Blackburn; Elizabeth S Mayne; Roanne S Keeton; Wendy A Burgers

    doi:10.1101/2020.08.04.20167940 Date: 2020-08-04 Source: medRxiv

    Background: The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases TRANS and at least 650 000 deaths MESHD from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence SERO and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay SERO using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods: We established an indirect enzyme-linked immunosorbent assay SERO ( ELISA SERO) using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody SERO responses in sera from South African patients (n=77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of six weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease MESHD. In addition, we tested the reactivity of pre-pandemic plasma SERO (n=58) and compared the performance SERO of our in-house ELISA SERO with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies SERO by a validated, high sensitivity SERO commercial ELISA SERO, and OD values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma SERO, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA SERO. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusions: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody SERO responses to SARS-CoV-2 in infected patients in our setting.

    Reconciling epidemiological models with misclassified case-counts for SARS-CoV-2 with seroprevalence SERO surveys: A case study in Delhi, India

    Authors: Rupam Bhattacharyya; Ritwik Bhaduri; Ritoban Kundu; Maxwell Salvatore; Bhramar Mukherjee

    doi:10.1101/2020.07.31.20166249 Date: 2020-08-04 Source: medRxiv

    Underreporting of COVID-19 cases and deaths MESHD is a hindrance to correctly modeling and monitoring the pandemic. This is primarily due to limited testing, lack of reporting infrastructure and a large number of asymptomatic infections MESHD asymptomatic TRANS. In addition, diagnostic tests (RT-PCR tests for detecting current infection MESHD) and serological antibody tests SERO for IgG (to assess past infections MESHD) are imperfect. In particular, the diagnostic tests have a high false negative rate. Epidemiologic models with a latent compartment for unascertained infections MESHD like the Susceptible-Exposed-Infected-Removed (SEIR) models can provide predictions for unreported cases and deaths MESHD under certain assumptions. Typically, the number of unascertained cases is unobserved and thus we cannot validate these estimates for a real study except for simulation studies. Population-based seroprevalence SERO studies can provide a rough estimate of the total number of infections MESHD and help us check epidemiologic model projections. In this paper, we develop a method to account for high false negative rates in RT-PCR in an extension to the classic SEIR model. We apply this method to Delhi, the national capital region of India, with a population of 19.8 million and a COVID-19 hotspot of the country, obtaining estimates of underreporting factor for cases at 34-53 times and that for deaths MESHD at 8-13 times. Based on a recently released serological survey for Delhi with an estimated 22.86% seroprevalence SERO, we compute adjusted estimates of the true number of infections MESHD reported by the survey (after accounting for misclassification of the antibody test SERO results) which is largely consistent with the model outputs, yielding an underreporting factor for cases from 30-42. Together with the model and the serosurvey, this implies approximately 96-98% cases in Delhi remained unreported and whereas only 109,140 cases were reported on July 10, the true number of infections MESHD varied somewhere between 4.4-4.6 million across different estimates. While repeated serological monitoring is resource intensive, model-based adjustments, run with the most up to date data, can provide a viable option to keep track of the unreported cases and deaths MESHD and gauge the true extent of transmission TRANS of this insidious virus.

    High SARS-CoV-2 seroprevalence SERO in Health Care Workers but relatively low numbers of deaths MESHD in urban Malawi

    Authors: Marah Grace Chibwana; Khuzwayo Chidiwa Jere; Jonathan Mandolo; Vincent Katunga-Phiri; Dumizulu Tembo; Ndaona Mitole; Samantha Musasa; Simon Sichone; Agness Lakudzala; Lusako Sibale; Prisca Matambo; Innocent Kadwala; Rachel Louise Byrne; Alice Mbewe; Marc Y.R. Henrion; Ben Morton; Chimota Phiri; Jane Mallewa; Henry C Mwandumba; Emily R Adams; Stephen B Gordon; Kondwani Charles Jambo

    doi:10.1101/2020.07.30.20164970 Date: 2020-08-01 Source: medRxiv

    Background In low-income countries, like Malawi, important public health measures including social distancing or a lockdown, have been challenging to implement owing to socioeconomic constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. However, due to limited capacity to test for severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD, there are no reliable estimates of the true burden of infection MESHD and death MESHD. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection MESHD in urban Malawi. Methods Five hundred otherwise asymptomatic TRANS HCWs were recruited from Blantyre City (Malawi) from 22nd May 2020 to 19th June 2020 and serum samples SERO were collected all participants. A commercial ELISA SERO was used to measure SARS-CoV-2 IgG antibodies SERO in serum SERO. We run local negative samples (2018 - 2019) to verify the specificity of the assay. To estimate the seroprevalence SERO of SARS CoV-2 antibodies SERO, we adjusted the proportion of positive results based on local specificity of the assay. Results Eighty-four participants tested positive for SARS-CoV-2 antibodies SERO. The HCW with a positive SARS-CoV-2 antibody SERO result came from different parts of the city. The adjusted seroprevalence SERO of SARS-CoV-2 antibodies SERO was 12.3% [CI 9.0-15.7]. Using age TRANS-stratified infection MESHD fatality estimates reported from elsewhere, we found that at the observed adjusted seroprevalence SERO, the number of predicted deaths MESHD was 8 times the number of reported deaths MESHD. Conclusion The high seroprevalence SERO of SARS-CoV-2 antibodies SERO among HCW and the discrepancy in the predicted versus reported deaths MESHD, suggests that there was early exposure but slow progression of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of locally parameterised mathematical models to more accurately predict the trajectory of the epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health response planning.

    Seroprevalence SERO of anti-SARS-CoV-2 IgG antibodies SERO in Kenyan blood SERO donors

    Authors: Sophie Uyoga; Ifedayo M.O. Adetifa; Henry K. Karanja; James Nyagwange; James Tuju; Perpetual Wanjiku; Rashid Aman; Mercy Mwangangi; Patrick Amoth; Kadondi Kasera; Wangari Ng'ang'a; Charles Rombo; Christine K. Yegon; Khamisi Kithi; Elizabeth Odhiambo; Thomas Rotich; Irene Orgut; Sammy Kihara; Mark Otiende; Christian Bottomley; Zonia N. Mupe; Eunice W. Kagucia; Katherine Gallagher; Anthony Etyang; Shirine Voller; John Gitonga; Daisy Mugo; Charles N. Agoti; Edward Otieno; Leonard Ndwiga; Teresa Lambe; Daniel Wright; Edwine Barasa; Benjamin Tsofa; Philip Bejon; Lynette I. Ochola-Oyier; Ambrose Agweyu; J. Anthony G. Scott; George M Warimwe

    doi:10.1101/2020.07.27.20162693 Date: 2020-07-29 Source: medRxiv

    Background There are no data on SARS-CoV-2 seroprevalence SERO in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti- SARS-CoV-2 antibody SERO prevalence SERO among blood SERO donors in Kenya. Methods We measured anti-SARS-CoV-2 spike IgG prevalence SERO by ELISA SERO on residual blood SERO donor samples obtained between April 30 and June 16, 2020. Assay sensitivity SERO and specificity were 83% (95% CI 59, 96%) and 99.0% (95% CI 98.1, 99.5%), respectively. National seroprevalence SERO was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age TRANS, sex and region, adjusted for assay performance SERO. Results Complete data were available for 3098 of 3174 donors, aged TRANS 15-64 years. By comparison with the Kenyan population, the sample over-represented males TRANS (82% versus 49%), adults TRANS aged TRANS 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence SERO was 5.6% (174/3098). Population-weighted, test-adjusted national seroprevalence SERO was 5.2% (95% CI 3.7, 7.1%). Seroprevalence SERO was highest in the 3 largest urban Counties; Mombasa (9.3% [95% CI 6.4, 13.2%)], Nairobi (8.5% [95% CI 4.9, 13.5%]) and Kisumu (6.5% [95% CI 3.3, 11.2%]). Conclusions We estimate that 1 in 20 adults TRANS in Kenya had SARS-CoV-2 antibodies SERO during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths MESHD had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths MESHD reported in parts of Europe and America when seroprevalence SERO was similar.

    Asymptomatic TRANS COVID-19; We Don’t Know What We Don’t Know

    Authors: Olen R. Brown

    id:10.20944/preprints202007.0681.v1 Date: 2020-07-28 Source: preprints.org

    Decisions affecting the COVID-19 pandemic, by the individual and those with highest authority, are being made on the basis of unreliable data. Data about cases and deaths MESHD are collected daily but represent only a sample of reality. Statistics convert sample data into more reliable estimates. However, statistics have no magical powers; reliability requires dependable data. It is futile to rail against this darkness; COVID-19 is not a scientific experiment. However, we must do better both with data collection and data analysis. In this review, I focus on one element of the data, the asymptomatic TRANS case of COVID-19. Without reliable information about this number, decision makers are significantly blinded. By its nature, the asymptomatic TRANS case is hidden but contaminating to understanding COVID-19. The true case rate and death MESHD rate per case are unknowable without knowing the fraction of cases that are asymptomatic TRANS. The best estimate of asymptomatic TRANS cases is in the CDC document: COVID-19 Pandemic Planning Scenarios. For four different scenarios the estimates range from 10% to 70%, with the best estimate of 40% for asymptomatic TRANS cases. However, even the definition of the asymptomatic TRANS case is problematic. In simplest terms, two elements are required: an infection MESHD and no symptoms. How is “no symptoms” to be usefully defined? It appears to be analogous to pontificating about black swans from studying only white swans. It implies infection MESHD, but how is infection MESHD defined? Is it presence of the virus, replication of the virus, or presence of antibodies SERO? Is asymptomatic disease MESHD asymptomatic TRANS an oxymoron? Without extensive, purposeful screening for specifically defined, essential symptoms and appropriate virus and antibody testing SERO over time, the class of asymptomatic TRANS cases remains unknown. Current estimates range from <20% to ˃80%. If low, it can be ignored; if high, it dramatically and proportionately lowers the case rate and the death MESHD rate per case. Consequentially, the asymptomatic TRANS rate dramatically affects our societal and political responses. In this focused review, we assess the limitations of the published estimates, bring attention to the importance of obtaining accurate data, and exhort that high priority be given in the scientific community to understanding the issue, asymptomatic TRANS COVID-19 cases.

    Longitudinal COVID-19 Surveillance and Characterization in the Workplace with Public Health and Diagnostic Endpoints

    Authors: Manjula Gunawardana; Jessica Breslin; John M Cortez; Sofia Rivera; Simon Webster; F Javier Ibarrondo; Otto O Yang; Richard B Pyles; Christina M Ramirez; Amy P Adler; Peter A Anton; Marc M Baum

    doi:10.1101/2020.07.25.20160812 Date: 2020-07-28 Source: medRxiv

    Background The rapid spread of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease MESHD 2019 (COVID-19) have precipitated a global pandemic heavily challenging our social behavior, economy, and healthcare infrastructure. Public health practices currently represent the primary interventions for managing the spread of the pandemic. We hypothesized that frequent, longitudinal workplace disease MESHD surveillance would represent an effective approach to controlling SARS-CoV-2 transmission TRANS among employees and their household members, reducing potential economic consequences and loss of productivity of standard isolation methods, while providing new insights into viral-host dynamics. Methodology and Findings On March 23, 2020 a clinical study (OCIS-05) was initiated at a small Southern California organization. Results from the first 3 months of the ongoing study are presented here. Study participants (27 employees and 27 household members) consented to provide frequent nasal or oral swab samples that were analyzed by RT-qPCR for SARS-CoV-2 RNA using CDC protocols. Only participants testing negative were allowed to enter the "safe zone" workplace facility. Optional blood SERO samples were collected at baseline and throughout the 3-month study. Serum SERO virus-specific antibody SERO concentrations (IgG, IgM, and IgA) were measured using a selective, sensitive, and quantitative ELISA assay SERO developed in house. A COVID-19 infection MESHD model, based on traditional SEIR compartmental models combined with Bayesian non-linear mixed models and modern machine learning, was used to predict the number of employees and household members who would have become infected in the absence of workplace surveillance. Two study participants were found to be infected by SARS-CoV-2 during the study. One subject, a household member, tested positive clinically by RT-qPCR prior to enrollment and experienced typical COVID-19 symptoms that did not require hospitalization. While on study, the participant was SARS-CoV-2 RNA positive for at least 71 days and had elevated virus-specific antibody SERO concentrations (medians: IgM, 9.83 ug mL-1; IgG, 11.5 ug mL-1; IgA, 1.29 ug mL-1) in serum samples SERO collected at three timepoints. A single, unrelated employee became positive for SARS-CoV-2 RNA over the course of the study, but remained asymptomatic TRANS with low associated viral RNA copy numbers. The participant did not have detectable serum SERO IgM and IgG concentrations, and IgA concentrations decayed rapidly (half-life: 1.3 d). The employee was not allowed entry to the safe zone workplace until testing negative three consecutive times over 7 d. No other employees or household members contracted COVID-19 over the course of the study. Our model predicted that under the current prevalence SERO in Los Angeles County without surveillance intervention, up to 7 employees (95% CI = 3-10) would have become infected with at most 1 of them requiring hospitalizations and 0 deaths MESHD. Conclusions Our clinical study met its primary objectives by using intense longitudinal testing to provide a safe work environment during the COVID-19 pandemic, and elucidating SARS-CoV-2 dynamics in recovering and asymptomatic TRANS participants. The surveillance plan outlined here is scalable and transferrable. The study represents a powerful example on how an innovative public health initiative can be dovetailed with scientific discovery.

    EPICOVID19: Psychometric assessment and validation of a short diagnostic scale for a rapid Covid-19 screening based on reported symptoms

    Authors: Luca Bastiani; Loredana Fortunato; Stefania Pieroni; Fabrizio Bianchi; Fulvio Adorni; Federica Prinelli; Andrea Giacomelli; Gabriele Pagani; Stefania Maggi; Caterina Trevisan; Marianna Noale; Nithiya Jesuthasan; Aleksandra Sojic; Carla Pettenati; Massimo Andreoni; Raffaele Antonelli Incalzi; Massimo Galli; Sabrina Molinaro

    doi:10.1101/2020.07.22.20159590 Date: 2020-07-25 Source: medRxiv

    Background Confirmed COVID-19 cases have been reported in 213 countries and regions and as of 12 July 2020, over 12 million cases, with 561617 deaths MESHD have been reported worldwide. The number of cases changes quickly and varies depending upon which source you use to track, so in the current epidemiological context, the early recognition is critical for the rapid identification of suspected cases (with SARS-CoV-2 infection MESHD-like symptoms and signs MESHD) to be immediately subjected to quarantine measures. Although surveys are widely used for identifying COVID-19 cases, outcomes and associated risks, no validated epidemiological tool exists for surveying SARS-CoV-2 infection MESHD in the population so far. Methods Our study is the phase II of the EPICOVID19 national survey, launched in April 2020 including a national convenience sample of 201121 adults TRANS, who voluntarily filled the EPICOVID19 questionnaire. The phase II questionnaire was mailed to all subjects who underwent tests for COVID-19 by nasopharyngeal swab (NPS) and who accepted to be involved in the second phase of the study, focused on the results reported for NPS and/or serological IgG/IgM tests. We evaluated the capability of the self-reported symptoms collected through the EPICOVID19 questionnaire to discriminate the COVID-19 among symptomatic subjects, in order to identify possible cases to undergo instrumental measurements and clinical examinations. We defined a method for the identification of a total score and validated it with reference to the serological and molecular clinical diagnosis, using four standard steps: identification of critical factors, confirmation of presence of latent variable, development of optimal scoring algorithm and validation of the scoring algorithm. Findings 2703 subjects [66% response rate] completed the Phase II questionnaire. Of 2703 individuals, 694 (25.7%) were NPS(+) and of these 84 (12.1% of the 694 NPS(+)) were asymptomatic TRANS. In the individuals who performed serological testing SERO, of the 472 who did IgG(+) and 421 who did IgM(+), 22.9% and 11.6% tested positive, respectively. Among IgG(+) 1 of 108 subjects was asymptomatic TRANS (0.9%) while 5/49 subjects among IgM(+) were asymptomatic TRANS (10.2%). Compared with NPS(-), among NPS(+) subjects there was a higher rate for Fever MESHD Fever HP (421 [60.7%] vs 391[19.5% ]; p<0.0001), Loss of Taste and/or Smell (365 [52.6%] vs 239 [11.9% ]; p<0.0001) and Cough MESHD Cough HP (352 [50.7%] vs 580 [28.9% ]; p<0.0001). Also for other symptoms the frequencies were significantly higher in NPS(+) subjects than in NPS(-) ones (p<0.001). Among groups with serological tests SERO, the symptoms with higher percentages in the subjects IgG(+) were Fever MESHD Fever HP (65 [60.2%] vs 43[11.8% ]; p<0.0001) and Pain MESHD Pain HP in muscles, bones, joints (73 [67.6%] vs 71 [19.5% ]; p<0.0001). For the COVID-19 self-reported symptoms items, exploratory (proportion variance explained [89.9%]) and confirmatory factor analysis results (SMSR 0.072; RMSEA 0.052) highlights the presence of one latent variable (factor) underlying the symptoms. We define the one-factor solution as EPICOVID19 diagnostic scale and optimal score for each items was identified: Respiratory problems (1.03), Chest pain MESHD Chest pain HP (1.07), Loss of Taste and/or Smell (0.97) and Tachycardia MESHD Tachycardia HP ( palpitations HP) (1.05) were the most important symptoms. The cut-off score was 2.56 ( Sensitivity SERO 76.56%; Specificity 68.24%) in NPS(+) and 2.59 (Se 80.37; Sp 80.17) in IgG(+) subjects.

    Characterizing the Qatar advanced-phase SARS-CoV-2 epidemic

    Authors: Laith J Abu-Raddad; Hiam Chemaitelly; Houssein H Ayoub; Zaina Al Kanaani; Abdullatif Al Khal; Einas Al Kuwari; Adeel A Butt; Peter Coyle; Andrew Jeremijenko; Anvar Hassan Kaleeckal; Ali Nizar Latif; Robert C Owen; Hanan F Abdul Rahim; Samya A Al Abdulla; Mohamed G Al Kuwari; Mujeeb C Kandy; Hatoun Saeb; Shazia Nadeem N. Ahmed; Hamad Eid Al Romaihi; Devendra Bansal; Louise Dalton; Sheikh Mohammad Al Thani; Roberto Bertollini

    doi:10.1101/2020.07.16.20155317 Date: 2020-07-19 Source: medRxiv

    ABSTRACT Background: Qatar has a population of 2.8 million, over half of whom are expatriate craft and manual workers (CMW). We aimed to characterize the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) epidemic in Qatar. Methods: A series of epidemiologic studies were conducted including analysis of the national SARS-CoV-2 PCR testing and hospitalization database, community surveys assessing current infection MESHD, ad-hoc PCR testing campaigns in workplaces and residential areas, serological testing SERO for antibody SERO on blood SERO specimens collected for routine clinical screening/management, national Coronavirus Diseases MESHD 2019 (COVID-19) death MESHD registry, and a mathematical model. Results: By July 10, 397,577 individuals had been PCR tested for SARS-CoV-2, of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI: 27.8-28.1%). PCR positivity of nasopharyngeal swabs in a national community survey (May 6-7) including 1,307 participants was 14.9% (95% CI: 11.5-19.0%); 58.5% of those testing positive were asymptomatic TRANS. Across 448 ad-hoc PCR testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI: 13.7-17.7%). SARS-CoV-2 antibody SERO prevalence SERO was 24.0% (95% CI: 23.3-24.6%) in 32,970 residual clinical blood SERO specimens. Antibody SERO prevalence SERO was only 47.3% (95% CI: 46.2-48.5%) in those who had at least one PCR positive result, but it was 91.3% (95% CI: 89.5-92.9%) among those who were PCR positive >3 weeks before serology testing. There were substantial differences in exposure to infection MESHD by nationality and sex, reflecting risk differentials between the craft/manual workers and urban populations. As of July 5, case severity rate, based on the WHO severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Model-estimated daily number of infections MESHD and active- infection MESHD prevalence SERO peaked at 22,630 and 5.7%, respectively, on May 21 and May 23. Attack rate TRANS (ever infection MESHD) was estimated at 53.5% on July 12. R0 TRANS ranged between 1.45-1.68 throughout the epidemic. Rt was estimated at 0.70 on June 15, which was hence set as onset date for easing of restrictions. Age TRANS was by far the strongest predictor of severe, critical, or fatal infection MESHD. Conclusions: Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to exhaustion of susceptibles. The epidemic demonstrated a classic susceptible-infected-recovered 'SIR' dynamics with a rather stable R0 TRANS of about 1.6. The young demographic structure of the population, in addition to a resourced public health response, yielded a milder disease MESHD burden and lower mortality than elsewhere.

    Disease MESHD-associated antibody SERO phenotypes and probabilistic seroprevalence SERO estimates during the emergence of SARS-CoV-2

    Authors: Xaquin Castro Dopico; Leo Hanke; Daniel J Sheward; Murray Christian; Sandra Muschiol; Nastasiya F Grinberg; Monika Adori; Laura Perez Vidakovics; Kim Chang Il; Sharesta Khoenkhoen; Pradeepa Pushparaj; Ainhoa Moliner Morro; Marco Mandolesi; Mattias Forsell; Jonathan Coquet; Martin Corcoran; Joanna Rorbach; Soo Aleman; Gordana Bogdanovic; Gerald Mcinerney; Tobias Allander; Chris Wallace; Ben Murrell; Jan Albert; Gunilla B Karlsson Hedestam

    doi:10.1101/2020.07.17.20155937 Date: 2020-07-17 Source: medRxiv

    Serological studies are critical for understanding pathogen-specific immune responses and informing public health measures (1,2). By developing highly sensitive and specific trimeric spike (S)-based antibody tests SERO, we report IgM, IgG and IgA responses to SARS-CoV-2 in COVID-19 patients (n=105) representing different categories of disease MESHD severity. All patients surveyed were IgG positive against S. Elevated anti- SARS-CoV-2 antibody SERO levels were associated with hospitalization, with IgA titers, increased circulating IL-6 and strong neutralizing responses indicative of intensive care status. Antibody SERO-positive blood SERO donors and pregnant women sampled during the pandemic in Stockholm, Sweden (weeks 14-25), displayed on average lower titers and weaker neutralizing responses compared to patients; however, inter-individual anti-viral IgG titers differed up to 1,000-fold. To provide more accurate estimates of seroprevalence SERO, given the frequency of weak responders and the limitations associated with the dichotomization of a continuous variable (3,4), we used a Bayesian approach to assign likelihood of past infection MESHD without setting an assay cut-off. Analysis of blood SERO donors (n=1,000) and pregnant women (n=900) sampled weekly demonstrated SARS-CoV-2-specific IgG in 7.2% (95% Bayesian CI [5.1-9.5]) of individuals two months after the peak of spring 2020 COVID-19 deaths MESHD. Seroprevalence SERO in these otherwise healthy cohorts increased steeply before beginning to level-off, following the same trajectory as the Stockholm region deaths MESHD over this time period.

    Increased serum SERO levels of soluble TNF-α receptor is associated with mortality of ICU COVID-19 patients

    Authors: Esmaeil Mortaz; Payam Tabarsi; Hamidreza Jamaati; Neda Dalil Roofchayee; Neda KakaDezfuli; Seyed MohammadReza Hashemian; Afshin Moniri; Majid Marjani; Majid Malekmohammd; Davood Manosuri; Mohammd Varahram; Gert Folkerts; Ian M Adcock

    doi:10.1101/2020.07.12.20152066 Date: 2020-07-15 Source: medRxiv

    Background: Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) that causes coronavirus disease MESHD 2019 (COVID-19) has spread to almost 100 countries, infected over 10M patients and resulted in 505K deaths MESHD worldwide as of 30th June 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute Respiratory Distress HP Syndrome MESHD (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum SERO levels of cytokines such as TNF- and IL-6 being reported. TNF- levels are increased during the cytokine storm in very ill patients and soluble receptors for IL-6 and IL-2 are present in the blood SERO of COVID-19 patients, Objectives: To elucidate the involvement of serum SERO levels of soluble TNF-Receptor of severe and mild COVID-19 patients to determine for severity of disease MESHD. Method: We recruited 16 severe COVID-19 patients in the ICU on ventilator support and 26 milder COVID-19 patients who were hospitalised but not within the intensive care unit (ICU) between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. After harvesting of whole blood SERO the serum SERO was isolated and soluble TNF-Receptor levels measured by ELISA SERO. Results: Serum SERO levels of the usually inhibitory soluble TNF receptor 1 (sTNFaR1) were significantly elevated in severe COVID-19 patients at admission to ICU. High serum SERO levels of sTNFaR1 were associated with mortality of severe COVID-19 patients treated within ICU. Conclusions: This pilot study demonstrates for role of STNF-aR1 receptor in severity of disease MESHD. Future studies should examine whether lower levels of systemic sTNFaR1 at admission may indicate a better disease MESHD outcome.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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