Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection

Abstract Background Pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating the acute response and recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, the aim of the study was to examine sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. Methods In this study, we assessed autoantibody (AAB) reactivity to 91 autoantigens previously linked to a range of classic autoimmune diseases in a cohort of 177 participants (65% women, 35% men, mean age of 35) with confirmed evidence of prior SARS-CoV-2 infection based on presence of antibody to the nucleocapsid protein of SARS-CoV-2. Data were compared to 53 pre-pandemic healthy controls (49% women, 51% men). For each participant, socio-demographic data, serological analyses, SARS-CoV-2 infection status and COVID-19 related symptoms were collected by an electronic survey of questions. The symptoms burden score was constructed based on the total number of reported symptoms (N = 21) experienced within 6 months prior to the blood draw, wherein a greater number of symptoms corresponded to a higher score and assigned as more severe burden. Results In multivariable analyses, we observed sex-specific patterns of autoreactivity associated with the presence or absence (as well as timing and clustering of symptoms) associated with prior COVID-19 illness. Whereas the overall AAB response was more prominent in women following asymptomatic infection, the breadth and extent of AAB reactivity was more prominent in men following at least mildly symptomatic infection. Notably, the observed reactivity included distinct antigens with molecular homology with SARS-CoV-2. Conclusion Our results reveal that prior SARS-CoV-2 infection, even in the absence of severe clinical disease, can lead to a broad AAB response that exhibits sex-specific patterns of prevalence and antigen selectivity. Further understanding of the nature of triggered AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.

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Paradoxical Sex-Specific Patterns of Autoantibodies Response to SARS-CoV-2 Infection

10.1101/2021.07.15.21260603 ◽

2021 ◽

Author(s):

Yunxian Liu ◽

Joseph E. Ebinger ◽

Rowann Mostafa ◽

Petra Budde ◽

Jana Gajewski ◽

...

Keyword(s):

Multivariate Analysis ◽

Sex Differences ◽

Symptom Burden ◽

Sex Bias ◽

Potential Importance ◽

Men And Women ◽

Acute Response ◽

Effective Interventions ◽

Immune Mediated ◽

Autoimmune Reactivity

Background. Amidst the millions of individuals affected directly by the pandemic, pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating not only the acute response but also recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, we deliberately examined sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. Methods. We used a bead-based array containing over 90 autoantigens previously linked to a range of classic autoimmune diseases to assess autoantibody (AAB) titers in 177 participants. All participants had confirmed evidence of prior SARS-CoV-2 infection based on presence of positive anti-nucleocapsid IgG serology results (Abbott Diagnostics, Abbott Park, Illinois). We used multivariate analysis to determine whether sex-bias was associated with increased rates of AABs reactivity and symptom burden after SARS-CoV2 infection. Results. 82.4% of AABs reactivity was associated with being male compared to 17.6% with female. We found a diversity of AABs responses that exhibited sex-specific patterns of frequency distribution as well as associations with symptomatology and symptom burden. Conclusion. Our results reveal a remarkable sex-specific prevalence and selectivity of AAB responses to SARS-CoV-2. Further understanding of the nature of triggered and persistent AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19.

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HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection

10.1101/2021.05.13.21257065 ◽

2021 ◽

Author(s):

Danillo G Augusto ◽

Tasneem Yusufali ◽

Noah D Peyser ◽

Xochitl Butcher ◽

Gregory M Marcus ◽

...

Keyword(s):

Critical Role ◽

Human Leukocyte ◽

Asymptomatic Infection ◽

Baseline Survey ◽

Symptomatic Infection ◽

Symptomatic Disease ◽

Leukocyte Antigen ◽

Hla Genotyping ◽

Asymptomatic Individuals ◽

Test Result

Background. Evidence has shown that a large proportion of SARS-CoV-2 infected individuals do not experience symptomatic disease. Owing to its critical role in immune response, we hypothesized that variation in the human leukocyte antigen (HLA) loci may underly asymptomatic infection. Methods. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Among 21,893 individuals who completed the baseline survey, our discovery (N=640) and replication (N=788) cohorts were comprised of self-identified White subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with asymptomatic vs. symptomatic infection. Results. HLA-B*15:01 was significantly increased in asymptomatic individuals in the discovery cohort compared to symptomatic (OR = 2.45; 95%CI 1.38-4.24, p = 0.0016, pcorr = 0.048), and we reproduced this association in the replication cohort (OR= 2.32; 95%CI = 1.10-4.43, p = 0.017). We found robust association of HLA-B*15:01 in the combined dataset (OR=2.40 95% CI = 1.54-3.64; p = 5.67 x10-5) and observed that homozygosity of this allele increases more than eight times the chance of remaining asymptomatic after SARS-CoV-2 infection (OR = 8.58, 95%CI = 1.74-34.43, p = 0.003). Finally, we demonstrated the association of HLA-B*15:01 with asymptomatic SARS-Cov-2 infection is enhanced by the presence of HLA-DRB1*04:01 Conclusion. HLA-B*15:01 is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.

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Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

10.1101/2020.11.24.20229948 ◽

2020 ◽

Cited By ~ 2

Author(s):

Joel Hellewell ◽

Timothy W. Russell ◽

Rupert Beale ◽

Gavin Kelly ◽

Catherine Houlihan ◽

...

Keyword(s):

Vulnerable Populations ◽

Research Unit ◽

Asymptomatic Infection ◽

Nasopharyngeal Swab ◽

Rt Pcr ◽

Symptomatic Infection ◽

Testing Frequency ◽

Peak Sensitivity ◽

Pcr Test ◽

Over Time

AbstractBackgroundRoutine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time.MethodsWe fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection, we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection.FindingsWe estimated that the probability that the PCR test detected infection peaked at 77% (54 - 88%) 4 days after infection, decreasing to 50% (38 - 65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33-76%) of symptomatic cases prior to onset and 94% (75-99%) of asymptomatic cases within 7 days if test results were returned within a day.InterpretationOur results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.FundingWellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI)

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The Promise of Direct-to-Consumer Telehealth for Disaster Response and Recovery

Prehospital and Disaster Medicine ◽

10.1017/s1049023x16000558 ◽

2016 ◽

Vol 31 (4) ◽

pp. 454-456 ◽

Cited By ~ 13

Author(s):

Lori Uscher-Pines ◽

Shira Fischer ◽

Ramya Chari

Keyword(s):

Health Care Providers ◽

Disaster Response ◽

Great Promise ◽

Care Providers ◽

Publication Type ◽

Direct To Consumer ◽

Acute Response ◽

Virtual Visits ◽

Response And Recovery ◽

Disaster Response And Recovery

AbstractTelehealth has great promise to improve and even revolutionize emergency response and recovery. Yet telehealth in general, and direct-to-consumer (DTC) telehealth in particular, are underutilized in disasters. Direct-to-consumer telehealth services allow patients to request virtual visits with health care providers, in real-time, via phone or video conferencing (online video or mobile phone applications). Although DTC services for routine primary care are growing rapidly, there is no published literature on the potential application of DTC telehealth to disaster response and recovery because these services are so new. This report presents several potential uses of DTC telehealth across multiple disaster phases (acute response, subacute response, and recovery) while noting the logistical, legal, and policy challenges that must be addressed to allow for expanded use.Uscher-PinesL, FischerS, ChariR. The promise of direct-to-consumer telehealth for disaster response and recovery. Prehosp Disaster Med. 2016;31(4):454–456.

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Social Vulnerability to Climate-Sensitive Hazards in the Southern United States

Weather Climate and Society ◽

10.1175/2011wcas1092.1 ◽

2011 ◽

Vol 3 (3) ◽

pp. 193-208 ◽

Cited By ~ 91

Author(s):

Christopher T. Emrich ◽

Susan L. Cutter

Keyword(s):

United States ◽

Social Vulnerability ◽

Demographic Data ◽

Management Strategies ◽

The United States ◽

Southern United States ◽

Hazard Exposure ◽

Strategic Initiatives ◽

Response And Recovery ◽

Spatial Impacts

Abstract The southern United States is no stranger to hazard and disaster events. Intense hurricanes, drought, flooding, and other climate-sensitive hazards are commonplace and have outnumbered similar events in other areas of the United States annually in both scale and magnitude by a ratio of almost 4:1 during the past 10 years. While losses from climate-sensitive hazards are forecast to increase in the coming years, not all of the populations residing within these hazard zones have the same capacity to prepare for, respond to, cope with, and rebound from disaster events. The identification of these vulnerable populations and their location relative to zones of known or probably future hazard exposure is necessary for the development and implementation of effective adaptation, mitigation, and emergency management strategies. This paper provides an approach to regional assessments of hazards vulnerability by describing and integrating hazard zone information on four climate-sensitive hazards with socioeconomic and demographic data to create an index showing both the areal extent of hazard exposure and social vulnerability for the southern United States. When examined together, these maps provide an assessment of the likely spatial impacts of these climate-sensitive hazards and their variability. The identification of hotspots—counties with elevated exposures and elevated social vulnerability—highlights the distribution of the most at risk counties and the driving factors behind them. Results provide the evidentiary basis for developing targeted strategic initiatives for disaster risk reduction including preparedness for response and recovery and longer-term adaptation in those most vulnerable and highly impacted areas.

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COVID-19: lessons to date from China

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-319261 ◽

2020 ◽

Vol 105 (12) ◽

pp. 1146-1150

Author(s):

Xiaoxia Lu ◽

Yuhan Xing ◽

Gary Wing-Kin Wong

Keyword(s):

Gastrointestinal Symptoms ◽

Paediatric Population ◽

Asymptomatic Infection ◽

Lessons Learned ◽

Severe Illness ◽

Older Children ◽

Symptomatic Infection ◽

Paediatric Age ◽

Community Transmission ◽

Novel Coronavirus

The pandemic due to a novel coronavirus has been sweeping across different regions of the globe since January 2020. Early reports of this infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) consisted of mostly adult patients. As the outbreak spreads rapidly beyond the epicentre of Wuhan, it becomes clear that infants and children of all ages are susceptible to this infection. In China, there have been more than 1200 paediatric cases. Most paediatric patients acquire the infection through household contact with infected adults. The disease in children is usually self-limiting and most infected children will recover uneventfully within 7–10 days. Other than symptoms of the respiratory tract, many children may present with gastrointestinal symptoms. Older children are more likely to have asymptomatic infection. Although deaths related to SARS-CoV-2 are rarely reported in the paediatric age group, young children and those with underlying medical conditions are more likely to develop severe illness. Only a small fraction of neonates born to infected mother would acquire the virus by vertical transmission. Because a large proportion of children and adolescents may have asymptomatic or mildly symptomatic infection, children are likely to play an important role in community transmission of this infection. Screening of children who have a definitive contact history will facilitate early diagnosis and isolation of all infected children. This review summarises the lessons learned in China with regard to the current understanding of SARS-CoV-2 infection in the paediatric population.

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Intervention on depression and insomnia symptoms during the COVID-19 pandemic

Annals of Medical Research and Practice ◽

10.25259/anmrp_4_2021 ◽

2021 ◽

Vol 2 ◽

pp. 5

Author(s):

Sadhna Verma ◽

James Donovan ◽

Surekha Bhat ◽

Hari Tunuguntla ◽

Renuka Tunuguntla ◽

...

Keyword(s):

Demographic Data ◽

Intervention Strategy ◽

Severity Index ◽

Screening Tools ◽

Depression Symptoms ◽

Effective Interventions ◽

Travel Restrictions ◽

Patient Health ◽

Insomnia Symptoms ◽

Insomnia Severity

Objectives: The COVID-19 pandemic has created significant psychological challenges globally. Evidence has been mounting of greater emotional distress and possible worsening of underlying psychiatric disorders, due to repercussions of COVID-19. In addition, the pandemic has created barriers to access for help, due to social distancing and travel restrictions. Thus, creating a major need for effective interventions that can be accessed safely from home and provide coping tools which can be learned and practiced while in isolation. An App based Yoga of Immortals (YOI) program is one such strategy to help cope with stressful situations. The objective of this study was to investigate if the YOI program can provide significant benefit for depressive and insomnia symptoms. Material and Methods: Participants in this study were asked to complete two brief online but well validated mental health screening tools before intervention. This was followed by a 7-week long YOI intervention. Following the intervention, participants were once again asked to complete the online validated questionnaires. The survey questionnaires included baseline demographic data and validated scales for measuring insomnia severity Insomnia severity Index (ISI) and levels of depression symptoms patient health questionnaire-8, (PHQ-8). All statistical analysis was performed using the Statistical Package for the Social Science. Results: SY YOI intervention of 7 weeks significantly improved the ISI scores as well as PHQ-8 scores in the study population (P < 0.0001 in all comparisons). Conclusion: YOI intervention is an effective intervention strategy for decreasing insomnia and depression symptoms, even during the pandemic.

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Dynamic analysis and evaluation of asymptomatic infection in the spread of COVID-19

10.1101/2021.12.07.21267442 ◽

2021 ◽

Author(s):

Chuanqing Xu ◽

Zonghao Zhang ◽

Xiaotong Huang ◽

Jingan Cui

Keyword(s):

Recovery Period ◽

Asymptomatic Infection ◽

Symptomatic Infection ◽

Actual Case ◽

Analysis And Evaluation ◽

Low Level ◽

Asymptomatic Infections ◽

Epidemic Development ◽

Short Time

AbstractCOVID-19 has spread worldwide for nearly two years. Many countries have experienced repeated epidemics, that is, after the epidemic has been controlled for a period of time, the number of new cases per day is low, and the outbreak will occur again a few months later. In order to study the relationship between this low level of infection and the number of asymptomatic infections, and to evaluate the role of asymptomatic infections in the development of the epidemic, we have established an improved infectious disease dynamics model that can be used to evaluate the spread of the COVID-19 epidemic, and fitted the epidemic data in the three flat periods in England. According to the obtained parameters, according to the calculation of the model, the proportion of asymptomatic infections in these three flat periods are 41%, 53% and 58% respectively. After the first flat period, the number of daily newly confirmed cases predicted by the model began to increase around July 1, 2020. After more than four months of epidemic spread, it reached a peak on November 12, which is consistent with the actual case situation. Unanimous. After the second flat period, the model predicts that the number of new confirmed cases per day will increase from about May 7, 2021, and after about 73 days of epidemic development, it will reach a peak on July 20, showing the overall trend of the epidemic. In the above, the predicted results of the model are consistent with the actual cases. After the third flat period, the number of daily newly diagnosed cases predicted by the model began to increase around December 1, 2021, and reached a peak in December, and the number of cases will drop to a very low level after May 2022. According to our research results, due to the large number of asymptomatic infections, the spread of the epidemic is not easy to stop completely in a short time. However, when the epidemic enters a period of flat time, nucleic acid testing is performed, and asymptomatic infections are isolated at home for 14 days (the recovery period of symptomatic infection is about 10 days) may be an option that can be considered to interrupt the transmission of the case.

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Incidence, Clinical Characteristics, and Risk Factors of SARS-CoV-2 Infection among Pregnant Individuals in the United States

Clinical Infectious Diseases ◽

10.1093/cid/ciab713 ◽

2021 ◽

Author(s):

Fatimah S Dawood ◽

Michael Varner ◽

Alan Tita ◽

Gabriella Newes-Adeyi ◽

Cynthia Gyamfi-Bannerman ◽

...

Keyword(s):

Infection Prevention ◽

Nasal Congestion ◽

The United States ◽

Asymptomatic Infection ◽

Incidence Rates ◽

Reproductive Age ◽

Symptom Duration ◽

Guidance And Counseling ◽

Symptomatic Infection ◽

Population Counts

Abstract Background Data about the risk of SARS-CoV-2 infection among pregnant individuals are needed to inform infection prevention guidance and counseling for this population. Methods We prospectively followed a cohort of pregnant individuals during August 2020–March 2021 at three U.S. sites. The three primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly mid-turbinate nasal swabs for SARS-CoV-2 RT-PCR testing, completed weekly illness symptom questionnaires, and submitted additional swabs with COVID-19–like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. Results Among 1098 pregnant individuals followed for a mean of 10 weeks, nine percent (99/1098) had SARS-CoV-2 infections during the study. Population weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1,000 (95% confidence interval [CI] 5.7–14.3) person-weeks for any infection, 5.7 per 1,000 (95% CI 1.7-9.7) for symptomatic infections, and 3.5 per 1,000 (95% CI 0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infection and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. The median symptom duration was 10 days (IQR6-16 days). Conclusion Pregnant individuals had a 1% risk of SARS-CoV-2 infection per week. Study findings provide information about SARS-CoV-2 infection risk during pregnancy to inform counseling for pregnant individuals about infection prevention practices, including COVID-19 vaccination.

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The Basics of Infectious Diseases

10.33442/vt202104 ◽

2021 ◽

Author(s):

Heinz-Josef Schmitt

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Asymptomatic Infection ◽

Host Tissue ◽

The Body ◽

Symptomatic Disease ◽

Immune Mediated ◽

Long Time ◽

Micro Organisms ◽

Underlying Diseases

Infectious Diseases result from exposure and contact between a host (human being) and an (uninvited) guest (micro-organism). Given the fact that billions of micro-organisms are in and around us at any time, overall, infectious diseases are comparatively rare; of the millions of different microbial species, only about 300 are known to cause human diseases. Besides exposure and contact, factors on the side of the host (genetic background, environment, underlying diseases and their therapy) and on the side of the micro-organisms (pathogenicity / virulence factors) are necessary to result in an infectious disease. “Colonization” means that a micro-organism can attach on skin or mucous membrane for some time or even indefinitely but does not invade host tissue and does not cause any symptoms. Colonizers may even induce an immune response. “Infection” is defined as a micro-organism invading through skin or mucous membranes the tissue of a host, leading to no disease (“asymptomatic infection”); or symptomatic disease. It is followed by health, disability, or death. Following the infection, microorganisms may persist in the body for a long time or even for life without causing any symptoms, which is called “latent infection”. Infectious diseases may not only be due to pathogenicity factors of a micro-organism, but may also result from (i.) direct destruction of host tissues (e.g., from viral replication); (ii.) the acute host (immune-) response; and from late immune responses resulting in immune-mediated “post-infectious diseases”. Some infections may cause an immune response that is directed against host-tissue, resulting in an “autoimmune-disease”. Given the increasing number of microbes, the increasing number of exposures, and the increasing number and fraction of susceptible/predisposed humans, it is obvious that infectious diseases will increase in the future. Vaccines and vaccination may help solve this problem.

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