Trends in testing of sexually transmissible infections (STIs), sexual health knowledge and behaviours, and pornography use in cross-sectional samples of young people in Victoria, Australia, 2015-21.

BACKGROUND: Sexually transmissible infections (STI) are prevalent and increasing among young Australians. This study examined trends in STI testing, sexual health knowledge/behaviours, and pornography use in young people aged 15- 29years in Victoria, Australia between 2015 and 2021. METHODS: Seven online cross-sectional surveys were conducted in a convenience sample of young people, recruiting a total of 7014 participants (67% female). Logistic regression analyses determined trends over time in binary outcomes. RESULTS: There was a decrease in reports of lifetime vaginal sex over time, while lifetime anal sex remained stable. Among those who had ever had vaginal sex, results showed an increase in the use of long-acting reversible contraceptives on the last occasion of vaginal sex. There was no change in STI testing or condom use with all partner types. Knowledge of STIs and sexual health changed over time: the proportion knowing that chlamydia can make women infertile decreased over time, while knowledge that taking the pill does not reduce fertility increased. There was no change in pornography use after adjusting for demographic variables. CONCLUSIONS: Although uptake of long-acting contraceptives increased, STI knowledge and testing, as well as consistent condom use, remained low. Public health interventions should continue to address these critical components of STI prevention.

Distress During the COVID-19 Pandemic Among Local Public Health Workers in New York State.

OBJECTIVE: Understanding the challenges public health workers have faced is critical to reinforcing, revitalizing, and strengthening the public health workforce. We measured and identified the level and causes of psychological distress among public health workers during the COVID-19 pandemic in New York State. METHODS: We used a knowledge, attitudes, beliefs, and behaviors survey to ask public health workers at local health departments about their experiences working in public health during the pandemic, including questions relating to harassment from the public, workload, and work/life balance. We used the Kessler-6 scale to measure participants' psychological distress using a 5-point Likert scale, with higher scores indicating greater psychological distress. We calculated descriptive statistics and conducted a regression analysis to determine the factors associated with public health worker psychological distress, and we coded open-ended comments for qualitative analysis. RESULTS: During September 7-20, 2021, 231 public health workers from 38 local health departments completed the survey. Respondents were predominantly non-Hispanic White (89.6%), female (82.1%), full-time employees (95.1%), and located in Upstate New York. On a bivariate level, the strongest predictor of distress was job satisfaction (-0.388), followed closely by COVID-19 fatigue (0.386) and feeling bullied or harassed by the public (0.331). In the regression analysis, 2 additional factors were associated with distress: considering leaving their job due to the pandemic and concerns about exposure. Themes from the qualitative analysis strongly supported these findings. CONCLUSIONS: Understanding the challenges public health workers have faced during the pandemic is critical to inform the actions needed-stronger state laws protecting against harassment, workforce incentives, and commensurate funding-to reinforce and revitalize our frontline public health workforce.

Recruiting and retaining community-based participants in a COVID-19 longitudinal cohort and social networks study: lessons from Victoria, Australia.

BACKGROUND: Longitudinal studies are critical to informing evolving responses to COVID-19 but can be hampered by attrition bias, which undermines their reliability for guiding policy and practice. We describe recruitment and retention in the Optimise Study, a longitudinal cohort and social networks study that aimed to inform public health and policy responses to COVID-19. METHODS: Optimise recruited adults residing in Victoria, Australia September 01 2020-September 30 2021. High-frequency follow-up data collection included nominating social networks for study participation and completing a follow-up survey and four follow-up diaries each month, plus additional surveys if they tested positive for COVID-19 or were a close contact. This study compared number recruited to a-priori targets as of September 302,021, retention as of December 31 2021, comparing participants retained and not retained, and follow-up survey and diary completion October 2020-December 2021. Retained participants completed a follow-up survey or diary in each of the final three-months of their follow-up time. Attrition was defined by the number of participants not retained, divided by the number who completed a baseline survey by September 302,021. Survey completion was calculated as the proportion of follow-up surveys or diaries sent to participants that were completed between October 2020-December 2021. RESULTS: At September 302,021, 663 participants were recruited and at December 312,021, 563 were retained giving an overall attrition of 15% (n = 100/663). Among the 563 retained, survey completion was 90% (n = 19,354/21,524) for follow-up diaries and 89% (n = 4936/5560) for monthly follow-up surveys. Compared to participants not retained, those retained were older (t-test, p <  0.001), and more likely to be female (χ2, p = 0.001), and tertiary educated (χ2, p = 0.018). CONCLUSION: High levels of study retention and survey completion demonstrate a willingness to participate in a complex, longitudinal cohort study with high participant burden during a global pandemic. We believe comprehensive follow-up strategies, frequent dissemination of study findings to participants, and unique data collection systems have contributed to high levels of study retention.

All-cause mortality among Danish nursing home residents before and during the COVID-19 pandemic: a nationwide cohort study.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671-35,943), 34,801 (95% CI: 34,180-35,432), and 35,708 (95% CI: 35,085-36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620-38,929), 36,956 (95% CI: 36,323-37,600), 37,475 (95% CI: 36,838-38,122), and 38,536 (95% CI: 37,798-39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38-46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18-32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Inclusion of Cultural and Linguistic Diversity in COVID-19 Public Health Research: Research Design Adaptations to Seek Different Perspectives in Victoria, Australia.

Participation of people from culturally and linguistically diverse (CALD) communities in public health research is often limited by challenges with recruitment, retention and second-language data collection. Consequently, people from CALD communities are at risk of their needs being marginalised in public health interventions. This paper presents intrinsic case analyses of two studies which were adapted to increase the cultural competence of research processes. Both cases were part of the Optimise study, a major mixed methods research study in Australia which provided evidence to inform the Victorian state government's decision-making about COVID-19 public health measures. Case study 1 involved the core Optimise longitudinal cohort study and Case study 2 was the CARE Victorian representative survey, an Optimise sub-study. Both case studies engaged cultural advisors and bilingual staff to adjust the survey measures and research processes to suit target CALD communities. Reflexive processes provided insights into the strengths and weaknesses of the inclusive strategies. Selected survey results are provided, demonstrating variation across CALD communities and in comparison to participants who reported speaking English at home. While in most cases a gradient of disadvantage was evident for CALD communities, some patterns were unexpected. The case studies demonstrate the challenge and value of investing in culturally competent research processes to ensure research guiding policy captures a spectrum of experiences and perspectives.

COVID-19 and Social Capital Loss: The Results of a Campus Outbreak.

This study examines the effects of a COVID-19 outbreak on levels of social capital on a college campus, drawing on survey data collected from students at two colleges-one that experienced an outbreak and one that did not. Social capital is examined as an individual level resource and as a campus level normative tool used to fight collective action problems. We test the hypothesis that the outbreak, as a "shock" to the campus, diminished social capital. We also test hypotheses on gender, race, and ethnicity and social capital, informed by prior research. Our findings suggest that the outbreak did reduce social capital at both the individual and campus levels, though individual social capital had a mitigating effect that increased campus social capital. We find also that gender was significantly linked to campus social capital, while race was predictive of individual level social capital.

The effects of social distancing and self-isolation on functional outcomes after radical prostatectomy during the coronavirus disease 2019 (COVID-19) pandemic.

Background: This study is aimed to analyze the effect of social distancing on functional outcomes (potency, continence recovery, and quality of life) on patients undergoing open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) during the COVID-19 pandemic. Materials and methods: We retrospectively assessed functional outcomes of 55 consecutive patients who underwent radical prostatectomy during the COVID-19 pandemic (group A: 12 ORP and 15 RARP) and compared these data with patients from the previous year (group B: 13 ORP and 15 RARP). Propensity-score matching was performed to analyze variables associated with potency, continence recovery and compared between the groups at 1 and 3months. Results: Patients from group A were less interested in postsurgical rehabilitation compared to those from group B (95.7% vs. 56.2%, p = 0.042). Continence recovery among group B patients also tended to be higher for RARP (p = 0.06) and ORP (p = 0.08) at 1 month, although statistical significance was not reached. The cumulative continence recovery at 3 months among group B patients was higher and statistically significantly advantageous for RARP (p = 0.00) and ORP (p < 0.01). Potency rates among younger group B patients following bilateral nerve-sparing procedures were statistically significantly advantageous for RARP (p = 0.026) and ORP (p = 0.011). Conclusions: Our results highlight the large impact of the COVID-19 pandemic on functional outcomes following radical prostatectomy. Future design and planning of home-based models for improved post-operative care should consider this evidence.

Behavioral factors associated with SARS-CoV-2 infection.

OBJECTIVE: To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection. DESIGN: Case-control web-based questionnaire study. SETTING: Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly. PARTICIPANTS: 8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality. EXPOSURE: Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic. MAIN OUTCOMES AND MEASURES: SARS-CoV-2 infection incidence rate ratios (IRR). RESULTS: Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52; UC: 0.63) and outdoor sports activities (NC: 0.75; UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79; UC: 0.98), physical distancing (NC: 0.79; UC: 0.82) and avoiding handshakes (NC: 0.74; UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection. CONCLUSIONS: In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

Behavioral factors associated with SARS-CoV-2 infection

Objective To study the association between behavioural factors and incidence rates of SARS-CoV-2 infection. Design Case–control web-based questionnaire study. Setting Questionnaire data were collected in the Capital Region of Denmark in December 2020 when limited restrictions were in place, while the number of daily SARS-CoV-2 cases increased rapidly. Participants 8913 cases of laboratory-confirmed SARS-CoV-2 infection were compared with two groups of controls: (1) 34 063 individuals with a negative SARS-CoV-2 test from the same date (negative controls, NCs) and 2) 25 989 individuals who had never been tested for a SARS-CoV-2 infection (untested controls, UC). Controls were matched on sex, age, test date and municipality. Exposure Activities during the 14 days prior to being tested positive for SARS-CoV-2 or during the same period for matched controls and precautions taken during the entire pandemic. Main outcomes and measures SARS-CoV-2 infection incidence rate ratios (IRR). Results Response rate was 41.4% (n=93 121). Using public transportation, grocery shopping (IRR: NC: 0.52;UC: 0.63) and outdoor sports activities (NC: 0.75;UC: 0.96) were not associated with increased rate of SARS-CoV-2 infection. Most precautions, for example, using hand sanitizer (NC: 0.79;UC: 0.98), physical distancing (NC: 0.79;UC: 0.82) and avoiding handshakes (NC: 0.74;UC: 0.77), were associated with a lower rate of infection. Activities associated with many close contacts, especially indoors, increased rate of infection. Except for working from home, all types of occupation were linked to increased rate of infection. Conclusions In a community setting with moderate restrictions, activities such as using public transportation and grocery shopping with the relevant precautions were not associated with an increased rate of SARS-CoV-2 infection. Exposures and activities where safety measures are difficult to maintain might be important risk factors for infection. These findings may help public health authorities tailor their strategies for limiting the spread of SARS-CoV-2.

COVID-19 vaccine hesitancy and political ideation among college students in Central New York: The influence of differential media choice.

COVID-19 vaccine hesitancy is context specific and highly dynamic in the United States. The objective of this study was to examine the underlying causes of COVID-19 vaccine use and hesitancy among students at two colleges in Central New York (USA) in order to better understand how to promote vaccination in this demographic. A Knowledge, Attitudes, Beliefs & Behaviors survey was designed to measure the relationship between gender, political ideology, media consumption, beliefs, mental health and anxiety, and pandemic-related behaviors. The survey was distributed by email to students in April 2021. Of 8,894 eligible respondents, 627 students completed the survey. Structural Equation Modeling was utilized to explore both direct and indirect relationships. Modeling suggests that the effect of political ideology (being more conservative) is to promote the consumption of right wing news, which in turn tends to increase vaccine hesitancy. Conservative political ideology does not directly lead to vaccine hesitancy, but it does encourage the consumption of news from sources that promote fear and hesitation about the vaccines. News sources significantly contribute to vaccine attitudes among this demographic.

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections.

Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1-2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines.

Mutations in viral nucleocapsid protein and endoRNase are discovered to associate with COVID19 hospitalization risk

SARS-CoV-2 is spreading worldwide with continuously evolving variants, some of which occur in the Spike protein and appear to increase viral transmissibility. However, variants that cause severe COVID-19 or lead to other breakthroughs have not been well characterized. To discover such viral variants, we assembled a cohort of 683 COVID-19 patients;388 inpatients (“cases”) and 295 outpatients (“controls”) from April to August 2020 using electronically captured COVID test request forms and sequenced their viral genomes. To improve the analytical power, we accessed 7137 viral sequences in Washington State to filter out viral single nucleotide variants (SNVs) that did not have significant expansions over the collection period. Applying this filter led to the identification of 53 SNVs that were statistically significant, of which 13 SNVs each had 3 or more variant copies in the discovery cohort. Correlating these selected SNVs with case/control status, eight SNVs were found to significantly associate with inpatient status (q-values < 0.01). Using temporal synchrony, we identified a four SNV-haplotype (t19839-g28881-g28882-g28883) that was significantly associated with case/control status (Fisher’s exact p = 2.84 × 10–11). This haplotype appeared in April 2020, peaked in June, and persisted into January 2021. The association was replicated (OR = 5.46, p-value = 4.71 × 10−12) in an independent cohort of 964 COVID-19 patients (June 1, 2020 to March 31, 2021). The haplotype included a synonymous change N73N in endoRNase, and three non-synonymous changes coding residues R203K, R203S and G204R in the nucleocapsid protein. This discovery points to the potential functional role of the nucleocapsid protein in triggering “cytokine storms” and severe COVID-19 that led to hospitalization. The study further emphasizes a need for tracking and analyzing viral sequences in correlations with clinical status.

Myopericarditis with Significant Left Ventricular Dysfunction Following COVID-19 Vaccination: A Case Report.

BACKGROUND Since Emergency Use Authorization of COVID-19 vaccines in December 2020, more is becoming known about their adverse effects. Growing numbers of myopericarditis cases after COVID-19 vaccination are being reported, mostly in younger adults. While most of these patients have recovered rapidly and without complications, it is still unclear whether patients who are older and have greater cardiac dysfunction secondary to myopericarditis will also experience the same recovery. CASE REPORT We report the case of a middle-aged man with myopericarditis and significant left ventricular dysfunction after the second dose of the Pfizer/BioNTech BNT162b2 COVID-19 vaccine. He presented several days after vaccination, and with non-steroidal anti-inflammatory treatment, he quickly recovered ventricular function, and symptoms resolved within 1 week after vaccination. CONCLUSIONS Vaccines are a key tool in combating the COVID-19 pandemic, yet many people are hesitant to seek vaccination, perhaps for fear of adverse events. Our report of a middle-aged patient with significant left ventricular dysfunction, who still experienced rapid recovery, should reassure the public about the safety of vaccines. Such rare adverse effects should not deter people from receiving COVID-19 vaccination.

Social capital as mediating factor on COVID-19 induced psychological distress: The case of college students living through an outbreak.

This investigation examines the interplay between individual-level social capital, psychological distress, and the effects of a coronavirus disease 2019 (COVID-19) outbreak on a college campus. Data were collected from students at two colleges in early 2021. Hypotheses were formed based on prior research on social capital and the COVID pandemic. A structural equation model was constructed to allow the modeling of both latent and observed variables. The Kessler-6 measures were used to create a latent psychological distress variable, which was the dependent variable. Predictor variables include whether the student experienced the outbreak, the student's race and gender, and the level of reported individual social capital (having supportive and rewarding relationships). Our findings suggest that the most robust predictor of reduced psychological distress was individual social capital, which also served as an intermediary between the outbreak and distress. Social capital mediates psychological distress in an outbreak.

Lower urinary tract signs and symptoms in patients with COVID-19.

BACKGROUND: The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. METHODS: The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. RESULTS: None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). CONCLUSION: Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.

Non-severe SARS-CoV-2 infection is characterised by very early T cell proliferation independent of type 1 interferon responses and distinct from other acute respiratory viruses. (preprint)

The correlates of natural protective immunity to SARS-CoV-2 in the majority who experience asymptomatic infection or non-severe disease are not fully characterised, and remain important as new variants emerge. We addressed this question using blood transcriptomics, multiparameter flow cytometry and T cell receptor (TCR) sequencing spanning the time of incident infection. We identified a type 1 interferon (IFN) response common to other acute respiratory viruses, and a cell proliferation response that discriminated SARS-CoV-2 from other viruses. These responses peaked by the time the virus was first detected, and in some preceded virus detection. Cell proliferation was most evident in CD8 T cells and associated with rapid expansion of SARS-CoV-2 reactive TCRs. We found an equally rapid increase in immunoglobulin transcripts, but circulating virus-specific antibodies lagged by 1-2 weeks. Our data support a protective role for rapid induction of type 1 IFN and CD8 T cell responses to SARS-CoV-2.

Lower Urinary Tract Signs and Symptoms in COVID-19 infected Patients (preprint)

Background:The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms.Methods:The effect of COVID-19 on lower urinary tract function was studied in a multi-centre study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. Results:None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19 % of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48% to 61% in the Tabriz cohort (p-value=0.03) and from 30 % to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 33% to 50%. (p-value =0.039).Conclusion:Patients admitted with COVID-19 infection did not report to have any lower urinary tract symptoms even those patient who had a positive Urine SARS-CoV-2 PCR.In addition, hematuria, WBC in urine as well as COVID-19 positivity in urine were found to be strong negative prognostic factors in admitted COVID-19 patients.

Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS­CoV-2 infection.

BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p<0.0001) but only anti-S1 measurements correlated with near-contemporary pseudovirus neutralising antibody titres (measured at 16-18 weeks, r = 0.57, p<0.0001). By 21 weeks' follow-up, 31/143 (21.7%) anti-S1 and 6/150 (4.0%) anti-NP measurements reverted to negative. Mathematical modelling revealed faster clearance of anti-S1 compared to anti-NP (median half-life of 2.5 weeks versus 4.0 weeks), earlier transition to lower levels of antibody production (median of 8 versus 13 weeks), and greater reductions in relative antibody production rate after the transition (median of 35% versus 50%). INTERPRETATION: Mild SARS-CoV-2 infection is associated with heterogeneous serological responses in Euroimmun anti-S1 and Roche anti-NP assays. Anti-S1 responses showed faster rates of clearance, more rapid transition from high to low level production rate and greater reduction in production rate after this transition. In mild infection, anti-S1 serology alone may underestimate incident infections. The mechanisms that underpin faster clearance and lower rates of sustained anti-S1 production may impact on the longevity of humoral immunity. FUNDING: Charitable donations via Barts Charity, Wellcome Trust, NIHR.

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV 2 infection (preprint)

We hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91-0.99), sensitivity 0.84 (0.7-0.93) and specificity 0.95 (0.85-0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17-0.69) and specificity 0.95 (0.85-0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.