A national survey of early treatment seeking behavior among those with incident SARS-CoV-2 infection

Background: Despite effective means to treat SARS-CoV-2 infection, the early treatment seeking behavior of those newly diagnosed with infection is not clear. Methods: We surveyed users of a national SARS-CoV-2 testing company to assess the frequency and correlates of early treatment seeking behavior for a positive test result. We recruited adults (18 years or older) who had tested positive for SARS-CoV-2 by PCR at a large clinical laboratory. To be eligible, individuals had to have a positive test result within 7 days of enrollment. Surveys were anonymous and voluntary. We collected data on demographic characteristics, general health care access and utilization, awareness of treatment for COVID-19, treatment seeking behavior, and treatments received. Descriptive statistics and odds ratios (OR) with 95% confidence intervals (95% CI) were calculated on StataSE. Results: Participants were surveyed from 3-7 January 2022: among the 15,991 who viewed a survey request, 7,647 individuals were eligible and provided responses. The median age of a respondent was 42 years (interquartile range: 32 to 54), 68.9% of respondents were women, and respondents represented 33 different states, districts, and territories. Among respondents, 23.1% reported they had sought treatment or medical advice for their current COVID-19 diagnosis. Of those who were very aware of treatment for COVID-19, 31.0% sought treatment versus 16.7% who were unaware (p-value< 0.001). The odds of treatment seeking behavior were higher for those that were contacted by a medical professional after their diagnosis (OR: 4.57 [95% CI: 3.89 to 5.37]), those with a primary doctor (OR: 2.94 [95% CI: 2.52 to 3.43]), those who self-measured their oxygen saturation (OR: 2.53 [95% CI: 2.25 to 2.84]), and those over 65 years of age (OR: 2.36 [95% CI: 2.02 to 2.76]). There was no difference in those seeking treatment based on heritage, ethnicity, prior COVID-19 diagnosis, state political affiliation, or vaccination status. The odds of seeking treatment were lower among men (OR: 0.88 [95% CI: 0.78 to 0.99]) and those without insurance (OR: 0.62 [95% CI: 0.52 to 0.72]). The most common treatment locations were clinics and most common treatments were Vitamin C, Vitamin D, Zinc, Tylenol, and NSAIDs. Conclusion: More public outreach is needed to raise awareness of the benefits of treatment for COVID-19. We found that people who were more aware about treatment for COVID-19 were more likely to seek medical advice or therapy. Efforts to increase awareness might increase early treatment for SARS-CoV-2 infection. Increased outreach with treatment facilitation from medical professionals and/or public health staff to those with newly detected SARS-CoV-2 infections, particularly among those at higher-risk of complications, might also be helpful.

Protective effect of a first SARS-CoV-2 infection from reinfection: a matched retrospective cohort study using PCR testing data in England

The duration of immunity after first SARS-CoV-2 infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. Using a retrospective population-based matched observational study approach, we identified cases with a first PCR positive test between 01 March 2020 and 30 September 2020 and cases were matched by age, sex, upper tier local authority of residence and testing route to individuals testing negative in the same week (controls) by PCR. After a 90-day pre-follow up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. There were 517,870 individuals in the matched cohort with 2,815 reinfection cases and 12,098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (OR 0.22, 0.21-0.23). Protection rose to 82% (OR 0.18, 0.17-0.19) after a sensitivity analysis excluded 934 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20-0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42-0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the Alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.

Bayesian updating and sequential testing: overcoming inferential limitations of screening tests

Background Bayes’ theorem confers inherent limitations on the accuracy of screening tests as a function of disease prevalence. Herein, we establish a mathematical model to determine whether sequential testing with a single test overcomes the aforementioned Bayesian limitations and thus improves the reliability of screening tests. Methods We use Bayes’ theorem to derive the positive predictive value equation, and apply the Bayesian updating method to obtain the equation for the positive predictive value (PPV) following repeated testing. We likewise derive the equation which determines the number of iterations of a positive test needed to obtain a desired positive predictive value, represented graphically by the tablecloth function. Results For a given PPV ($$\rho$$ ρ ) approaching k, the number of positive test iterations needed given a prevalence of disease ($$\phi$$ ϕ ) is: $$n_i =\lim _{\rho \rightarrow k}\left\lceil \frac{ln\left[ \frac{\rho (\phi -1)}{\phi (\rho -1)}\right] }{ln\left[ \frac{a}{1-b}\right] }\right\rceil \qquad \qquad (1)$$ n i = lim ρ → k l n ρ ( ϕ - 1 ) ϕ ( ρ - 1 ) l n a 1 - b ( 1 ) where $$n_i$$ n i = number of testing iterations necessary to achieve $$\rho$$ ρ , the desired positive predictive value, ln = the natural logarithm, a = sensitivity, b = specificity, $$\phi$$ ϕ = disease prevalence/pre-test probability and k = constant. Conclusions Based on the aforementioned derivation, we provide reference tables for the number of test iterations needed to obtain a $$\rho (\phi )$$ ρ ( ϕ ) of 50, 75, 95 and 99% as a function of various levels of sensitivity, specificity and disease prevalence/pre-test probability. Clinical validation of these concepts needs to be obtained prior to its widespread application.

Investigating the Genetic Profile of the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia (ALS-FTD) Continuum in Patients of Diverse Race, Ethnicity and Ancestry

Preliminary evidence suggests that commonly used genetic tests may be less likely to identify a genetic etiology for ALS-FTD in patients of underrepresented race, ethnicity, and ancestry (REA), as compared to European REA. Patients of underrepresented REA may therefore be less likely to receive accurate and specific genetic counseling information and less likely to have access to gene-targeted therapies currently in clinical trials. We compiled outcome data from 1911 ALS-FTD patients tested at a commercial laboratory over a seven-year period for C9orf72 hexanucleotide repeat expansion (HRE) alone or C9orf72 and multigene sequencing panel testing. We compared the incidence of pathogenic (P), likely pathogenic (LP), and uncertain variants in C9orf72 and other ALS-FTD genes, as well as age at testing, in patients of different REA. The diagnostic rate in patients of European REA (377/1595, 23.64%) was significantly higher than in patients of underrepresented REA (44/316, 13.92%) (p < 0.001). Patients of European REA were more likely to have the C9orf72 HRE (21.3%) than patients of underrepresented REA (10.4%) (p < 0.001). The overall distribution of positive test outcomes in all tested genes was significantly different between the two groups, with relatively more P and LP variants in genes other than C9orf72 identified in patients of underrepresented REA. The incidence of uncertain test outcomes was not significantly different between patients of European and underrepresented REA. Patients with positive test outcomes were more likely to be younger than those with negative or uncertain outcomes. Although C9orf72 HRE assay has been advocated as the first, and in some cases, only genetic test offered to patients with ALS-FTD in the clinical setting, this practice may result in the reduced ascertainment of genetic ALS-FTD in patients of diverse REA.

Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1–28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.

Reduced Odds of SARS-CoV-2 Reinfection after Vaccination among New York City Adults, June–August 2021

BackgroundBelief in immunity from prior infection and concern that vaccines might not protect against new variants are contributors to vaccine hesitancy. We assessed effectiveness of full and partial COVID-19 vaccination against reinfection when Delta was the predominant variant in New York City.MethodsWe conducted a case-control study in which case-patients with reinfection during June 15– August 31, 2021 and control subjects with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Conditional logistic regression was used to calculate matched odds ratios (mOR) and 95% confidence intervals (CI).ResultsOf 349,598 adult residents who tested positive for SARS-CoV-2 infection in 2020, did not test positive again >90 days after initial positive test through June 15, 2021, and did not die before June 15, 2021, 1,067 were reinfected during June 15–August 31, 2021. Of 1,048 with complete matching criteria data, 499 (47.6%) were known to be symptomatic for COVID-19-like-illness, and 75 (7.2%) were hospitalized. Unvaccinated individuals, compared with fully vaccinated individuals, had elevated odds of reinfection (mOR, 2.23; 95% CI, 1.90, 2.61), of symptomatic reinfection (mOR, 2.17; 95% CI, 1.72, 2.74), and of reinfection with hospitalization (mOR, 2.59; 95% CI, 1.43, 4.69). Partially versus fully vaccinated individuals had 1.58 (95% CI: 1.22, 2.06) times the odds of reinfection. All three vaccines authorized or approved for use in the U.S. were similarly effective.ConclusionAmong adults with previous SARS-CoV-2 infection, vaccination reduced odds of reinfections when the Delta variant predominated.

Evaluating the Efficacy of a Screening Protocol for Severe Acute Respiratory Syndrome Coronavirus 2 Virus in Asymptomatic Preoperative/Preprocedural Patients at a Military Hospital

ABSTRACT Introduction Facing the COVID-19 pandemic, many hospitals implemented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening protocols before aerosol-generating procedures (AGPs) in an effort to protect patients and health care workers. Given the limited prior evidence on the effectiveness of such protocols, we report the process improvement experience at a military treatment facility. Materials and Methods We evaluated the outcomes of patients undergoing AGPs from March to September 2020, divided into three cohorts: a preprotocol (PP) cohort who did not receive screening, an early testing (ET) cohort representing the early months of the screening protocol, and a late testing (LT) cohort managed under adaptive modifications to the screening protocol. We recorded identifiable post-procedure COVID-19 diagnoses. The study was approved as a process improvement protocol and was determined not to meet criteria for human subject research through an institutional approval process. Results Across the three cohorts, 4520 procedures were performed: 422 PP, 1297 ET, and 2801 LT. Among 4098 procedures in the ET and LT cohorts, 12 asymptomatic patients tested positive for SARS-CoV-2 (0.29% positivity rate). One left the health system before completing the procedure and another proceeded urgently under COVID precautions, while 10 were rescheduled and completed at a later date; 7 were cleared using a test-based strategy, while 3 were cleared using a time-based strategy. Of 445 patients who had SARS-CoV-2 tests performed within 30 days following their procedures, three patients with negative preoperative tests had a positive test within 30 days, all in the LT cohort but had evidence of acquiring the infection after the procedure or had a false-positive test. Conclusions Our strategy of preprocedural SARS-CoV-2 testing successfully identified asymptomatic infected patients before surgery. Care was delayed for most of these patients without apparent detriment. Adaptation to a time-based strategy for clearance might reduce such delays, but other considerations may still influence how soon procedures should be completed after a positive test.

Occupational risk of SARS-CoV-2 infection and reinfection during the second pandemic surge: a cohort study

ObjectivesThis cohort study including essential workers, assessed the risk and incidence of SARS-CoV-2 infection during the second surge of COVID-19 according to baseline serostatus and occupational sector.MethodsEssential workers were selected from a seroprevalence survey cohort in Geneva, Switzerland and were linked to a state centralised registry compiling SARS-CoV-2 infections. Primary outcome was the incidence of virologically confirmed infections from serological assessment (between May and September 2020) to 25 January 2021, according to baseline antibody status and stratified by three predefined occupational groups (occupations requiring sustained physical proximity, involving brief regular contact or others).Results10 457 essential workers were included (occupations requiring sustained physical proximity accounted for 3057 individuals, those involving regular brief contact, 3645 and 3755 workers were classified under ‘Other essential occupations’). After a follow-up period of over 27 weeks, 5 (0.6%) seropositive and 830 (8.5%) seronegative individuals had a positive SARS-CoV-2 test, with an incidence rate of 0.2 (95% CI 0.1 to 0.6) and 3.2 (95% CI 2.9 to 3.4) cases per person-week, respectively. Incidences were similar across occupational groups. Seropositive essential workers had a 93% reduction in the hazard (HR of 0.07, 95% CI 0.03 to 0.17) of having a positive test during the follow-up with no significant between-occupational group difference.ConclusionsA 10-fold reduction in the hazard of being virologically tested positive was observed among anti-SARS-CoV-2 seropositive essential workers regardless of their sector of occupation, confirming the seroprotective effect of a previous SARS-CoV2 exposure at least 6 months after infection.

Investigation of Vaccine Breakthrough Infections by Vaccine strategy during the Delta Variant Wave in France

Herein, we describe the characteristics of vaccine breakthrough infections (VBI) in fully vaccinated individuals according to five vaccine strategies during the Delta wave in France. Inclusion criterion was a positive test at least 2 weeks after a full vaccine schedule: homologous vaccination with Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273); heterologous vaccination with Astrazeneca and Pfizer-BioNTech (ChadOx1/BNT162b2); single-dose vaccines Johnson & Johnson (Ad26.COV2.S) or Astrazeneca (ChadOx1). A total of 1630 VBI from patients fully vaccinated between February and July were included in this study. SARS-CoV-2 sequencing performed for 1366 samples showed that the delta variant represented 94.1% (1286/1366). Delta-VBI were mainly symptomatic (mild symptoms) with no difference according to the vaccine strategy (p=0.362). The median RT-PCR Ct values at diagnosis were significantly different between symptomatic and asymptomatic cases only for BNT162b2 group (17.7 (15.07, 20.51) vs 19.00 (16.00, 23.00), p=0.004). Up to 50% of VBI was classified as early-VBI (infected less than one month after full immunization) for BNT162b2, mRNA-1273, ChadOx1, and J Ad26.COV2.S. People aged 14-49 yo were overrepresented in early VBI compared to non-early VBI for BNT162b2 and mRNA-1273 (73.92% vs 37.87% for BNT162b2 and 77.78% vs 46.67 % for mRNA-1273, p<0.05). Our data emphasize a high prevalence of Delta-VBI occurring only one month after full immunization in young patients that might be related to relaxation of barrier gestures.

When is a positive test for pediatric growth hormone deficiency a true positive test?

Given the low prevalence rate of growth hormone deficiency (GHD) and the high false positive rates for growth hormone stimulation tests, the probability of GHD in a child with short stature and positive growth hormone stimulation tests is 0.028 (about 1 in 36). Without further information, most positive growth hormone stimulation tests will be false positives. Further study may yield the necessary improvements in the diagnostic accuracy for GHD in children.