Examining the role of COVID-19 testing availability on intention to isolate: A Randomized hypothetical scenario.

BACKGROUND: Little information exists on how COVID-19 testing influences intentions to engage in risky behavior. Understanding the behavioral effects of diagnostic testing may highlight the role of adequate testing on controlling viral transmission. In order to evaluate these effects, simulated scenarios were conducted evaluating participant intentions to self-isolate based on COVID-19 diagnostic testing availability and results. METHODS: Participants from the United States were recruited through an online survey platform (Amazon Mechanical Turk) and randomized to one of three hypothetical scenarios. Each scenario asked participants to imagine having symptoms consistent with COVID-19 along with a clinical diagnosis from their physician. However, scenarios differed in either testing availability (testing available v. unavailable) or testing result (positive v. negative test). The primary outcome was intention to engage in high-risk COVID-19 behaviors, measured using an 11-item mean score (range 1-7) that was pre-registered prior to data collection. Multi-variable linear regression was used to compare the mean composite scores between conditions. The randomized survey was conducted between July 23rd to July 29th, 2020. RESULTS: A total of 1400 participants were recruited through a national, online, opt-in survey. Out of 1194 respondents (41.6% male, 58.4% female) with a median age of 38.5 years, participants who had no testing available in their clinical scenario showed significantly greater intentions to engage in behavior facilitating COVID-19 transmission compared to those who received a positive confirmatory test result scenario (mean absolute difference (SE): 0.14 (0.06), P = 0.016), equating to an 11.1% increase in mean score risky behavior intentions. Intention to engage in behaviors that can spread COVID-19 were also positively associated with male gender, poor health status, and Republican party affiliation. CONCLUSION: Testing availability appears to play an independent role in influencing behaviors facilitating COVID-19 transmission. Such findings shed light on the possible negative externalities of testing unavailability. TRIAL REGISTRATION: Effect of Availability of COVID-19 Testing on Choice to Isolate and Socially Distance, NCT04459520, https://clinicaltrials.gov/ct2/show/NCT04459520.

Diagnostics for COVID-19: moving from pandemic response to control.

Diagnostics have proven to be crucial to the COVID-19 pandemic response. There are three major methods for the detection of SARS-CoV-2 infection and their role has evolved during the course of the pandemic. Molecular tests such as PCR are highly sensitive and specific at detecting viral RNA, and are recommended by WHO for confirming diagnosis in individuals who are symptomatic and for activating public health measures. Antigen rapid detection tests detect viral proteins and, although they are less sensitive than molecular tests, have the advantages of being easier to do, giving a faster time to result, of being lower cost, and able to detect infection in those who are most likely to be at risk of transmitting the virus to others. Antigen rapid detection tests can be used as a public health tool for screening individuals at enhanced risk of infection, to protect people who are clinically vulnerable, to ensure safe travel and the resumption of schooling and social activities, and to enable economic recovery. With vaccine roll-out, antibody tests (which detect the host's response to infection or vaccination) can be useful surveillance tools to inform public policy, but should not be used to provide proof of immunity, as the correlates of protection remain unclear. All three types of COVID-19 test continue to have a crucial role in the transition from pandemic response to pandemic control.

Estimating the impact of virus testing strategies on the COVID-19 case fatality rate using fixed-effects models.

The SARS-CoV2 has now spread worldwide causing over four million deaths. Testing strategies are highly variable between countries and their impact on mortality is a major issue. Retrospective multicenter study with a prospective database on all inpatients throughout mainland France. Using fixed effects models, we exploit policy discontinuities at region borders in France to estimate the effect of testing on the case fatality rate. In France, testing policies are determined at a regional level, generating exogenous variation in testing rates between departments on each side of a region border. We compared all contiguous department pairs located on the opposite sides of a region border. The increase of one percentage point in the test rate is associated with a decrease of 0.0015 percentage point in the death rate, that is, for each additional 2000 tests, we could observe three fewer deaths. Our study suggests that COVID-19 population testing could have a significant impact on the mortality rate which should be considered in decision-making. As concern grows over the current second wave of COVID-19, our findings support the implementation of large-scale screening strategies in such epidemic contexts.

A novel benchmark for COVID-19 pandemic testing effectiveness enables the accurate prediction of new Intensive Care Unit admissions.

The positivity rate of testing is currently used both as a benchmark of testing adequacy and for assessing the evolution of the COVID-19 pandemic. However, since the former is a prerequisite for the latter, its interpretation is often conflicting. We propose as a benchmark for COVID-19 testing effectiveness a new metric, termed 'Severity Detection Rate' (SDR), that represents the daily needs for new Intensive Care Unit (ICU) admissions, per 100 cases detected (t - i) days ago, per 10,000 tests performed (t - i) days ago. Based on the announced COVID-19 monitoring data in Greece from May 2020 until August 2021, we show that beyond a certain threshold of daily tests, SDR reaches a plateau of very low variability that begins to reflect testing adequacy. Due to the stabilization of SDR, it was possible to predict with great accuracy the daily needs for new ICU admissions, 12 days ahead of each testing data point, over a period of 10 months, with Pearson r = 0.98 (p = 10-197), RMSE = 7.16. We strongly believe that this metric will help guide the timely decisions of both scientists and government officials to tackle pandemic spread and prevent ICU overload by setting effective testing requirements for accurate pandemic monitoring. We propose further study of this novel metric with data from more countries to confirm the validity of the current findings.

Advancements in detection of SARS-CoV-2 infection for confronting COVID-19 pandemics.

As one of the major approaches in combating the COVID-19 pandemics, the availability of specific and reliable assays for the SARS-CoV-2 viral genome and its proteins is essential to identify the infection in suspected populations, make diagnoses in symptomatic or asymptomatic individuals, and determine clearance of the virus after the infection. For these purposes, use of the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for detection of the viral nucleic acid remains the most valuable in terms of its specificity, fast turn-around, high-throughput capacity, and reliability. It is critical to update the sequences of primers and probes to ensure the detection of newly emerged variants. Various assays for increased levels of IgG or IgM antibodies are available for detecting ongoing or past infection, vaccination responses, and persistence and for identifying high titers of neutralizing antibodies in recovered individuals. Viral genome sequencing is increasingly used for tracing infectious sources, monitoring mutations, and subtype classification and is less valuable in diagnosis because of its capacity and high cost. Nanopore target sequencing with portable options is available for a quick process for sequencing data. Emerging CRISPR-Cas-based assays, such as SHERLOCK and AIOD-CRISPR, for viral genome detection may offer options for prompt and point-of-care detection. Moreover, aptamer-based probes may be multifaceted for developing portable and high-throughput assays with fluorescent or chemiluminescent probes for viral proteins. In conclusion, assays are available for viral genome and protein detection, and the selection of specific assays depends on the purposes of prevention, diagnosis and pandemic control, or monitoring of vaccination efficacy.

Mechanisms of socioeconomic differences in COVID-19 screening and hospitalizations.

BACKGROUND: Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. OBJECTIVE: To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. DESIGN: Observational cohort study. SETTING: Outpatient and emergency care. PATIENTS: 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. INTERVENTIONS: Nasopharyngeal PCR test for SARS-CoV-2 infection. MEASUREMENTS: Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. RESULTS: We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91-3.59] times (at age 20) to 2.37 [1.54-3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. LIMITATIONS: Constraints on availability of test kits forced providers to selectively test for SARS-Cov-2. CONCLUSION: Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates.

COVID-19 Threat to the World: Current and Possible Diagnostic/Treatment Strategies.

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in a world-wide crisis. To contain the virus, it is important to find infected individuals and isolate them to stop transmission. Various diagnostic techniques are used to check for infection. With the havoc that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created, it is imperative to work on alternative diagnostic techniques that can be used at both point of care with little or no expertise and at mass testing (i.e., when screening). Despite extensive research, to this date no specific effective treatment or cure is available to neutralize this viral infection. Globally, researchers are working to develop effective treatments, and several vaccines have been approved for public use. We found the studies that we explored for this review using appropriate key words for indexing in PubMed and Google Scholar from 2019 to 2020. We compile various techniques that have been used worldwide to diagnose and treat SARS-CoV-2 and discuss novel methods that may be modified for use in diagnosis and treatment. It is crucial to develop a more specific serological test for diagnosis that can rule out the possibility of COVID-19 and be used for mass testing. An affordable, safe, targeted, effective treatment must be developed to cure this disease, which has created a public health emergency of international concern.

Neurosurgical Outcomes, Protocols, and Resource Management During Lockdown: Early Institutional Experience from One of the World's Largest COVID 19 Hotspots.

BACKGROUND: As the COVID-19 pandemic surpasses 1 year, it is prudent to reflect on the challenges faced and the management strategies employed to tackle this overwhelming health care crisis. We undertook this study to validate our institutional protocols, which were formulated to cater to the change in volume and pattern of neurosurgical cases during the raging pandemic. METHODS: All admitted patients scheduled to undergo major neurosurgical intervention during the lockdown period (15 March 2020 to 15 September 2020) were included in the study. The data involving surgery outcomes, disease pattern, anesthesia techniques, patient demographics, as well as COVID-19 status, were analyzed and compared with similar retrospective data of neurosurgical patients operated during the same time period in the previous year (15 March 2019 to 15 September 2019). RESULTS: Barring significant increase in surgery for stroke (P = 0.008) and hydrocephalus (P <0.001), the overall case load of neurosurgery during the study period in 2020 was 42.75% of that in 2019 (P < 0.001), attributable to a significant reduction in elective spine surgeries (P < 0.001). However, no significant difference was observed in the overall incidence of emergency and essential surgeries undertaken during the 2 time periods (P = 0.482). There was an increased incidence in the use of monitored anesthesia care techniques during emergency and essential neurosurgical procedures by the anesthesia team in 2020 (P < 0.001). COVID-19 patients had overall poor outcomes (P = 0.003), with significant increase in mortality among those subjected to general anesthesia vis-a-vis monitored anesthesia care (P = 0.014). CONCLUSIONS: Despite a significant decrease in neurosurgical workload during the COVID-19 lockdown period in 2020, the volume of emergency and essential surgeries did not change much compared with the previous year. Surgery in COVID-19 patients is best avoided, unless critical, as the outcome in these patients is not favorable. The employment of monitored anesthesia care techniques like awake craniotomy and regional anesthesia facilitate a better outcome in the ongoing COVID-19 era.

Clinical features and corresponding immune function status of recurrent viral polymerase chain reaction positivity in patients with COVID-19 : A meta- analysis and systematic review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) was declared a global pandemic in March 2020. Since then, several studies have found COVID-19 patients with recurrent viral polymerase chain reaction (PCR) positivity. METHODS: On May 6, 2021, an exhaustive literature search of the Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure databases, Embase, Wan Fang Data, VIP database, Sinomed database, BioRxiv, MedRxiv, and Research Square was conducted to find describing the laboratory indicators of recurrent and non-recurrent viral PCR positivity in patients with COVID-19. The data were statistically analyzed using STATA version 15.0. RESULTS: In total, 22 studies-comprising 5154 laboratory-confirmed COVID-19 cases-were included in the analyses. Patients with less severe COVID-19 illness (i.e. those clinically classified as mild or common-type) seemed to exhibit recurrent PCR positivity more commonly than patients with more severe illness (i.e. those classified as severe or critical). There were also significant differences between the two groups in terms of the rates of headaches and dizziness, in addition to the levels of aspartate aminotransferase, C reactive protein, interleukin-6, and lactate dehydrogenase. Further, there were variations in the ratio of CD4+ T cells/CD8+ T cells on admission to the hospital. CONCLUSION: In comparison to COVID-19 patients with non-recurrent viral PCR positivity, patients with recurrent virus PCR positivity seem to experience more severe immune function suppression upon hospital admission.

Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: An Observational Multicenter Study.

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

Test positivity - Evaluation of a new metric to assess epidemic dispersal mediated by non-symptomatic cases.

Epidemic control may be hampered when the percentage of asymptomatic cases is high. Seeking remedies for this problem, test positivity was explored between the first 60 to 90 epidemic days in six countries that reported their first COVID-19 case between February and March 2020: Argentina, Bolivia, Chile, Cuba, Mexico, and Uruguay. Test positivity (TP) is the percentage of test-positive individuals reported on a given day out of all individuals tested the same day. To generate both country-specific and multi-country information, this study was implemented in two stages. First, the epidemiologic data of the country infected last (Uruguay) were analyzed. If at least one TP-related analysis yielded a statistically significant relationship, later assessments would investigate the six countries. The Uruguayan data indicated (i) a positive correlation between daily TP and daily new cases (r = 0.75); (ii) a negative correlation between TP and the number of tests conducted per million inhabitants (TPMI, r = -0.66); and (iii) three temporal stages, which differed from one another in both TP and TPMI medians (p < 0.01) and, together, revealed a negative relationship between TPMI and TP. No significant relationship was found between TP and the number of active or recovered patients. The six countries showed a positive correlation between TP and the number of deaths/million inhabitants (DMI, r = 0.65, p < 0.01). With one exception -a country where isolation was not pursued-, all countries showed a negative correlation between TP and TPMI (r = 0.74). The temporal analysis of country-specific policies revealed four patterns, characterized by: (1) low TPMI and high DMI, (2) high TPMI and low DMI; (3) an intermediate pattern, and (4) high TPMI and high DMI. Findings support the hypothesis that test positivity may guide epidemiologic policy-making, provided that policy-related factors are considered and high-resolution geographical data are utilized.

COVID-19 in Africa: an ovarian victory?

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly attacks the respiratory system and is characterized by pneumonia, cytokine storm, coagulation disorders and severe immune downregulation. Although public health experts predicted worst outcomes in Africa, the incidence, hospitalization and mortality rates have been lower in Africa compared to other continents. Interestingly, lower incidence and mortality rates have been observed in women from Africa compared to their cohorts from other continents. Also, in the US non-Hispanic Black females have lower COVID-19 and death rates compared to their white counterparts. It's unclear why this significant difference exists; however, the ovarian function, genetics and immunological statuses could play a major role. Women of African descent have elevated levels of estrogen compared with Caucasians hence we anticipate that estrogen might offer some protection against the SARS-CoV-2 infections. The racial differences in lifestyle, age and inaccessibility to contraceptive usage might also play a role. Here, we provide insight on how the high levels of estrogen in African women might contribute to the lower cases and fatalities in Africa. Specifically, estrogen might offer protection against COVID-19 by suppressing hyper-production of cytokines, promoting anti-inflammatory cytokines, stimulating antibody production and suppressing endoplasmic reticulum (ER) stress. This will as well provide useful information on how future pandemics could be managed using Africa as a case study.

The mobility gap: estimating mobility thresholds required to control SARS-CoV-2 in Canada.

BACKGROUND: Nonpharmaceutical interventions remain the primary means of controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until vaccination coverage is sufficient to achieve herd immunity. We used anonymized smartphone mobility measures to quantify the mobility level needed to control SARS-CoV-2 (i.e., mobility threshold), and the difference relative to the observed mobility level (i.e., mobility gap). METHODS: We conducted a time-series study of the weekly incidence of SARS-CoV-2 in Canada from Mar. 15, 2020, to Mar. 6, 2021. The outcome was weekly growth rate, defined as the ratio of cases in a given week versus the previous week. We evaluated the effects of average time spent outside the home in the previous 3 weeks using a log-normal regression model, accounting for province, week and mean temperature. We calculated the SARS-CoV-2 mobility threshold and gap. RESULTS: Across the 51-week study period, a total of 888 751 people were infected with SARS-CoV-2. Each 10% increase in the mobility gap was associated with a 25% increase in the SARS-CoV-2 weekly case growth rate (ratio 1.25, 95% confidence interval 1.20-1.29). Compared to the prepandemic baseline mobility of 100%, the mobility threshold was highest in the summer (69%; interquartile range [IQR] 67%-70%), and dropped to 54% in winter 2021 (IQR 52%-55%); a mobility gap was present in Canada from July 2020 until the last week of December 2020. INTERPRETATION: Mobility strongly and consistently predicts weekly case growth, and low levels of mobility are needed to control SARS-CoV-2 through spring 2021. Mobility measures from anonymized smartphone data can be used to guide provincial and regional loosening and tightening of physical distancing measures.

Implementation of a COVID-19 surveillance programme for healthcare workers in a teaching hospital in an upper-middle-income country.

INTRODUCTION: The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described. MATERIAL AND METHODS: A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020. RESULTS: A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity. CONCLUSION: COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

Rapid SARS-CoV-2 antigen detection potentiates early diagnosis of COVID-19 disease.

As the COVID-19 epidemic is still ongoing, a more rapid detection of SARS-CoV-2 infection such as viral antigen-detection needs to be evaluated for early diagnosis of COVID-19 disease. Here, we report the dynamic changes of SARS-CoV-2 viral antigens in nasopharyngeal swabs of COVID-19 patients and its association with the viral nucleic acid clearance and clinical outcomes. Eighty-five COVID-19 patients were enrolled for detection of SARS-CoV-2 viral antigens, including 57 anti-SARS-CoV-2 antibody negative cases and 28 antibody positive cases. The viral antigen could be detected in 52.63% (30/57) patients with SARS-CoV-2 antibody negative at the early stage of SARS-CoV-2 infection, especially in the first 5 days after disease onset (p = 0.0018) and disappeared in about 8 days after disease onset. Viral antigens were highly detectable in patients with low Ct value (less than 30) of SARS-CoV-2 nucleic acid RT-PCT assay, suggesting the expression of viral antigen was associated with high viral load. Furthermore, positive antigen detection indicated disease progression, nine cases with positive antigen (9/30, 30.0%), in contrast to two cases (2/27, 7.40%) (p = 0.0444) with negative antigen, which progressed into severe disease. Thus, the viral antigens were persistent in early stages of infection when virus was in highly replicating status, and viral antigen detection promises to rapidly screen positive patients in the early stage of SARS-CoV-2 infection.

Statistical methods for comparing test positivity rates between countries: Which method should be used and why?

The test positivity (TP) rate has emerged as an important metric for gauging the illness burden due to COVID-19. Given the importance of COVID-19 TP rates for understanding COVID-related morbidity, researchers and clinicians have become increasingly interested in comparing TP rates across countries. The statistical methods for performing such comparisons fall into two general categories: frequentist tests and Bayesian methods. Using data from Our World in Data (ourworldindata.org), we performed comparisons for two prototypical yet disparate pairs of countries: Bolivia versus the United States (large vs. small-to-moderate TP rates), and South Korea vs. Uruguay (two very small TP rates of similar magnitude). Three different statistical procedures were used: two frequentist tests (an asymptotic z-test and the 'N-1' chi-square test), and a Bayesian method for comparing two proportions (TP rates are proportions). Results indicated that for the case of large vs. small-to-moderate TP rates (Bolivia versus the United States), the frequentist and Bayesian approaches both indicated that the two rates were substantially different. When the TP rates were very small and of similar magnitude (values of 0.009 and 0.007 for South Korea and Uruguay, respectively), the frequentist tests indicated a highly significant contrast, despite the apparent trivial amount by which the two rates differ. The Bayesian method, in comparison, suggested that the TP rates were practically equivalent-a finding that seems more consistent with the observed data. When TP rates are highly similar in magnitude, frequentist tests can lead to erroneous interpretations. A Bayesian approach, on the other hand, can help ensure more accurate inferences and thereby avoid potential decision errors that could lead to costly public health and policy-related consequences.