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1.
Int J Infect Dis ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031343

ABSTRACT

OBJECTIVES: We aimed to validate a newly developed antigen-detecting rapid diagnostic test (Ag-RDT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using anterior nasal specimens. METHODS: Between February 12 and September 30, 2021, 16 patients (age range, <1 month-76 years) were enrolled, and samples were collected simultaneously from anterior nasal and nasopharyngeal sites continuously during hospitalization. The primary endpoints were the diagnostic accuracy of the Ag-RDT and utility of anterior nasal specimens. RESULTS: In total, 226 sets of paired samples were obtained. In 88.2% of specimens, the viral load was high at the nasopharyngeal site. The mean cycle threshold (Ct) values for the anterior nasal and nasopharyngeal sites were 32.4 and 29.9, respectively. Using the real-time polymerase chain reaction results as a reference, the Ag-RDT showed 100% sensitivity up to day 6 of the illness using specimens with moderate or high viral load (Ct <30) from either site. From day 7, the sensitivity was 70.4-90.6% and 83.9-84.6% for the anterior nasal and nasopharyngeal sites, respectively. The specificity remained at 100%. CONCLUSIONS: Our novel Ag-RDT meets the World Health Organization criteria and provides stable sensitivity and specificity and accurate results with anterior nasal specimens.

2.
Clin Microbiol Infect ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031210

ABSTRACT

OBJECTIVES: To compare SARS-CoV-2 RNA load in nasopharyngeal specimens from patients with breakthrough COVID-19 caused by the Delta or Omicron variants. METHODS: Retrospective, observational study including 240 consecutive adult out-patients of whom 121 (74 females;median age, 40 years) had COVID-19 due to Omicron and 119 (65 females;median age, 48 years) caused by the Delta variant. Viral RNA load was quantitated by the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MS, USA). A viability platinum chloride (PtCl4) RT-PCR assay was used to discriminate between potentially infectious viral particles and free (uncapsidated) viral RNA. RESULTS: Overall, viral RNA loads were significantly higher (P=0.003) for the Omicron (median, 8.1 log10 copies/ml;range, 4.0-10.9) than the Delta variant (median, 7.5 log10 copies/ml;range, 3.0-11.6). A trend towards higher viral loads was noticed for Omicron compared to Delta across the following time frames since vaccination: days 16-90 (median, 6.83 vs. 5.88 log10 copies/ml;range, 3.91-10.68 vs. 3.67-9.66;P=0.10);days 91-180 (median, 8.09 vs. 7.46 log10 copies/ml;range, 4.30-10.92 vs. 3.03-11.56;P=0.003) and days 181-330 (median, 8.56 vs. 8.10 log10 copies/ml;range, 6.51-10.29 vs. 3.03-10.61;P=0.11). The PtCl4 treated/untreated RT-PCR CT ratio for N target was slightly higher for Omicron than Delta (median, 0.62;range, 0.57-0.98 vs. median, 0.57;range, 0.61-0.87), although statistical significance was not reached (P=0.10). CONCLUSION: Time elapsed since vaccination has a major impact on SARS-CoV-2 RNA loads in nasopharyngeal specimens, particularly for the Omicron variant. The Omicron variant may be better adapted for replication in the upper respiratory tract than the Delta variant, in which this is unlikely given its more efficient generation of viral particles.

4.
2022 IEEE International Symposium on Information Theory, ISIT 2022 ; 2022-June:963-968, 2022.
Article in English | Scopus | ID: covidwho-2018913

ABSTRACT

Polymerase chain reaction (PCR) testing is the gold standard for diagnosing COVID-19. Unfortunately, the outputs of these tests are imprecise and therefore quantitative group testing methods, which rely on precise measurements, are not applicable. Motivated by the ever-increasing demand to identify individuals infected with SARS-CoV-19, we propose a new model that leverages tropical arithmetic to characterize the PCR testing process. In many cases, some of which are highlighted in this work, tropical group testing is provably more powerful than traditional binary group testing in that it requires fewer tests than classical approaches, while additionally providing a mechanism to identify the viral load of each infected individual. © 2022 IEEE.

5.
Scientific Reports ; 12(1):14544, 2022.
Article in English | MEDLINE | ID: covidwho-2016834

ABSTRACT

SARS-CoV-2 is notable for its extremely high level of viral replication in respiratory epithelial cells, relative to other cell types. This may partially explain the high transmissibility and rapid global dissemination observed during the COVID-19 pandemic. Polymerase chain reaction (PCR) cycle threshold (Ct) number has been widely used as a proxy for viral load based on the inverse relationship between Ct number and amplifiable genome copies present in a sample. We examined two PCR platforms (Centers for Disease Control and Prevention 2019-nCoV Real-time RT-PCR, Integrated DNA Technologies;and TaqPath COVID-19 multi-plex combination kit, ThermoFisher Scientific) for their performance characteristics and Ct distribution patterns based on results generated from 208,947 clinical samples obtained between October 2020 and September 2021. From 14,231 positive tests, Ct values ranged from 8 to 39 and displayed a pronounced bimodal distribution. The bimodal distribution persisted when stratified by gender, age, and time period of sample collection during which different viral variants circulated. This finding may be a result of heterogeneity in disease progression or host response to infection irrespective of age, gender, or viral variants. Quantification of respiratory mucosal viral load may provide additional insight into transmission and clinical indicators helpful for infection control.

6.
Scientific Reports ; 12(1):14637, 2022.
Article in English | MEDLINE | ID: covidwho-2016832

ABSTRACT

Determining accurate estimates for the characteristics of the severe acute respiratory syndrome coronavirus 2 in the upper and lower respiratory tracts, by fitting mathematical models to data, is made difficult by the lack of measurements early in the infection. To determine the sensitivity of the parameter estimates to the noise in the data, we developed a novel two-patch within-host mathematical model that considered the infection of both respiratory tracts and assumed that the viral load in the lower respiratory tract decays in a density dependent manner and investigated its ability to match population level data. We proposed several approaches that can improve practical identifiability of parameters, including an optimal experimental approach, and found that availability of viral data early in the infection is of essence for improving the accuracy of the estimates. Our findings can be useful for designing interventions.

7.
Heliyon ; 8(9):e10525, 2022.
Article in English | ScienceDirect | ID: covidwho-2007724

ABSTRACT

Background Several risk factors have been used to predict severity of coronavirus disease 2019 (COVID-19), real-time reverse transcriptase polymerase chain reaction (RT-PCR) cycle threshold (Ct) values have not been included. Methods A retrospective analysis of laboratory-confirmed COVID-19 patients who were hospitalized between March 2 and September 1, 2020, in an academic hospital in Riyadh that serves as a Middle East respiratory syndrome coronavirus (MERS-CoV) referral center was conducted. Nasopharyngeal (NP) and endotracheal (ET) samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR, and viral load (VL) was determined based on the Ct values of E genes. The Ct values were distributed into four groups, with group Ct1 (≤19) indicating the highest VL and Ct4 (≥31) indicating the lowest VL. Univariate logistic regression was used to analyze age, gender, and comorbidities in relation to Ct groups for a primary endpoint of either invasive mechanical ventilation (IMV) or mortality. Significant variables were further analyzed by multivariate logistic regression. Results The analysis included 728 patients hospitalized with COVID-19 (38% female;median age = 53 years;41.3% diabetic;39.4% hypertensive). Overall, 13.6% of these patients required IMV, and the in-hospital mortality rate was 15.5%. The IMV rate was higher in the Ct1 and Ct2 groups (15.2% and 15.5%, respectively) than in the Ct4 group (6.4%;p = 0.01). The mortality rate was also higher in the Ct1 and Ct2 groups (19.4% and 18.9%, respectively) than in the Ct4 group (8.9%;p = 0.02). The univariate analysis showed that lower Ct values and increasing age were associated with an increased risk of IMV (OR: 1.03;95% CI: 1.01, 1.04;P < 0.0001) and mortality (OR: 1.04;95% CI: 1.03, 1.06;P < 0.0001). The multivariate analysis showed that Ct1 was associated with the highest risk of mortality (OR: 2.29;95% CI: 1.16, 5.52;P = 0.016), while Ct2 was associated with the highest risk of IMV (OR: 3.1;95% CI: 1.47, 6.53;P = 0.003). Conclusion The SARS-CoV-2 RT-PCR Ct values of hospitalized COVID-19 patients can be used as predictors of IMV and mortality, and this effect increases when combined with age. Clinicians could use these predictors to triage older patients for risk stratification and allocate IMV.

8.
Wien Klin Wochenschr ; : 1-6, 2022.
Article in English | PMC | ID: covidwho-2007148

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone different molecular changes, sprouting genetic variants of the original wildtype. Clinical comparisons between patients infected with alpha versus delta are scarce. METHODS: In this retrospective observational study, adult patients hospitalized with coronavirus disease 2019 (COVID-19) due to confirmed SARS-CoV2 alpha or delta infection were included. Patient characteristics, virologic and laboratory parameters, as well as the clinical course were compared in patients infected with alpha vs. delta variants. RESULTS: A total of 106 patients infected with alpha and 215 patients infected with delta were included. Patients infected with the delta variant were admitted to hospital earlier after symptom onset (6 vs. 7 days, p< 0.001). Blood levels of Creactive protein (43.3 vs. 62.9mg/l, p= 0.02) and neutrophil count (3.81 vs. 4.53G/l, p= 0.06) were lower in delta patients. Furthermore, at hospital admission cycle threshold (CT) values were significantly lower in patients infected with the delta variant (22.3 vs. 24.9, p< 0.001). Patients infected with the delta variant needed supplemental oxygen less often during disease course (50% vs. 64%, p= 0.02). Furthermore, there was a statistically non-significant trend towards a lower ICU admission rate among delta patients (16% vs. 24%, p= 0.08) CONCLUSION: Patients diagnosed with the delta variant were admitted to the hospital earlier, had a less severe course of disease and a higher viral replication on admission. This may provide a window of opportunity for antivirals in the hospital setting.

11.
HIV AIDS (Auckl) ; 14: 341-354, 2022.
Article in English | MEDLINE | ID: covidwho-1993630

ABSTRACT

Background: In Ethiopia, second-line anti-retroviral therapy (ART) for HIV/AIDS patients was started some years ago; however, few studies have reported the unfavorable outcomes of second-line ART. Therefore, this study aimed to assess the incidence and predictors of unfavorable outcomes and their association with change in viral load among adult HIV/AIDS patients on second-line treatment at selected public hospitals in Addis Ababa, Ethiopia. Methods: A retrospective follow-up study was conducted at selected public hospitals in Addis Ababa, Ethiopia, on 421 HIV/AIDS patients on second-line ART from 2016 to 2021. Cox proportional hazard models with a linear mixed effect model were jointly modeled using the JM package of R software with time-dependent lagged parameterizations, and a 95% confidence interval was used to select significant variables. Results: Overall, 89 HIV/AIDS patients developed unfavorable outcomes. The incidence density was 7.48/100 person-years (95% CI: 6.08, 9.2). Secondary and tertiary educational level (AHR=0.47, 95% CI: 0.25, 0.89, and AHR=0.27, 95% CI: 0.1, 0.72), CD4 count less than 100 cells/mm3 (AHR=2.15, 95% CI: 1.21, 3.83), poor adherence (AHR=3.59, 95% CI: 1.73, 7.49), and TB comorbidity (AHR=2.23, 95% CI: 1.21, 4.14) at the start of second-line ART were significant predictors of incidence of unfavorable outcome. Time-dependent lagged value viral load was significantly associated with the risk of unfavorable outcome (AHR=1.28, 95% CI: 1.01, 1.63). Conclusion: In the study area, the incidence of an unfavorable outcome of second-line ART was high. Secondary and tertiary educational level, CD4 count less than 100 cells/mm3, poor adherence, and TB comorbidity at the start of second-line ART were significant predictors of incidence of unfavorable outcomes. Thus, strengthening routine viral load measurement, increase patient adherence, intensive counseling, and strong TB screening are needed in the study setting.

12.
Jurnal Respirologi Indonesia ; 42(1):76-85, 2022.
Article in English | CAB Abstracts | ID: covidwho-1994966

ABSTRACT

Background: This study aimed to examine the effectiveness of Remdesivir in reducing Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) viral load and its safety for antiviral therapy in Coronavirus disease 2019 (COVID-19) treatment.

13.
Global Health: Science and Practice ; 10(3), 2022.
Article in English | CAB Abstracts | ID: covidwho-1994496

ABSTRACT

Introduction: We introduce the iDARE methodology and present the results of iDARE implementation in Uganda, Kenya, and Tanzania during the coronavirus disease (COVID-19) pandemic. iDARE Methodology: iDARE drives locally led solutions that address barriers to achieving improved health outcomes. WI-HER supported the governments of Uganda, Kenya, and Tanzania, to design and implement solutions to improve (1) HIV health outcomes, (2) gender-based violence identification and response, and (3) mass drug administration coverage, respectively.

14.
Jurnal Respirologi Indonesia ; 42(1):67-75, 2022.
Article in English | GIM | ID: covidwho-1989879

ABSTRACT

Background: Adverse event studies of favipiravir used to treat COVID-19 have been ongoing since it was established as a treatment option. A better understanding of the side effects of favipiravir from recent studies is important for developing and assessing the introduction of effective treatments for COVID-19. Method: The author conducted a systematic review based on research studies and case reports on favipiravir monotherapy in COVID-19. Access to the included studies is via PubMed, SCOPUS, Science Direct, SpringerLink, and MedRxiv.

15.
European Journal of General Dentistry ; 2022.
Article in English | Scopus | ID: covidwho-1984494

ABSTRACT

Objectives The medical and health facilities are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study tested the preprocedural prophylactic mouthwash rinses to reduce the oral viral load. The findings from this study will help the practitioners to select the best mouthwash for the patients to mitigate the risk of transmission during aerosolizing. This study aimed to evaluate the effectiveness of four commonly used types of mouthwash in reducing intraoral viral load among hospitalized coronavirus disease 2019 patients. Materials and Methods This prospective cohort study was conducted with 116 patients referred to the Masih Daneshvari Hospital in Tehran, Hamadan University of Medical Sciences of Hamadan City, and Mashhad University of Medical Sciences. Patients were randomized into four groups with each group rinsed their mouth with 20 mL of 2% povidone-iodine, 1% hydrogen peroxide, normal saline as a control study group, or 0.12% chlorhexidine, respectively, for 20 seconds. The standard reverse transcription polymerase chain reaction method evaluated the virus load before and at 1 hour, 2 hours, and 4 hours after using the mentioned mouthwash. Results Our results revealed that chlorhexidine and H 2O 2showed the highest efficiency in reducing SARS-Co-2 load in the oral cavity and nasopharyngeal region of patients;they increased the Ct values by 9 to 10 (before: 25.84 vs. after 32. 4, p < 0.455) (17.333 vs. after 26.497, p <0.097). Conclusion Our findings suggest that chlorhexidine and H 2O 2could be used in dental clinics to reduce the risk of transmitting the SARS-CoV-2 virus from infected individuals to dentists before dental procedures. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

16.
Journal of Immunological Methods ; : 113339, 2022.
Article in English | ScienceDirect | ID: covidwho-1983466

ABSTRACT

Summary The “gold standard” method for detection of SARS-CoV-2 is the real time reverse transcription-polymerase chain reaction, but due to pre-analytical and technical limitations, biological samples with low viral load are not sometimes detected. For this purpose a digital RT-PCR method on-chip was developed for detection of the SARS-CoV-2 virus, using two TaqMan™ Assays for quantification of the N Protein (Nucleocapsid) and the S Protein (Spike), and the QuantStudio™ 3D Digital PCR instrument. The method was applied to assess the nasopharyngeal swabs of asymptomatic subjects recruited in the UNICORN Study. The digital RT-PCR method is characterized by a higher sensitivity than the RT-qPCR method, even if performed with the same TaqMan™, and could be a promising tool for SARS-CoV-2 viral load quantification.

17.
Journal of Pure and Applied Microbiology ; : 9, 2022.
Article in English | Web of Science | ID: covidwho-1979856

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To assess the effect of COVID-19 disease on hematology, coagulation profiles, renal and liver function over the course of the disease, the following laboratory tests were performed: WBCs per mm3, lymphocytes count, Platelet, D-dimmer, AST, Albumin, LDH, Ferritin, CRP, blood culture and viral loads. Patients were grouped according to their initial viral load (Group1: low viral load (L), Group 2: moderate viral load (I), and Group 3, high viral load (H)). The study population median age of the patients was 58 years, and 69% were male. Generally, all patients were admitted to the intensive care unit. Most of the patients (79.5%) had an intermediate viral load, 14.5% had a high viral load, and 5.7% had a low viral load. The Kusakal-Walli's test revealed a significant difference in the levels of white blood cells, lymphocytes, platelet, D-dimer, AST, CRP, and ferritin (p <0.0001). One hundred twentytwo isolates were recovered from 5362 blood cultures;where as 75% were multiple resistant to three classes of antibiotics and more. True bacteremia was most commonly caused by Klebsiella pneumoniae (45%), Acinetobacter baumannii (30%), and C. albicans (7%). The potential risk factors of advanced age, lymphopenia, D-dimer concentrations greater than 2??g/mL, and ferritin concentrations greater than 400ng/mL may assist clinicians to improve the management of the case and reduce mortality.

18.
BMC Infect Dis ; 22(1): 672, 2022 Aug 05.
Article in English | MEDLINE | ID: covidwho-1978765

ABSTRACT

BACKGROUND: Factors that lead to successful SARS-CoV-2 transmission are still not well described. We investigated the association between a case's viral load and the risk of transmission to contacts in the context of other exposure-related factors. METHODS: Data were generated through routine testing and contact tracing at a large university. Case viral loads were obtained from cycle threshold values associated with a positive polymerase chain reaction test result from October 1, 2020 to April 15, 2021. Cases were included if they had at least one contact who tested 3-14 days after the exposure. Case-contact pairs were formed by linking index cases with contacts. Chi-square tests were used to evaluate differences in proportions of contacts testing positive. Generalized estimating equation models with a log link were used to evaluate whether viral load and other exposure-related factors were associated with a contact testing positive. RESULTS: Median viral load among the 212 cases included in the study was 5.6 (1.8-10.4) log10 RNA copies per mL of saliva. Among 365 contacts, 70 (19%) tested positive following their exposure; 36 (51%) were exposed to a case that was asymptomatic or pre-symptomatic on the day of exposure. The proportion of contacts that tested positive increased monotonically with index case viral load (12%, 23% and 25% corresponding to < 5, 5-8 and > 8 log10 copies per mL, respectively; X2 = 7.18, df = 2, p = 0.03). Adjusting for cough, time between test and exposure, and physical contact, the risk of transmission to a close contact was significantly associated with viral load (RR = 1.27, 95% CI 1.22-1.32). CONCLUSIONS: Further research is needed to understand whether these relationships persist for newer variants. For those variants whose transmission advantage is mediated through a high viral load, public health measures could be scaled accordingly. Index cases with higher viral loads could be prioritized for contact tracing and recommendations to quarantine contacts could be made according to the likelihood of transmission based on risk factors such as viral load.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Contact Tracing , Humans , Quarantine , Viral Load
19.
J Infect Chemother ; 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1977492

ABSTRACT

INTRODUCTION: Compared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT). METHODS: We prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures. RESULTS: Sixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = -0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL. CONCLUSIONS: In NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.

20.
EBioMedicine ; 83: 104208, 2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1977202

ABSTRACT

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

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