Diagnostic performance of four lateral flow immunoassays for COVID-19 antibodies in Peruvian population.

Serological assays have been used in seroprevalence studies to inform the dynamics of COVID-19. Lateral flow immunoassay (LFIA) tests are a very practical technology to use for this objective; however, one of their challenges may be variable diagnostic performance. Given the numerous available LFIA tests, evaluation of their accuracy is critical before real-world implementation. We performed a retrospective diagnostic evaluation study to independently determine the diagnostic accuracy of 4 different antibody-detection LFIA tests: Now Check (Bionote), CareStart (Access bio), Covid-19 BSS (Biosynex) and OnSite (CTK Biotech). The sample panel was comprised of specimens collected and stored in biobanks; specifically, specimens that were RT-PCR positive for SARS-CoV-2 collected at various times throughout the COVID-19 disease course and those that were collected before the pandemic, during 2018 or earlier, from individuals with upper respiratory symptoms but were negative for tuberculosis. Clinical performance (sensitivity and specificity) was analyzed overall, and subset across individual antibody isotypes, and days from symptoms onset. A very high specificity (98% - 100%) was found for all four tests. Overall sensitivity was variable, ranging from 29% [95% CI: 21%-39%] to 64% [95% CI: 54%-73%]. When considering detection of IgM only, the highest sensitivity was 42% [95% CI: 32%-52%], compared to 57% [95% CI: 47%-66%] for IgG only. When the analysis was restricted to at least 15 days since symptom onset, across any isotype, the sensitivity reached 90% for all four brands. All four LFIA tests proved effective for identifying COVID-19 antibodies when two conditions were met: 1) at least 15 days have elapsed since symptom onset and 2) a sample is considered positive when either IgM or IgG is present. With these considerations, the use of this assays could help in seroprevalence studies or further exploration of its potential uses.

Integrating tuberculosis and COVID-19 molecular testing in Lima, Peru: a cross-sectional, diagnostic accuracy study.

BACKGROUND: Integrated molecular testing could be an opportunity to detect and provide care for both tuberculosis and COVID-19. Many high tuberculosis burden countries, such as Peru, have existing GeneXpert systems for tuberculosis testing with GeneXpert Xpert MTB/RIF Ultra (Xpert Ultra), and a GeneXpert SARS-CoV-2 assay, GeneXpert Xpert Xpress SARS-CoV-2 (Xpert Xpress), is also available. We aimed to assess the feasibility of integrating tuberculosis and COVID-19 testing using one sputum specimen with Xpert Ultra and Xpert Xpress in Lima, Peru. METHODS: In this cross-sectional, diagnostic accuracy study, we recruited adults presenting with clinical symptoms or suggestive history of tuberculosis or COVID-19, or both. Participants were recruited from a total of 35 primary health facilities in Lima, Peru. Participants provided one nasopharyngeal swab and one sputum sample. For COVID-19, we tested nasopharyngeal swabs and sputum using Xpert Xpress; for tuberculosis, we tested sputum using culture and Xpert Ultra. We compared diagnostic accuracy of sputum testing using Xpert Xpress with nasopharyngeal swab testing using Xpert Xpress. Individuals with positive Xpert Xpress nasopharyngeal swab results were considered COVID-19 positive, and a positive culture indicated tuberculosis. To assess testing integration, the proportion of cases identified in sputum by Xpert Xpress was compared with Xpert Xpress on nasopharyngeal swabs, and sputum by Xpert Ultra was compared with culture. FINDINGS: Between Jan 11, 2021, and April 26, 2022, we recruited 600 participants (312 [52%] women and 288 [48%] men). In-study prevalence of tuberculosis was 13% (80 participants, 95% CI 11-16) and of SARS-CoV-2 was 35% (212 participants, 32-39). Among tuberculosis cases, 13 (2·2%, 1·2-3·7) participants were concurrently positive for SARS-CoV-2. Regarding the diagnostic yield of integrated testing, Xpert Ultra detected 96% (89-99) of culture-confirmed tuberculosis cases (n=77), and Xpert Xpress-sputum detected 67% (60-73) of COVID-19 cases (n=134). All five study staff reported that integrated molecular testing was easy and acceptable. INTERPRETATION: The diagnostic yield of Xpert Xpress on sputum was moderate, but integrated testing for tuberculosis and COVID-19 with GeneXpert was feasible. However, systematic testing for both diseases might not be the ideal approach for everyone presenting with presumptive tuberculosis or COVID-19, as concurrent positive cases were rare during the study period. Further research might help to identify when integrated testing is most worthwhile and its optimal implementation. FUNDING: Canadian Institutes of Health Research and International Development Research Centre. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Diagnostic performance of GENEDIA W and ActiveXpress+ COVID-19 antigens tests among symptomatic individuals in Peru and The United Kingdom.

OBJECTIVES: In order to generate independent performance data regarding accuracy of COVID-19 antigen-based rapid diagnostic tests (Ag-RDTs), prospective diagnostic evaluation studies across multiple sites are required to evaluate their performance in different clinical settings. This report describes the clinical evaluation the GENEDIA W COVID-19 Ag Device (Green Cross Medical Science Corp., Chungbuk, Korea) and the ActiveXpress+ COVID-19 Complete Testing Kit (Edinburgh Genetics Ltd, UK), in two testing sites Peru and the United Kingdom. METHODS: Nasopharyngeal swabs collected from 456 symptomatic patients at primary points of care in Lima, Peru and 610 symptomatic participants at a COVID-19 Drive-Through testing site in Liverpool, England were analyzed by Ag-RDT and compared to RT-PCR. Analytical evaluation of both Ag-RDTs was assessed using serial dilutions of direct culture supernatant of a clinical SARS-CoV-2 isolate from the B.1.1.7 lineage. RESULTS: For GENEDIA brand, the values of overall sensitivity and specificity were 60.4% [95% CI 52.4-67.9%], and 99.2% [95% CI 97.6-99.7%] respectively; and for Active Xpress+ the overall values of sensitivity and specificity were 66.2% [95% CI 54.0-76.5%], and 99.6% [95% CI 97.9-99.9%] respectively. The analytical limit of detection was determined at 5.0 x 102 pfu/ml what equals to approximately 1.0 x 104 gcn/ml for both Ag-RDTs. The UK cohort had lower median Ct values compared to that of Peru during both evaluations. When split by Ct, both Ag-RDTs had optimum sensitivities at Ct<20 (in Peru; 95% [95% CI 76.4-99.1%] and 100.0% [95% CI 74.1-100.0%] and in the UK; 59.2% [95% CI 44.2-73.0%] and 100.0% [95% CI 15.8-100.0%], for the GENDIA and the ActiveXpress+, respectively). CONCLUSIONS: Whilst the overall clinical sensitivity of the Genedia did not meet WHO minimum performance requirements for rapid immunoassays in either cohort, the ActiveXpress+ did so for the small UK cohort. This study illustrates comparative performance of Ag-RDTs across two global settings and considers the different approaches in evaluation methods.

Integrated testing for TB and COVID-19.

Integrated testing for TB and COVID-19 may help find those TB patients who are not accessing care in the context of the COVID-19 pandemic. Some molecular platforms with assays for both diseases are already commercially available; however, integrated testing approaches need to be systematically evaluated to ensure their appropriate implementation.

Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial.

OBJECTIVE: To assess the effectiveness and safety of hydroxychloroquine (HCQ) prophylaxis for the prevention of SARS-CoV-2 infection in healthcare workers (HCW) on duty during the COVID-19 pandemic. RESULTS: A total of 68 HCWs met the eligibility criteria were randomly allocated to receive HCQ (n = 36) or not (n = 32). There were no significant differences between groups in respects to age, gender, or medical history. Eight participants met the primary efficacy endpoint of SAR-CoV-2 infection during the study period; there was no difference in incidence of SARS-CoV-2 infections between both study arms (HCQ: 5 vs Control: 3, p = 0.538). The relative risk of SARS-CoV-2 infection in the HCQ arm was 1.69 compared to the control group (95%CI 0.41-7.11, p = 0.463); due to poor participant accrual, the resulting statistical power of the primary efficacy outcome was 11.54%. No serious adverse events occurred; however, two (2/36, 5.6%) participants no longer wished to participate in the study and withdrew consent due to recurring grade 1 and 2 adverse events. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04414241. (Registered on June 4, 2020).

Tuberculosis and comorbidities: treatment challenges in patients with comorbid diabetes mellitus and depression.

Tuberculosis is one of the leading causes of death worldwide, primarily affecting low- and middle income countries and individuals with limited-resources within fractured health care systems. Unfortunately, the COVID-19 pandemic has only served to aggravate the already existing diagnostic gap, decreasing the number of people who get diagnosed and thereby complete successful treatment. In addition to this, comorbidities act as an external component that when added to the TB management equation, renders it even more complex. Among the various comorbidities that interact with TB disease, diabetes mellitus and depression are two of the most prevalent among non-communicable diseases within the TB population and merits a thoughtful consideration when the healthcare system provides care for them. TB patients with diabetes mellitus (TB-DM) or depression both have an increased risk of mortality, relapse and recurrence. Both of these diseases when in presence of TB present a 'vicious-circle-like' mechanism, meaning that the effect of each disease can negatively add up, in a synergistic manner, complicating the patient's health state. Among TB-DM patients, high glucose blood levels can decrease the effectiveness of anti-tuberculosis drugs; however, higher doses of anti-tuberculous drugs could potentially decrease the effects of DM drugs. Among the TB-depression patients, not only do we have the adherence to treatment problems, but depression itself can biologically shift the immunological profile responsible for TB containment, and the other way around, TB itself can alter the hormonal balance of several neurotransmitters responsible for depression. In this paper, we review these and other important aspects such as the pharmacological interactions found in the treatment of TB-DM and TB-depression patients and the implication on TB care and pharmacological considerations.

COVID-19 in Latin America and the Caribbean: Two years of the pandemic.

Worldwide, nations have struggled during the coronavirus disease 2019 (COVID-19) pandemic. However, Latin America and the Caribbean faced an unmatched catastrophic toll. As of March 2022, the region has reported approximately 15% of cases and 28% of deaths worldwide. Considering the relatively late arrival of SARS-CoV-2, several factors in the region were determinants of the humanitarian crisis that ensued. Pandemic unpreparedness, fragile healthcare systems, forthright inequalities, and poor governmental support facilitated the spread of the virus throughout the region. Moreover, reliance on repurposed and ineffective drugs such as hydroxychloroquine and ivermectin-to treat or prevent COVID-19-was publicised through misinformation and created a false sense of security and poor adherence to social distancing measures. While there were hopes that herd immunity could be achieved after the region's disastrous first peak, the emergence of the Gamma, Lambda, and Mu variants made this unattainable. This review explores how Latin America and the Caribbean fared during the first 2 years of the pandemic, and how, despite all the challenges, the region became a global leader in COVID-19 vaccination, with 63% of its population fully vaccinated.

Randomized clinical trial to compare the efficacy of ivermectin versus placebo to negativize nasopharyngeal PCR in patients with early COVID-19 in Peru (SAINT-Peru): a structured summary of a study protocol for randomized controlled trial.

OBJECTIVES: The primary objective is to determine the effect of a daily dose of ivermectin administered in three consecutive days to non-severe COVID-19 patients with no more than 96 hours of symptoms, on the detection of SARS-CoV-2 RNA by PCR from nasopharyngeal swabs at day seven post-treatment initiation. The secondary objectives are: 1. To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab on days 4, 7, 14 and 21 post-treatment initiation 2. To assess the efficacy of ivermectin on the improvement of symptoms 3. To assess the proportion of seroconversions at day 21 4. To assess the safety of ivermectin at the proposed dose 5. To determine the magnitude of the immune response against SARS-CoV-2 6. To assess correlation of the presence of intestinal helminths on participants on baseline and day 14 with COVID-19 progression and treatment. TRIAL DESIGN: SAINT PERU is a triple-blinded, randomized, placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection. PARTICIPANTS: The trial is conducted in two national hospitals in Lima-Peru. The study population is patients with a positive PCR test for SARS-CoV-2 in a nasopharyngeal specimen, symptomatic for 96 hours or less, with non-severe COVID-19 disease at baseline, regardless of the presence of risk factors for progression to severity. The study will not include pregnant women or minors (17 years old or younger). Inclusion criteria 1. COVID-19 symptomatology (cough, fever, anosmia, etc.) lasting no more than 96 hours, with a positive nasopharyngeal swab PCR test for SARS-CoV-2. 2. 18 years or older. 3. No use of ivermectin in the month prior to the visit. 4. No known history of ivermectin allergy. 5. Capable to give informed consent. 6. Not current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, cobicistat or critical CYP3A4 substrate drugs such as warfarin. Exclusion criteria 1. COVID-19 pneumonia diagnosed by the attending physician (oxygen saturation < 95% or lung examination) 2. Positive pregnancy test for women at childbearing age. 3. Positive IgG against SARS-CoV-2 by rapid diagnostic test at screening. Participants will be recruited by the investigators at the emergency services of the study sites. They are expected to remain in the trial for a period of 21 days. Follow-up visits will be conducted by the trial medical staff at the participant's home or at a hospital in case of hospitalization. Follow-up visits will assess clinical and laboratory parameters of the patients. INTERVENTION AND COMPARATOR: Ivermectin (300 mcg/kg) or placebo will be administered in one daily dose for three consecutive days. Currently, there is no solid data on the efficacy of ivermectin against the virus in vivo; therefore the use of placebo in the control group is ethically justified. MAIN OUTCOMES: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1. Mean viral load as determined by PCR cycle threshold (Ct) on days 4, 7, 14, and 21 2. Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial 2. Proportion of patients with a positive rapid diagnostic test at day 21 3. Proportion of drug-related adverse events during the trial 4. Median levels of IgG, IgM, IgA measured by Luminex RANDOMIZATION: Participants will be randomized to receive one dose of 300 mcg/kg ivermectin or placebo daily for three consecutive days. The epidemiologist will generate a list of correlative numbers, in randomized blocks of size 4, with the assignment to the treatment groups (a and b). The randomization list will be kept in an encrypted file accessible only to the trial statistician. This list will be handed directly to the pharmacist. Independently, the principal investigator will randomly assign the intervention (ivermectin) to one of the two groups (a or b) by tossing a coin, and will inform the pharmacist of the result of this process. The pharmacist will prepare and label the treatment vials according to the randomization list prepared by the epidemiologist and the treatment assignment given by the principal investigator. Eligible patients will be allocated in a 1:1 ratio using this randomization list. BLINDING (MASKING): The clinical trial team, the statistician, and the patients will be blinded as to arm allocation. The vials with placebo will be visibly identical to the ones with the active drug. Treatment will be administered by staff not involved in the clinical care or participant's follow up. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The planned sample size is 186 SARS-CoV-2 PCR positive patients: 93 patients to treatment and 93 to the placebo group. TRIAL STATUS: Current protocol version: 2.0 dated January 15th, 2021. Recruitment started on Aug 29th, 2020. Recruitment is expected to be completed April 30th 2021. TRIAL REGISTRATION: "Ensayo Clínico aleatorizado de Fase IIa para comparar la efectividad de la ivermectina versus placebo en la negativización del PCR en pacientes en fase temprana de COVID-19" Peru National Health Institute REPEC with number: PER-034-20 , registered July 17th 2020 (National Peruvian Registration before the first participant enrolled). "Randomized Phase IIA Clinical Trial to Evaluate the Efficacy of Ivermectin to Obtain Negative PCR Results in Patients With Early Phase COVID-19" Clinicaltrials.gov: NCT04635943 , retrospectively registered in November 19th 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.