Nucleic Acid Testing Research Articles

Logistic regression analysis of the value of biomarkers, clinical symptoms, and imaging examinations in COVID-19 for SARS-CoV-2 nucleic acid detection.

The detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid detection provides a direct basis for diagnosing Coronavirus Disease 2019. However, nucleic acid test false-negative results are common in practice and may lead to missed diagnosis. Certain biomarkers, clinical symptoms, and imaging examinations are related to SARS-CoV-2 nucleic acid detection and potential predictors. We examined nucleic acid test results, biomarkers, clinical symptoms, and imaging examination data for 116 confirmed cases and asymptomatic infections in Zhuhai, China. Patients were divided into nucleic acid-positive and -false-negative groups. Predictive values of biomarkers, symptoms, and imaging for the nucleic acid-positive rate were calculated by Least Absolute Shrinkage and Selection Operators regression analysis and binary logistic regression analysis, and areas under the curve of these indicators were calculated. Hemoglobin (OR = 1.018, 95% CI: 1.006-1.030; P = .004) was higher in the respiratory tract-positive group than the nucleic acid-negative group, but platelets (OR = 0.996, 95% CI: 0.993-0.999; P = .021) and eosinophils (OR = 0.013, 95% CI: 0.001-0.253; P = .004) were lower; areas under the curve were 0.563, 0.614, and 0.642, respectively. Some biomarkers can predict SARS-CoV-2 viral nucleic acid detection rates in Coronavirus Disease 2019 and are potential auxiliary diagnostic tests.

Atom-Modified gDNA Enhances Cleavage Activity of TtAgo Enabling Ultra-Sensitive Nucleic Acid Testing.

The DNA-guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2'-fluorine (2'F)-modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2'F-nucleotides at the 3'-end (2'F-gDNA) can promote the assembly of the TtAgo-guide-target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40-fold activity enhancement and decreasing minimum reaction temperature from 65 to 60°C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2'F-gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G-quadruplex and Thioflavin T, the FAST assay achieves one-pot real-time fluorescence analysis with ultra-sensitivity, providing a limit of detection up to 5 copies (20µL reaction mixture) for miR-21 detection. In summary, an atom-modification-based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo-based nucleic acid testing technology with ultra-sensitivity and high-specificity.

Severe fever with thrombocytopenia syndrome with central nervous system symptom onset: a case report and literature review

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported.Case presentationA 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis.ConclusionThis case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.

Efficacy and safety of Chinese herbal medicine to prevent and treat COVID-19 household close contacts in Hong Kong: an open-label, randomized controlled trial

ObjectivesTo evaluate the efficacy and safety of CHM in the prevention of COVID-19 infection and treatment for COVID-19 related symptoms.DesignProspective open-label randomized controlled trial.SettingParticipants’ home in Hong Kong.ParticipantsParticipants who had household close contact with COVID-19-infected family members.InterventionsClose contacts were stratified into 4 groups (cohort A, B, C, D) based on symptoms and infection status and were randomized in 4:1 ratio to receive CHM granules (9g/sachet, two times daily) or blank control for 7 days with 2 weeks of follow-up.Main outcome measuresThe primary outcome measure was the rate of positive nucleic acid tests. Secondary outcomes were the proportion of developed COVID-19 related symptoms and adverse events during the whole 3-week study period. Subgroup analysis was used to evaluate demographic factors associated with positive infection rates.ResultsA total of 2163 contacts were enrolled and randomly assigned to the CHM group (1720 contacts) and blank control (443 contacts) group. During the 21 days, the rate of PCR-positive cases in cohort A was markedly lower in the CHM group (3.6%) compared to the control group (7.0%) (P=0.036). Overall, the rate of infection in the CHM group was significantly lower than that in the control group (10.69% vs. 6.03%; RR 0.56, 95% CI 0.39-0.82) after 7-day treatment. No serious adverse events were reported during the medication period.ConclusionThe preliminary findings indicate that CHM may be effective and safe in preventing COVID-19. Future double-blind, randomized controlled trials and long-term follow-up are needed to fully evaluate the efficacy of CHM in a larger contact population.Clinical trial registrationClinicalTrials.gov, identifier NCT05269511

Development of advanced control material for reverse transcription-mediated bacterial nucleic acid amplification tests.

Detection of bacterial RNA by nucleic acid amplification tests (NAATs), such as reverse transcription PCR (RT-PCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP), offers distinct advantages over DNA-based methods. However, such assays also present challenges in ascertaining positive and internal control material that can reliably monitor success over all phases of testing (bacterial lysis, nucleic acid recovery, reverse transcription, amplification, and signal detection): since they are unable to distinguish between amplification of bacterial RNA transcripts and the DNA templates that encode them, using intact organisms as controls can inform cell lysis but not successful detection of RNA. We developed a control strategy for RNA-based bacterial NAATs that allows ready discrimination of RNA from DNA templates using self-splicing bacterial introns, such that those nucleic acids ultimately encode different sequences. We engineered two vectors encoding synthetic transgenes based on this principle, one that is active in the Gram-negative bacterium Escherichia coli and one that functions in both E. coli and the Gram-positive organism Staphylococcus aureus. We subsequently designed RT-LAMP assays that either target RNA and DNA from transgenic organisms or target RNA exclusively and demonstrated the specificity of amplification using purified nucleic acids. Using multiplex fluorescent RT-LAMP of heat-lysed specimens, we showed the practicality of deploying such transgenic organisms as an internal control to ascertain sample integrity and assay performance during clinical diagnostic testing. Our approach has broad utility for RNA-based bacterial NAATs, especially point-of-care assays and other applications where nucleic acids are nonspecifically liberated for testing.

A Wax Interface-Enabled One-Pot Multiplexed Nucleic Acid Testing Platform for Rapid and Sensitive Detection of Viruses and Variants.

High-quality, low-cost, and rapid detection is essential for the society to reopen the economy during the critical period of transition from Coronavirus Disease 2019 (COVID-19) pandemic response to pandemic control. In addition to performing sustainable and target-driven tracking of SARS-CoV-2, conducting comprehensive surveillance of variants and multiple respiratory pathogens is also critical due to the frequency of reinfections, mutation immune escape, and the growing prevalence of the cocirculation of multiple viruses. By utilizing a 0.05 cents wax interface, a Stable Interface assisted Multiplex Pathogenesis Locating Estimation in Onepot (SIMPLEone) using nested RPA and CRISPR/Cas12a enzymatic reporting system is successfully developed. This smartphone-based SIMPLEone system achieves highly sensitive one-pot detection of SARS-CoV-2 and its variants, or multiple respiratory viruses, in 40 min. A total of 89 clinical samples, 14 environmental samples, and 20 cat swab samples are analyzed by SIMPLEone, demonstrating its excellent sensitivity (3-6 copies/reaction for non-extraction detection of swab and 100-150 copies/mL for RNA extraction-based assay), accuracy (>97.7%), and specificity (100%). Furthermore, a high percentage (44.2%) of co-infection cases are detected in SARS-CoV-2-infected patients using SIMPLEone's multiplex detection capability.

Research status of colloidal gold detection technology in medicine

Research status of colloidal gold detection technology in medicine

Second time’s the charm? Assessing the sensitivity and yield of inpatient diagnostic algorithms for pulmonary tuberculosis in a low-prevalence setting

Abstract Background Among persons with suspected pulmonary tuberculosis, CDC guidelines recommend collecting three respiratory specimens 8-24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to one nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of one, two, or three AFB smears +/- NAAT to detect pulmonary tuberculosis in a low-prevalence setting. Methods We conducted a retrospective study of hospitalized persons at eight Massachusetts acute care facilities who underwent mycobacterial culture on one or more respiratory specimens between July 2016–December 2022. We evaluated percent positivity and yield on serial AFB smears and on NAAT among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Results Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41/104 cases (39%). A second AFB smear was positive in 11/49 cases (22%) in which it was performed. No third AFB smears were positive following two initial negative smears. 36/52 smear-negative cases had NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving one or two NAATs (74-79%), even without AFB smears, compared with three smears alone (60%). Conclusions Tuberculosis diagnostic testing with two AFB smears offered the same yield as three AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of one or two NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.

West Nile and Usutu viruses are efficiently inactivated in platelet concentrates by UVC light using the THERAFLEX UV-Platelets system.

West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne flaviviruses (Flaviviridae) that originated in Africa, have expanded their geographical range during the last decades and caused documented infections in Europe in the last years. Acute WNV and USUV infections have been detected in asymptomatic blood donors by nucleic acid testing. Thus, inactivation of both viral pathogens before blood transfusion is necessary to ensure blood product safety. This study aimed to investigate the efficacy of the THERAFLEX UV-Platelets system to inactivate WNV and USUV in platelet concentrates (PCs). Plasma-reduced PCs were spiked with the virus suspension. Spiked PC samples were taken after spiking (load and hold sample) and after UVC illumination on the Macotronic UV illumination machine with different light doses (0.05, 0.1, 0.15 and 0.2 (standard) J/cm2). Virus loads of WNV and USUV before and after illumination were measured by titration. Infectivity assays showed that UVC illumination inactivated WNV and USUV in a dose-dependent manner. At a UVC dose of 0.2 J/cm2, the WNV titre was reduced by a log10 factor of 3.59 ± 0.43 for NY99 (lineage 1) and 4.40 ± 0.29 for strain ED-I-33/18 (lineage 2). USUV titres were reduced at the same UVC dose by a log10 factor of 5.20 ± 0.70. Our results demonstrate that the THERAFLEX UV-Platelets procedure is an effective technology to inactivate WNV and USUV in contaminated PCs.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103-106 CFU/sample for soil and liver samples. The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases.

A portable, easy-to-use paper-based biosensor for rapid in-field detection of fecal contamination on fresh produce farms

Laboratory-based nucleic acid amplification tests (NAATs) are highly sensitive and specific, but they require the transportation of samples to centralized testing facilities and have long turnaround times. During the Coronavirus Disease 2019 (COVID-19) pandemic, substantial advancement has been achieved with the development of paper-based point-of-care (POC) NAATs, offering features such as low cost, being easy to use, and providing rapid sample-to-answer times. Although most of the POC NAATs innovations are towards clinical settings, we have developed a portable, paper-based loop-mediated isothermal amplification (LAMP) testing platform for on-farm applications, capable of detecting Bacteroidales as a fecal contamination biomarker. Our integrated platform includes a drop generator, a heating and imaging unit, and paper-based biosensors, providing sensitive results (limit of detection 3 copies of Bacteroidales per cm2) within an hour of sample collection. We evaluated this integrated platform on a commercial lettuce farm with a concordance of 100% when compared to lab-based tests. Our integrated paper-based LAMP testing platform holds great promise as a reliable and convenient tool for on-site NAATs. We expect that this innovation will encourage the fresh produce industry to adopt NAATs as a complementary tool for decision-making in growing and harvesting. We also hope that our work can stimulate further research in the development of on-farm diagnostic tools for other agricultural applications, leading to improved food safety and technology innovation.

Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT)

IntroductionA prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test—called the Genital InFlammation Test (GIFT)—for detecting genital inflammation associated with sexually...

Multi-objective robust optimization of staff scheduling for emergency under stochastic demand

Large-scale centralized emergency rescue staff scheduling under emergencies has always been a challenge. With a specific focus on nucleic acid testing amid the COVID-19 pandemic, this study introduces a model that considers dynamic changes in staff supply at rescue points, the varying demand at sampling points over time, and their impact on the spread of the epidemic. We quantified the emergency weight of sampling points by the demand and the regional risk degree and adopted robust optimization with base constraint. With the objectives of minimum comprehensive service distance, maximum weighted value of demand satisfaction rate, and minimum loss caused by unmet demand, a multi-stage, multi-medical rescue point medical staff scheduling model for nucleic acid sampling points with the influence caused by uncertain demand disturbance was built, and an improved NSGA-II-HC algorithm was designed to solve the optimization problem under the influence of demand disturbances. The testing results proved that the NSGA-II-HC algorithm can tackle the issue of insufficient uniformity and diversity in the solution set of NSGA-II while Multi-Objective Particle Swarm Optimization (MOPSO) failed to do so. Taking the epidemic data of Guangzhou city in May 2021 as a case study, our model and algorithm are verified to be feasible. We offer a scheme selection strategy according to the loss degree of two conflicting objectives, the comprehensive service distance and shortage loss. The results suggest that, compared with the demand deterministic model, the decision mechanism under the robust model can reduce the deviation from the optimization objective due to the demand disruption

Evolution and Impact of Nucleic Acid Amplification Test (NAAT) for Diagnosis of Coronavirus Disease.

Evolution and Impact of Nucleic Acid Amplification Test (NAAT) for Diagnosis of Coronavirus Disease.

Unveiling Complexity: A Case Study of Evans Syndrome Secondary to Atypical Pneumonia

Evans syndrome (ES) is a combined presentation of immune thrombocytopenia along with autoimmune hemolytic anemia with a positive direct antihuman globulin test. Approximately half of the cases of ES may be secondary to diverse causes, including infections, systemic autoimmune, transplantation, and lymphoproliferative syndromes. We discuss a 53-year-old male who came with complaints of low-grade fever, breathlessness, and cough and was found to have low hemoglobin levels and reduced platelet count. His Coomb’s test was positive, and his chest X-ray suggested pneumonia. The serum nucleic acid amplification test was positive for mycoplasma. A diagnosis of atypical pneumonia with ES was confirmed.

Molecular identification of the bacterium acute conjunctivitis by the method of sequensing gen 16S rRNA

Conjunctivitis is the most common eye disease, characterized by contextual inflammation, which can be caused by bacteria. The diagnosis of conjunctivitis is established based various factors, including the patients’s medical history, onset of eye symptoms, non-ocular symptoms, previous disease history, family medical history, allergies, and physical examination of the eyes, which may include assessments of visual acuity and vision field. Some cases of conjunctivitis require laboratory examinations to confirm the diagnosis. These may include cytological examination with Giemsa staining, Chlamydia Diagnostic Test, Nucleic acid amplification tests (NAATs) or Polymerase chain reaction (PCR), and microbiological tests. Microbiological examination helps identify the bacteria responsible for conjunctivitis and aids in treatment by prescribing antibiotics to suppress the growth of the infecting bacteria. While identification tests are not routinely performed, researchers often seek to determine the specific type of bacteria causing conjunctivitis infections, which may require several laboratory tests. Bacterial virulence plays a significant role, with genetic mutations potentially leading to severe infections of varying severity. Virulence genes encode proteins that express pathogenic properties. The species responsible for conjunctivitis can be definitively identified definitively through microbiological examination, utilizing methods such as the 16S Ribosomal RNA Sequencing (rRNA) technique, known for its accuracy and speed. This study aims to analyze the results of rRNA sequencing in cases of acute bacterial conjunctivitis caused by 16S rRNA genotyping. The research employed an exploratory metholodolot, with the results analyzed using the The Basic Local Alignment Search Tool (BLAST) tracking program database on the National Center for Biotechnology Information (NCBI) website. The findings revealed that Sphingomonas paucimobilis encoded the 16S rRNA using Universal Primary 27 F and 1492 R, obtained in a sequence size of 1351bp. The isolate demonstrated similarities to Sphingomonas paucimobilis.

Severe BCG immune reconstitution inflammatory syndrome lymphadenitis successfully managed with pre-antiretroviral counseling and a non-surgical approach: a case report

BackgroundBacillus Calmette-Guérin (BCG) reactions are the most common cause of immune reconstitution inflammatory syndrome (IRIS) in HIV-positive infants who initiate antiretroviral therapy (ART). There is limited evidence regarding the incidence of BCG-IRIS; however, reports from outpatient cohorts have estimated that 6–9% of infants who initiated ART developed some form of BCG-IRIS within the first 6 months. Various treatment approaches for infants with BCG-IRIS have been reported, but there is currently no widely accepted standard-of-care.Case PresentationA 5-month-old male HIV-exposed infant BCG vaccinated at birth was admitted for refractory oral candidiasis, moderate anemia, and moderate acute malnutrition. He had a HIV DNA-PCR collected at one month of age, but the family never received the results. He was diagnosed with HIV during hospitalization with a point-of-care nucleic acid test and had severe immune suppression with a CD4 of 955 cells/µL (15%) with clinical stage III disease. During pre-ART counseling, the mother was educated on the signs and symptoms of BCG-IRIS and the importance of seeking follow-up care and remaining adherent to ART if symptoms arose. Three weeks after ART initiation, he was readmitted with intermittent subjective fevers, right axillary lymphadenopathy, and an ulcerated papule over the right deltoid region. He was subsequently discharged home with a diagnosis of local BCG-IRIS lymphadenitis. At six weeks post-ART initiation, he returned with suppurative lymphadenitis of the right axillary region that had completely eviscerated through the skin without signs of disseminated BCG disease. He was then started on an outpatient regimen of topical isoniazid, silver nitrate, and oral prednisolone. Throughout this time, the mother maintained good ART adherence despite this complication. After 2.5 months of ART and one month of specific treatment for the lymphadenitis, he had marked mass reduction, improved adenopathy, increased CD4 count, correction of anemia, and resolution of his acute malnutrition. He completely recovered and was symptom free two months after initial treatment without surgical intervention.ConclusionsThis case details the successful management of severe suppurative BCG-IRIS with a non-surgical approach and underlines the importance of pre-ART counseling on BCG-IRIS for caregivers, particularly for infants who initiate ART with advanced HIV.

Performances of two rapid LAMP-based techniques for the intrapartum detection of Group B Streptococcus vaginal colonization

PurposeGroup B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods.MethodsWe compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area.ResultsA total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3–92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7–99.8), and 91.9% (95% CI 87.3–95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001).ConclusionBoth techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies.

Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system

In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on the patient population studied. We aimed to analyse severe COVID-19 outcomes and to investigate the effects of the pandemic time period and the risks associated with individual IMIDs, classes of immunomodulatory medications (IMMs), chronic comorbidities, and COVID-19 vaccination status. In this retrospective cohort study, clinical data were derived from the electronic health records of an integrated health-care system serving patients in 51 hospitals and 1085 clinics across seven US states (Providence St Joseph Health). Data were observed for patients (no age restriction) with one or more IMID and for unmatched controls without IMIDs. COVID-19 was identified with a positive nucleic acid amplification test result for SARS-CoV-2. Two timeframes were analysed: March 1, 2020-Dec 25, 2021 (pre-omicron period), and Dec 26, 2021-Aug 30, 2022 (omicron-predominant period). Primary outcomes were hospitalisation, mechanical ventilation, and mortality in patients with COVID-19. Factors, including IMID diagnoses, comorbidities, long-term use of IMMs, and COVID-19 vaccination status, were analysed with multivariable logistic regression (LR) and extreme gradient boosting (XGB). Of 2 167 656 patients tested for SARS-CoV-2, 290 855 (13·4%) had confirmed COVID-19: 15 397 (5·3%) patients with IMIDs and 275 458 (94·7%) without IMIDs. In the pre-omicron period, 169 993 (11·2%) of 1 517 295 people who were tested for COVID-19 tested positive, of whom 23 330 (13·7%) were hospitalised, 1072 (0·6%) received mechanical ventilation, and 5294 (3·1%) died. Compared with controls, patients with IMIDs and COVID-19 had higher rates of hospitalisation (1176 [14·6%] vs 22 154 [13·7%]; p=0·024) and mortality (314 [3·9%] vs 4980 [3·1%]; p<0·0001). In the omicron-predominant period, 120 862 (18·6%) of 650 361 patients tested positive for COVID-19, of whom 14 504 (12·0%) were hospitalised, 567 (0·5%) received mechanical ventilation, and 2001 (1·7%) died. Compared with controls, patients with IMIDs and COVID-19 (7327 [17·3%] of 42 249) had higher rates of hospitalisation (13 422 [11·8%] vs 1082 [14·8%]; p<0·0001) and mortality (1814 [1·6%] vs 187 [2·6%]; p<0·0001). Age was a risk factor for worse outcomes (adjusted odds ratio [OR] from 2·1 [95% CI 2·0-2·1]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001), whereas COVID-19 vaccination (from 0·082 [0·080-0·085]; p<0·0001 to 0·52 [0·50-0·53]; p<0·0001) and booster vaccination (from 2·1 [2·0-2·2]; p<0·0001 to 3·0 [2·9-3·0]; p<0·0001) status were associated with better outcomes. Seven chronic comorbidities were significant risk factors during both time periods for all three outcomes: atrial fibrillation, coronary artery disease, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, chronic liver disease, and cancer. Two IMIDs, asthma (adjusted OR from 0·33 [0·32-0·34]; p<0·0001 to 0·49 [0·48-0·51]; p<0·0001) and psoriasis (from 0·52 [0·48-0·56] to 0·80 [0·74-0·87]; p<0·0001), were associated with a reduced risk of severe outcomes. IMID diagnoses did not appear to be significant risk factors themselves, but results were limited by small sample size, and vasculitis had high feature importance in LR. IMMs did not appear to be significant, but less frequently used IMMs were limited by sample size. XGB outperformed LR, with the area under the receiver operating characteristic curve for models across different time periods and outcomes ranging from 0·77 to 0·92. Our results suggest that age, chronic comorbidities, and not being fully vaccinated might be greater risk factors for severe COVID-19 outcomes in patients with IMIDs than the use of IMMs or the IMIDs themselves. Overall, there is a need to take age and comorbidities into consideration when developing COVID-19 guidelines for patients with IMIDs. Further research is needed for specific IMIDs (including IMID severity at the time of SARS-CoV-2 infection) and IMMs (considering dosage and timing before a patient's first COVID-19 infection). Pfizer, Novartis, Janssen, and the National Institutes of Health.

Concomitant and sequential administration of nirmatrelvir‐ritonavir and azvudine in patients with COVID‐19 caused by the Omicron variant: Safety and efficacy

AbstractBackgroundThis study assessed the safety and efficacy of nirmatrelvir‐ritonavir (Paxlovid®) and azvudine when administered sequentially or concomitantly in patients with coronavirus 2019 (COVID‐19) caused by the Omicron variant.MethodsNinety‐three patients confirmed to be infected with the Omicron variant by nucleic acid detection were retrospectively investigated. Information was collected on general health status, medication, and adverse drug reactions (ADRs) according to whether nirmatrelvir‐ritonavir and azvudine were administered sequentially or concomitantly. Data on times of onset, clinical manifestations, and outcomes of ADRs and on conversion to a negative nucleic acid test were also recorded.ResultsPossible ADRs were recorded in 41 patients (44.1%). There were 22 gastrointestinal reactions in 18 patients and 18 hematological abnormalities in 16 after sequential or concomitant treatment with nirmatrelvir‐ritonavir and azvudine. Liver enzyme levels increased in nine cases and creatinine clearance decreased in two. Cases of atrial fibrillation (n = 1), sleep disorder (n = 2), rash (n = 2), dizziness (n = 1), and weakness (n = 5) were also documented. Only vomiting, poor appetite, diarrhea, xerostomia, bitter taste, and rash were considered probable ADRs; others were thought to be possible ADRs. In all cases, the nucleic acid test did not turn negative after the first antiviral was applied. The nucleic acid test of 28 patients did not turn negative before discharge. The remaining 65 patients (69.9%) returned a negative nucleic acid test after receiving the second antiviral agent.ConclusionsTreatment with nirmatrelvir‐ritonavir and azvudine is safe and effective whether administered sequentially or concomitantly in patients with COVID‐19 caused by the Omicron variant.