Negative Nucleic Acid Amplification Test Research Articles

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

Single-dose cefixime 800 mg plus doxycycline 100 mg twice a day for 7 days compared with single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g for treatment of urogenital, rectal, and pharyngeal gonorrhoea: a randomised clinical trial

ObjectivesTo evaluate the efficacy and tolerability of a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg twice a day for 7 days, compared with a recommended single dose of ceftriaxone plus single dose of oral azithromycin, for treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhoea. MethodsA noninferiority, open-label, multicentre randomized controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18–65 years of age diagnosed with uncomplicated urogenital, rectal, or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with single dose of cefixime 800 mg plus doxycycline 100 mg twice a day for 1 week or a single dose of ceftriaxone 1 g intramuscularly plus single dose of azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation. ResultsIn all, 161 patients were randomized and 152 were included in per-protocol analyses. All 76 (100%; 95% CI, 0.95–1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70 of the 76 patients (92%; 95% CI, 0.84–0.97) and NAAT negative in 66 of the 76 patients (87%; 95% CI, 0.77–0.94). At week 3, culture and NAAT were negative in 65 of the 76 patients (86%; 95% CI, 0.76–0.93). Per-protocol risk difference was 14.5%; 95% CI, 6.56–22.38. All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases. DiscussionThe combination of cefixime and doxycycline did not achieve noninferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea.

Impact of SARS-CoV-2 Arrival Surveillance Screening by Nucleic Acid Amplification Versus Rapid Antigen Detection on Subsequent COVID-19 Infections in Military Trainees.

For persons entering congregate settings, optimal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arrival surveillance screening method, nucleic acid amplification test (NAAT) versus rapid antigen detection test (RADT), is debated. To aid this, we sought to determine the risk of secondary symptomatic coronavirus disease 19 (COVID-19) among military trainees with negative arrival NAAT or RADT screening. Individuals who arrived for US Air Force basic military training from 1 January-31 August 2021 were placed into training groups and screened for SARS-CoV-2 via NAAT or RADT. Secondary symptomatic COVID-19 cases within 2 weeks of training were then measured. A case cluster was defined as ≥5 individual symptomatic COVID-19 cases. 406 (1.6%) of 24 601 trainees screened positive upon arrival. The rate of positive screen was greater for those tested with NAAT versus RADT (2.5% vs 0.4%; RR: 5.4; 95% CI: 4.0-7.3; P < .001). The proportion of training groups with ≥1 positive individual screen was greater in groups screened via NAAT (57.5% vs 10.8%; RR: 5.31; 95% CI: 3.65-7.72; P < .001). However, NAAT versus RADT screening was not associated with a difference in number of training groups to develop a secondary symptomatic case (20.3% vs 22.5%; RR: .9; 95% CI: .66-1.23; P = .53) or case cluster of COVID-19 (4% vs 6.6%; RR: .61; 95% CI: .3-1.22; P = .16). NAAT versus RADT arrival surveillance screening method impacted individual transmission of COVID-19 but had no effect on number of training groups developing a secondary symptomatic case or case cluster. This study provides consideration for RADT arrival screening in congregate settings.

Real-World Effectiveness of Nirmatrelvir/Ritonavir and Dexamethasone Among Hospitalized Patients with COVID-19: A Prospective Cohort Study.

Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting. A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery. About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively. Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.

Characteristics of the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.2 Subvariant in Jilin, China from March to May 2022.

In the midst of the pandemic, new coronavirus mutants continue to emerge; the most relevant variant worldwide is omicron. Here, patients who recovered from the disease living in Jilin Province were analyzed to identify factors affecting the severity of omicron infection and to provide insights into its spread and early indication. In this study, 311 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were divided into two groups. Data on the patients' demographic characteristics and laboratory tests, including platelet count (PLT), neutrophil count (NE), C-reactive protein (CRP), serum creatinine (SCR), and neutrophil-to-lymphocyte ratio (NLR), were collected. The biomarkers for moderate and severe coronavirus disease 2019 (COVID-19) and factors affecting the incubation period and time to subsequent negative nucleic acid amplification test (NAAT) were also investigated. Age, gender, vaccination, hypertension, stroke, chronic obstructive pulmonary disease (COPD)/chronic bronchitis/asthma, and some laboratory tests were statistically different between the two groups. In the receiver operating characteristic (ROC) analysis, PLT and CRP had higher area under the ROC curve values. In the multivariate analysis, age, hypertension, COPD/chronic bronchitis/asthma, and CRP were correlated with moderate and severe COVID-19. Moreover, age was correlated with longer incubation. In the Kaplan-Meier curve analysis, gender (male), CRP, and NLR were associated with longer time to subsequent negative NAAT. Older patients with hypertension and lung diseases were likely to have moderate or severe COVID-19, and younger patients might have a shorter incubation. A male patient with high CRP and NLR levels might take more time to turn back negative in the NAAT.

Antepartum SARS-CoV-2 infection and adverse birth outcomes in South African women.

SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking. We conducted a longitudinal study from April 2020 to March 2021, in South Africa, where symptomatic or asymptomatic pregnant women were investigated for SARS-CoV-2 infection during the antepartum period. We aimed to evaluate if there was an association between antepartum SARS-CoV-2 infection on birth outcomes. SARS-CoV-2 infection was investigated by nucleic acid amplification test (NAAT), histological examination was performed in a sub-set of placentas. Overall, 793 women were tested for SARS-CoV-2 antenatally, including 275 (35%) who were symptomatic. SARS-CoV-2 infection was identified in 138 (17%) women, of whom 119 had symptoms (COVID-19 group) and 19 were asymptomatic. The 493 women who were asymptomatic and had a negative SARS-CoV-2 NAAT were used as the referent comparator group for outcomes evaluation. Women with COVID-19 compared with the referent group were 1.66-times (95% confidence interval (CI) = 1.02-2.71) more likely to have a low-birthweight newborn (30% vs 21%) and 3.25-times more likely to deliver a very low-birthweight newborn (5% vs 2%). Similar results for low-birthweight were obtained comparing women with SARS-CoV-2 confirmed infection (30%) with those who had a negative NAAT result (22%) independent of symptoms presentation. The placentas from women with antenatal SARS-CoV-2 infection had higher percentage of chorangiosis (odds ratio (OR) = 3.40, 95% CI = 1.18-.84), while maternal vascular malperfusion was more frequently identified in women who tested negative for SARS-CoV-2 (aOR = 0.28, 95% CI = 0.09-0.89). Our study demonstrates that in a setting with high HIV infection prevalence and other comorbidities antenatal SARS-CoV-2 infection was associated with low-birthweight delivery.

Spontaneous clearance of asymptomatic anogenital and pharyngeal Neisseria gonorrhoeae: a secondary analysis from the NABOGO trial

IntroductionSpontaneous clearance of asymptomatic Neisseria gonorrhoeae (NG) does occur, but data are scarce. We aimed to assess spontaneous clearance among patients with asymptomatic anal, pharyngeal, vaginal and urethral NG infections...

Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19-Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection - United States, June 2021-February 2022.

Previous infection with SARS-CoV-2, the virus that causes COVID-19, has been estimated to confer up to 90% protection against reinfection, although this protection was lower against the Omicron variant compared with that against other SARS-CoV-2 variants (1-3). A test-negative design was used to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19-associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test (NAAT) or diagnosis of COVID-19.† The analysis used data from Cosmos, an electronic health record (EHR)-aggregated data set (4), and compared vaccination status of 3,761 case-patients (positive NAAT result associated with hospitalization) with 7,522 matched control-patients (negative NAAT result). After previous SARS-CoV-2 infection, estimated vaccine effectiveness (VE) against COVID-19-associated hospitalization was 47.5% (95% CI=38.8%-54.9%) after 2 vaccine doses and 57.8% (95% CI=32.1%-73.8%) after a booster dose during the Delta-predominant period (June 20-December 18, 2021), and 34.6% (95% CI=25.5%-42.5%) after 2 doses and 67.6% (95% CI=61.4%-72.8%) after a booster dose during the Omicron-predominant period (December 19, 2021-February 24, 2022). Vaccination provides protection against COVID-19-associated hospitalization among adults with previous SARS-CoV-2 infection, with the highest level of protection conferred by a booster dose. All eligible persons, including those with previous SARS-CoV-2 infection, should stay up to date with vaccination to prevent COVID-19-associated hospitalization.

Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial

Neisseria gonorrhoeae causes gonorrhoea, a common sexually transmitted infection. Emerging strains resistant to first-line ceftriaxone threaten N gonorrhoeae management. Hence, alternative treatments are needed. We aimed to evaluate the efficacy of ertapenem, gentamicin, and fosfomycin as alternative treatments for anogenital N gonorrhoeae. In a randomised, controlled, double-blind, non-inferiority trial (three experimental groups and one control group) at the Centre for Sexual Health in Amsterdam, Netherlands, we included adults aged 18 years or older, with anorectal or urogenital gonorrhoea. With random permuted blocks, participants were randomly assigned (1:1:1:1) to receive intramuscular 500 mg ceftriaxone (control group), intramuscular 1000 mg ertapenem, intramuscular 5 mg/kg gentamicin (maximum 400 mg), or oral 6 g fosfomycin. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the predefined primary infected site, 7-14 days after treatment. The primary analysis was per protocol (ie, excluding those lost to follow-up). The modified intention-to-treat analysis included all randomly assigned patients with anogenital gonorrhoea considering those lost-to-follow-up as treatment failure. Non-inferiority was established if the lower Hochberg-corrected 95% CI for difference between the experimental and control groups was greater than -10%. For the analysis of adverse events, we included all participants who received medication. The trial was registered at ClinicalTrials.gov (NCT03294395) and is complete. Between Sept 18, 2017, and June 5, 2020, from 2160 patients invited to participate, we assigned 346 (16%) participants to receive either ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), or fosfomycin (n=38). The fosfomycin group was terminated early after interim analysis revealed less than 60% efficacy. In the primary per-protocol analysis, 93 (100%) of 93 patients in the ceftriaxone group, 86 (99%) of 87 patients in the ertapenem group, 79 (93%) of 85 patients in the gentamicin group, and four (12%) of 33 patients in the fosfomycin group cleared N gonorrhoeae (risk difference vs ceftriaxone -0·01 [95% CI -0·08 to 0·05] for ertapenem and -0·07 [-0·16 to -0·01] for gentamicin). Thus, ertapenem proved non-inferior to ceftriaxone. In mITT analysis, risk differences versus ceftriaxone were -0·08 (-0·17 to 0·003) for ertapenem and -0·11 (-0·21 to -0·04) for gentamicin. We observed a higher proportion of patients with at least one adverse event in the ertapenem group (58 [56%] of 103) and fosfomycin group (36 [95%] of 38) versus the ceftriaxone group (24 [23%] of 103). Single-dose 1000 mg ertapenem is non-inferior to single-dose 500 mg ceftriaxone in gonorrhoea treatment. Yet, 5 mg/kg gentamicin (maximum 400 mg) is not non-inferior to ceftriaxone. Ertapenem is a potential effective alternative for anogenital N gonorrhoeae infections and merits evaluation for ceftriaxone-resistant infections. ZonMw and GGD-Amsterdam. For the Dutch translation of the abstract see Supplementary Materials section.

Duration of Viral Nucleic Acid Shedding and Early Reinfection With Severe Respiratory Syndrome Coronavirus 2 in Healthcare Workers and First Responders.

We estimated the distributions of duration of SARS-CoV-2 nucleic acid shedding and time to reinfection among 137 persons with at least two positive nucleic acid amplification test (NAAT) results from March to September 2020. We analyzed gaps of varying length between subsequent positive and negative NAAT results and estimated a mean duration of nucleic acid shedding of 30.1 (95% CI 26.3, 34.5) days. The mean time to reinfection was 89.1 (95% CI 75.3, 103.5) days. Together, these indicate that a 90-day period between positive NAAT results can reliably define reinfection in immunocompetent persons although reinfection can occur at shorter intervals.

Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis

BackgroundRectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment.MethodsIn this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks.ResultsFrom August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, −11.3 percentage points; 95% CI, −19.5 to −3.2).ConclusionsA 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.)

Yield of Severe Acute Respiratory Syndrome Coronavirus 2 Lower Respiratory Tract Testing After a Negative Nasopharyngeal Test Among Hospitalized Persons Under Investigation for Coronavirus Disease 2019.

Among hospitalized persons under investigation for coronavirus disease 2019 (COVID-19), more repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs) after a negative NAAT were positive from lower than from upper respiratory tract specimens (1.9% vs 1.0%, P = .033). Lower respiratory testing should be prioritized among patients displaying respiratory symptoms with moderate-to-high suspicion for COVID-19 after 1 negative upper respiratory NAAT.

Ertapenem is Non-Inferior to Ceftriaxone for the Treatment of Anogenital Gonorrhea in a Single Intramuscular Dose: The NABOGO Randomized Double Blind Non-Inferiority Trial

Background: Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging strains resistant to first-line ceftriaxone threaten Ng management. Hence, alternative treatments are needed. We evaluated the efficacy of ertapenem, gentamicin and fosfomycin as alternatives for Ng. Methods: We included adults 18 years or older, with anorectal or urogenital gonorrhea in a randomized controlled, double-blind, non-inferiority trial (three experimental- and one control-arm). Participants were randomized (1:1:1:1) to receive: intramuscular (IM) 500mg ceftriaxone, IM 1000mg ertapenem, IM 5mg/kg gentamicin (maximum 400mg), or 6g fosfomycin orally. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the primary infected site, 7-14 days after treatment. Non-inferiority was established if the lower Hochberg-corrected 95% confidence interval for difference between experimental and control arms was greater than -10%. Findings: Between 18 September 2017 and 5 June 2020, we assigned 346 participants to ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), and fosfomycin (n=38). The fosfomycin arm was terminated early after interim analysis revealed <60% efficacy. In the primary modified intent-to-treat (mITT) analysis, all patients (93/93) in the ceftriaxone, 99% (86/87) in the ertapenem, 93% (79/85) in the gentamicin, and 12% (4/33) in the fosfomycin arm cleared Ng [risk difference, ertapenem versus ceftriaxone, -0.01(95 CI: -0.06,0.03); gentamicin versus ceftriaxone -0.07(95%CI: -0.16,-0.005)]. Both the secondary mITT analysis (clearance within 7-28 days), and the per-protocol analyses were consistent with the primary mITT analysis. Interpretation: Single-dose 1000mg ertapenem is non-inferior to single-dose 500mg ceftriaxone in gonorrhea treatment. Clinical Trial Registration Details: The study was registered at clinicaltrials.gov (NCT03294395). Funding Information: The NABOGO trial was funded by ZonMW (project no. 848015001) and the Amsterdam Public Health Service Research and Development fund (project no. 75722378). Declaration of Interests: Dr. Jongen, Dr. Heijman, Dr. Wind, Dr. Hoornenborg, Dr. de Korne-Elenbaas, Dr. Knol, Dr. de Laat, Dr. Mathot, Dr. Prins, Dr. Bruisten, and Dr. van Dam had nothing to disclose. Dr. Boyd reports grants from ANRS, grants from SIDACTION, outside the submitted work. Dr. Schim van der Loeff reports grants from ZonMw, during the conduct of the study. Dr. de Vries reports grants from ZonMW, grants from Public Health Servicces Amsterdam, during the conduct of the study. Ethics Approval Statement: We obtained ethics approval from the Academic Medical Center Ethics Committee in Amsterdam, including permission to use ertapenem i.m. for the study (METC 2017_092, NL 60555.018.17). All patients provided written informed consent.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BackgroundIsolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs.MethodsWe conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence.ResultsFewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44–.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], −7.4 [0.8] hours per patient), total duration of PUI status (−19.5 [1.9] hours per patient), and average ID physician work-hours (−57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL.ConclusionsCORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

Insights from Patterns of SARS-CoV-2 Immunoglobulin G Serology Test Results from a National Clinical Laboratory, United States, March-July 2020.

Serologic tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provide information on past infection and immune response. To better understand the persistence of immune response and the proportion of the population who can develop one, the authors assessed patterns of immunoglobulin G (IgG) positivity over time in individuals tested for SARS-CoV-2 RNA or IgG at a large national reference laboratory. More than 2.4 million SARS-CoV-2 IgG serology (initiated April 21, 2020) and 6.6 million nucleic acid amplification testing (NAAT) (initiated March 9, 2020) results on persons from across the United States as of July 10, 2020 were analyzed. Additional IgG serology results through August 11, 2020 were used for one household analysis. SARS-CoV-2 IgG positivity was observed in 91% (19,434/21,452) of individuals tested after a positive NAAT result and in 10% (7,831/80,968) after a negative NAAT result. Factors associated with seropositivity include age, region of patient residence, and interval between NAAT and IgG serology. The probability of persistent IgG seropositivity declined from 98.6% after 1 week to 74.3% after 2 months, less so in individuals ages ≥55 years than in younger groups. Specimens within 2 days from pairs of same-household members showed 92% IgG antibody concordance. Household adults were more frequently IgG positive prior to household children testing positive (36% versus 8%). IgG serology testing can identify an immune response to SARS-CoV-2 that varies based on age, sex, and duration since exposure. Loss of detectable IgG seropositivity occurs, in some patients, over weeks or months. Adults may be infecting household children.

Clinical, Laboratory, and Radiologic Characteristics of Patients With Initial False-Negative Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Test Results.

BackgroundConcerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood.MethodsWe retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics.ResultsSixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive.ConclusionsOur findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.

Cardiogenic Shock Caused by SARS-CoV-2 in a Patient with Serial Negative Nucleic Acid Amplification Tests. Case Report

Myocarditis is an unusual manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been associated with increased severity of disease and mortality. The diagnosis of coronavirus disease 2019 (COVID-19) is based on positivity of nucleic acid amplification tests (NAAT) of respiratory samples. We report the case of a patient with cardiogenic shock caused by SARS-CoV-2 myocarditis with serial negative upper and lower respiratory nucleic acid amplification tests. Diagnosis was made by serology (positive IgM + IgA and IgG) from patient’s serum sample of day 10 after symptoms’ initiation.

Outcomes from an infectious disease physician-guided evaluation of hospitalized persons under investigation for coronavirus disease 2019 (COVID-19) at a large US academic medical center.

We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.

Test of cure study: a feasibility study to estimate the time to test of cure (TOC) for Neisseria gonorrhoeae and Chlamydia trachomatis infections

ObjectivesTest of cure (TOC) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infection is an important tool in the public health management of STIs. However, there are limited data about...

Diagnosis of HIV infection in breastfed infants of mothers on antiretroviral therapy.

We read with interest the article by Strehlau et al. [1] on the diagnosis of two children infected with HIV in a recent issue of AIDS. On the basis of the findings that two breastfed children who showed positive results of nucleic acid amplification tests (NAAT) of HIV within 1 month after birth, became negative NAAT and had no detectable viral load for several months, and finally turned out to be infected with HIV with definite evidence after weaning around 1 year of age, the authors hypothesized that breast milk from the mothers of these two children had HIV-specific or HIV-nonspecific factors that caused the undetectability of HIV in these two children until cessation of breastfeeding. However, we consider that the results should be cautiously interpreted, and that the persistent negativity of repeated HIV tests was possibly true and these two children were likely infected postnatally, because of the two following reasons. First, it has been demonstrated that strong uterine contractions during delivery can cause mother-to-fetus transfusion, leading to transfer of maternal circulation cells and other constituents into fetus [2]. The initial positive results of HIV in the first month of life in these two children [1] were probably caused by the exposure to maternal HIV. In other words, the virus detected in the first month of life was derived from their mothers, but not produced by the babies themselves. The fact that neonatal use of antiretroviral agents, such as zidovudine or nevirapine can prevent mother-to-child transmission indicate that infants have been exposed to, but not yet infected with HIV. Virtually all infants born to HIV-infected mothers are exposed to the maternal virus during birth process, regardless of detectable HIV in newborns; detectability means exposure to a relatively large amount of virions, and undetectability means, a relatively small amount of virions below the detection limits. Second, these two children received breastfeeding, which can increase mother-to-child transmission of HIV [3]. Although HIV was not detectable in the breast milk supernatant of one child's mother, HIV exposure by breastfeeding was highly possible. Breastfeeding requires at least several times per day for a period of several months, during which bloody milk and nipple bleeding are not uncommon. Undetectability of HIV in one milk sample cannot reflect the actual scenarios. Additionally, as the authors mentioned, cell-associated HIV in breast milk is known to be strongly correlated with postnatal transmission [1]. Thus, although the maternal postpartum antiretroviral therapy probably delayed the transmission, the HIV infection in these two children was highly associated with breastfeeding. WHO recommends that breastfed infants should continue antiretroviral prophylaxis for 1 week after complete cessation of breastfeeding [4]. However, these two children did not continue to receive antiretroviral agent while they were breastfed. To differentiate whether these two children had been infected with HIV from early life or around 1 year of age, we consider that determination of anti-HIV titers in the longitudinal serum or plasma samples from the children can provide valuable information. As maternal IgG antibodies can transplacentally transfer to fetus and the maternal antibodies in infants can persist for as long as 18 months, anti-HIV is not tested in children less than 18 months age to define HIV infection. However, based on the half-life of maternal IgG antibodies being 21–24 days, anti-HIV titers in an infant who has not been infected with HIV will progressively decline to an expected level after a known period of time, whereas anti-HIV titers in an infant who has been infected will be relatively constant, or will initially decrease and then increase, or will present an increasing trend, depending upon the time of HIV infection. Thus, observation of dynamic changes of anti-HIV levels in these two children can differentiate the time of HIV infection, if serial serum samples collected at different times are available. Acknowledgements Conflicts of interest There are no conflicts of interest.