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Background: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals., Methods: We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated., Results: Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7)., Conclusions: Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients., Competing Interests: Potential conflicts of interest. S. R. reports grant support from BioFire. H. Q. M. reports grant/research support from CSL Sequiris and CSK. J. G. P. reports serving as a former consultant for CSL Seqirus and receipt of grants from the National Institutes of Health (NIH) and CSL Seqirus. E. A. reports serving as a former consultant for Hillevax and Moderna, presenting a Merck-supported lecture at the Latin American Vaccine Summit, and receipt of grant/research support from Pfizer for pneumococcal pneumonia studies. C. G. G. reports being a former advisor to Merck, participation on a data and safety monitoring board (DSMB) or advisory board for Merck, and receipt of grant/research support from AHRQ, CDC, US Food and Drug Administration, NIH, and Syneos Health. N. M.B. reports grant/contracts from NIH to the University of North Carolina School of Medicine, Doris Duke Charitable Foundation, and North Carolina Collaboratory; participation on a DSMB or advisory board for the Snowball Study Technical Interchange; a leadership or fiduciary role on the American Society of Tropical Medicine and Hygiene Scientific Committee; and other financial or nonfinancial interests with the COVID-19 Equity Evidence Academy (RADx-UP CDCC) Steering Committee and North Carolina Occupational Safety and Health Education Research Center. S. H. M. reports grants/contracts from NIH, the American Academy of Pediatrics, and the Doris Duke Charitable Foundation. E. A. B. reports research support to the Marshfield Clinic Research Institute from the CDC. E. S. reports grants or contracts to institution from Vanderbilt University Medical Center (originating at CDC #75D30121C11656). S. G. reports support for attending meetings and/or travel from the Infectious Diseases Society of America for Infectious Disease Week 2022 and 2023. K. G. M., L. M., S. B.-W., and V. O. report funding to Westat via the CDC (contract 75D30121C11571). M. S. S. reports a leadership role as Associate Director of the American Academy of Pediatrics’ Pediatric Research in Office Settings (PROS), paid to Trustees of Columbia University. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Short-term rehabilitation units present unique infection control challenges because of high turnover and medically complex residents. In June 2021, the Maricopa County Department of Public Health was notified of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE)., Methods: Facility electronic medical records were reviewed for residents who spent > 1 night on the affected unit between June 10 and July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. Coronavirus disease 2019 VE estimates using Cox proportional hazards models were calculated., Results: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2-positive case-patients were mostly male (58%) and White (78%) with a median age of 65 (range, 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases, 32 noncases) received 2 doses and 9% (4 cases, 6 noncases) received 1 dose of messenger RNA (mRNA) vaccine. Among nonimmunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% confidence interval, 15-95). More cases were hospitalized (33%) or died (38%) than noncases (10% hospitalized; 16% died)., Conclusions: In this large SARS-CoV-2 Delta outbreak in a high-turnover short-term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in nonimmunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

During July-August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections., Methods: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations., Results: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05)., Conclusions: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

Background: To inform prevention strategies, we assessed the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and settings in which transmission occurred in a Georgia public school district., Methods: During 1 December 2020-22 January 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (eg, sports, elementary school classroom), index case role (ie, staff, student), and index case symptomatic status., Results: We identified 86 index cases and 1119 contacts, 688 (61.5%) of whom received testing. Fifty-nine of 679 (8.7%) contacts tested positive; 15 of 86 (17.4%) index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SARs were in indoor, high-contact sports settings (23.8% [95% confidence interval {CI}, 12.7%-33.3%]), staff meetings/lunches (18.2% [95% CI, 4.5%-31.8%]), and elementary school classrooms (9.5% [95% CI, 6.5%-12.5%]). The SAR was higher for staff (13.1% [95% CI, 9.0%-17.2%]) vs student index cases (5.8% [95% CI, 3.6%-8.0%]) and for symptomatic (10.9% [95% CI, 8.1%-13.9%]) vs asymptomatic index cases (3.0% [95% CI, 1.0%-5.5%])., Conclusions: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include coronavirus disease 2019 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection., Methods: From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time., Results: We identified 47 contacts, median age 24 (3-75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18-49, and ≥50 years of age, respectively; P = .03)., Conclusions: Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission., Methods: We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020-25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test., Results: Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%-36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4-106.9) and 7.1 (95% CI: 1.2-42.5), respectively., Conclusions: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited., Methods: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture., Results: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03-.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4-.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values < 29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%)., Conclusions: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Repeating the BinaxNOW antigen test for severe acute respiratory syndrome coronavirus 2 using 2 groups of readers within 30 minutes resulted in high concordance (98.9%) in 2110 encounters. Same-day repeat antigen testing did not significantly improve test sensitivity (77.2% to 81.4%) while specificity remained high (99.6%)., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Respiratory tract infections are common, often seasonal, and caused by multiple pathogens. We assessed whether seasonal respiratory illness patterns changed during the COVID-19 pandemic., Methods: We categorized emergency department (ED) visits reported to the National Syndromic Surveillance Program according to chief complaints and diagnosis codes, excluding visits with diagnosed SARS-CoV-2 infections. For each week during 1 March 2020 through 26 December 2020 ("pandemic period"), we compared the proportion of ED visits in each respiratory category with the proportion of visits in that category during the corresponding weeks of 2017-2019 ("pre-pandemic period"). We analyzed positivity of respiratory viral tests from 2 independent clinical laboratories., Results: During March 2020, cough, shortness of breath, and influenza-like illness accounted for twice as many ED visits compared with the pre-pandemic period. During the last 4 months of 2020, all respiratory conditions, except shortness of breath, accounted for a smaller proportion of ED visits than during the pre-pandemic period. Percent positivity for influenza virus, respiratory syncytial virus, human parainfluenza virus, adenoviruses, and human metapneumovirus was lower in 2020 than 2019. Although test volume decreased, percent positivity was higher for rhinovirus/enterovirus during the final weeks of 2020 compared with 2019, with ED visits similar to the pre-pandemic period., Conclusions: Broad reductions in respiratory test positivity and respiratory ED visits (excluding COVID-19) occurred during 2020. Interventions for mitigating spread of SARS-CoV-2 likely also reduced transmission of other pathogens. Timely surveillance is needed to understand community health threats, particularly when current trends deviate from seasonal norms., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has principally been performed through the use of real-time reverse-transcription polymerase chain reaction testing. Results of such tests can be reported as cycle threshold (Ct) values, which may provide semi-quantitative or indirect measurements of viral load. Previous reports have examined temporal trends in Ct values over the course of a SARS-CoV-2 infection., Methods: Using testing data collected during a prospective household transmission investigation of outpatient and mild coronavirus disease 2019 cases, we examined the relationships between Ct values of the viral RNA N1 target and demographic, clinical, and epidemiological characteristics collected through participant interviews and daily symptom diaries., Results: We found that Ct values are lowest (corresponding to a higher viral RNA concentration) soon after symptom onset and are significantly correlated with the time elapsed since onset (P < .001); within 7 days after symptom onset, the median Ct value was 26.5, compared with a median Ct value of 35.0 occurring 21 days after onset. Ct values were significantly lower among participants under 18 years of age (P = .01) and those reporting upper respiratory symptoms at the time of sample collection (P = .001), and were higher among participants reporting no symptoms (P = .05)., Conclusions: These results emphasize the importance of early testing for SARS-CoV-2 among individuals with symptoms of respiratory illness, and allow cases to be identified and isolated when their viral shedding may be highest., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 [62%]) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive predictive value (83% [95% confidence interval [CI], 55%-95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: On 8 October 2008, members of a tour group experienced diarrhea and vomiting throughout an airplane flight from Boston, Massachusetts, to Los Angeles, California, resulting in an emergency diversion 3 h after takeoff. An investigation was conducted to determine the cause of the outbreak, assess whether transmission occurred on the airplane, and describe risk factors for transmission., Methods: Passengers and crew were contacted to obtain information about demographics, symptoms, locations on the airplane, and possible risk factors for transmission. Case patients were defined as passengers with vomiting or diarrhea (> or =3 loose stools in 24 h) and were asked to submit stool samples for norovirus testing by real-time reverse-transcription polymerase chain reaction., Results: Thirty-six (88%) of 41 tour group members were interviewed, and 15 (41%) met the case definition (peak date of illness onset, 8 October 2008). Of 106 passengers who were not tour group members, 85 (80%) were interviewed, and 7 (8%) met the case definition after the flight (peak date of illness onset, 10 October 2008). Multivariate logistic regression analysis showed that sitting in an aisle seat (adjusted relative risk, 11.0; 95% confidence interval, 1.4-84.9) and sitting near any tour group member (adjusted relative risk, 7.5; 95% confidence interval, 1.7-33.6) were associated with the development of illness. Norovirus genotype II was detected by reverse-transcription polymerase chain reaction in stool samples from case patients in both groups., Conclusions: Despite the short duration, transmission of norovirus likely occurred during the flight.

Background: As part of efforts to prevent the introduction of communicable diseases into the United States, the Centers for Disease Control and Prevention (CDC) conducts surveillance for selected diseases in international travelers. One of these diseases, tuberculosis (TB), received substantial attention in May 2007 when the CDC issued travel restrictions and a federal isolation order for a person with drug-resistant TB who traveled internationally against public health recommendations., Methods: Reports of TB in international travelers in the CDC's Quarantine Activity Reporting System (QARS) from 1 June 2006 through 31 May 2007 (year 1) were compared with reports from 1 June 2007 through 31 May 2008 (year 2). These reports were classified using the CDC and American Thoracic Society guidelines and analyzed for epidemiologic characteristics and trends., Results: Among QARS reports, 4.6% were classified as active TB disease and 1.7% as no TB disease. Active TB disease reports increased from 2.5% of QARS reports in year 1 to 6.4% in year 2 (p < .001). The proportion of active TB disease reports leading to a federal travel restriction increased from 6.8% in year 1 to 15.4% in year 2 (p = .08)., Conclusions: The significant increase in reports of international travelers with TB disease likely represents more attention to and a higher index of suspicion for TB. The increased use of federal travel restrictions was associated with the development of new procedures to limit travel for public health reasons. Continued efforts are needed to decrease the number of persons with TB who travel while potentially contagious.