Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Mellis A[original query] |
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Association of symptoms and viral culture positivity for SARS-CoV-2-Tennessee, April-July 2020
Biddle JE , Bonenfant G , Grijalva CG , Zhu Y , Halasa NB , Chappell JD , Mellis A , Reed C , Talbot HK , Zhou B , Rolfes MA . Influenza Other Respir Viruses 2024 18 (6) e13318 ![]() ![]() BACKGROUND: Understanding how symptoms are associated with SARS-CoV-2 culture positivity is important for isolation and transmission control guidelines. METHODS: Individuals acutely infected with SARS-CoV-2 in Tennessee and their household contacts were recruited into a prospective study. All participants self-collected nasal swabs daily for 14 days and completed symptom diaries from the day of illness onset through day 14 postenrollment. Nasal specimens were tested for SARS-CoV-2 using RT-qPCR. Positive specimens with cycle threshold values < 40 were sent to the Centers for Disease Control and Prevention (CDC) for viral culture. First, we modeled the association between symptoms and the risk of culture positivity using an age-adjusted generalized additive model (GAM) accounting for repeated measurements within participants and a symptom-day spline. Next, we investigated how timing of symptom resolution was associated with the timing of culture resolution. RESULTS: In a GAM restricted to follow-up days after symptoms began, the odds of a specimen being culture positive was significantly increased on days when wheezing, loss of taste or smell, runny nose, nasal congestion, sore throat, fever, or any symptom were reported. For all symptoms except sore throat, it was more common for participants to have culture resolution before symptom resolution than for culture to resolve after or on the same day as symptom resolution. CONCLUSIONS: Overall, symptomatic individuals were more likely to be SARS-CoV-2 viral culture positive. For most symptoms, culture positivity was more likely to end before symptoms resolved. However, a proportion of individuals remained culture positive after symptom resolved, across all symptoms. |
Highly pathogenic avian influenza A(H5N1) virus infections in humans
Garg S , Reinhart K , Couture A , Kniss K , Davis CT , Kirby MK , Murray EL , Zhu S , Kraushaar V , Wadford DA , Drehoff C , Kohnen A , Owen M , Morse J , Eckel S , Goswitz J , Turabelidze G , Krager S , Unutzer A , Gonzales ER , Abdul Hamid C , Ellington S , Mellis AM , Budd A , Barnes JR , Biggerstaff M , Jhung MA , Richmond-Crum M , Burns E , Shimabukuro TT , Uyeki TM , Dugan VG , Reed C , Olsen SJ . N Engl J Med 2024 BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.). |
Estimated effectiveness of influenza vaccines in preventing secondary infections in households
Grijalva CG , Nguyen HQ , Zhu Y , Mellis AM , McGonigle T , Meece JK , Biddle JE , Halasa NB , Reed C , Fry AM , Yang Y , Belongia EA , Talbot HK , Rolfes MA . JAMA Netw Open 2024 7 (11) e2446814 ![]() IMPORTANCE: Influenza vaccine effectiveness (VE) is commonly assessed against prevention of illness that requires medical attention. Few studies have evaluated VE against secondary influenza infections. OBJECTIVE: To determine the estimated effectiveness of influenza vaccines in preventing secondary infections after influenza was introduced into households. DESIGN, SETTINGS, AND PARTICIPANTS: During 3 consecutive influenza seasons (2017-2020), primary cases (the first household members with laboratory-confirmed influenza) and their household contacts in Tennessee and Wisconsin were enrolled into a prospective case-ascertained household transmission cohort study. Participants collected daily symptom diaries and nasal swabs for up to 7 days. Data were analyzed from September 2022 to February 2024. EXPOSURES: Vaccination history, self-reported and verified through review of medical and registry records. MAIN OUTCOMES AND MEASURES: Specimens were tested using reverse transcription-polymerase chain reaction to determine influenza infection. Longitudinal chain binomial models were used to estimate secondary infection risk and the effectiveness of influenza vaccines in preventing infection among household contacts overall and by virus type and subtype and/or lineage. RESULTS: The analysis included 699 primary cases and 1581 household contacts. The median (IQR) age of the primary cases was 13 (7-38) years, 381 (54.5%) were female, 60 (8.6%) were Hispanic, 46 (6.6%) were non-Hispanic Black, 553 (79.1%) were Non-Hispanic White, and 343 (49.1%) were vaccinated. Among household contacts, the median age was 31 (10-41) years, 833 (52.7%) were female, 116 (7.3%) were Hispanic, 78 (4.9%) were non-Hispanic Black, 1283 (81.2%) were non-Hispanic White, 792 (50.1%) were vaccinated, and 356 (22.5%) had laboratory-confirmed influenza during follow-up. The overall secondary infection risk of influenza among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The risk was highest among children and was 20.3% (95% CI, 16.4% to 24.9%) for influenza A and 15.9% (95% CI, 11.8% to 21.0%) for influenza B. The overall estimated VE for preventing secondary infections among unvaccinated household contacts was 21.0% (95% CI, 1.4% to 36.7%) and varied by type; estimated VE against influenza A was 5.0% (95% CI, -22.3% to 26.3%) and 56.4% (95% CI, 30.1% to 72.8%) against influenza B. CONCLUSIONS AND RELEVANCE: After influenza was introduced into households, the risk of secondary influenza among unvaccinated household contacts was approximately 15% to 20%, and highest among children. Estimated VE varied by influenza type, with demonstrated protection against influenza B virus infection. |
Personal protective equipment use by dairy farmworkers exposed to cows infected with highly pathogenic avian influenza A(H5N1) viruses - Colorado, 2024
Marshall KE , Drehoff CC , Alden N , Montoya S , Stringer G , Kohnen A , Mellis A , Ellington S , Singleton J , Reed C , Herlihy R . MMWR Morb Mortal Wkly Rep 2024 73 (44) 999-1003 The risk for transmission of highly pathogenic avian influenza A(H5N1) virus from dairy cows to humans is currently low; however, personal protective equipment (PPE) use during work activities on dairy farms has not been well described. PPE use can protect farmworkers when they are working with highly pathogenic avian influenza A(H5N1)-infected cows. The Colorado Department of Public Health and Environment (CDPHE) and the Colorado Department of Agriculture (CDA) offered PPE to all Colorado farms before or during an A(H5N1) outbreak in cows in 2024. CDPHE surveyed 83 dairy workers from three farms with a confirmed bovine A(H5N1) outbreak. Frequently reported farm worker activities included milking cows or working in the milking parlor (51%), cleaning cow manure (49%), and transporting cows (46%). Frequently reported PPE items available to workers before A(H5N1) outbreaks included gloves (88%), eye protection (e.g., safety glasses or goggles) (76%), rubber boots or boot covers (71%), and head covers (69%). N95 respirator use was low among workers who were exposed to ill cows after detection of A(H5N1) virus (26%). PPE use while working with ill cows increased a mean of 28% after detection of A(H5N1) virus on surveyed farms; use of eye protection while milking cows increased the most (40%). Public health PPE distribution, education, and collaboration with CDA might have increased PPE use on dairy farms with A(H5N1) virus-infected cows and mitigated risk for farmworkers acquiring A(H5N1) virus. |
Serologic evidence of recent infection with highly pathogenic avian influenza a(H5) virus among dairy workers - Michigan and Colorado, June-August 2024
Mellis AM , Coyle J , Marshall KE , Frutos AM , Singleton J , Drehoff C , Merced-Morales A , Pagano HP , Alade RO , White EB , Noble EK , Holiday C , Liu F , Jefferson S , Li ZN , Gross FL , Olsen SJ , Dugan VG , Reed C , Ellington S , Montoya S , Kohnen A , Stringer G , Alden N , Blank P , Chia D , Bagdasarian N , Herlihy R , Lyon-Callo S , Levine MZ . MMWR Morb Mortal Wkly Rep 2024 73 (44) 1004-1009 Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers. |
Influenza A virus within-host evolution and positive selection in a densely sampled household cohort over three seasons
Bendall EE , Zhu Y , Fitzsimmons WJ , Rolfes M , Mellis A , Halasa N , Martin ET , Grijalva CG , Talbot HK , Lauring AS . Virus Evol 2024 10 (1) veae084 ![]() ![]() ![]() While influenza A virus (IAV) antigenic drift has been documented globally, in experimental animal infections, and in immunocompromised hosts, positive selection has generally not been detected in acute infections. This is likely due to challenges in distinguishing selected rare mutations from sequencing error, a reliance on cross-sectional sampling, and/or the lack of formal tests of selection for individual sites. Here, we sequenced IAV populations from 346 serial, daily nasal swabs from 143 individuals collected over three influenza seasons in a household cohort. Viruses were sequenced in duplicate, and intrahost single nucleotide variants (iSNVs) were identified at a 0.5% frequency threshold. Within-host populations exhibited low diversity, with >75% mutations present at <2% frequency. Children (0-5 years) had marginally higher within-host evolutionary rates than adolescents (6-18 years) and adults (>18 years, 4.4 × 10(-6) vs. 9.42 × 10(-7) and 3.45 × 10(-6), P < .001). Forty-five iSNVs had evidence of parallel evolution but were not over-represented in HA and NA. Several increased from minority to consensus level, with strong linkage among iSNVs across segments. A Wright-Fisher approximate Bayesian computational model identified positive selection at 23/256 loci (9%) in A(H3N2) specimens and 19/176 loci (11%) in A(H1N1)pdm09 specimens, and these were infrequently found in circulation. Overall, we found that within-host IAV populations were subject to genetic drift and purifying selection, with only subtle differences across seasons, subtypes, and age strata. Positive selection was rare and inconsistently detected. |
Influenza virus shedding and symptoms: Dynamics and implications from a multiseason household transmission study
Morris SE , Nguyen HQ , Grijalva CG , Hanson KE , Zhu Y , Biddle JE , Meece JK , Halasa NB , Chappell JD , Mellis AM , Reed C , Biggerstaff M , Belongia EA , Talbot HK , Rolfes MA . PNAS Nexus 2024 3 (9) pgae338 Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza. |
Reduced risk of SARS-CoV-2 infection among household contacts with recent vaccination and past COVID-19 infection: Results from two multi-site case-ascertained household transmission studies
Rolfes MA , Talbot HK , Morrissey KG , Stockwell MS , Maldonado Y , McLean HQ , Lutrick K , Bowman NM , Rao S , Izurieta HS , Zhu Y , Chappell J , Battan-Wraith S , Merrill LS , McClaren S , Sano E , Petrie JG , Biddle J , Johnson S , Salvatore P , Smith-Jeffcoat SE , Asturias EJ , Lin JT , Ellingson KD , Belongia EA , Olivo V , Mellis AM , Grijalva CG . Am J Epidemiol 2024 Households are a primary setting for transmission of SARS-CoV-2. We examined the role of prior SARS-CoV-2 immunity on the risk of infection in household close contacts. Households in the United States with an individual who tested positive for SARS-CoV-2 during September 2021-May 2023 were enrolled if the index case's illness began ≤6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. The effects of prior SARS-CoV-2 immunity (vaccination, prior infection, or hybrid immunity) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Of 1,532 contacts (905 households), 8% had immunity from prior infection alone, 51% from vaccination alone, 29% hybrid immunity, and 11% had no prior immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The adjusted risk of SARS-CoV-2 infection was lowest among contacts with vaccination and prior infection (aRR: 0.81, 95% CI: 0.70, 0.93, compared with contacts with no prior immunity) and was lowest when the last immunizing event occurred ≤6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). In high-transmission settings like households, immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection. |
Asymptomatic and mildly symptomatic influenza virus infections by season -- Case-ascertained household transmission studies, United States, 2017-2023
Biddle JE , Nguyen HQ , Talbot HK , Rolfes MA , Biggerstaff M , Johnson S , Reed C , Belongia EA , Grijalva CG , Mellis AM . medRxiv 2024 Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing the effectiveness of symptom-based surveillance systems. |
Association of symptoms and viral culture positivity for SARS-CoV-2—Tennessee, April–July 2020
Biddle J , Bonenfant G , Grijalva C , Zhu Y , Halasa N , Chappell J , Mellis A , Reed C , Talbot H , Zhou B , Rolfes M . Influ Other Respir Viruses 2024 18 (6) Background: Understanding how symptoms are associated with SARS-CoV-2 culture positivity is important for isolation and transmission control guidelines. Methods: Individuals acutely infected with SARS-CoV-2 in Tennessee and their household contacts were recruited into a prospective study. All participants self-collected nasal swabs daily for 14 days and completed symptom diaries from the day of illness onset through day 14 postenrollment. Nasal specimens were tested for SARS-CoV-2 using RT-qPCR. Positive specimens with cycle threshold values < 40 were sent to the Centers for Disease Control and Prevention (CDC) for viral culture. First, we modeled the association between symptoms and the risk of culture positivity using an age-adjusted generalized additive model (GAM) accounting for repeated measurements within participants and a symptom-day spline. Next, we investigated how timing of symptom resolution was associated with the timing of culture resolution. Results: In a GAM restricted to follow-up days after symptoms began, the odds of a specimen being culture positive was significantly increased on days when wheezing, loss of taste or smell, runny nose, nasal congestion, sore throat, fever, or any symptom were reported. For all symptoms except sore throat, it was more common for participants to have culture resolution before symptom resolution than for culture to resolve after or on the same day as symptom resolution. Conclusions: Overall, symptomatic individuals were more likely to be SARS-CoV-2 viral culture positive. For most symptoms, culture positivity was more likely to end before symptoms resolved. However, a proportion of individuals remained culture positive after symptom resolved, across all symptoms. © 2024 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd. |
Symptoms, viral loads, and rebound among COVID-19 outpatients treated with nirmatrelvir/ritonavir compared to propensity score matched untreated individuals
Smith-Jeffcoat SE , Biddle JE , Talbot HK , Morrissey KG , Stockwell MS , Maldonado Y , McLean HQ , Ellingson KD , Bowman NM , Asturias E , Mellis AM , Johnson S , Kirking HL , Rolfes MAR , Olivo V , Merrill L , Battan-Wraith S , Sano E , McLaren SH , Vargas CY , Goodman S , Sarnquist CC , Govindaranjan P , Petrie JG , Belongia EA , Ledezma K , Pryor K , Lutrick K , Bullock A , Yang A , Haehnel Q , Rao S , Zhu Y , Schmitz J , Hart K , Grijalva CG , Salvatore PP . Clin Infect Dis 2024 78 (5) 1175-1184 ![]() ![]() 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. |
SARS-CoV-2 viral shedding and rapid antigen test performance - Respiratory Virus Transmission Network, November 2022-May 2023
Smith-Jeffcoat SE , Mellis AM , Grijalva CG , Talbot HK , Schmitz J , Lutrick K , Ellingson KD , Stockwell MS , McLaren SH , Nguyen HQ , Rao S , Asturias EJ , Davis-Gardner ME , Suthar MS , Kirking HL . MMWR Morb Mortal Wkly Rep 2024 73 (16) 365-371 ![]() ![]() As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test). |
Sex differences in COVID-19 symptom severity and trajectories among ambulatory adults
Massion SP , Howa AC , Zhu Y , Kim A , Halasa N , Chappell J , McGonigle T , Mellis AM , Deyoe JE , Reed C , Rolfes MA , Talbot HK , Grijalva CG . Influenza Other Respir Viruses 2023 17 (12) e13235 BACKGROUND: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood. METHODS: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model. RESULTS: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males (p < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed. CONCLUSIONS: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males. |
Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 2022 (preprint)
Mellis AM , Lauring AS , Talbot HK , McLean HQ , Morrissey KG , Stockwell MS , Bowman NM , Maldonado Y , Ellingson KD , Rao S , Biddle JE , Johnson S , Ogokeh C , Salvatore PP , Reed C , Smith-Jeffcoat SE , Meece JK , Hanson KE , Belongia EA , Bendall EE , Gilbert J , Olivo V , Merrill LS , McLaren SH , Sano E , Vargas CY , Saiman L , Silverio Francisco RA , Bullock A , Lin J , Govindarajan P , Goodman SH , Sarnquist CC , Lutrick K , Ledezma KI , Ramadan FA , Pryor K , Miiro FN , Asturias E , Dominguez S , Olson D , Izurieta HS , Chappell J , Lindsell C , Halasa N , Hart K , Zhu Y , Schmitz J , Rolfes MA , Grijalva CG . medRxiv 2023 19 Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Method(s): Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Finding(s): 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation(s): The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding(s): Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study (preprint)
Mellis AM , Meece JK , Halasa NB , Chappell JD , McLean HQ , Grijalva CG , Hanson KE , Zhu Y , Kim A , Deyoe J , Ivacic LC , Reed C , Talbot HK , Rolfes MA . medRxiv 2022 18 (10) 1699-1703 We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged >=50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities (preprint)
McLean HQ , Grijalva CG , Hanson KE , Zhu YG , Deyoe JE , Meece JK , Halasa NB , Chappell JD , Mellis A , Reed C , Belongia EA , Talbot HK , Rolfes MA . medRxiv 2021 OBJECTIVES: Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age. |
Association of culturable-virus detection and household transmission of SARS-CoV-2 - California and Tennessee, 2020-2022
Deyoe JE , Kelly JD , Grijalva CG , Bonenfant G , Lu S , Anglin K , Garcia-Knight M , Pineda-Ramirez J , Briggs Hagen M , Saydah S , Abedi GR , Goldberg SA , Tassetto M , Zhang A , Donohue KC , Davidson MC , Diaz Sanchez R , Djomaleu M , Mathur S , Shak JR , Deeks SG , Peluso MJ , Chiu CY , Zhu Y , Halasa NB , Chappell JD , Mellis A , Reed C , Andino R , Martin JN , Zhou B , Talbot HK , Midgley CM , Rolfes MA . J Infect Dis 2023 From two SARS-CoV-2 household transmission studies (enrolling April 2020 - January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals. |
Household transmission of influenza A viruses in 2021-2022
Rolfes MA , Talbot HK , McLean HQ , Stockwell MS , Ellingson KD , Lutrick K , Bowman NM , Bendall EE , Bullock A , Chappell JD , Deyoe JE , Gilbert J , Halasa NB , Hart KE , Johnson S , Kim A , Lauring AS , Lin JT , Lindsell CJ , McLaren SH , Meece JK , Mellis AM , Moreno Zivanovich M , Ogokeh CE , Rodriguez M , Sano E , Silverio Francisco RA , Schmitz JE , Vargas CY , Yang A , Zhu Y , Belongia EA , Reed C , Grijalva CG . JAMA 2023 329 (6) 482-489 IMPORTANCE: Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season. OBJECTIVE: To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US. DESIGN, SETTING, AND PARTICIPANTS: This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment. EXPOSURES: Household contacts living with a primary case. MAIN OUTCOMES AND MEASURES: Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted. RESULTS: During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons. CONCLUSIONS AND RELEVANCE: Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association. |
Early and increased influenza activity among children - Tennessee, 2022-23 influenza season
Thomas CM , White EB , Kojima N , Fill MA , Hanna S , Jones TF , Newhouse CN , Orejuela K , Roth E , Winders S , Chandler DR , Grijalva CG , Schaffner W , Schmitz JE , DaSilva J , Kirby MK , Mellis AM , Rolfes MA , Sumner KM , Flannery B , Talbot HK , Dunn JR . MMWR Morb Mortal Wkly Rep 2023 72 (3) 49-54 Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed. |
Impact of Age and Symptom Development on SARS-CoV-2 Transmission in Households With Children-Maryland, New York, and Utah, August 2020-October 2021.
Sumner KM , Karron RA , Stockwell MS , Dawood FS , Stanford JB , Mellis A , Hacker E , Thind P , Castro MJE , Harris JP , Deloria Knoll M , Schappell E , Hetrich MK , Duque J , Jeddy Z , Altunkaynak K , Poe B , Meece J , Stefanski E , Tong S , Lee JS , Dixon A , Veguilla V , Rolfes MA , Porucznik CA . Open Forum Infect Dis 2022 9 (8) ofac390 BACKGROUND: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. METHODS: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. RESULTS: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). CONCLUSIONS: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages. |
SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study.
Mellis AM , Meece JK , Halasa NB , Chappell JD , McLean HQ , Grijalva CG , Hanson KE , Zhu Y , Kim A , Deyoe J , Ivacic LC , Reed C , Talbot HK , Rolfes MA . J Infect Dis 2022 226 (10) 1699-1703 ![]() ![]() We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020--May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset. |
Household Transmission and Clinical Features of SARS-CoV-2 Infections.
McLean HQ , Grijalva CG , Hanson KE , Zhu Y , Deyoe JE , Meece JK , Halasa NB , Chappell JD , Mellis AM , Reed C , Belongia EA , Talbot HK , Rolfes MA . Pediatrics 2022 149 (3) OBJECTIVES: Examine age differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk from primary cases and infection risk among household contacts and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower in primary cases age 12 to 17 years than from primary cases 18 to 49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contact pairs age ≥65 years (76%) and 5 to 11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age. |
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