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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332884

ABSTRACT

Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual's virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.

3.
BMC Infect Dis ; 22(1): 314, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1770495

ABSTRACT

BACKGROUND: To improve understanding of the antibody response to SARS-CoV-2 infection, we examined seroprevalence, incidence of infection, and seroconversion among a cohort of young adults living on university campuses during the fall of 2020. METHODS: At the beginning (semester start) and end (semester end) of an 11-week period, serum collected from 107 students was tested using the qualitative Abbott Architect SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Results were matched to interim weekly surveillance viral testing and symptom data. RESULTS: With the SARS-CoV-2 IgG assay, 15 (14.0%) students were seropositive at semester start; 29 (27.1%) students were seropositive at semester end; 10 (9.3%) were seropositive at both times. With the AdviseDx SARS-CoV-2 IgG II assay, 17 (16.3%) students were seropositive at semester start, 37 (35.6%) were seropositive at semester end, and 16 (15.3%) were seropositive at both times. Overall, 23 students (21.5%) had positive viral tests during the semester. Infection was identified by serial testing in a large majority of individuals who seroconverted using both assays. Those seropositive at semester end more frequently reported symptomatic infections (56.5%) than asymptomatic infections (30.4%). CONCLUSION: Differences between antibody targets were observed, with more declines in antibody index values below the threshold of positivity with the anti-nucleocapsid assay compared to the anti-spike assay. Serology testing, combined with serial viral testing, can detect seroconversions, and help understand the potential correlates of protection provided by antibodies to SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Enzyme-Linked Immunosorbent Assay , Humans , Seroconversion , Seroepidemiologic Studies , Students , Universities
4.
Cell Rep ; : 110688, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1763614

ABSTRACT

The emergence of the SARS-CoV-2 Omicron (B.1.1.529) variant with a surprising number of spike mutations raises concerns about reduced sensitivity of this virus to antibody neutralization and subsequent vaccine breakthrough infections. Here, we infect Moderna mRNA-vaccinated or previously infected hamsters with the Omicron BA.1 variant. While the Moderna mRNA vaccine reduces viral loads in the respiratory tissues upon challenge with an early S-614G isolate, the vaccine efficacy is not as pronounced after infection with the Omicron variant. Previous infection with the early SARS-CoV-2 isolate prevents replication after rechallenge with either virus in the lungs of previously infected hamsters, but the Omicron variant replicates efficiently in nasal turbinate tissue. These results experimentally demonstrate in an animal model that the antigenic changes in the Omicron variant are responsible for vaccine breakthrough and re-infection.

5.
Nature ; 603(7902): 687-692, 2022 03.
Article in English | MEDLINE | ID: covidwho-1641974

ABSTRACT

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.


Subject(s)
COVID-19/pathology , COVID-19/virology , Disease Models, Animal , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cricetinae , Female , Humans , Lung/pathology , Lung/virology , Male , Mesocricetus , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Viral Load
6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295837

ABSTRACT

The SARS-CoV-2 Delta variant is highly transmissible and contains mutations that confer partial immune escape. We compared RT-PCR cycle threshold (Ct) data from 699 test-positive anterior nasal swab specimens from fully vaccinated (n = 310) or unvaccinated (n=389) individuals. We observed low Ct values (<25) in 212 of 310 fully vaccinated (68%) and 246 of 389 (63%) unvaccinated individuals. Testing a subset of these low-Ct samples revealed infectious SARS-CoV-2 in 15 of 17 specimens (88%) from unvaccinated individuals and 37 of 39 (95%) from vaccinated people. To determine whether infectious virus titers differed in vaccinated and unvaccinated persons, we performed plaque assays on an additional set of 48 samples with Ct <25, finding no difference in infectious virus titer between groups.

7.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294542

ABSTRACT

University settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls;a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.

8.
Clin Infect Dis ; 73(6): e1348-e1355, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1479943

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral , Humans , RNA , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , Sensitivity and Specificity , Universities
9.
Emerg Infect Dis ; 27(11): 2776-2785, 2021 11.
Article in English | MEDLINE | ID: covidwho-1444021

ABSTRACT

University settings have demonstrated potential for coronavirus disease (COVID-19) outbreaks; they combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin-Madison, Madison, Wisconsin, USA. During August-October 2020, a total of 3,485 students, including 856/6,162 students living in dormitories, tested positive. Case counts began rising during move-in week, August 25-31, 2020, then rose rapidly during September 1-11, 2020. The university initiated multiple prevention efforts, including quarantining 2 dormitories; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, in which the university is located, did not find evidence of transmission from a large cluster of cases in the 2 quarantined dorms during the outbreak. Coordinated implementation of prevention measures can reduce COVID-19 spread in university settings and may limit spillover to the surrounding community.


Subject(s)
COVID-19 , Universities , Disease Outbreaks , Humans , SARS-CoV-2 , Wisconsin/epidemiology
10.
Open Forum Infect Dis ; 8(9): ofab405, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1434432

ABSTRACT

BACKGROUND: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks occurred at universities during Fall 2020, but little is known about risk factors for campus-associated infections or immunity provided by anti-SARS-CoV-2 antibodies in young adults. METHODS: We conducted surveys and serology tests among students living in dormitories in September and November to examine infection risk factors and antibody presence. Using campus weekly reverse-transcription polymerase chain reaction (RT-PCR) test results, the relationship between survey responses, SARS-CoV-2 antibodies, and infections was assessed. RESULTS: Of 6136 students, 1197 completed the survey and 572 also completed serologic testing in September compared with 517 and 414 in November, respectively. Participation in fraternity or sorority events (adjusted risk ratio [aRR], 1.9 [95% confidence interval {CI}, 1.4-2.5]) and frequent alcohol consumption (aRR, 1.6 [95% CI, 1.2-2.2]) were associated with SARS-CoV-2 infection. Mask wearing during social events (aRR, 0.6 [95% CI, .6-1.0]) was associated with decreased risk. None of the 20 students with antibodies in September tested positive for SARS-CoV-2 during the semester, while 27.8% of students who tested RT-PCR positive tested negative for antibodies in November. CONCLUSIONS: Frequent drinking and attending social events were associated with SARS-CoV-2 infection. Antibody presence in September appeared to be protective from reinfection, but this finding was not statistically significant.

11.
Clin Infect Dis ; 73(Suppl 1): S54-S57, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1387815

ABSTRACT

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%).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Sensitivity and Specificity , Wisconsin/epidemiology
12.
N Engl J Med ; 385(4): 320-329, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1287848

ABSTRACT

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Viral Load , Adolescent , Adult , COVID-19/diagnosis , COVID-19/virology , COVID-19 Nucleic Acid Testing , COVID-19 Vaccines/immunology , Carrier State/diagnosis , Carrier State/prevention & control , Emergency Responders , Female , Health Personnel , Humans , Male , Middle Aged , Patient Acuity , Prospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome , Young Adult
13.
Clin Infect Dis ; 73(Suppl 1): S54-S57, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1205576

ABSTRACT

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%).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Sensitivity and Specificity , Wisconsin/epidemiology
14.
J Med Virol ; 93(3): 1568-1572, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196489

ABSTRACT

The SARS-CoV-2 pandemic has led to an unprecedented demand for diagnostic tests. Many studies have modeled the efficiency gains of specimen pooling, but few have systematically evaluated the dilution effect of pooling on the sensitivity of tests. Using the frequency distribution of cycle threshold (Ct ) values of our first 838 SARS-CoV-2 positive specimens, we modeled 100 specimens on the same frequency distribution. Given this distribution, we then tested dilutions of 1:5, 1:10, and 1:50 to find the percentage of specimens positive at each Ct value with each pool size. Using the frequency distribution and the percentage of specimens positive at each Ct value, we estimate that pools of 5 lead to 93% sensitivity, pools of 10 lead to 91% sensitivity, and pools of 50 lead to 81% sensitivity. Pools of 5 and 10 lead to some specimens with Ct values of ≥32 becoming negative, while pools of 50 lead to some specimens with Ct values of ≥28 becoming negative. These sensitivity estimates can inform laboratories seeking to implement pooling approaches as they seek to balance test efficiency with sensitivity.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , COVID-19/virology , Diagnostic Tests, Routine/methods , Humans , Pandemics/prevention & control , RNA, Viral/genetics , Sensitivity and Specificity , Specimen Handling/methods
15.
MMWR Morb Mortal Wkly Rep ; 69(5152): 1642-1647, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-1005171

ABSTRACT

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).


Subject(s)
Antigens, Viral/analysis , COVID-19 Testing/methods , COVID-19/diagnosis , SARS-CoV-2/immunology , Student Health Services , Adolescent , Adult , Asymptomatic Diseases , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Universities , Wisconsin/epidemiology , Young Adult
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