Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington.

BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health-Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.

Vaccine Effectiveness against SARS-CoV-2 Variant P.1 in Nursing-Facility Residents, Washington, USA, April 2021.

A SARS-CoV-2 P.1 (Gamma) variant outbreak occurred at a skilled nursing facility in Washington, USA, in April 2021. Effectiveness of 2 doses of mRNA vaccines against P.1 infection among residents in this outbreak was 75.0% (95% CI 44.5%-88.7%), similar to effectiveness for other pre-Delta variants among long-term care residents.

Investigation and Serologic Follow-Up of Contacts of an Early Confirmed Case-Patient with COVID-19, Washington, USA.

We describe the contact investigation for an early confirmed case of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the United States. Contacts of the case-patient were identified, actively monitored for symptoms, interviewed for a detailed exposure history, and tested for SARS-CoV-2 infection by real-time reverse transcription PCR (rRT-PCR) and ELISA. Fifty contacts were identified and 38 (76%) were interviewed, of whom 11 (29%) reported unprotected face-to-face interaction with the case-patient. Thirty-seven (74%) had respiratory specimens tested by rRT-PCR, and all tested negative. Twenty-three (46%) had ELISA performed on serum samples collected ≈6 weeks after exposure, and none had detectable antibodies to SARS-CoV-2. Among contacts who were tested, no secondary transmission was identified in this investigation, despite unprotected close interactions with the infectious case-patient.

COVID-19 in a Long-Term Care Facility - King County, Washington, February 27-March 9, 2020.

On February 28, 2020, a case of coronavirus disease (COVID-19) was identified in a woman resident of a long-term care skilled nursing facility (facility A) in King County, Washington.* Epidemiologic investigation of facility A identified 129 cases of COVID-19 associated with facility A, including 81 of the residents, 34 staff members, and 14 visitors; 23 persons died. Limitations in effective infection control and prevention and staff members working in multiple facilities contributed to intra- and interfacility spread. COVID-19 can spread rapidly in long-term residential care facilities, and persons with chronic underlying medical conditions are at greater risk for COVID-19-associated severe disease and death. Long-term care facilities should take proactive steps to protect the health of residents and preserve the health care workforce by identifying and excluding potentially infected staff members and visitors, ensuring early recognition of potentially infected patients, and implementing appropriate infection control measures.

Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility - King County, Washington, March 2020.

Older adults are susceptible to severe coronavirus disease 2019 (COVID-19) outcomes as a consequence of their age and, in some cases, underlying health conditions (1). A COVID-19 outbreak in a long-term care skilled nursing facility (SNF) in King County, Washington that was first identified on February 28, 2020, highlighted the potential for rapid spread among residents of these types of facilities (2). On March 1, a health care provider at a second long-term care skilled nursing facility (facility A) in King County, Washington, had a positive test result for SARS-CoV-2, the novel coronavirus that causes COVID-19, after working while symptomatic on February 26 and 28. By March 6, seven residents of this second facility were symptomatic and had positive test results for SARS-CoV-2. On March 13, CDC performed symptom assessments and SARS-CoV-2 testing for 76 (93%) of the 82 facility A residents to evaluate the utility of symptom screening for identification of COVID-19 in SNF residents. Residents were categorized as asymptomatic or symptomatic at the time of testing, based on the absence or presence of fever, cough, shortness of breath, or other symptoms on the day of testing or during the preceding 14 days. Among 23 (30%) residents with positive test results, 10 (43%) had symptoms on the date of testing, and 13 (57%) were asymptomatic. Seven days after testing, 10 of these 13 previously asymptomatic residents had developed symptoms and were recategorized as presymptomatic at the time of testing. The reverse transcription-polymerase chain reaction (RT-PCR) testing cycle threshold (Ct) values indicated large quantities of viral RNA in asymptomatic, presymptomatic, and symptomatic residents, suggesting the potential for transmission regardless of symptoms. Symptom-based screening in SNFs could fail to identify approximately half of residents with COVID-19. Long-term care facilities should take proactive steps to prevent introduction of SARS-CoV-2 (3). Once a confirmed case is identified in an SNF, all residents should be placed on isolation precautions if possible (3), with considerations for extended use or reuse of personal protective equipment (PPE) as needed (4).

Association of IL28B genotype with fibrosis progression and clinical outcomes in patients with chronic hepatitis C: a longitudinal analysis.

UNLABELLED: Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinical outcome is unclear. Our aim was to study the relationship between IL28B genotype and both histological and clinical outcomes in patients with chronic hepatitis C (CHC). Hepatic fibrosis was scored using the Ishak (0-6) scale; progression was defined as a 2-point increase in Ishak score between biopsies. Multiple logistic and Cox regressions were used to identify variables associated with fibrosis progression. In all, 1,483 patients were included in a baseline cross-sectional analysis, from which 276 were eligible for a paired biopsy analysis (median time between biopsies 4 years), and 400 for a clinical outcome analysis. At baseline biopsy, patients with IL28B CC genotype had significantly higher portal inflammation (2.4 versus 2.2) and alanine aminotransferase (ALT) levels (133 versus 105 U/L; P < 0.05 for all). In the paired biopsy analysis, there was no difference in the frequency of fibrosis progression between patients with IL28B CC and non-CC genotypes (17% versus 23%). In logistic regression, only higher baseline alkaline phosphatase, lower platelets, and greater hepatic steatosis were associated with fibrosis progression. Patients with IL28B CC were twice as likely to develop adverse clinical outcomes compared to non-CC (32% versus 16%; P = 0.007). CONCLUSION: IL28B CC genotype was associated with greater hepatic necroinflammation, higher ALT, and worse clinical outcomes in CHC patients. This suggests that IL28B CC is associated with a state of enhanced immunity that, on the one hand, can promote viral clearance, but alternately can increase necroinflammation and hepatic decompensation without enhancing fibrosis progression.

Signs, Symptoms, and Comorbidities Associated With Onset and Prognosis of COVID-19 in a Nursing Home.

BACKGROUND: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. METHODS: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. RESULTS: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. CONCLUSIONS AND IMPLICATIONS: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor.

Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United States.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors.

BACKGROUND: HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI) improves the response to NNRTI-containing regimens. The genetic basis for NNRTI hypersusceptibility was partly defined in our earlier analyses of a paired genotype-phenotype dataset of viral isolates from treatment-experienced patients, in which we identified reverse transcriptase mutations V118I, H208Y, and T215Y as being strongly associated with NNRTI hypersusceptibility. OBJECTIVES: We evaluated the role of these mutations in NNRTI hypersusceptibility by site-directed mutagenesis and phenotypic analysis of HIV-1 recombinants. METHODS: Drug susceptibility and replication capacity were determined in single cycle assays. Hypersusceptibility was defined by a statistically significant (P < 0.01; Student's t-test) mean fold-change in 50% inhibitory concentration (IC50) of less than 0.4. RESULTS: The single mutations V118I, H208Y, and T215Y did not show hypersusceptibility to efavirenz with mean fold-change of 0.58, 0.55, and 0.70, respectively (P < 0.01 and P = 0.12). The H208Y/T215Y and V118I/H208Y/T215Y mutants showed marked hypersusceptibility to efavirenz, having mean fold-change values of 0.27 and 0.20, respectively (P < 0.001). In addition, H208Y/T215Y, V118I/T215Y, and V118I/H208Y/T215Y were hypersusceptible to delavirdine and nevirapine. The V118I/T215Y mutant was not replication impaired; whereas H208Y/T215Y and V118I/H208Y/T215Y had significantly (P < 0.01) reduced replication capacities of 40 and 35% of wild-type, respectively. CONCLUSION: Different combinations of V118I, H208Y, and T215Y produce NNRTI hypersusceptibility. The V118I/T215Y mutant is hypersusceptible to delavirdine and nevirapine without reduced replication capacity, whereas the H208Y/T215Y and V118I/H208Y/T215Y mutants are hypersusceptible to all NNRTI and show impaired replication. These findings suggest that more than one mechanism is involved in NNRTI hypersusceptibility.

Steroid hormones acutely regulate expression of a Nudix protein-encoding gene in the endometrial epithelium of sheep.

Steroid hormones regulate endometrial gene expression to meet the needs of developing embryos. Our hypothesis is that steroid hormones transiently induce expression of genes in the endometrial epithelium to make the uterine environment different between the earliest days of pregnancy. We identified one such gene product using differential display-polymerase chain reactions. The gene product that was strongly induced in ewes between day 3 and 6 of the estrous cycle was cloned and sequenced to identify it as encoding a member of the Nudix family of hydrolase enzymes. Northern blot analyses indicated that NUDT16 mRNA concentrations were elevated 10-fold in the endometrium of sheep from day 5 to 9 of the estrous cycle and returned to basal levels by day 11. In assays of RNA samples from 15 different tissues from an adult ewe, the concentrations of NUDT16 mRNA were greatest in endometrium. In situ hybridization localized NUDT16 mRNA exclusively to the endometrial epithelial cells of the glands and uterine lumen. In ovariectomized ewes, NUDT16 mRNA was induced by a regimen of alternating estrogen and progesterone therapy designed to mimic the hormonal experiences of a ewe at day 6 of the estrous cycle. The final estrogen treatment in the regimen was critical to the expression of NUDT16 as well as progesterone receptor and estrogen receptor-beta genes. Characterization of the NUDT16 gene identified putative steroid hormone response elements, which can now be investigated to understand its unique pattern of regulation in the earliest days of pregnancy.