Unbiased Screens Show CD8+ T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein.

Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8+ T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8+ T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8+ T cell immunity to SARS-CoV-2.

Estimates of SARS-CoV-2 Hospitalization and Fatality Rates in the Prevaccination Period, United States.

Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.

Reemergence of Bordetella parapertussis, United States, 2019-2023.

To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.

COVID-19 Vaccination Site Accessibility, United States, December 11, 2020-March 29, 2022.

During December 11, 2020-March 29, 2022, the US government delivered ≈700 million doses of COVID-19 vaccine to vaccination sites, resulting in vaccination of ≈75% of US adults during that period. We evaluated accessibility of vaccination sites. Sites were accessible by walking within 15 minutes by 46.6% of persons, 30 minutes by 74.8%, 45 minutes by 82.8%, and 60 minutes by 86.7%. When limited to populations in counties with high social vulnerability, accessibility by walking was 55.3%, 81.1%, 86.7%, and 89.4%, respectively. By driving, lowest accessibility was 96.5% at 15 minutes. For urban/rural categories, the 15-minute walking accessibility between noncore and large central metropolitan areas ranged from 27.2% to 65.1%; driving accessibility was 79.9% to 99.5%. By 30 minutes driving accessibility for all urban/rural categories was >95.9%. Walking time variations across jurisdictions and between urban/rural areas indicate that potential gains could have been made by improving walkability or making transportation more readily available.

Experimental SARS-CoV-2 Infection of Elk and Mule Deer.

To assess the susceptibility of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) to SARS-CoV-2, we performed experimental infections in both species. Elk did not shed infectious virus but mounted low-level serologic responses. Mule deer shed and transmitted virus and mounted pronounced serologic responses and thus could play a role in SARS-CoV-2 epidemiology.

Bus Riding as Amplification Mechanism for SARS-CoV-2 Transmission, Germany, 20211.

To examine the risk associated with bus riding and identify transmission chains, we investigated a COVID-19 outbreak in Germany in 2021 that involved index case-patients among bus-riding students. We used routine surveillance data, performed laboratory analyses, interviewed case-patients, and conducted a cohort study. We identified 191 case-patients, 65 (34%) of whom were elementary schoolchildren. A phylogenetically unique strain and epidemiologic analyses provided a link between air travelers and cases among bus company staff, schoolchildren, other bus passengers, and their respective household members. The attack rate among bus-riding children at 1 school was ≈4 times higher than among children not taking a bus to that school. The outbreak exemplifies how an airborne agent may be transmitted effectively through (multiple) short (<20 minutes) public transport journeys and may rapidly affect many persons.

COVID-19 Death Determination Methods, Minnesota, USA, 2020-20221.

Accurate and timely mortality surveillance is crucial for elucidating risk factors, particularly for emerging diseases. We compared use of COVID-19 keywords on death certificates alone to identify COVID-19 deaths in Minnesota, USA, during 2020-2022, with use of a standardized mortality definition incorporating additional clinical data. For analyses, we used likelihood ratio χ2 and median 1-way tests. Death certificates alone identified 96% of COVID-19 deaths confirmed by the standardized definition and an additional 3% of deaths that had been classified as non-COVID-19 deaths by the standardized definition. Agreement between methods was >90% for most groups except children, although agreement among adults varied by demographics and location at death. Overall median time from death to filing of death certificate was 3 days; decedent characteristics and whether autopsy was performed varied. Death certificates are an efficient and timely source of COVID-19 mortality data when paired with SARS-CoV-2 testing data.

Prevalence of SARS-CoV-2 Infection among Children and Adults in 15 US Communities, 2021

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 US communities. Survey-weighted estimates of SARS-CoV-2 infection and vaccine willingness among participants at each site were compared within demographic groups by using linear regression models with inverse variance weighting. Among 22,284 persons >2 months of age and older, median prevalence of infection (prior, active, or both) was 12.9% across sites and similar across age groups. Within each site, average prevalence of infection was 3 percentage points higher for Black than White persons and average vaccine willingness was 10 percentage points lower for Black than White persons and 7 percentage points lower for Black persons than for persons in other racial groups. The higher prevalence of SARS-CoV-2 infection among groups with lower vaccine willingness highlights the disparate effect of COVID-19 and its complications.

Non-HIV Immunocompetent Patient with COVID-19 and Severe Pneumocystis jirovecii Pneumonia Co-Infection.

Pneumocystis jirovecii pneumonia is an opportunistic infection that affects HIV-infected and immunocompromised persons and rarely affects immunocompetent patients. However, after the advent of the COVID-19 pandemic, some COVID-19 patients without immunocompromise or HIV were infected with P. jirovecii. Clinical manifestations were atypical, easily misdiagnosed, and rapidly progressive, and the prognosis was poor.

Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Development and Evaluation of Surveillance System for Identifying Jail-Associated COVID-19 Cases in Minnesota, USA, 2022.

Confinement facilities are high-risk settings for the spread of infectious disease, necessitating timely surveillance to inform public health action. To identify jail-associated COVID-19 cases from electronic laboratory reports maintained in the Minnesota Electronic Disease Surveillance System (MEDSS), Minnesota, USA, the Minnesota Department of Health developed a surveillance system that used keyword and address matching (KAM). The KAM system used a SAS program (SAS Institute Inc., https://www.sas.com) and an automated program within MEDSS to identify confinement keywords and addresses. To evaluate KAM, we matched jail booking data from the Minnesota Statewide Supervision System by full name and birthdate to the MEDSS records of adults with COVID-19 for 2022. The KAM system identified 2,212 cases in persons detained in jail; sensitivity was 92.40% and specificity was 99.95%. The success of KAM demonstrates its potential to be applied to other diseases and congregate-living settings for real-time surveillance without added reporting burden.

Prognostic value of serum amyloid A protein as a biomarker in the diagnosis of 2019 novel coronavirus disease (COVID-19).

BACKGROUND: The current study aimed to evaluate the prognostic value of serum amyloid A protein)SAA(protein as a biomarker in diagnosing 2019 novel coronavirus disease)COVID-19(infection. METHODS: The study was conducted on 123 patients with definitive COVID-19 infection referred to Shahid Beheshti and Sina hospitals in Hamedan province, Iran. Five-milliliter blood samples were taken from all included patients and serum was isolated using a centrifuge at 10,000 rpm for 10 min. Laboratory tests were conducted, including c-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), potassium level, sodium blood test, platelets (PLT), complete blood count (CBC), lymphocyte count, and neutrophil count. The SAA enzyme-linked immunosorbent assay (ELISA) Kit was applied to measure the SAA level in serum samples. RESULTS: 123 patients included 73 males and 50 females, age ±50. Sixty-six (53.7 %) patients had negative CRP while 80 (65 %) patients had normal ESR. Potassium levels were not normal among 111 (94.9 %) patients. Seventy-seven (63.1 %) patients had normal CBC, while 108 (87.8 %) patients had neutrophils above the normal range. 94 (97.9 %) patients over the age of 50 were positive for SAA. In terms of gender, men were the most frequent patients with SAA. There was a statistically significant relationship between the serum level of SAA and outcomes of patients with COVID-19 (p = 0.0001). 94 % of patients with SAA ≤50 were recovered from COVID-19 infection. The sensitivity rate of SAA compared to polymerase chain reaction (PCR) and computed tomography scan (CT scan) tests was 93 % and 99 %, respectively. Moreover, the accuracy of SAA compared to PCR and CT scan tests was 52 % and 96 %, respectively. CONCLUSION: Results indicate the SAA is a sensitive, but not specific biomarker in the early detection of COVID-19. The quantitative levels of SAA can be useful in predicting treatment outcomes among patients with COVID-19.

Sex Difference in Characteristics and Predictors of In-Hospital Mortality among Patients with COVID-19.

INTRODUCTION: With a surge in the prevalence of coronavirus disease-2019 (COVID-19) in Beijing starting in October 2022, hospitalisation rates increased markedly. This study aimed to evaluate factors associated with in-hospital mortality in patients with COVID-19. METHODS: Using data from hospitalised patients, sex-based differences in clinical characteristics, in-hospital management, and in-hospital mortality among patients diagnosed with COVID-19 were evaluated. Predictive factors associated with mortality in 1,091 patients admitted to the Beijing Anzhen Hospital (Beijing, China) for COVID-19 between October 2022 and January 2023 were also evaluated. RESULTS: Data from 1,091 patients hospitalised with COVID-19 were included in the analysis. In-hospital mortality rates for male and female patients were 14.9% and 10.4%, respectively. Multifactorial logistic analysis indicated that lymphocyte percentage (LYM%) (odds ratio [OR] 0.863, 95% confidence interval [CI] 0.805-0.925; p < 0.001), uric acid (OR 1.004, 95% CI: 1.002-1.006; p = 0.001), and high-sensitivity C-reactive protein (OR 1.094, 95% CI: 1.012-1.183; p = 0.024) levels were independently associated with COVID-19-related in-hospital mortality. Among female patients, multifactorial analysis revealed that LYM% (OR 0.856, 95% CI: 0.796-0.920; p < 0.001), older age (OR 1.061, 95% CI: 1.020-1.103; p = 0.003), obesity (OR 2.590, 95% CI: 1.131-5.931; p = 0.024), and a high high-sensitivity troponin I level (OR 2.602, 95% CI: 1.157-5.853; p = 0.021) were risk factors for in-hospital mortality. Receiver operating characteristic (ROC) curve analysis, including area under the ROC curve, showed that the efficacy of LYM% in predicting in-hospital death was 0.800 (sensitivity, 63.2%; specificity, 83.2%) in male patients and 0.815 (sensitivity, 87.5%; specificity, 64.4%) in female patients. CONCLUSION: LYM% is a consistent predictor of in-hospital mortality for both sexes. Older age and markers of systemic inflammation, myocardial injury, and metabolic dysregulation are also associated with a high mortality risk. These findings may help identify patients who require closer monitoring and tailored interventions to improve outcomes.

Clinical characteristics of 13 cases of Coronavirus infection complicated with severe central nervous system lesions in Shanxi children's hospital.

BACKGROUND: The new coronavirus Omicron variant strain spread rapidly worldwide and is currently the primary mutant strain prevalent in the world. OBJECTIVE: To explore the clinical features of severe central nervous system lesions in children infected with novel coronavirus Omicron mutant strain, so as to provide a reference for clinical diagnosis and treatment. MATERIALS AND METHODS: The clinical data of 13 children diagnosed with novel coronavirus Omicron variant strain complicated with severe central nervous system infection from December 13, 2022, to January 31, 2023, in the Children's Intensive Care Medicine Department of Shanxi Children's Hospital were retrospectively analyzed. RESULTS: Among the 13 children, there were 9 males (69%) and 4 females (31%); the ages ranged from 1-year-old 16 days to 13 years old, with a median age of 9 years old, and most of them were school-age children (84.6%). The 13 children were usually healthy, but this time they were all positive for the new coronavirus nucleic acid test. The 13 children had obvious signs of the abnormal nervous system when they were admitted to the hospital, among which 12 cases (92.3%) showed convulsions, 11 children had obvious disturbance of consciousness (84.6%) when they were admitted to the hospital, and 5 children had circulatory disorders (38.4%). Among the 13 children, 2 were cured (15.3%), 5 children had serious sequelae (38.4%) when they were discharged from the hospital, and 6 children died of severe illness (46.3%). CONCLUSION: This study illuminates the clinical characteristics of severe central nervous system complications in children with coronavirus variant infection, highlighting rapid onset, swift progression, relatively poor prognosis, and notable symptoms such as high fever, convulsions, altered consciousness, elevated interleukin-6 levels, increased cerebrospinal fluid lactate levels, and early imaging changes.

Systematic review of empiric studies on lockdowns, workplace closures, and other non-pharmaceutical interventions in non-healthcare workplaces during the initial year of the COVID-19 pandemic: benefits and selected unintended consequences.

BACKGROUND: We conducted a systematic review aimed to evaluate the effects of non-pharmaceutical interventions within non-healthcare workplaces and community-level workplace closures and lockdowns on COVID-19 morbidity and mortality, selected mental disorders, and employment outcomes in workers or the general population. METHODS: The inclusion criteria included randomized controlled trials and non-randomized studies of interventions. The exclusion criteria included modeling studies. Electronic searches were conducted using MEDLINE, Embase, and other databases from January 1, 2020, through May 11, 2021. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Meta-analysis and sign tests were performed. RESULTS: A total of 60 observational studies met the inclusion criteria. There were 40 studies on COVID-19 outcomes, 15 on anxiety and depression symptoms, and five on unemployment and labor force participation. There was a paucity of studies on physical distancing, physical barriers, and symptom and temperature screening within workplaces. The sign test indicated that lockdown reduced COVID-19 incidence or case growth rate (23 studies, p < 0.001), reproduction number (11 studies, p < 0.001), and COVID-19 mortality or death growth rate (seven studies, p < 0.05) in the general population. Lockdown did not have any effect on anxiety symptoms (pooled standardized mean difference = -0.02, 95% CI: -0.06, 0.02). Lockdown had a small effect on increasing depression symptoms (pooled standardized mean difference = 0.16, 95% CI: 0.10, 0.21), but publication bias could account for the observed effect. Lockdown increased unemployment (pooled mean difference = 4.48 percentage points, 95% CI: 1.79, 7.17) and decreased labor force participation (pooled mean difference = -2.46 percentage points, 95% CI: -3.16, -1.77). The risk of bias for most of the studies on COVID-19 or employment outcomes was moderate or serious. The risk of bias for the studies on anxiety or depression symptoms was serious or critical. CONCLUSIONS: Empiric studies indicated that lockdown reduced the impact of COVID-19, but that it had notable unwanted effects. There is a pronounced paucity of studies on the effect of interventions within still-open workplaces. It is important for countries that implement lockdown in future pandemics to consider strategies to mitigate these unintended consequences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration # CRD42020182660.

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis.

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.

Implementation of Inpatient Electronic Consultations During the COVID-19 Crisis and Its Sustainability Beyond the Pandemic: Quality Improvement Study.

BACKGROUND: Limiting in-person contact was a key strategy for controlling the spread of the highly infectious novel coronavirus (COVID-19). To protect patients and staff from the risk of infection while providing continued access to necessary health care services, we implemented a new electronic consultation (e-consult) service that allowed referring providers to receive subspecialty consultations for patients who are hospitalized and do not require in-person evaluation by the specialist. OBJECTIVE: We aimed to assess the impact of implementing e-consults in the inpatient setting to reduce avoidable face-to-face referrals during the COVID-19 pandemic. METHODS: This quality improvement study evaluated all inpatient e-consults ordered from July 2020 to December 2022 at the University of California Irvine Medical Center. The impact of e-consults was assessed by evaluating use (eg, number of e-consults ordered), e-consult response times, and outcome of the e-consult requests (eg, resolved electronically or converted to the in-person evaluation of patient). RESULTS: There were 1543 inpatient e-consults ordered across 11 participating specialties. A total of 53.5% (n=826) of requests were addressed electronically, without the need for a formal in-person evaluation of the patient. The median time between ordering an e-consult and a specialist documenting recommendations in an e-consult note was 3.7 (IQR 1.3-8.2) hours across all specialties, contrasted with 7.3 (IQR 3.6-22.0) hours when converted to an in-person consult (P<.001). The monthly volume of e-consult requests increased, coinciding with surges of COVID-19 cases in California. After the peaks of the COVID-19 crisis subsided, the use of inpatient e-consults persisted at a rate well above the precrisis levels. CONCLUSIONS: An inpatient e-consult service was successfully implemented, resulting in fewer unnecessary face-to-face consultations and significant reductions in the response times for consults requested on patients who are hospitalized and do not require an in-person evaluation. Thus, e-consults provided timely, efficient delivery of inpatient consultation services for appropriate problems while minimizing the risk of direct transmission of the COVID-19 virus between health care providers and patients. The service also demonstrated its value as a tool for effective inpatient care coordination beyond the peaks of the pandemic leading to the sustainability of service and value.

Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients.

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

Spiritual Needs of Iranian Patients with COVID-19: A Qualitative Study.

Facing crises, life problems, and illnesses, many people turn to religion, spirituality, and faith as a psychosocial adjustment approach. This qualitative study assessed the spiritual needs of fourteen Iranian patients who recovered from COVID-19. Qualitative content analysis resulted in three themes, including "composure" with three categories of "prayer", "hope", and "connection"; "meaning in the life" comprising two categories of "a new prospect of life" and "the power of nature"; and "global responsibility" involving one category of "the relationships between individuals, communities, and the world". This study highlighted that patients relied on spirituality to cope with COVID-19 disease.

[Clinical and laboratory parameters and pathomorphological features of the lungs in patients who have had COVID-19 viral pneumonia]. / Kliniko-laboratornye pokazateli i patomorfologicheskie osobennosti legkikh u patsientov, perenesshikh virusnuyu pnevmoniyu COVID-19.

Post-Covid syndrome is characterized by general somatic manifestations, changes in the psycho-emotional sphere, cognitive disorders, disorders of the cardiovascular, respiratory systems and excretory function. However, there is little information in the literature about the mechanisms of thanatogenesis in patients who have had COVID-19. An analysis of clinical and laboratory parameters and pathomorphological changes was carried out in 9 autopsy cases of patients who had previously suffered a new coronavirus infection (COVID-19). The age of the deceased ranged from 80 to 96 years. At the time of hospitalization, the concentration of IgG varied from 32.61 to 1013.5 RLU, IgM - from 0.29 to 16.98 U/ml. The period from clinical diagnosis to death ranged from 12 to 46 days, and the time from clinical recovery (negative polymerase chain reaction) to death ranged from 2 to 30 days. In all cases, unresolved viral pneumonia and diffuse alveolar damage (exudative-proliferative phase) were diagnosed.