Modelling the effects of social distancing, antiviral therapy, and booster shots on mitigating Omicron spread.

As the COVID-19 situation changes because of emerging variants and updated vaccines, an elaborate mathematical model is essential in crafting proactive and effective control strategies. We propose a COVID-19 mathematical model considering variants, booster shots, waning, and antiviral drugs. We quantify the effects of social distancing in the Republic of Korea by estimating the reduction in transmission induced by government policies from February 26, 2021 to February 3, 2022. Simulations show that the next epidemic peak can be estimated by investigating the effects of waning immunity. This research emphasizes that booster vaccination should be administered right before the next epidemic wave, which follows the increasing waned population. Policymakers are recommended to monitor the waning population immunity using mathematical models or other predictive methods. Moreover, our simulations considering a new variant's transmissibility, severity, and vaccine evasion suggest intervention measures that can reduce the severity of COVID-19.

COVID-19 Vaccine-Associated Pneumonitis in the Republic of Korea: A Nationwide Multicenter Survey.

BACKGROUND: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. METHODS: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. RESULTS: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. CONCLUSION: These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Migratory Pneumonia in Prolonged SARS-CoV-2 Infection in Patients Treated With B-cell Depletion Therapies for B-cell Lymphoma.

OBJECTIVE: To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms. MATERIALS AND METHODS: From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37-71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features. RESULTS: All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, follow-up CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25. CONCLUSION: COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.

Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment.

BACKGROUND: Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells. METHODS: To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products. RESULTS: Our results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products. DISCUSSION: In conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients. ONE SENTENCE SUMMARY: Ex-vivo expanded SARS-CoV-2 antigen specific T cells developed as third-party partial HLA-matching products may be a promising approach for treating severe COVID-19 patients that do not respond to previous treatment options.

How Important Is Behavioral Change during the Early Stages of the COVID-19 Pandemic? A Mathematical Modeling Study.

How important is the speed and intensity of behavioral change due to government policies, such as enhanced social distancing or lockdown, when an emerging infectious disease occurs? In this study, we introduce a deterministic SEIR model considering the behavior-changed susceptible group to investigate the effect of the speed and intensity of behavioral change on the transmission dynamics of COVID-19. We used epidemiological data from South Korea and Italy for the simulation study, because South Korea and Italy were the first countries to report an outbreak of COVID-19 after China and the prevention and response policy of each government were similar during the first outbreak of COVID-19. Simulation results showed that it took approximately twenty fewer days in Korea than in Italy until 90% of susceptible individuals changed their behavior during the first outbreak. It was observed that the behavior-changed susceptible individuals reduced the COVID-19 transmission rate by up to 93% in Korea and 77% in Italy. Furthermore, if the intensity and speed of behavioral change in Italy were the same as in Korea, the expected number of cumulative confirmed cases would have been reduced by approximately 95%, from 210,700 to 10,700, until the end of the lockdown period. We assumed that behavioral change is influenced by the number of confirmed cases and does not take into account social and cultural differences, as well as the state of the healthcare system, between the two countries. Our mathematical modeling showed how important the high intensity and fast speed of behavioral change to reduce the number of confirmed cases in the early period of an epidemic are.

Non-Pharmacological Nursing Interventions for Prevention and Treatment of Delirium in Hospitalized Adult Patients: Systematic Review of Randomized Controlled Trials.

Delirium is a common neurobehavioral complication in hospitalized patients that can occur in the acute phase and lead to poor long-term outcomes. The purpose of this study was to identify non-pharmacological nursing interventions for the prevention and treatment of delirium in hospitalized adult patients. We conducted a systematic review to synthesize the findings of published studies. We searched the PubMed, EMBASE, CINAHL, and Cochrane Library CENTRAL databases for randomized controlled trials in January 2021. We report this systematic review according to the PRISMA 2009 checklist. The study was registered on PROSPERO (CRD42021226538). Nine studies were systematically reviewed for non-pharmacological nursing interventions for the prevention and treatment of delirium. The types of non-pharmacological nursing interventions included multicomponent intervention, multidisciplinary care, multimedia education, music listening, mentoring of family caregivers concerning delirium management, bright light exposure, ear plugs, and interventions for simulated family presence using pre-recorded video messages. These results could help nurses select and utilize non-pharmacological nursing interventions for the prevention and treatment of delirium in clinical nursing practice.

Quantitative SARS-CoV-2 Spike Antibody Response in COVID-19 Patients Using Three Fully Automated Immunoassays and a Surrogate Virus Neutralization Test.

Quantitative SARS-CoV-2 antibody assays against the spike (S) protein are useful for monitoring immune response after infection or vaccination. We compared the results of three chemiluminescent immunoassays (CLIAs) (Abbott, Roche, Siemens) and a surrogate virus neutralization test (sVNT, GenScript) using 191 sequential samples from 32 COVID-19 patients. All assays detected >90% of samples collected 14 days after symptom onset (Abbott 97.4%, Roche 96.2%, Siemens 92.3%, and GenScript 96.2%), and overall agreement among the four assays was 91.1% to 96.3%. When we assessed time-course antibody levels, the Abbott and Siemens assays showed higher levels in patients with severe disease (p < 0.05). Antibody levels from the three CLIAs were correlated (r = 0.763-0.885). However, Passing-Bablok regression analysis showed significant proportional differences between assays and converting results to binding antibody units (BAU)/mL still showed substantial bias. CLIAs had good performance in predicting sVNT positivity (Area Under the Curve (AUC), 0.959-0.987), with Abbott having the highest AUC value (p < 0.05). SARS-CoV-2 S protein antibody levels as assessed by the CLIAs were not interchangeable, but showed reliable performance for predicting sVNT results. Further standardization and harmonization of immunoassays might be helpful in monitoring immune status after COVID-19 infection or vaccination.

Comparison of SARS-CoV-2 Antibody Responses and Seroconversion in COVID-19 Patients Using Twelve Commercial Immunoassays.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have high clinical utility in managing the pandemic. We compared antibody responses and seroconversion of coronavirus disease 2019 (COVID-19) patients using different immunoassays. METHODS: We evaluated 12 commercial immunoassays, including three automated chemiluminescent immunoassays (Abbott, Roche, and Siemens), three enzyme immunoassays (Bio-Rad, Euroimmun, and Vircell), five lateral flow immunoassays (Boditech Med, SD biosensor, PCL, Sugentech, and Rapigen), and one surrogate neutralizing antibody assay (GenScript) in sequential samples from 49 COVID-19 patients and 10 seroconversion panels. RESULTS: The positive percent agreement (PPA) of assays for a COVID-19 diagnosis ranged from 84.0% to 98.5% for all samples (>14 days after symptom onset), with IgM or IgA assays showing higher PPAs. Seroconversion responses varied across the assay type and disease severity. Assays targeting the spike or receptor-binding domain protein showed a tendency for early seroconversion detection and higher index values in patients with severe disease. Index values from SARS-CoV-2 binding antibody assays (three automated assays, one LFIA, and three EIAs) showed moderate to strong correlations with the neutralizing antibody percentage (r=0.517-0.874), and stronger correlations in patients with severe disease and in assays targeting spike protein. Agreement among the 12 assays was good (74.3%-96.4%) for detecting IgG or total antibodies. CONCLUSIONS: Positivity rates and seroconversion of SARS-CoV-2 antibodies vary depending on the assay kits, disease severity, and antigen target. This study contributes to a better understanding of antibody response in symptomatic COVID-19 patients using currently available assays.

Lymphopenia as a Biological Predictor of Outcomes in COVID-19 Patients: A Nationwide Cohort Study.

We aimed to identify whether lymphopenia is a reliable prognostic marker for COVID-19. Using data derived from a Korean nationwide longitudinal cohort of 5628 COVID-19 patients, we identified propensity-matched cohorts (n = 770) with group I of severe lymphopenia (absolute lymphocyte counts [ALC]: <500/mm3, n = 110), group II of mild-to-moderate lymphopenia (ALC: ≥500-<1000/mm3, n = 330), and group III, no lymphopenia (ALC: ≥1000/mm3, n = 330). A significantly higher mortality rate was associated with lymphopenia severity: 40% in group I, 22.7% in group II, and 13.0% in group III (p < 0.001). At 28 days, the estimated inferior overall survival associated with intensified lymphopenia: 62.7% in group I, 79.9% in group II, and 89.0% in group III (p < 0.001). Lymphopenia contributed significantly toward a greater need for interventions in all groups but at varying degrees: requirements of invasive ventilation, intensive oxygen supply, or adequate oxygen supply, respectively (p < 0.001). The lymphopenia intensity was independently associated with higher COVID-19 mortality in multivariable analysis; adjusted odds ratios of 5.63 (95% CI, 3.0-10.72), and 2.47 (95% CI, 1.5-4.13) for group I and group II, respectively. Lymphopenia and its severity levels may serve as reliable predictive factors for COVID-19 clinical outcomes; thus, lymphopenia may provide the prognostic granularity required for clinical use in the management of patients with COVID-19.