Development and Roll-Out of A Coronavirus Disease 2019 Clinical Pathway for Standardized Qualified Care in Public Hospitals in Korea.

Despite the coronavirus disease 2019 (COVID-19) vaccination roll-out, variant-related outbreaks have occurred repeatedly in Korea. Although public hospitals played a major role in COVID-19 patients' care, difficulty incorporating evolving COVID-19 treatment guidelines called for a clinical pathway (CP). Eighteen public hospitals volunteered, and a professional review board was created. CPs were formulated containing inclusion/exclusion criteria, application flow charts, and standardized order sets. After CP roll-out, key parameters improved, such as increased patient/staff five-point satisfaction scores (0.41/0.57) and decreased hospital stays (1.78 days)/medical expenses (17.5%). The CPs were updated consistently after roll-out as new therapeutics drugs were introduced and quarantine policies changed.

Clinical findings, viral load, and outcomes of COVID-19: Comparison of patients with negative and positive initial chest computed tomography.

Reports detailing the clinical characteristics, viral load, and outcomes of patients with normal initial chest CT findings are lacking. We sought to compare the differences in clinical findings, viral loads, and outcomes between patients with confirmed COVID-19 who initially tested negative on chest CT (CT negative) with patients who tested initially positive on chest CT (CT positive). The clinical data, viral loads, and outcomes of initial CT-positive and CT-negative patients examined between January 2020 and April 2020 were retrospectively compared. The efficacy of viral load (cyclic threshold value [Ct value]) in predicting pneumonia was evaluated using receiver operating characteristic (ROC) curve and area under the curve (AUC). In total, 128 patients underwent initial chest CT (mean age, 54.3 ± 19.0 years, 50% male). Of those, 36 were initially CT negative, and 92 were CT positive. The CT-positive patients were significantly older (P < .001) than the CT-negative patients. Only age was significantly associated with the initial presence of pneumonia (odds ratio, 1.060; confidence interval (CI), 1.020-1-102; P = .003). In addition, age (OR, 1.062; CI, 1.014-1.112; P = .011), fever at diagnosis (OR, 6.689; CI, 1.715-26.096; P = .006), and CRP level (OR, 1.393; CI, 1.150-1.687; P = .001) were significantly associated with the need for O2 therapy. Viral load was significantly higher in the CT-positive group than in the CT-negative group (P = .017). The cutoff Ct value for predicting the presence of pneumonia was 27.71. Outcomes including the mean hospital stay, intensive care unit admission, and O2 therapy were significantly worse in the CT-positive group than in the CT-negative group (all P < .05). In conclusion, initially CT-negative patients showed better outcomes than initially CT-positive patients. Age was significantly associated with the initial presence of pneumonia, and viral load may help in predicting the initial presence of pneumonia.

Infectivity of Coronavirus Disease 2019: A Prospective Cohort Study in the Korean Metropolitan Area.

BACKGROUND: Although several characteristics of coronavirus disease 2019 (COVID-19), an ongoing pandemic disease, have been identified, data on the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. METHODS: This prospective cohort study was conducted to analyze the infectivity of SARS-CoV-2 based on data of all patients diagnosed with COVID-19 confirmed using real-time polymerase chain reaction test from January to April 2020 in Gyeonggi-do, the largest province in Korea. RESULTS: Of the 502 patients, 298 consisting of 106 clusters with 5,909 contacts were included. Of these, 277 (93.0%) were symptomatic, and the most common symptoms were cough, fever, sputum, sore throat, and headache. A total of 94 patients (31.5%) had pneumonia, while 8 (2.7%) died during the follow-up period. The secondary attack rate (SAR) in the study population was 3.5% (204/5,909). In exposure settings, the SAR was higher in religious gathering (13.5% [95% confidence interval, 10.7-16.8%]), workplaces (8.49% [95% CI, 6.08-11.74%]), and schools (6.38% [95% CI, 3.39-11.69%]) than in health care facilities (1.92% [95% CI, 1.45-2.55%]). Sore throat at any period, dyspnea at diagnosis or any period, lower cycle threshold value in the lower respiratory tract samples, leukocytosis, and higher bilirubin levels were associated with higher infectivity of COVID-19. The presence of symptoms was not related to the infectivity. CONCLUSION: In establishing the infection control strategies for COVID-19, the variables associated with high infectivity may be considered.

Clinical and Laboratory Factors Associated with Symptom Development in Asymptomatic COVID-19 Patients at the Time of Diagnosis.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Comparison of Antibody Response Elicited by ChAdOx1 and BNT162b2 COVID-19 Vaccine.

BACKGROUND: ChAdOx1 and BNT162b2 vaccines are currently commonly used against coronavirus disease 2019 worldwide. Our study was designed to determine the serostatus and relative levels of anti-S and neutralizing antibodies in patients who were administered either ChAdOx1 or BNT162b2 vaccine. In addition, we investigated whether the antibody response to each vaccine differed according to sex and age. METHODS: Healthcare workers (HCWs) at a general hospital who were vaccinated with two doses of either ChAdOx1 or BNT162b2 were invited to participate in this prospective cohort study. Blood samples of HCWs vaccinated with both ChAdOx1 doses over a period of 12 weeks were collected at weeks 4 and 8 post first vaccination and 2 weeks post second vaccination. Blood samples of HCWs vaccinated with BNT162b2 were collected in the third week after the first dose, and the second dose was then administered on the same day; two weeks post second dose (5 weeks after the first dose), blood samples were collected to assess the antibody response. The titers of anti-S antibodies against the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor-binding domain and the neutralizing antibodies in the collected blood were evaluated. RESULTS: Of the 309 HCWs enrolled in the study, 205 received ChAdOx1 and 104 received BNT162b2. Blood samples from participants receiving either the ChAdOx1 or BNT162b2 vaccine exhibited substantial anti-S and neutralizing antibody seropositivity subsequent to the second dose. All participants (100%) from both vaccine groups were seropositive for anti-S antibody, while 98% (201/205) of ChAdOx1-vaccinated individuals and 100% (104/104) of BNT162b2-vaccinated individuals were seropositive for neutralizing antibodies. The median levels of anti-S and neutralizing antibodies were significantly higher in the BNT162b2-vaccinated group than the ChAdOx1-vaccinated group; in particular, anti-S antibody titers of 1,020 (interquartile range, 571.0-1,631.0) U/mL vs. 2,360 (1,243-2,500) U/mL, P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively, and neutralizing antibody titers of 85.0 (65.9-92.1%) vs. 95.8 (94.4-96.6%), P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively. In the ChAdOx1 vaccine group, the neutralizing antibody level was significantly higher in women than in men (85.7 [70.3-92.5%] vs. 77.7 [59.2-91.0%], P < 0.05); however, the neutralizing antibody titer in the BNT162b2 vaccine group did not vary between the two sexes (95.9 [95.2-96.6%] vs. 95.2 [93.5-96.3%], P = 0.200). Analysis of the correlation of antibody profiles with age revealed that the levels of anti-S antibodies and signal inhibition rate (SIR) of neutralizing antibodies decreased significantly with age. CONCLUSION: Both the ChAdOx1- and BNT162b2-vaccinated groups showed high seropositivity for anti-S and neutralizing antibodies. The SIR of neutralizing antibodies in the ChAdOx1 vaccine group was higher in women than in men. Enhanced antibody responses were observed in participants vaccinated with BNT162b2 compared to those vaccinated with the ChAdOx1 vaccine.

Reactogenicity after the first and second doses of BNT162b2 mRNA coronavirus disease vaccine: a single-center study.

PURPOSE: This study was conducted to determine differences in adverse events associated with the first and second doses of the BNT162b2 coronavirus disease 2019 vaccine based on the age and sex of recipients. MATERIALS AND METHODS: An online survey on the post-vaccination adverse events of healthcare workers was conducted from March 2021 to April 2021. The differences in the types of adverse events, including severity, onset time, and duration of symptoms, and how the adverse events were dealt with by the patient were analyzed based on the age and sex. The profiles of adverse events were compared after the first and second vaccination doses. RESULTS: Among the 131 participants who participated in the online survey out of 208 vaccine recipients, 43 and 80 recipients of the BNT162b2 vaccine experienced adverse events after the first and second dose, respectively. No sex-related differences were observed in the profiles of adverse events in vaccinated recipients. The overall frequency of adverse events did not differ based on age after the first dose. After the second dose, the frequency of adverse events, including both local and systemic reactions was significantly higher in the younger age group than in the older age group. CONCLUSION: The BNT162b2 vaccine resulted in a higher frequency of adverse events after the second dose than after the first dose especially in the younger age group; however, no sex-related differences associated with these adverse events were observed.

Rapidly Declining SARS-CoV-2 Antibody Titers within 4 Months after BNT162b2 Vaccination.

The efficacy and safety of the BNT162b2 vaccine are known, but antibodies are expected to decrease over time after vaccination. We collected blood samples from 104 fully vaccinated health care workers at 3 and 5 weeks after first vaccination and 4 months after second vaccination. Antibody titers and neutralizing antibodies were measured. In our study, both antibody titers and neutralizing antibodies increased significantly at 5 weeks after first vaccination but decreased rapidly at 4 months after second vaccination. Additionally, the results showed a significant decrease regardless of gender or age. Further studies are needed to help determine the interval of SARS-CoV-2 vaccinations.

SARS-CoV-2 Antibody Response to the BNT162b2 mRNA Vaccine in Persons with Past Natural Infection.

There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was asymptomatic during quarantine, but the other had mild upper respiratory infection symptoms 1 day before admission, and the symptoms continued for 9 days. There was no pneumonic infiltration in chest X-ray in both patients, and no COVID-19 specific treatment was administered. Total immunoglobulin antibody and neutralizing antibody to anti-spike protein receptor-binding domain of severe acute respiratory syndrome coronavirus 2 were confirmed to be present in both HCWs in blood tests performed at 2 weeks and 4 weeks after discharge. Antibody response to mRNA vaccination showed marked elevation after the first vaccination, which was 30-40 times higher than that of antibody titer after natural infection in each patient (83.2 U/mL vs. > 2,500 U/mL in patient 1; 61.6 U/mL vs. > 2,500 U/mL in patient 2). Signal inhibition rate of neutralizing antibodies was also increased to over 97%. Due to this increased effect, there was little difference in antibody levels after the first and second dose. Both patients 1 and 2 suffered more from adverse vaccine reactions after the second vaccination than from COVID-19 symptoms.

Predication of oxygen requirement in COVID-19 patients using dynamic change of inflammatory markers: CRP, hypertension, age, neutrophil and lymphocyte (CHANeL).

The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.

Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis.

The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

What surgeons should know about emergency operation for COVID-19 confirmed patients: A case report.

INTRODUCTION: This case is shared to reiterate and confirm the principles of ensuring the safety of the surgical team caring for COVID-19-confirmed patients, thus, preventing the spread of infection within the hospital. CASE PRESENTATION: A 54-year-old male, COVID-19-confirmed patient complaining of abdominal pain since two days prior was transferred to our hospital. Perforated appendicitis with a periappendiceal abscess was diagnosed by computed tomography. Laparoscopic appendectomy was performed in a negative-pressure operating room. The surgical team wore enhanced personal protective equipment. Electrocautery was not used during surgery and no other special instruments were applied to reduce aerosol generation. No special instruments or filters were used for the removal of intra-abdominal gas. The operation was completed successfully and no immediate surgical complications occurred. The patient advanced to a normal diet on the 4th postoperative day. The patient was treated with antibiotics for bacteremia and antiviral therapy for underlying pneumonia in the setting of COVID-19 with most symptoms dissipating by the 7th postoperative day. The patient was discharged on the 30th postoperative day without any complications. DISCUSSION: A well-designed manual, a well-trained surgical team, and a negative-pressure operating room are essential for safe laparoscopic appendectomies in COVID-19 patients. CONCLUSION: When surgery is performed in a negative-pressure operating room by a well-trained surgical team, a laparoscopic appendectomy can be successfully performed under the principles of obtaining optimum clinical outcomes while faithfully ensuring the safety of healthcare providers and the hospital environment.

Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19.

Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARS-CoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results. The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.

Clinical Course and Outcomes of 3,060 Patients with Coronavirus Disease 2019 in Korea, January-May 2020.

BACKGROUND: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. METHODS: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. RESULTS: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3-4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5-7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50-59, 60-69, 70-79, and ≥ 80 years of age, respectively. CONCLUSION: In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.