Immunogenicity Differences of the ChAdOx1 nCoV-19 Vaccine According to Pre-Existing Adenovirus Immunity.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6-125.0) vs. 51.0 (17.9-122.3), p = 0.024), 2-3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5-926.5) vs. 555.0 (287.3-926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5-655.3) vs. 176.0 (94.3-255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

Risk factors of pneumothorax and pneumomediastinum in COVID-19: a matched case-control study.

BACKGROUND: During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case-control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. METHODS: This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1-2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. RESULTS: 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72-0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041). CONCLUSIONS: Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Clinical efficacy and safety of interferon (Type I and Type III) therapy in patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Interferon (IFN) has been highlighted in several randomized controlled trials as an attractive therapeutic candidate based plausible mode of action, suppressed response in severe COVID-19, and inhibition of SARS-CoV-2 replication. This study investigated the efficacy and safety of IFN in patients with COVID-19 according to clinical severity. Randomized controlled trials evaluating the efficacy and safety of IFN (systemic or inhaled IFN-α, -ß, and -λ) treatment in adult patients with COVID-19 were identified by systematically searching electronic databases until January 2023. Risk of bias were assessed using the Cochrane risk of bias tool, meta-analysis, and certainty of evidence grading were followed for the systematic review. We included 11 trials comprising 6,124 patients. Compared with exclusive standard care or placebo, IFN therapy did not provide significant clinical benefits for mortality at day 28 (pooled risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.62-1.18, 9 studies, low-certainty evidence) and progression to mechanical ventilation (pooled RR = 1.08, 95% CI: 0.81-1.43, 6 studies, low-certainty evidence) in patients with COVID-19. IFN therapy resulted in significantly increased hospital discharge on day 14 relative to the control arm (pooled RR = 1.29, 95% CI: 1.04-1.59). These results were inconsistent compared to other comparable outcomes such as recovery at day 14 and time to clinical improvement. The IFN-treated arm was as safe as the control arm, regardless of clinical severity (pooled RR = 0.87, 95% CI: 0.64-1.19, 9 studies, low-certainty evidence). In conclusion, IFN therapy was safe but did not demonstrate favorable outcomes for major clinical indices in patients with COVID-19, particularly those with higher than moderate severity. IFN therapy was not associated with worsening outcomes in patients with severe COVID-19. Future clinical trials should evaluate the clinical efficacy of IFN therapy in patients with mild COVID-19 or at an earlier stage. Trial registration: The protocol for this review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42022301413.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study.

PURPOSE: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. RESULTS: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. CONCLUSION: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis.

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82-0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71-0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81-0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70-0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71-0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89-1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events.Trial registration: Clinical Trials Registry India identifier: CTRI/2020/05/025369.The proper registration is PROSPERO: registration number CRD42021294120.

Surveillance of Close Contacts and Implications of Pediatric Patients with COVID-19-Experiences from a Single Residential Treatment Center.

Residential treatment centers (RTCs) are successful in isolating and closely monitoring adults confirmed with coronavirus disease 2019 (COVID-19), but there are concerns for children who need care. This study was conducted as a retrospective analysis of the surveillance of guardians who entered an RTC with infected pediatric patients to identify the secondary attack rate of COVID-19 to close contacts in a single RTC and to provide directions for developing guidelines for caregivers who co-isolate with infected children. When caregivers were admitted to this RTC, aside from negative confirmation before discharge, tests were additionally performed one or two times. There were 57 index children and adolescent patients who entered the RTC with their parents as caregivers. The secondary attack rate by pediatric patients to close contacts outside their households was 25% (95% confidence interval, 10.0 to 40.0) (8 out of 32 contacts). The transmissibility of SARS-CoV-2 in children was close to zero at 6 days after the confirmation tests. It is reasonable to test the close contacts of pediatric patients after 7 days of isolation to identify infections among caregivers.

Korean Society of Infectious Diseases/National Evidence-based Healthcare Collaborating Agency Recommendations for Anti-SARS-CoV-2 Monoclonal Antibody Treatment of Patients with COVID-19.

Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.

Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients: A Retrospective Cohort Study.

PURPOSE: Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. MATERIALS AND METHODS: This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or life-threatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. RESULTS: Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002). No transfusion-related side effects were observed. CONCLUSION: CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Revised Korean Society of Infectious Diseases/National Evidence-based Healthcarea Collaborating Agency Guidelines on the Treatment of Patients with COVID-19.

Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives. There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily. Some effective treatment options, albeit of variable efficacy, have been discovered. Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly. Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence.

Correction: A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies.

[This corrects the article DOI: 10.1371/journal.pone.0241169.].

Effects of early corticosteroid use in patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. METHODS: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. RESULTS: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. CONCLUSIONS: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Clinical characteristics and online mental health care of asymptomatic or mildly symptomatic patients with coronavirus disease 2019.

Comparing to data in patients with severe coronavirus diseases 2019 (COVID-19), there are few studies on the prevalence anxiety and/or depression in patients with asymptomatic or mildly symptomatic COVID-19. We investigated the clinical characteristics and the prevalence of anxiety and/or depression among asymptomatic or mildly symptomatic patients with COVID-19 and monitored their mental health using an online assessment. An online survey for monitoring and assessing the mental health of patients with COVID-19 using a mobile phone was conducted. We used the Hospital Anxiety and Depression Scale to measure anxiety and/or depression levels. Of the 234 patients, 66 patients were asymptomatic (28.2%), while the remaining 168 patients were mildly symptomatic. The prevalence of anosmia (p = 0.001) and ageusia (p = 0.008) significantly decreased with the increasing age. In addition, 19.8% and 14.0% patients had anxiety and/or depression in the first survey, and one week after the first survey, respectively. Compared to patients without anxiety and/or depression, those with anxiety and/or depression had a longer quarantine duration. We found that anomia and ageusia were relatively common in the young age group. Furthermore, one-fifth asymptomatic or mildly symptomatic patients with COVID-19 had anxiety and/or depression.

Interim Guidelines on Antiviral Therapy for COVID-19.

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies.

Novel coronavirus (named SARS-CoV-2) can spread widely in confined settings including hospitals, cruise ships, prisons, and places of worship. In particular, a healthcare-associated outbreak could become the epicenter of coronavirus disease (COVID-19). This study aimed to evaluate the effects of different intervention strategies on the hospital outbreak within a tertiary hospital. A mathematical model was developed for the COVID-19 transmission within a 2500-bed tertiary hospital of South Korea. The SEIR (susceptible-exposed-infectious-recovered) model with a compartment of doctor, nurse, patient, and caregiver was constructed. The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Front door screening for detecting suspected cases had only 42% effectiveness. Screening for prohibiting the admission of COVID-19 patients was more effective than the measures for patients before emergency room or outpatient clinic. This model suggests that under the assumed conditions, some effective measures have a great influence on the incidence of COVID-19 within a hospital. The implementation of the preventive measures could reduce the size of a hospital outbreak.

Assessing Viral Shedding and Infectivity of Asymptomatic or Mildly Symptomatic Patients with COVID-19 in a Later Phase.

BACKGROUND: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. METHOD: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. RESULT: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. CONCLUSIONS: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection.

Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19.

OBJECTIVES: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). METHODS: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. RESULTS: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0-55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0-21.0 days) and 18.0 days (IQR 15.0-22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). CONCLUSIONS: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.