Lupus anticoagulants as a prospective independent predictor in COVID-19 patients.

OBJECTIVE: Lupus anticoagulant (LA) are commonly detected during SARS-CoV-2 infection. However, the relationship between LA and clinical significance is still unclear. METHODS: A retrospective chart analysis was performed on COVID-19 patients who were tested for LA at our hospital from March 2020 to November 2021. We analyzed the patient's characteristics based on the result of the LA test. In addition, subgroup analysis performed the LA-positive group who had undergone serial LA tests. RESULTS: A total of 219 COVID-19 patients were enrolled in the study, 148 patients (67.6%) were positive for LA test. The LA-positive group received more treatment of high flow nasal cannula (LA-positive 73.0%, LA-negative 57.7%, p = 0.024). The LA-positive group showed prolonged aPTT, higher levels of CRP and fibrinogen (all p's < 0.05). Among 148 LA-positive patients, 127 patients (86.5%) were found to be LA-positive within 10 days of SARS-CoV-2 positive, and LA-positive group confirmed a median time to LA loss of 10 days. However, there was a group that was negative for LA in the early stages of infection and became positive about 13 days later. A subgroup analysis showed that these patients had different characteristics due to their longer hospital stays and higher D-dimer levels. CONCLUSIONS: In COVID-19 patients, LA is expected to be associated to disease severity. Since the clinical significance of LA is different depending on the onset time of LA positivity, the LA test is suggested to be done at diagnosis of SARS-CoV-2 infection, even if LA is negative, follow-up test should be considered within 10 days.

Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).

OBJECTIVES: There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation. We evaluated the risk of transmission from healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable virus shedding kinetics. METHODS: This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14 to April 3, 2022 in units with 5 or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022. RESULTS: Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1 to 5 days after their return. Of these, 9 (4%) had an epidemiologic link other than with the returning HCW, and 9 (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (n=32), the median time from symptom onset to negative conversion of viable virus was 4 days (95% CI, 3 to 5 days). CONCLUSIONS: Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.

Comparison of Secondary Attack Rate and Viable Virus Shedding between Patients with SARS-CoV-2 Delta and Omicron Variants: A Prospective Cohort Study.

BACKGROUNDS: There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. METHODS: We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. RESULTS: A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further five patients gave undetectable or inconclusive RNA PCR results and one was suspected of being co-infected with both variants. Omicron group had a higher secondary attack rate (31% [38/124]) versus 7% [34/456], p<0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4 days, IQR [1 -7], vs. 8.5 days, IQR [5 - 12 days], p<0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR 1.96), and immunocompromised status (HR 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or 1st booster-vaccinated status (HR 0.49), and Omicron infection (HR 0.44) were independently associated with shorter viable virus shedding. CONCLUSION: Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections. This article is protected by copyright. All rights reserved.

Bacterial Co-Infection and Empirical Antibacterial Therapy in Patients With COVID-19.

BACKGROUND: The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. METHODS: In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. RESULTS: Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300): 6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or in-hospital mortality rates in the study cohort before or after the propensity score-matching. CONCLUSION: In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.

Protracted course of SARS-CoV-2 pneumonia in moderately to severely immunocompromised patients.

There have been few studies comparing the clinical characteristics and outcomes of SARS-CoV-2 pneumonia in individuals with and without moderately to severely immunocompromised conditions. We reviewed adult patients with SARS-CoV-2 infection who had radiologic evidence of pneumonia at a tertiary hospital in Seoul, South Korea, from February 2020 to April 2022. Moderately to severely immunocompromised status was defined as medical conditions or treatments that resulted in increased risk of severe COVID-19 and weakened immune response to COVID-19 vaccine as recommended by Centers for Disease Control and Prevention. The time to pneumonia development was defined as the time from symptom onset to the time when radiologic evidence of pneumonia was obtained. Viral clearance was defined as a Ct value > 30. COVID-19-related death was defined as 90-day death following imaging-confirmed pneumonia without any other plausible cause of death. A total of 467 patients with SARS-CoV-2 pneumonia were analyzed. Of these, 102 (22%) were moderately to severely immunocompromised. The median (IQR) time to pneumonia development was significantly longer in moderately to severely immunocompromised patients (9.5 [6-14] days) than the comparator (6 [3-8] days), p < 0.001), as was the median time to viral clearance (21 versus 12 days, p < 0.001). Moderately to severely immunocompromised status (aOR, 18.39; 95% CI, 5.80-58.30; p < 0.001) was independently associated with COVID-19-related death. Patients with moderately to severely immunocompromised conditions are likely to experience a more protracted course of SARS-CoV-2 pneumonia and a worse outcome than those without these conditions.

No significant influence of pre-vaccination antipyretic use on specific antibody response to a BNT162b2 vaccine booster against COVID-19.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474-21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563-18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Clinical scoring system to predict viable viral shedding in patients with COVID-19.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends 5-10 days of isolation for patients with COVID-19, depending on symptom duration and severity. However, in clinical practice, an individualized approach is required. We thus developed a clinical scoring system to predict viable viral shedding. METHODS: We prospectively enrolled adult patients with SARS-CoV-2 infection admitted to a hospital or community isolation facility between February 2020 and January 2022. Daily dense respiratory samples were obtained, and genomic RNA viral load assessment and viral culture were performed. Clinical predictors of negative viral culture results were identified using survival analysis and multivariable analysis. RESULTS: Among 612 samples from 121 patients including 11 immunocompromised patients (5 organ transplant recipients, 5 with hematologic malignancy, and 1 receiving immunosuppressive agents) with varying severity, 154 (25%) revealed positive viral culture results. Multivariable analysis identified symptom onset day, viral copy number, disease severity, organ transplant recipient, and vaccination status as independent predictors of culture-negative rate. We developed a 4-factor predictive model based on viral copy number (-3 to 3 points), disease severity (1 point for moderate to critical disease), organ transplant recipient (2 points), and vaccination status (-2 points for fully vaccinated). Predicted culture-negative rates were calculated through the symptom onset day and the score of the day the sample was collected. CONCLUSIONS: Our clinical scoring system can provide the objective probability of a culture-negative state in a patient with COVID-19 and is potentially useful for implementing personalized de-isolation policies beyond the simple symptom-based isolation strategy.

Daily, self-test rapid antigen test to assess SARS-CoV-2 viability in de-isolation of patients with COVID-19.

Background: Isolation of COVID-19 patients is a crucial infection control measure to prevent further SARS-CoV-2 transmission, but determining an appropriate timing to end the COVID-19 isolation is a challenging. We evaluated the performance of the self-test rapid antigen test (RAT) as a potential proxy to terminate the isolation of COVID-19 patients. Materials and methods: Symptomatic COVID-19 patients were enrolled who were admitted to a regional community treatment center (CTC) in Seoul (South Korea). Self-test RAT and the collection of saliva samples were performed by the patients, on a daily basis, until patient discharge. Cell culture and subgenomic RNA detection were performed on saliva samples. Results: A total of 138 pairs of saliva samples and corresponding RAT results were collected from 34 COVID-19 patients. Positivity of RAT and cell culture was 27% (37/138) and 12% (16/138), respectively. Of the 16 culture-positive saliva samples, seven (43.8%) corresponding RAT results were positive. Using cell culture as the reference standard, the overall percent agreement, percent positive agreement, and percent negative agreement of RAT were 71% (95% CI, 63-78), 26% (95% CI, 12-42), and 82% (95% CI, 76-87), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the RAT for predicting culture results were 44% (95% CI, 20-70), 75% (95% CI, 66-82), 18% (95% CI, 8-34), and 91% (95% CI, 84-96), respectively. Conclusion: About half of the patients who were SARS-CoV-2 positive based upon cell culture results gave negative RAT results. However, the remaining positive culture cases were detected by RAT, and RAT showed relatively high negative predictive value for viable viral shedding.

Correlation of Postvaccination Fever With Specific Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 BNT162b2 Booster and No Significant Influence of Antipyretic Medication.

Background: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine booster elicits sufficient antibody responses that protect against coronavirus disease 2019, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 2-dose primary series. Spike-specific immunoglobulin G (IgG) titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for 7 days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (ß = .305, P < .001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk, 3.97 [95% confidence interval, 2.48-6.35]); however, the IgG titers after the booster dose were not associated with the presence or degree of fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions should not interfere with the elevation of specific IgG titers.

Preliminary Guidelines for the Clinical Evaluation and Management of Long COVID.

Long-lasting coronavirus disease 2019 (COVID-19) symptoms beyond 12 weeks, the so-called 'long COVID' have been increasingly reported worldwide. Long COVID can be manifested in various forms, and there is an increasing demand for proper assessment and management. However, it is challenging when trying to determine the best-practice standards of care based on the current evidence because there is no internationally agreed clinical definition or clear treatment pathway. Therefore, the present guidelines have been drafted to provide advice on diagnosis and management based on the latest updated available evidence and the consensus of expert opinion. So far, no standard test and drug treatment can be strongly recommended for patients with long COVID because of a lack of evidence. The present guidelines provide advice based on 12 key questions, including appropriate interventions for long COVID that can be used in clinical practice. Continuous careful observation and studies related to long COVID are needed for the long-term impact of COVID-19 and proper management for long COVID to be determined.

No significant influence of pre-vaccination antipyretic use on specific antibody response to a BNT162b2 vaccine booster against COVID-19

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 hours before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95% CI, 11,474-21,203) for the cases and 16,850 AU/mL (95% CI, 15,563-18,243) for the controls (p=0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 hours before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Clinical scoring system to predict viable viral shedding in patients with COVID-19

Background : The Centers for Disease Control and Prevention (CDC) recommends 5–10 days of isolation for patients with COVID-19, depending on symptom duration and severity. However, in clinical practice, an individualized approach is required. We thus developed a clinical scoring system to predict viable viral shedding. Methods : We prospectively enrolled adult patients with SARS-CoV-2 infection admitted to a hospital or community isolation facility between February 2020 and January 2022. Daily dense respiratory samples were obtained, and genomic RNA viral load assessment and viral culture were performed. Clinical predictors of negative viral culture results were identified using survival analysis and multivariable analysis. Results : Among 612 samples from 121 patients including 11 immunocompromised patients (5 organ transplant recipients, 5 with hematologic malignancy, and 1 receiving immunosuppressive agents) with varying severity, 154 (25%) revealed positive viral culture results. Multivariable analysis identified symptom onset day, viral copy number, disease severity, organ transplant recipient, and vaccination status as independent predictors of culture-negative rate. We developed a 4-factor predictive model based on viral copy number (-3 to 3 points), disease severity (1 point for moderate to critical disease), organ transplant recipient (2 points), and vaccination status (-2 points for fully vaccinated). Predicted culture-negative rates were calculated through the symptom onset day and the score of the day the sample was collected. Conclusions : Our clinical scoring system can provide the objective probability of a culture-negative state in a patient with COVID-19 and is potentially useful for implementing personalized de-isolation policies beyond the simple symptom-based isolation strategy.

Pronounced antibody elevation after SARS-CoV-2 BNT162b2 mRNA booster vaccination in nursing home residents.

BACKGROUND: Infection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the third (booster) dose of SARS-CoV-2 vaccination in nursing home residents have not been fully characterized. METHODS: This study included 117 individuals: 54 nursing home residents (mean age, 83.8 years; 39 SARS-CoV-2-naive and 15 previously infected) and 63 healthcare workers (mean age, 45.8 years; 32 SARS-CoV-2-naive and 31 previously infected). Anti-spike (receptor-binding domain [RBD]) and anti-nucleocapsid antibody responses to BNT162b2 mRNA vaccination and their related factors were evaluated using pre- (shortly and 6 months after the second dose) and post-booster vaccination samples. RESULTS: The median anti-spike (RBD) IgG level in SARS-CoV-2-naive residents 6 months after the second dose was the lowest among the four groups, with a decreasing rate of over 90%. The median rate of increase before and after the third dose in SARS-CoV-2-naive residents was significantly higher than that in SARS-CoV-2-naive healthcare workers (64.1- vs. 37.0-fold, P = 0.003), with the highest level among the groups. The IgG ratio of SARS-CoV-2-naive residents to healthcare workers after the second and third doses changed from one-fifth (20%) to one-half (50%). The rate of increase after the third dose in previously infected individuals was three- to fourfold, regardless of residents or healthcare workers. CONCLUSIONS: Advanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could obtain sufficient antibody responses with the additional booster dose, despite more than 6 months after the second.

Post-vaccination antibody evaluation for nosocomial SARS-CoV-2 delta variant breakthrough infection.

Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.