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.

A child with crescentic glomerulonephritis following SARS-CoV-2 mRNA (Pfizer-BioNTech) vaccination.

BACKGROUND: There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. CASE-DIAGNOSIS/TREATMENT: A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. CONCLUSIONS: This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted.

Erratum: Correction of Funding in the Article "Rates of COVID-19 Infection Among Healthcare Workers in Designated COVID-19 Wards and General Wards".

This corrects the article on p. e308 in vol. 37, PMID: 36345254.

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.

Waning of humoral immunity depending on the types of COVID-19 vaccine.

BACKGROUND: There are limited data on the rates of the waning of antibody levels after two-dose and booster vaccination according to the different platforms of COVID-19 vaccines. METHODS: We enrolled healthcare workers (HCWs) in a tertiary care hospital who received homologous two-dose vaccination, followed by a homologous or heterologous booster mRNA vaccine. SARS-CoV-2 S1-specific IgG was measured using ELISA. A linear mixed regression model was used to compare the slope from the peak antibody titre to the lowest antibody titres 3 months after vaccination. RESULTS: A total of 113 HCWs (BNT162b2 (n = 48 [42%]), ChAdOx1 nCoV-19 (n = 52 [46%]) or mRNA-1273 (n = 13 [12%])) were enrolled in this prospective cohort study. More gradual antibody waning was observed over 3 months with the two-dose ChAdOx1 nCoV-19 (ChAdOx1) than with the two-dose BNT162b2 or mRNA-1273 (p < 0.001 and p = 0.001, respectively). In addition, homologous mRNA-1273 booster induced a more durable antibody response than homologous BNT162b2 booster (p < 0.001) or heterologous ChAdOx1-BNT162b2 booster (p < 0.001). CONCLUSIONS: Two-dose homologous ChAdOx1 vaccination or homologous mRNA-1273 booster appears to induce more-durable antibody responses than 2-dose homologous mRNA vaccination, homologous BNT162b2 booster, or 2-dose ChAdOx1 followed by BNT62b2 booster, although our findings are based on the relatively short term (3-month) follow-up after the vaccinations and the evaluation of the slopes from different antibody peak levels. Further studies on long-term durability depending on the types of vaccines are needed.

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.

Effect of COVID-19 vaccination on transmission among healthcare workers in South Korea

Background: SARS-CoV-2 infection of healthcare workers (HCWs) occasionally occurs via acquisition from their colleagues. Data regarding the infection rates of HCWs with close contact and non–close contacts of HCWs are limited. In addition, the protective effect of COVID-19 vaccination against transmission between HCWs is unknown. We evaluated the infection rates of HCWs with close contact and non–close contact of infected HCWs and the effect of COVID-19 vaccination on transmission among HCWs in a tertiary-care hospital in South Korea. Methods: This study was performed in a tertiary-care hospital in Korea. We analyzed the COVID-19 cases and contacts among HCWs from January to December 2021. We reviewed the vaccination status of confirmed and exposed HCWs, the type of vaccination, and the infection rate according to the contact. We performed subgroup analyses in individuals who had been diagnosed since July 2021 when the δ (delta) variant became the dominant strain in South Korea. Transmission was defined based on their spatiotemporal epidemiologic association. Results: During the study period, 173 HCWs had COVID-19, and 2,693 HCWs were exposed to them. Among them, 18 (1.52%) of 1,186 close contacts and 13 (0.86%) of 1,507 non–close contacts had a positive SARS-CoV-2 test (P = .11). When the index cases had been fully vaccinated, the infection rate of close contacts was 0.85% (7 of 820), whereas the infection rate of close contacts was 3.01% (11 of 366) when the index had not been fully vaccinated (P = .005). However, the infection rate of non–close contacts was not different according to the vaccination status of index (0.83% vs 0.89%;P = .90). During the period of δ (delta) variant being dominant, the infection rate of close contacts was significantly lower when the index case had been fully vaccinated index than in cases with a non–fully vaccinated index case (0.85% vs 5.88%;P < .001). Conclusions: Transmission to colleagues was significantly lower from vaccinated HCWs than from nonvaccinated HCWs, and this finding was more significant in the era of the δ (delta) variant. Our findings support the importance of vaccination in HCWs.Funding: NoneDisclosures: None

Usefulness of universal SARS-CoV-2 PCR testing for inpatients and their caregivers during the omicron era.

Background: Since January 2022, the Omicron variant has become the dominant strain in South Korea, and COVID-19 cases among hospitalized patients and their guardians or caregivers have increased. We evaluated the usefulness of universal periodic screening for SARS-CoV-2 in patients and resident caregivers in a South Korean tertiary care hospital. Methods: We evaluated the reason for testing in COVID-19 confirmed patients and resident caregivers during their hospitalization from March 3 to 31, 2022. The rate of positive PCR universal testing in hospital (or residency) (HD) on days 3 and 7 in asymptomatic patients and caregivers were evaluated. The test for SARS-CoV-2 was done by RT-PCR. Results: During the study period, 677 patients were diagnosed with COVID-19. The reasons for testing were the symptoms (226 (33%)), pre-admission test (183 (27%)), exposure to COVID-19 (124 (18%)), universal testing on HD 3 (94 (14%)), and that on HD 7 (34 (5%)). Caregivers (n = 340) were tested during their residency due to exposure to COVID-19 cases, 103 (30%); universal testing on HD 3, 90 (26%); symptom development, 46 (14%); pre-stay, 39 (11%); and universal testing on HD 7, 29 (9%). The positive test rates of inpatients and caregivers on HD 3 and HD 7 were as follows: 1.4% (93/6553) and 2.1% (55/2646) in inpatients, and 1.3% (79/5989) and 1.7% (35/2106) in caregivers, respectively. Conclusions: Universal testing, regardless of symptom or epidemiologic link, is useful for detecting pre-symptomatic and asymptomatic COVID-19 cases among hospitalized patients and caregivers and preventing a nosocomial outbreak during the Omicron era.

Rates of COVID-19 Infection Among Healthcare Workers in Designated COVID-19 Wards and General Wards.

BACKGROUND: To evaluate the effects of isolating coronavirus disease 2019 (COVID-19) patients in general wards, we compared the rates of COVID-19 infection in nurses and nursing assistants working in COVID-19 designated wards and in general wards of our hospital from 1 October 2021 to 21 April 2022. METHODS: This study was conducted in a 2,700-bed tertiary care hospital in Seoul, Korea. Designated wards comprised single, negative pressure rooms and a 100% outdoor air system. RESULTS: During the study period, a total of 2,698 nurses and nursing assistants were employed at our hospital, of whom 310 (11%) were working in the designated wards, and the remaining 2,388 (89%) in the general wards, and among whom 1,158 (43%) were diagnosed with COVID-19. The healthcare workers (HCWs) in the designated wards were less frequently diagnosed with COVID-19 than those in the general wards (31% vs. 45%, P < 0.001). During the period before patients with COVID-19 were isolated in general wards, and during the period after these cases were isolated in general ward, HCWs in designated wards were less frequently infected with the virus than those in general wards (7% vs. 11%, P = 0.039; and 23% vs. 33%, P < 0.001, respectively). CONCLUSION: HCWs in designated wards have a lower rate of contracting COVID-19 than those in general wards. A lack of exposure to undiagnosed cases and their caregivers, greater care with social distancing outside the hospital, higher rates of 3-dose vaccinations, and the use of isolation rooms with negative pressure may be associated with this finding.

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.

Fit-failure rate associated with simulated reuse and extended use of N95 respirators assessed by a quantitative fit test.

OBJECTIVE: We quantitatively assessed the fit failure rate of N95 respirators according to the number of donning/doffing and hours worn. DESIGN: Experimental study. SETTING: A tertiary-care referral center in South Korea. PARTICIPANTS: In total, 10 infection control practitioners participated in the fit test. METHODS: The first experiment comprised 4 consecutive 1-hour donnings and fit tests between each donning. The second experiment comprised 2 consecutive 3-hour donnings and fit tests between each donning. The final experiment comprised fit tests after an 1-hour donning or a 2-hour donning. RESULTS: For 1-hour donnings, 60%, 70%, and 90% of the participants had fit failures after 2, 3, and 4 consecutive donnings, respectively. For 3-hour donnings, 50% had fit failure after the first donning and 70% had failures after 2 consecutive donnings. All participants passed the fit test after refitting whenever fit failure occurred. The final experiment showed that 50% had fit failure after a single use of 1 hour, and 30% had fit failure after a single use of 2 hours. CONCLUSIONS: High fit-failure rates were recorded after repeated donning and extended use of N95 respirators. Caution is needed for reuse (≥1 time) and extended use (≥1 hour) of N95 respirators in high-risk settings such as those involving aerosol-generating procedures. Although adequate refitting may recover the fit factor, the use of clean gloves and strict hand hygiene afterward should be ensured when touching the outer surfaces of N95 respirators for refitting.

Evaluation of In-Hospital Cluster of COVID-19 Associated With a Patient With Prolonged Viral Shedding Using Whole-Genome Sequencing.

BACKGROUND: Patients with hematologic malignancies may produce replication-competent virus beyond 20 days of SARS-CoV-2 infection. However, data regarding the transmission of SARS-CoV-2 from patients with prolonged viral shedding is limited. METHODS: In May 2022, four additional cases of COVID-19 were reported in a hematologic ward at a tertiary care hospital in South Korea, after an 8-week isolation of a patient with prolonged viral shedding. We performed whole-genome sequencing (WGS) of SARS-CoV-2 to evaluate the possibility of post-isolation transmission from this prolonged viral shedding. RESULTS: A patient (case 1) with acute myeloid leukemia was released from isolation 54 days after the diagnosis of COVID-19 based on rising Ct value of up to 29.3, and moved to a six-patient room. On days 10 and 11 post-isolation, his doctor (case 2) and 2 patients who were his roommates (case 3, 4) had positive SARS-CoV-2 PCR results. Additionally, 16 days post-isolation, another patient (case 5) in a remote room had positive SARS-CoV-2 PCR result. All the three patients were hospitalized for ≥ 14 days when they were diagnosed with SARS-CoV-2 infection. Except for case 3, the remaining 4 cases were available for WGS, which revealed that case 1 exhibited a 7 nucleotides difference in comparison to cases 4 and 5 and case 2 displayed a 20 nucleotides difference compared with case 1, while sequences of cases 4 and 5 were identical. CONCLUSIONS: Despite the possibility of transmission from the patient with prolonged viral shedding, no evidence of the transmission of SARS-CoV-2 from the patient with prolonged positive RT-PCR using WGS was found.