Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model.

BACKGROUND: Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. METHODS: We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. RESULTS: Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1-2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1ß, interferon (IFN)-ß, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. CONCLUSIONS: This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

Coronavirus Disease 2019 Messenger RNA Vaccines Associated With Delayed Onset of Breakthrough Infections and Fewer Radiographic Abnormalities.

This retrospective study of incoming travelers with coronavirus disease 2019 showed that individuals immunized by messenger RNA vaccines had significantly longer postvaccination intervals (median, 30.5 days) to breakthrough infection, lower white blood cell counts and lactate dehydrogenase levels on admission, and fewer radiographic abnormalities than those immunized by inactivated virus vaccine, who paradoxically had lower respiratory viral load.

False Coronavirus Disease 2019 Cases due to Contamination by Inactivated Virus Vaccine.

A false-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction result can lead to unnecessary public health measures. We report 2 individuals whose respiratory specimens were contaminated by an inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises. Incidentally, whole genome sequencing of CoronaVac showed adaptive deletions on the spike protein, which do not result in observable changes of antigenicity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Intranasal or Intratesticular Route Induces Testicular Damage.

BACKGROUND: The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pathogenesis of testicular damage is uncertain. METHODS: We investigated the virological, pathological, and immunological changes in testes of hamsters challenged by wild-type SARS-CoV-2 and its variants with intranasal or direct testicular inoculation using influenza virus A(H1N1)pdm09 as control. RESULTS: Besides self-limiting respiratory tract infection, intranasal SARS-CoV-2 challenge caused acute decrease in sperm count, serum testosterone and inhibin B at 4-7 days after infection; and chronic reduction in testicular size and weight, and serum sex hormone at 42-120 days after infection. Acute histopathological damage with worsening degree of testicular inflammation, hemorrhage, necrosis, degeneration of seminiferous tubules, and disruption of orderly spermatogenesis were seen with increasing virus inoculum. Degeneration and death of Sertoli and Leydig cells were found. Although viral loads and SARS-CoV-2 nucleocapsid protein expression were markedly lower in testicular than in lung tissues, direct intratesticular injection of SARS-CoV-2 demonstrated nucleocapsid expressing interstitial cells and epididymal epithelial cells, While intranasal or intratesticular challenge by A(H1N1)pdm09 control showed no testicular infection or damage. From 7 to 120 days after infection, degeneration and apoptosis of seminiferous tubules, immune complex deposition, and depletion of spermatogenic cell and spermatozoa persisted. Intranasal challenge with Omicron and Delta variants could also induce similar testicular changes. This testicular damage can be prevented by vaccination. CONCLUSIONS: SARS-CoV-2 can cause acute testicular damage with subsequent chronic asymmetric testicular atrophy and associated hormonal changes despite a self-limiting pneumonia in hamsters. Awareness of possible hypogonadism and subfertility is important in managing convalescent coronavirus disease 2019 in men.

Probable Animal-to-Human Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant AY.127 Causing a Pet Shop-Related Coronavirus Disease 2019 (COVID-19) Outbreak in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related Coronavirus Disease 2019 (COVID-19) outbreaks have not been reported. METHODS: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least 3 patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the reverse transcription polymerase chain reaction (RT-PCR)-positive samples. RESULTS: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by enzyme immunoassay. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment. CONCLUSIONS: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus.

Explosive outbreak of SARS-CoV-2 Omicron variant is associated with vertical transmission in high-rise residential buildings in Hong Kong.

The phenomenon of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-rise residential buildings (HRRBs) is unique in our densely populated cosmopolitan city. The compulsory testing of a whole building under the scheme of restriction-testing declaration (RTD) during the fourth wave (non-Omicron variant) and fifth wave (mostly Omicron variant) of COVID-19 outbreak in Hong Kong allowed us to study the prevalence of this phenomenon, which may represent a form of airborne transmission. From 23 January 2021 to 24 March 2022, 25,450 (5.8%) of 436,397 residents from 223 (63.0%) of 354 HRRBs under RTD were test-positive for SARS-CoV-2. Using the clustering of cases among vertically aligned flats with shared drainage stack and lightwell as a surrogate marker of vertical transmission, the number of vertically aligned flats with positive COVID-19 cases was significantly higher in the fifth wave compared with the fourth wave (14.2%, 6471/45,531 vs 0.24%, 3/1272; p < 0.001; or 2212 vs 1 per-million-flats; p < 0.001). Excluding 22,801 residents from 38 HRRBs who were tested negative outside the 12-week periods selected in fourth and fifth waves, the positive rate among residents was significantly higher among residents during the fifth wave than the fourth wave (6.5%, 25,434/389,700 vs 0.07%, 16/23,896; p < 0.001). Within the flats with COVID-19 cases, the proportion of vertically aligned flats was also significantly higher in the fifth wave than in the fourth wave (95.6%, 6471/6766 vs 30.0%, 3/10, p < 0.001). The proportion of HRRBs with COVID-19 cases was significantly higher during the corresponding 12-week period chosen for comparison (78.2%, 219/280 vs 11.1%, 4/36; p < 0.001). Whole-genome phylogenetic analysis of 332 viral genomes showed that Omicron BA.2 was the predominant strain, supporting the high transmissibility of BA.2 by airborne excreta-aerosol route in HRRBs of Hong Kong.

Emergence of a Severe Acute Respiratory Syndrome Coronavirus 2 Virus Variant With Novel Genomic Architecture in Hong Kong.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, divergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have emerged continuously, mostly through the genomic accumulation of substitutions. We report the discovery of a SARS-CoV-2 variant with a novel genomic architecture characterized by absent ORF7a, ORF7b, and ORF8, and a C-terminally modified ORF6 product resulting from partial 5'-untranslated region (UTR) duplication and transposition.

Nosocomial Outbreak of Coronavirus Disease 2019 by Possible Airborne Transmission Leading to a Superspreading Event.

BACKGROUND: Nosocomial outbreaks with superspreading of coronavirus disease 2019 due to a possible airborne transmission have not been reported. METHODS: Epidemiological analysis, environmental samplings, and whole-genome sequencing (WGS) were performed for a hospital outbreak. RESULTS: A superspreading event that involved 12 patients and 9 healthcare workers (HCWs) occurred within 9 days in 3 of 6 cubicles at an old-fashioned general ward with no air exhaust built within the cubicles. The environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was significantly higher in air grilles (>2 m from patients' heads and not within reach) than on high-touch clinical surfaces (36.4%, 8 of 22 vs 3.4%, 1 of 29, P = .003). Six (66.7%) of 9 contaminated air exhaust grilles were located outside patient cubicles. The clinical attack rate of patients was significantly higher than of HCWs (15.4%, 12 of 78 exposed patients vs 4.6%, 9 of 195 exposed HCWs, P = .005). Moreover, the clinical attack rate of ward-based HCWs was significantly higher than of nonward-based HCWs (8.1%, 7 of 68 vs 1.8%, 2 of 109, P = .045). The episodes (mean ±â€…standard deviation) of patient-care duty assignment in the cubicles was significantly higher among infected ward-based HCWs than among noninfected ward-based HCWs (6.0 ±â€…2.4 vs 3.0 ±â€…2.9, P = .012) during the outbreak period. The outbreak strains belong to SARS-CoV-2 lineage B.1.36.27 (GISAID clade GH) with the unique S-T470N mutation on WGS. CONCLUSIONS: This nosocomial point source superspreading event due to possible airborne transmission demonstrates the need for stringent SARS-CoV-2 screening at admission to healthcare facilities and better architectural design of ventilation systems to prevent such outbreaks. Portable high-efficiency particulate filters were installed in each cubicle to improve ventilation before resumption of clinical service.

Absence of Vaccine-enhanced Disease With Unexpected Positive Protection Against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by Inactivated Vaccine Given Within 3 Days of Virus Challenge in Syrian Hamster Model.

BACKGROUND: Mass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described. METHODS: Two-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters. RESULTS: The 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer. CONCLUSIONS: Vaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial.

BACKGROUND: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19. METHODS: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688. FINDINGS: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study. INTERPRETATION: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted. FUNDING: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Posterior Oropharyngeal Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. METHODS: The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between 1 February 2020 and 15 April 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. RESULTS: A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 nasopharyngeal specimens (NPsp). Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% confidence interval [CI] 55.1-67.6%) and 53.3% (95% CI 46.8-59.6%). The overall, negative and positive percent agreement were 76.0% (95% CI 70.2-80.9%), 65.4% (95% CI 55.5-74.2%), 85.2% (95% CI 77.4-90.8%). Better positive percent agreement was observed in POPS-NPsp obtained within 7 days (96.6%, 95% CI 87.3-99.4%) compared with after 7 days of symptom onset (75.0%, 95% CI 61.4-85.2%). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the 2 specimen types. CONCLUSIONS: POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.

Consistent Detection of 2019 Novel Coronavirus in Saliva.

The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.

A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19.

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.

First Report of a Fatal Case Associated with EV-D68 Infection in Hong Kong and Emergence of an Interclade Recombinant in China Revealed by Genome Analysis.

A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10-year-old boy was reported in Hong Kong in 2014. To examine if a new strain has emerged in Hong Kong, we sequenced the partial genome of the EV-D68 strain identified from the fatal case and the complete VP1, and partial 5'UTR and 2C sequences of nine additional EV-D68 strains isolated from patients in Hong Kong. Sequence analysis indicated that a cluster of strains including the previously recognized A2 strains should belong to a separate clade, clade D, which is further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7 (including the fatal case) belonged to the previously described, newly emerged subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV-D68 strains, each from subclades B1, B3, and D1, were selected for complete genome sequencing and recombination analysis. While no evidence of recombination was noted among local strains, interclade recombination was identified in subclade D2 strains detected in mainland China in 2008 with VP2 acquired from clade A. This study supports the reclassification of subclade A2 into clade D1, and demonstrates interclade recombination between clades A and D2 in EV-D68 strains from China.

Hospital Outbreak of Pulmonary and Cutaneous Zygomycosis due to Contaminated Linen Items From Substandard Laundry.

BACKGROUND: Healthcare laundry-related infection is rare, and pulmonary zygomycosis due to contaminated hospital linens has never been reported. METHODS: We reported an outbreak investigation of zygomycosis in a university-affiliated teaching hospital. Air samplers, sponge swabs and Replicate Organism Detection and Counting (RODAC) contact plates were used for environmental sampling. The fungal isolates from clinical and environmental samples were identified by morphology, MALDI-TOF MS, and ITS1-5.8S-ITS2 rRNA gene cluster sequencing. RESULTS: From 2 June 2015 to 18 July 2015, 6 immunosuppressed patients developed pulmonary (n = 4) and/or cutaneous (n = 3) infection by a spore-forming mold, Rhizopus microsporus, through direct inhalation and skin contact of contaminated linen items supplied by a designated laundry. Seventy (27.8%) of 252 freshly laundered clothing and 15 (3.4%) of 443 nonclothing laundered linen items (pillow case, bed sheet, draw sheet) were contaminated by R. microsporus, which was significantly higher than those from other hospital laundries (0%, n = 451; P < .001) supplying linen to hospitals with no cases of zygomycosis reported during the same period. The fungal isolates from patients and linens were phylogenetically related. In sum, 61% of environmental samples and 100% of air samples at the designated laundry were also positive for zygomycetes, suggesting heavy environmental contamination. RODAC contact plates revealed mean total viable bacteria counts of freshly laundered items (1028 ± 611 CFU/100 cm(2)) far exceeded the "hygienically clean" standard of 20 CFU/100 cm(2) set by the US healthcare textile certification requirement. CONCLUSIONS: Suboptimal conditions of washing, drying, and storage contributed to the massive linen contamination and the outbreak of zygomycosis.

Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza-A Territory-Wide Study.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Invasive fungal infections in the Paediatric Intensive Care Unit: A Hong Kong Study.

INTRODUCTION: Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children's Hospital.

Methods: Retrospective review of all PICU admissions from April 2019 to May 2021. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary outcomes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher's exact test.

Results: There were 692 PICU admissions over the study period from April 2019 to May 2021. There were 24 death cases during this period of time. The crude mortality was 3%. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. There were 4 (29%) patients who had received hematopoietic stem cells transplant because of oncological problems. Six patients (43%) were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Six (43%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. Rhizopus or Aspergillus infection (5/14) were associated with nonsurvival (p = 0.031).

Conclusion: All patients with IFIs managed in the PICU have haemato-oncology diseases or are recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group are associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.