To the Editor—A recent press release issued by the Department of Health of the Hong Kong SAR Government urged public not to buy or consume an oral health supplement “HemoHIM”.1 This product has been withdrawn from the market in Hong Kong, Taiwan and Singapore. In Hong Kong, from April to September 2021, four women presented to public hospitals because of acute hepatitis (Table).2 All patients had consumed a health supplement named HemoHIM (Atomy; Gongju, South Korea) and liver function improved after cessation of use. No alternative medical causes were identified. A sample of HemoHIM was analysed by high-performance liquid chromatography with diode-array detection and liquid chromatography–tandem mass spectrometry, revealing the presence of methoxsalen, psoralen, and benign herbal markers. Subsequent analysis of additional samples from different sources showed consistent laboratory findings. Methoxsalen (also known as 8-methoxypsoralen, 8-MOP) and psoralen are naturally occurring furocoumarins. They can be found in a number of plant species at various concentrations and are collectively referred to as psoralens. Psoralens have photosensitising property, thus methoxsalen is formulated as drugs used in PUVA (Psoralen and ultraviolet light UVA) treatment for psoriasis and vitiligo.3 Psoralens bind to DNA when exposed to ultraviolet light, inhibiting DNA synthesis and causing a decrease in cell proliferation. Methoxsalen- and psoralen-containing herbs have been reported to cause liver injuries.3 4 The listed herbal ingredients of HemHIM should not contain psoralen or methoxsalen. Further investigations are needed to explain the occurrence of these chemical compounds in the product. Several plant species used in traditional Chinese medicine have been reported to contain psoralens,5 including Fructus Psoraleae (補骨脂, the dried seeds of Psoralea corylifolia), which contains a relatively high concentration of psoralens.2 3 Frontline doctors should be vigilant to patients presenting with symptoms of liver injury after consumption of HemoHIM or other supplements containing Fructus Psoraleae.

CK Chan drafted the letter and all authors contributed to the critical revision of the letter for important intellectual content. All authors approved the final version for publication and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

1. Hong Kong SAR Government. DH investigates suspected poisoning cases relating to oral product “HemoHIM”. 1 Nov 2021. Available from: https://www.info.gov.hk/gia/general/202111/01/P2021110100785.htm. Accessed 15 Nov 2021.

2. LiverTox: clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Roussel Uclaf Causality Assessment Method (RUCAM) in drug induced liver injury. Updated 4 May 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548272/. Accessed 15 Nov 2021.

3. Cheung WI, Tse ML, Ngan T, et al. Liver injury associated with the use of Fructus Psoraleae (Bol-gol-zhee or Bu-gu-zhi) and its related proprietary medicine. Clin Toxicol (Phila) 2009;47:683-5. Crossref

4. Li A, Gao M, Zhao N, Li P, Zhu J, Li W. Acute liver failure associated with Fructus Psoraleae: a case report and literature review. BMC Complement Altern Med 2019;19:84. Crossref

5. Guo Jia Zhong Yi Yao Guan Li Ju “Zhonghua Ben Cao” Bian Wei Hui. Zhong Hua Ben Cao (中華本草) [in Chinese]. Shanghai: Shanghai Ke Xue Ji Shu Chu Ban She; 1999.

To the Editor—We previously reported serological findings of 302 healthcare workers (HCWs) who completed two doses of mRNA (BNT162b2/Comirnaty; Fosun-BioNTech Pharma) and inactivated COVID-19 vaccine (CoronaVac; Sinovac Life Sciences, Beijing, China).1 Both vaccines were found to be immunogenic in the majority of HCWs. The BNT162b2 resulted in a 11-fold higher level of anti-spike IgG (Abbott SARS-CoV-2 IgG II Quant assay, mean=11572.6 AU/mL vs 1005.2 AU/mL; P<0.001) and a higher surrogate neutralising antibody (sNAb) [GenScript cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit] positive rate (100% vs 94.4%; P<0.001).

We report week 12 serological data of our cohort. Among 197 CoronaVac and 100 BNT162b2 recipients, baseline characteristics of the two vaccine arms were comparable except sex (60.9% and 38% female in CoronaVac and BNT162b2, respectively) [online supplementary Table 1]. There was no difference in anti-spike immunoglobulin G (IgG) positive rate at week 12 (98.5% in CoronaVac vs 99% in BNT162b2; P=1) [Table 1]. Waning of IgG level was observed in both vaccine arms with a larger magnitude of decline in BNT162b2 (-72% vs -64.6%; P<0.001). Despite the more pronounced decline, the median anti-spike IgG of BNT162b2 remained 11-fold higher than that of CoronaVac at week 12 (2840.25 AU/mL vs 253.60 AU/mL; P<0.001).

Decline in sNAb was also observed in both arms but the magnitude was significantly smaller in BNT162b2 (-28.3% in CoronaVac vs -2.3% in BNT162b2; P<0.001). Using the manufacturer’s positive cut-off at 30% signal inhibition or above, significantly more CoronaVac recipients had lost their sNAb at week 12 (94.4% sNAb positive at week 2, 62.4% at week 12) whereas 99% of BNT162b2 recipients remained sNAb positive. Throughout the three time points, BNT162b2 arm had higher levels of anti-spike IgG and sNAb (P<0.001) [Fig].

Among the 286 HCWs who had positive sNAb after two doses of vaccine, 64 had lost their sNAb while 222 had sustained sNAb at week 12. Sustained sNAb at week 12 were associated with younger age, BNT162b2 and higher antibody at any time point (Table 2). Multivariate logistic regression analysis showed that only higher IgG and sNAb level at 2 weeks after the second dose were significantly associated with sustained sNAb at week 12 (online supplementary Table 2).

These results demonstrate rapid antibody decline after both mRNA and inactivated vaccine with a more durable sNAb in the BNT162b2 arm. However, further studies are needed to clarify the impact of waning antibody on vaccine efficacy and protection against severe infection.

Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: JST Zee.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors acknowledge the excellent work and contributions by staff at the Clinical Pathology Laboratory of Hong Kong Sanatorium & Hospital.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study obtained ethics approval (Ref RC-2021-07) from the Research Ethics Committee of the Hong Kong Sanatorium & Hospital Medical Group.

1. Zee JS, Lai KT, Ho MK, et al. Serological response to mRNA and inactivated COVID-19 vaccine in healthcare workers in Hong Kong: preliminary results. Hong Kong Med J 2021;27:312-3. Crossref

To the Editor—We read with interest the recent Editorial on gross negligence manslaughter.1 The third defendant in “DR” was employed by a clinic. She intravenously administered to healthy clients processed cells originally harvested from the client. The deceased received infusion on 3 October 2012 and passed away on 10 October from multiorgan failure due to septic shock caused by Mycobacterium abscessus. The indictment provided, inter alia2:

1. the therapy was experimental for cancer patients, with unproven or uncertain efficacy;
2. there was no scientifically proven benefit on healthy patients;
3. the preparation involved prolonged culturing of blood cells with risk of contamination.

Any intravenous infusion outside a research setting must either be a registered pharmaceutical product of good manufacturing practice standard or comply with stringent quality requirements of a national blood transfusion service. It is foreseeable by any medical practitioner that lack of assurance of sterility would result in microbial contamination. Consideration through hindsight is not involved.

The Rose case is distinguishable.3 An optometrist performed routine eye examination for a 7-year-old on 15 February 2012, without retinal examination, which would have revealed papilloedema. Five months later, the boy passed away suddenly. The Court of Appeal quashed the gross negligence manslaughter conviction, as the boy was asymptomatic “with no material pre-existing history” in February; the significance of retinal examination was only realised with hindsight.3 We respectfully submit that the DR decision was consistent with the established gross negligence manslaughter law, with no significant ambiguity. Medical practitioners managing patients in accordance with standard medical practices would unlikely face criminal sanction.

Both authors contributed to the drafting of the letter and critical revision for important intellectual content. Both authors approved the final version for publication and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

1. Leung GK. Medical manslaughter: the role of hindsight. Hong Kong Med J 2021;27:240-1. Crossref

2. HKSAR v Mak Wan Ling. HKCFI 3069; 2020. Available from: https://legalref.judiciary.hk/lrs/common/search/search_result_detail_frame.jsp?DIS=132426&QS=%28mak%2Bwan%2Bling%29&TP=RS. Accessed 23 Aug 2021.

3. Regina v Rose HM. EWCA Crim 1168; 2017. Available from: https://www.bailii.org/ew/cases/EWCA/Crim/2017/1168.html. Accessed 23 Aug 2021.

To the Editor—We refer to the multicentre review in Hong Kong Medical Journal about respiratory syncytial virus (RSV) and children with heart disease in Hong Kong.1 There is no universal guideline in Hong Kong regarding RSV immunoprophylaxis for children with heart disease because of a lack of local data on RSV infection. The authors found predictors of severe RSV infection in patients with heart disease were heart failure, pulmonary hypertension, and severe airway abnormalities associated with congenital heart disease, and conclude RSV infection poses a heavy disease burden on children with heart disease. There is no vaccine for the prevention of RSV disease, but prophylaxis is possible with palivizumab, which is available in Hong Kong.2 Indications for palivizumab are well established and include prematurity (under 35 weeks’ gestation), certain congenital heart defects, bronchopulmonary dysplasia, and infants with congenital malformations of the airway.2 However, the lack of distinct RSV seasonality in the subtropical city of Hong Kong can potentially affect the cost-effectiveness of prophylaxis immunisation.2 3 We recently managed a 4-month-old infant with Noonan syndrome and hypertrophic obstructive cardiomyopathy, who contracted RSV and developed respiratory failure, requiring venovenous extracorporeal membrane oxygenation support. Noonan syndrome is an autosomal dominant genetic disorder that may present with mildly unusual facial features, short height and skeletal malformations, and a very common syndromic cause of congenital heart disease, including pulmonary valvular stenosis, atrial septal defects, ventricular septal defects and hypertrophic cardiomyopathy.1 3 4 The mother also had Noonan syndrome and hypertrophic obstructive cardiomyopathy. Children aged ≤12 months with haemodynamically significant cardiomyopathy are at a higher risk for RSV infections and may benefit from palivizumab prophylaxis. Therefore, if resources are available, palivizumab prophylaxis should be advocated.1 5 6

Both authors contributed to the drafting of the letter and critical revision for important intellectual content. Both authors approved the final version for publication and take responsibility for its accuracy and integrity.

The authors have no conflicts of interest to disclose.

This Letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

1. Lee SH, Hon KL, Chiu WK, Ting YW, Lam SY. Epidemiology of respiratory syncytial virus infection and its effect on children with heart disease in Hong Kong: A multicentre review. Hong Kong Med J 2019;25:363-71. Crossref

2. Lee SY, Kwok KL, Ng DK, Hon KL. Palivizumab for infants <29 weeks in Hong Kong without a clear-cut season for respiratory syncytial virus infection-a cost-effectiveness analysis. J Trop Pediatr 2018;64:418-25. Crossref

3. Hon KL, Leung TF, Cheng WY, et al. Respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis. J Crit Care 2012;27:464-8. Crossref

4. Yu KP, Luk HM, Leung GK, et al. Genetic landscape of RASopathies in Chinese: three decades’ experience in Hong Kong. Am J Med Genet C Semin Med Genet 2019;181:208-17. Crossref

5. Kim AY, Jung SY, Choi JY, et al. Retrospective multicenter study of respiratory syncytial virus prophylaxis in Korean children with congenital heart diseases. Korean Circ J 2016;46:719-26. Crossref

6. American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014;134:415-20. Crossref

To the Editor—Children and infants initially appeared to be largely spared from the coronavirus disease 2019 (COVID-19) pandemic. However, the United Kingdom and United States have recently reported an apparent rise in the number of children presenting with multisystem inflammatory disease, some of whom also tested positive for COVID-19.1

A multisystem inflammatory syndrome in children potentially associated with COVID-19 has been reported, with the following suggested definition: persistent fever, inflammation, evidence of single or multi-organ dysfunction; may fulfil full or partial criteria for Kawasaki disease; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing maybe positive or negative and other microbial causes excluded.2

About 50% of these patients have no microbiological evidence of COVID-19 infection, which fits into one of the hypothetical scenarios in our epidemiological analysis based on early data from the United Kingdom, suggesting a statistically significant correlation between COVID-19 and Kawasaki disease (P=0.0048) [Table].3 4 The pathophysiology of COVID-19 is likely to be a hyperinflammatory process of a massive cytokine storm; however, this clinical presentation can also be vasculitic in nature as there is evidence of SARS-CoV leading to vasculitis.4 5 This apparent link could also be due to the similarities in clinical presentation between COVID-19 and other sepsis syndromes including systemic inflammatory response syndrome, severe acute respiratory syndrome, toxic shock syndrome, Kawasaki disease shock syndrome, and multi-organ dysfunction syndrome.

Although this phenomenon is reported in Western countries, the majority of cases are non-Caucasians.6 As the incidence of Kawasaki disease is up to 10 times higher in Asian than in Western populations, it is inconceivable that this phenomenon could only be observed in Western countries, unless there is an underlying genetic, environment predisposition, presentation of a new variant of the SARS-CoV-2 virus, or misinterpretation of data.3

We postulate that SARS-CoV-2 may just happen to be one of the many respiratory viruses that can cause a multisystem inflammatory syndrome in children. The ‘novel phenomenon’ is in fact septic or toxic shock syndrome associated with viral triggered inflammation, potentially attributed to a new variant of SARS-CoV-2. However, we shall remain sceptical before any definitive conclusions can be drawn. Meanwhile, we caution the loose coining of too many confusing abbreviations or syndromes associated with SARS-CoV diseases, such as SARS, MERS (Middle East respiratory syndrome), COVID-19, MIS-C (multisystem inflammatory syndrome in children), PIMS/PIMS-TS (paediatric inflammatory multisystem syndrome), COVID toe syndrome, and COVID skin syndrome.7

All authors contributed to the drafting of the letter and critical revision for important intellectual content. All authors approved the final version for publication and take responsibility for its accuracy and integrity.

As the editor of the journal, KL Hon was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

1. Paediatric Intensive Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi system inflammatory disease. 2020. Available from: https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020. pdf. Accessed 30 Apr 2020.

2. Royal College of Paediatrics and Child Health. Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Available from: https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem- inflammatory syndrome-20200501.pdf. Accessed 14 May 2020.

3. Campbell D, Sample I. At least 12 UK children have needed intensive care due to illness linked to Covid-19. The Guardian [newspaper on the internet]. 27 Apr 2020: Health. Available from: https://www.theguardian.com/world/2020/apr/27/nhs-warns-of-rise-in-children-with-new- illness-that-may-be-linked-to-coronavirus. Accessed 30 Apr 2020.

4. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607-8. Crossref

5. Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): A report from China. J Pathol 2003;200:282-9. Crossref

6. Public Health England. The weekly surveillance report in England (Week 16 April 2020 to 22 April 2020). Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/880848/COVID19_Weekly_Report_22_April.pdf. Accessed 28 Apr 2020.

7. Hon KL, Leung AK, Wong JC. Proliferation of syndromes and acronyms in paediatric critical care: are we more or less confused? Hong Kong Med J 2020;26:260-2.Crossref