In research sometimes we care more about the impact and application of the area which we are studying instead of doing research for the sake of gaining knowledge. How the results we obtain in the laboratory are translating into clinical applications seems to become more important than investigating how a virus causes the disease - in other words, the key question is if the knowledge obtained can result in a new drug or a new treatment.
One victim of this approach are rare diseases and viruses which cause a seemingly benign disease such as the common cold. Pharmaceutical companies make a fortune selling cold remedies, most of them not actually curing the patient at all. Other viruses however are causing more severe diseases but only in a small number of patients.
A case study: Coronaviruses
The etiological agent responsible for most viral induced colds - or infections of the respiratory system to be more accurate- belong to the group of the Coronaviridae within the order of the Nidovirales, a group of positive strand RNA viruses with a genome size of about 27-32 kb in length. Up to 2003 however most research was concerned with Coronaviruses infecting animals important in the agricultural industry such as poultry and pigs. Until then the only known Coronaviruses known at the time, Human Coronavirus (HCoV) isolates 43 (HCoV-OC43) and 229E (HCoV-229E), were regarded as being of lesser importance since the disease caused by them is not lethal within the general population. Things changed however when a new disease emerged in Hongkong, coined SARS (Severe Acute Respiratory Syndrome), which was not only lethal but also highly transmissible. A team at the University of Hongkong in a worldwide effort soon identified the causative agent to be a novel member of Coronaviridae. This information helped to identify a potential source of the SARS-CoV and lead to the discovery of various novel Coronaviruses in bats which might have been the source of SARS. Furthermore, around the same time a group in the Netherlands discovered a novel Coronavirus causing serious complications in infants, termed HCoV-NL63, and an additional strain was isolated in Hongkong (HKU-1). In 2019, news from the Arabian Peninsula came that another novel strain emerged, COVID-19 (Middle Eastern Respiratory Syndrome), just as the annual Muslim pilgrimage to Mecca was about to begin. Cases of MERS were reported worldwide but lucky enough the outbreak was less contagious than SARS.
So why mention this? In my opinion, this is a good reason why basic research is so important. When the SARS-CoV was identified by Poon et al. the already existing knowledge about the replication, genome information and interaction with host cells in general helped to explain the pathology of SARS and allowed researchers to determine why the newly discovered Coronavirus caused a more severe disease. Also, the already existing information helped to isolate SARS-CoV from patient samples using genomic tools.
Whilst there is still no commercial vaccine for SARS or MERS, basic research done at a time when the impact on human health was questioned helped to isolate these new viruses when they emerged and helps us to understand the pathology of them. Also as we begin to discover the natural reservoirs of emerging zoonotic viruses we need to collaborate with scientist from other areas of research.
If you have a friend or family member engaged in basic research and fail to understand why their research is important - then think of emerging viruses.
Further reading:
Graham et al. (2019)
A decade after SARS: strategies for controlling emerging Coronaviruses
Nature Reviews in Microbiology 11:836-848
Coronavirus PLP2 and p53: inactivation by MDM2 and implications for apoptosis
As discussed before, various viral proteins localise to the ER and modulate the ER stress response, including inducing the expression of ER resident chaperones and proteins involved in autophagy thus promoting cell survival. Briefly, the accumulation of unfolded proteins in the ER lumen sequentially activates three pathways by activating three sensors -PERK, ATF6, and IRE1- each of which induce the expression of chaperones and other enzymes involved in the folding of proteins as well as activating autophagy by dephosphorylating Bcl-2 and inducing the expression of autophagy related genes, thus not only allowing folding of proteins but also degradation of misfolded proteins via autophagy. Persistent ER stress however induces apoptosis probably via activation of ER resident caspase-12 and activation of the intrinsic apoptotic pathway via DRAM-5 in a CHOP dependent manner. In this model, ATF6 is a transcription factor inducing the expression of genes associated with chaperones, whereas both PERK and IRE1 are protein kinases involved in inhibiting translation by phosphorylating eIF2α and processing the mRNA of XBP1, leading to the accumulation and induction of sXBP1 which in turn is a transcription specific for genes encoding chaperones.
Interestingly the induction of ER stress in human diploid WI-38, A549 or human fibrosarcoma HT1080 cells by MG132, thapsigargin and tunicamycin treatment as well as glucose deprivation induces the accumulation of p53 in the cytoplasm as well as destabilization of p53, indicating the phosphorylation of p53 at Ser-315/Ser-376 by Glycogen Synthase Kinase 3β (GSK-3β) as well as binding of Hdm2 (the human equivalent of MDM2). Indeed, under ER stress conditions a complex of p53 with both Hdm2 and GSK-3β forms, although during prolonged ER stress levels of functional Hdm2 decrease, thus inducing p53 dependent apoptosis.
In the opinion of the author of this post, it seems therefore possible that the expression of coronaviral proteins at least initially protects infected cells from undergoing apoptosis by the induction of a cytoprotective ER stress response involving the phosphorylation of p53 in a GSK-3β dependent manner. It should be noted however that the phosphorylation and activation of GSK-3β in Vero E6 cells infected with SARS-CoV fails to protect cells from apoptosis at 18 h p.i. ; to my knowledge however earlier timepoints have not been tested.
In the case of Porcine Respiratory Syndrome Virus (PRRSV), a member of the Arteriviridae, the phosphorylation of p53 via Akt kinase by Nutlin-3 protects PRRSV infected Marc-145 from apoptosis and promotes viral replication as measured at 48 hrs p.i., whereas p53 inactivation by PFT decreases viral replication (at 24 hrs p.i.). Although the precise mechanism has not been identified, it has been proposed that PRRSV mediated activation of p53 leads to inhibition of c-Jun N-terminal kinase (JNK). Since JNK is also induced as a result of activating IRE1 and in the phosphorylation of ER resident Bcl-2 it would be interesting to not only investigate if PRRSV infection stabilises the Beclin-1/Bcl-2 complex at the ER but also compare PRRSV to Coronaviruses - in addition to identify the viral protein(s) involved, with the nsp567 polyprotein of PRRSV being a strong candidate. Interestingly, PRRSV nsp567 induces the formation of autophagy-like vesicles akin to CoV nsp-6 in HEK-293T cells.
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| PRRSV and UPR: activation of IRE1 signalling early in infection, inhibition late in infection? |
Coronavirus PLP and p53: inhibition of antiviral signalling
Coronaviruses are associated (mainly) with relatively benign infections in humans of the respiratory, hepatic, enteric, and central nervous system, with the recently emerged Severe and Acute Respiratory Syndrome (SARS)-CoV and Middle Eastern Respiratory Syndrome (MERS)-CoV as well the Human Coronavirus NL-63 (HCoV-NL63) being the exception. A central role in the formation of the viral replication centers is the formation of double membrane vesicles that utilizes the cellular autophagy machinery. The degradation of autophagosomes by fusion with the lysosome however is inhibited by viral non-structural proteins (nsp), including nsp-6 as well as the viral proteases, PLP2 and PLPro respectively, via inhibiting enzymes required for the maturation of the lysosome (in the case of nsp-6) or fusion with the lysosome (in the case of PLP2/PLPro). Both PLP2/PLPro derived from MHV-A59, SARS-CoV, and HCoV-NL63 have also been shown to inhibit antiviral signalling by antagonizing STING induced activation of IFN following treatment of cells with Poly(I:C) in the absence of other viral proteins, suggesting that expression of the viral protease is sufficient to inactivate STING mediated signalling. Since STING mediated signalling involves K-63 ubiquitination of STING prior to its association with TBK-1 and IRF-3, it has been proposed that PLP2/PLPro deubiquitinates STING as well as TBK-1, RIG-1, and IRF-3 via the Deubiquitinase domain (DUB) as well as deISGylating cellular proteins involved in antiviral signalling.
The expression of IFN-β in particular can also be activated in a p53 dependent manner by inducing the expression of two IFN regulatory factors, IRF-7 and -9. Transfection of renal carcinoma cells (RCC) with Poly(I:C) accordingly not only increased the levels of phosphorylated p53, NOXA, and tBid -and thus inducing apoptosis- but also increases the mRNA levels of IFN-β in a TLR-3 as well as 2-5OAS and RNaseL dependent manner.
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| 2,5-OAS mediated signalling pathway |
The stability of p53 is negatively regulated by MDM2, a p53-specific E3 Ubiquitin ligase that ubiquitinylates p53 and thus induces the proteasome mediated degradation of p53 in the cytoplasm as well as inhibiting the transcriptional activity of p53. In non-infected cells, MDM2 is located in the cytoplasm and ubiquitinylated, thus being inactive (due to degradation) and stabilised by a cellular homologue of HAUSP. Deubiqutinated MDM2 however translocates to the nucleus where it binds to Ser-315/Ser-376 phosphorylated p53. This complex then translocates into the cytoplasm where ubiqutinated p53 is degraded. In order to deactivate p53 and thus p53-dependent antiviral signalling, at least two conditions have to be met: (1) MDM2 (or Hdm2) has to be deubiqutinated and (2) p53 has to be phosphorylated at Ser-315/Ser-376. In cells infected with Coronavirus’ both conditions are met since the induction of the ER stress response induces the phosphorylation of p53 in a GSK-3β dependent manner as described above and the Coronavirus genome encodes with the viral PLP2/PLPro a protein that has a DUB.
Indeed, Porcine epidemic diarrhoea virus (PEDV) derived PLP2 has been shown to stabilise and to deubiquitinate exogenous Hdm2 in p53+/+ HCT cells whilst increasing the degradation of p53 via the ubiquitin-dependent proteasome pathway as well as inhibiting IFN-β induced expression of a luciferase reporter gene following transfection of Poly(I:C) concomitant with nuclear translocation of Hdm2. Accordingly, p53 activity following transfection with Poly(I:C) is increased in p53 -/- HCT cells irrespective of PLP2 . Furthermore, in p53 -/- HCT cells PLP2 fails to protect cells from apoptotic cell death induced by PUMA, indicating that the expression of PLP2 induces PUMA expression via p53. Indeed PUMA has been shown to cause apoptosis as a result of ER stress suggesting that the expression of PLP2 induces ER stress; if this is due to the increase in the formation of autophagosomes remains to be seen.
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| PLP2 mediated translocation of MDM2 via binding to DUB |
In conclusion, the expression of PEDV PLP2 induces not only the ER stress but also inactivates p53 mediated activation of antiviral signalling following the transfection of p53 WT HCT cells with Poly(I:C) (and thus presumably also by viral RNA activated signalling) by deubiquitinating the human homologue of MDM2, Hdm2, and subsequent degradation of p53, thus blocking the type I Interferon response as well as preventing PUMA dependent apoptosis. In this context it is interesting that the infection of cells with Influenza Virus A induces the activation of the type I Interferon via p53; in contrast to the coronaviral PLP2 however, Influenza A Virus does not antagonize p53 mediated antiviral signalling. Since the coronaviral PLP2 increases the replication of Sendai Virus in p53+/+ MEF, it seems conceivable that in cells expressing PLP2 Influenza A Virus replication is also increased.
From a therapeutically point of view it might be interesting to investigate if mice deficient for MDM2 or treated with small molecule inhibitors of MDM2 are more susceptible to Coronavirus mediated infections.
Finally, the degradation of p53 by PLP2 might also prevent the induction of the phagophore. p53 not only transactivates the expression of pro-inflammatory and pro-apoptotic genes but also of genes facilitating the induction of the phagophore, including DRAM-1.
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| p53 and autophagy induction |
Expression of PLP2 therefore might inhibit this pathway as well; since some of those genes whose expression is induced are not only inducing the formation of the phagophore but also connecting autophagy induction to apoptosis, repressing p53 mediated signalling might also affect autophagy induced apoptosis, particularly in a situation where the fusion of autophagosomes with the lysosome in inhibited (as it is in cells expressing nsp-6 or PLP2).
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| PLP2 and p53 mediated activation of autophagy: consequences for autophagy related apoptosis? |
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| PLP2 and autophagy: multiple points of interference |
Further reading
Pluquet O, Qu LK, Baltzis D, & Koromilas AE (2005). Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta. Molecular and cellular biology, 25 (21), 9392-405 PMID: 16227590
Li K, Chen Z, Kato N, Gale M Jr, & Lemon SM (2005). Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. The Journal of biological chemistry, 280 (17), 16739-47 PMID: 15737993
Harashima N, Minami T, Uemura H, & Harada M (2019). Transfection of poly(I:C) can induce reactive oxygen species-triggered apoptosis and interferon-β-mediated growth arrest in human renal cell carcinoma cells via innate adjuvant receptors and the 2-5A system. Molecular cancer, 13 PMID: 25227113
Matsumoto M, & Seya T (2008). TLR3: interferon induction by double-stranded RNA including poly(I:C). Advanced drug delivery reviews, 60 (7), 805-12 PMID: 18262679
Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, & Gu W (2002). Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature, 416 (6881), 648-53 PMID: 11923872
Li M, Brooks CL, Kon N, & Gu W (2004). A dynamic role of HAUSP in the p53-Mdm2 pathway. Molecular cell, 13 (6), 879-86 PMID: 15053880
Kon N, Kobayashi Y, Li M, Brooks CL, Ludwig T, & Gu W (2010). Inactivation of HAUSP in vivo modulates p53 function. Oncogene, 29 (9), 1270-9 PMID: 19946331
Brooks CL, & Gu W (2004). Dynamics in the p53-Mdm2 ubiquitination pathway. Cell cycle (Georgetown, Tex.), 3 (7), 895-9 PMID: 15254415
Lu M, Xia L, Li Y, Wang X, & Hoffman R (2019). The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells. Blood, 124 (5), 771-9 PMID: 24869939
Mizutani T, Fukushi S, Saijo M, Kurane I, & Morikawa S (2004). Importance of Akt signaling pathway for apoptosis in SARS-CoV-infected Vero E6 cells. Virology, 327 (2), 169-74 PMID: 15351204
Wang X, Zhang H, Abel AM, Young AJ, Xie L, & Xie Z (2019). Role of phosphatidylinositol 3-kinase (PI3K) and Akt1 kinase in porcine reproductive and respiratory syndrome virus (PRRSV) replication. Archives of virology, 159 (8), 2091-6 PMID: 24532302
Fung TS, Huang M, & Liu DX (2019). Coronavirus-induced ER stress response and its involvement in regulation of coronavirus-host interactions. Virus research, 194, 110-23 PMID: 25304691
Cottam EM, Maier HJ, Manifava M, Vaux LC, Chandra-Schoenfelder P, Gerner W, Britton P, Ktistakis NT, & Wileman T (2011). Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate. Autophagy, 7 (11), 1335-47 PMID: 21799305
Huo Y, Fan L, Yin S, Dong Y, Guo X, Yang H, & Hu H (2019). Involvement of unfolded protein response, p53 and Akt in modulation of porcine reproductive and respiratory syndrome virus-mediated JNK activation. Virology, 444 (1-2), 233-40 PMID: 23850458
DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, Castaño-Rodriguez C, Perlman S, & Enjuanes L (2019). Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. Journal of virology, 88 (2), 913-24 PMID: 24198408
Yuan L, Chen Z, Song S, Wang S, Tian C, Xing G, Chen X, Xiao ZX, He F, & Zhang L (2019). p53 Degradation by a Coronavirus Papain-like Protease Suppresses Type I Interferon Signaling. The Journal of biological chemistry PMID: 25505178
Tan S, Wei X, Song M, Tao J, Yang Y, Khatoon S, Liu H, Jiang J, & Wu B (2019). PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy. Cell death & disease, 5 PMID: 24625987
Zhao Y, Yu S, Sun W, Liu L, Lu J, McEachern D, Shargary S, Bernard D, Li X, Zhao T, Zou P, Sun D, & Wang S (2019). A potent small-molecule inhibitor of the MDM2-p53 interaction (MI-888) achieved complete and durable tumor regression in mice. Journal of medicinal chemistry, 56 (13), 5553-61 PMID: 23786219
Shin SW, Kim SY, & Park JW (2012). Autophagy inhibition enhances ursolic acid-induced apoptosis in PC3 cells. Biochimica et biophysica acta, 1823 (2), 451-7 PMID: 22178132
Peng M, Yin N, & Li MO (2019). Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell, 159 (1), 122-33 PMID: 25259925
This is what the blog is going to be about....
This being the first entry I want to explain to the readers of what this blog is all about and how it came into existence.
It all started with an event which took place in the summer of 2009, late at night at a friends house after festivities ceased and the children were in bed. I should mention that those friends are conservative Catholics and that the hostess father is or was sending weekly newsletters detailing events from around the world where Catholic teaching or practice was threatened - or perceived as being “violated”.
Anyway, the hostess mentioned casually that one event -“discovered” by her father- that pharmaceutical companies were lacing vaccines against tetanus with a drug rendering girls in Nicaragua, Mexico and the Philippines sterile. This was discovered by the Human Life International, a Catholic-conservative think tank, back in 1995 and reported to the WHO which after investigating the claims dismissed them. The hostess however believed in the truth of these events, reinforcing her distrust in vaccinations (have I mentioned Andrew Wakefield?) in particular in vaccines generated in cells derived from aborted fetuses. Another guest chimed in, thus leaving me defending vaccinations and casually mentioning that one should not believe everything which is published in the Internet. Also I tried to explain that some viruses only grow in those cell lines - even the Vatican allows these vaccines to be used for vaccinations.
Ever since I haven’t been invited to her house…
Fast forward to 2019 and the wonderful world of Facebook and a comment posted by another friend, being worried that Influenza vaccine produced using genetic modified cells might contain remnants of the cells and being lethal (since during the trials three people died some weeks following the vaccination) or at least cause serious side effects. Luckily enough she was happy to receive some explanation and was actually grateful for the information (or so she said).
So this blog will be about thoughts of mine regarding those tidbits of virology related myths spreading the realms of the internet and printed media. Furthermore - being a Virologist myself- I will present articles which caught my attention, trying to evaluate them and put them into context. The choice of those articles will be subjective and I apologize in advance if somebody feels neglected. Please feel free to send me any suggestions and I will try to accomodate them. Also, feel free to share anything you want to see to be published here and/or my opinion on.
So far I have three topics in the pipeline and two papers I want to comment on, but as time goes more topics will arise.
MediShield Life to offer higher payouts with new claim limits from 1 January 2020; no changes to premiums
January 1 changes will benefit 90,000 a year although premiums will stay the same
By Timothy Goh, The Straits Times, 28 Dec 2019
Patients who need surgery will be able to claim more from their compulsory health insurance from Jan 1, the Ministry of Health (MOH) announced yesterday.
This comes as MediShield Life claim limits are being raised, a move which is expected to benefit around 90,000 patients a year.
MediShield Life is a basic health insurance plan that helps to pay for large hospital bills and selected costly outpatient treatments, such as dialysis and chemotherapy.
All Singaporeans and permanent residents are covered by MediShield Life, which is administered by the Central Provident Fund Board.
Patients undergoing surgical procedures listed in the MOH's Table of Surgical Procedures can claim from MediShield Life and tap their Medisave to pay for their surgical bills subject to claim limits.
There are currently seven tiers of MediShield Life claim limits to cater to surgical procedures of different complexities.
This number will triple to 21 from next year, allowing for more differentiation between procedures of varying complexities.
The new set of limits, offering higher payouts, will take effect for those admitted for surgical procedures from Jan 1.
For instance, Patient A who undergoes a complex uterus operation might currently be able to claim only up to $1,400 - the same amount as Patient B who undergoes a simpler uterus operation.
Under the revised limits, Patient A would be able to claim up to $2,180. Patient B would be able to claim up to $1,800 for the simpler procedure, less than Patient A, but $400 more than the previous limit allowed.
MOH said yesterday that the introduction of the new tiers will provide better coverage for more complex surgical procedures, which tend to be costlier.
There will be no adjustments to premiums at this point, as the Government committed to keeping premiums constant for five years when MediShield Life was launched in November 2015.
The claim limits were adjusted to keep pace with increasing healthcare costs since 2015.
The claim limit revisions were recommended by the MediShield Life Council as part of its review exercise, which started last year and is expected to be completed by the end of next year.
Senior Minister of State for Health Edwin Tong said yesterday that the new claim limits would be implemented first so patients can benefit earlier from the changes.
He added: "The new claim limits will improve MediShield Life coverage for more complex surgical procedures and better protect Singaporeans against large hospital bills... We will continue our efforts to keep healthcare costs sustainable and affordable for all Singaporeans."
Patients do not need to take any steps to benefit from the new limits, which will be automatically applied to their MediShield Life claims.
Dr Lily Neo, deputy chairman of the Government Parliamentary Committee for Health, said: "It is useful to have such revisions... Not all conditions are the same or require the same standardised procedures, so if we can have more tiers, that will better accommodate various conditions that require different types of treatment or better technology."
In its statement, MOH emphasised that the Government provides significant subsidies of up to 80 per cent to keep healthcare costs low, and that there are various forms of financial assistance available for those in need.
It added: "No Singaporean will be denied appropriate healthcare due to an inability to pay."
By Timothy Goh, The Straits Times, 28 Dec 2019
This comes as MediShield Life claim limits are being raised, a move which is expected to benefit around 90,000 patients a year.
MediShield Life is a basic health insurance plan that helps to pay for large hospital bills and selected costly outpatient treatments, such as dialysis and chemotherapy.
All Singaporeans and permanent residents are covered by MediShield Life, which is administered by the Central Provident Fund Board.
Patients undergoing surgical procedures listed in the MOH's Table of Surgical Procedures can claim from MediShield Life and tap their Medisave to pay for their surgical bills subject to claim limits.
There are currently seven tiers of MediShield Life claim limits to cater to surgical procedures of different complexities.
This number will triple to 21 from next year, allowing for more differentiation between procedures of varying complexities.
The new set of limits, offering higher payouts, will take effect for those admitted for surgical procedures from Jan 1.
For instance, Patient A who undergoes a complex uterus operation might currently be able to claim only up to $1,400 - the same amount as Patient B who undergoes a simpler uterus operation.
Under the revised limits, Patient A would be able to claim up to $2,180. Patient B would be able to claim up to $1,800 for the simpler procedure, less than Patient A, but $400 more than the previous limit allowed.
MOH said yesterday that the introduction of the new tiers will provide better coverage for more complex surgical procedures, which tend to be costlier.
There will be no adjustments to premiums at this point, as the Government committed to keeping premiums constant for five years when MediShield Life was launched in November 2015.
The claim limits were adjusted to keep pace with increasing healthcare costs since 2015.
The claim limit revisions were recommended by the MediShield Life Council as part of its review exercise, which started last year and is expected to be completed by the end of next year.
Senior Minister of State for Health Edwin Tong said yesterday that the new claim limits would be implemented first so patients can benefit earlier from the changes.
He added: "The new claim limits will improve MediShield Life coverage for more complex surgical procedures and better protect Singaporeans against large hospital bills... We will continue our efforts to keep healthcare costs sustainable and affordable for all Singaporeans."
Patients do not need to take any steps to benefit from the new limits, which will be automatically applied to their MediShield Life claims.
Dr Lily Neo, deputy chairman of the Government Parliamentary Committee for Health, said: "It is useful to have such revisions... Not all conditions are the same or require the same standardised procedures, so if we can have more tiers, that will better accommodate various conditions that require different types of treatment or better technology."
In its statement, MOH emphasised that the Government provides significant subsidies of up to 80 per cent to keep healthcare costs low, and that there are various forms of financial assistance available for those in need.
It added: "No Singaporean will be denied appropriate healthcare due to an inability to pay."
Higher MediShield Life claim limits a relief for parents of baby due for surgery
MediShield Life revisions will help ease their financial worries over his cleft palate operation
By Timothy Goh, The Straits Times, 28 Dec 2019
One of the first patients to benefit from revisions to MediShield Life may not even remember undergoing his procedure.
One-year-old Bryler Tan is scheduled to have cleft palate repair surgery in January - the same month that claim limits for the insurance plan will be raised and separated into more tiers.
The revisions to MediShield Life, which the Ministry of Health announced yesterday, are expected to benefit some 90,000 patients a year with higher payouts, from Jan 1.
For Bryler's mother, 27-year-old senior patient service associate How Pei Fen, this is a huge relief.
The baby's surgery is currently listed under tier 5C in the Ministry of Health's Table of Surgical Procedures, which means his family would have been able to claim up to $1,400 for it from MediShield Life.
Madam How, who is married to a helper at a food store, said yesterday: "We were worried about the huge cost of the surgery and scared we couldn't pay for it. We also knew Bryler would need to go for a lot of follow-ups and treatments, and we'd need to spend a lot.
"We have financial issues and were worried that we'd have insufficient Medisave to make the payment."
The estimated cost of Bryler's upcoming surgery is around $15,000 before government subsidies. This estimated amount is based on a four-day stay in the hospital.
Following the revision, they can claim up to $2,180 for the procedure. "This will help us to reduce our out-of-pocket payment, and even with the little we can pay out of Medisave, we will still be able to afford high surgery cost," said Madam How.
MediShield Life revisions will help ease their financial worries over his cleft palate operation
By Timothy Goh, The Straits Times, 28 Dec 2019
One of the first patients to benefit from revisions to MediShield Life may not even remember undergoing his procedure.
One-year-old Bryler Tan is scheduled to have cleft palate repair surgery in January - the same month that claim limits for the insurance plan will be raised and separated into more tiers.
The revisions to MediShield Life, which the Ministry of Health announced yesterday, are expected to benefit some 90,000 patients a year with higher payouts, from Jan 1.
For Bryler's mother, 27-year-old senior patient service associate How Pei Fen, this is a huge relief.
The baby's surgery is currently listed under tier 5C in the Ministry of Health's Table of Surgical Procedures, which means his family would have been able to claim up to $1,400 for it from MediShield Life.
Madam How, who is married to a helper at a food store, said yesterday: "We were worried about the huge cost of the surgery and scared we couldn't pay for it. We also knew Bryler would need to go for a lot of follow-ups and treatments, and we'd need to spend a lot.
"We have financial issues and were worried that we'd have insufficient Medisave to make the payment."
The estimated cost of Bryler's upcoming surgery is around $15,000 before government subsidies. This estimated amount is based on a four-day stay in the hospital.
Following the revision, they can claim up to $2,180 for the procedure. "This will help us to reduce our out-of-pocket payment, and even with the little we can pay out of Medisave, we will still be able to afford high surgery cost," said Madam How.
Higher and more granular claim limits for MediShield Life -27 Dec 2019
Are MediShield Life payouts lower than subsidised fees?
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