what is endogenous control rppv positivewhat is endogenous control rppv positive

tiempo.com. find in their investigation regarding viral culture of SARS Cov2 in order to assess infectivity (horizontal transmission or capacity for a virus to spreads among hosts) and virulence (a pathogens ability to infect or damage a host): We, therefore, reviewed the evidence from studies reporting data on viral culture or isolation as well as reverse transcriptase-polymerase chain reaction (RT-PCR), to understand more about how the PCR results reflect infectivity.. Real-time reverse transcription polymerase chain reaction (RT-PCR) assays are the tool of choice for determining if someone has an active viral shedding of SARS-CoV-2. sergio.s.hernandez@uit.no, Department of Physics and Technology, UiT The Artic University of Norway The endogenous control gene should have constant expression in all the samples compared. on endometrial carcinomas [4] selected three different control genes from a similar but expanded gene panel. You typically use this when you are comparing the expression of a gene of interest across multiple samples. RPPV: Right Posterior Portal Vein. This protein is found within vaccines or produced as a result a result of vaccination, in addition to being a part of the SARS-CoV-2 virus. Active reference means the signal is generated as the result of PCR amplification. Hi, Either one can be very reliable if used appropriately. If the virus is found in the person (PCR TRUE POSITIVE), that virus is injected into a culture cell. The test is considered void when the synthetic RNA is not detected post-extraction and a re-test is prescribed. The threshold alone might or might not tell whether someone carries infective viral RNA. Economists also include independent variables to help determine to which extent a result can be attributed to an exogenous or endogenous cause. You do the PCR. SARS-CoV-2 is detected by using one of the following assays: The UW SARS-CoV-2 Real-time RT-PCR assay targets two distinct regions within the N gene of SARS-CoV-2 (the causative agent for COVID-19). What proportion of Covid-19 cases are asymptomatic? Positive Control DNA. Thus, this control adds additional confidence to the results of the run. %PDF-1.5 % This function should have some predictive power to be useful. The authors claim: Cycle thresholds are the times that the amplifying test has to be repeated to get a positive result. When available, BAL and sputum have the highest positivity rates of any specimen type. UW Laboratory Medicine Virology will prioritize maintaining clinically-actionable turnaround time for inpatient settings. Rainfall to plant growth is correlated and studied by economists since the amount of rainfall is important to commodity crops such as corn and wheat. of gene expression in renal biopsies from patients with different kidney diseases [2]. infectious, or virulent? If these positive controls are assayed in separate wells/tubes from the experimental sample, they serve as a control to determine whether or not the reverse transcription and/or PCR reaction conditions are optimal. Then the test would be a FALSE POSITIVE because the SARS Cov2 virus is not present in the sample. Are you infectious if you have a positive PCR test result for COVID-19? For the Spanish data (Figures 4, 6 and 7) the key points are: What if we take into account excess deaths instead? The quantitative differences in mRNA produced during a qPCR assay do not just depend on gene activitythey also depend on experimental conditions, particularly the initial amount of cDNA. For example, in a model studying supply and demand, the price of a good is an endogenous factor because the price can be changed by the producer (supplier) in response to consumer demand. Figure 3 illustrates this. To mitigate this, an internal control can be used. hb```%;@(1S8` $.epvabtH,H_%p rGY=DG8]wdav8+sP-o)P9}kR\S$PGIR">C9 For example, heat waves might come in June, July, August or even September (2020 -Spain[7]) in Europe and direct comparison between years should consider this. Here, for instance, you can also control for different efficiencies of the RT enzyme during the cDNA reaction. wRaHOd%In'~(Is8 Endogenous variables have values that shift as part of a functional relationship between other variables within the model. But traces of the virus might still be present in the person. The y axis gives the coefficient of determination R2 as a function of days of delay. Kartheek. What Does Ceteris Paribus Mean in Economics? would imply PCR positives predict the number of deaths in the future since governments could expect what is to come in the future on the basis of the number of PCR positive cases recorded on a given day. The authors briefly explain why: This detection problem is ubiquitous for RNA viruss detection. 15i*0=po7.8M]{,eS8]xu{M^8rO_Eg?p'L5KkO9.m!D%9\!Q|n*.HT.4ggY4CS}Y%2]*HP4E`)S=. :>(od1{tt )0esXA1 Ack S,Lrt00t4u40wt2X4p4 m4Q F4d/o\|@IAWQF.*K2\sr/;0:p(_ p-v;"SdM%9 `0K1y ] H+00*l"Ai 4J Conclusion: symptoms and signs of Covid19 are necessary to support the claim that the subject is or can be infectious. This control type is not placed in a designated well but instead is present in every sample well. We suggest that the hypothesis of CEBM, i.e. Examples of endogenous internal control genes that have been widely used for PCR process control monitor include 18s . Five qualitative one-step Real-Time RT-PCR assays; the UW SARS-CoV-2 Real-time RT-PCR assay, the Hologic SARS-CoV-2 Real-time RT-PCR assay, the cobas SARS-CoV-2 assay, the DiaSorin Molecular Simplexa COVID-19 Direct assay and the Abbott Alinity m SARS-CoV-2 assay. Send to the laboratory as soon as possible. This would need 1) a model (correlation) that maps PCR POSITIVES and/or symptoms to infectivity as tested by viral culture or 2) viral culture for every individual case. 1. Figure 4. will not die. endstream endobj startxref For this purpose known quantities of endogenous protein are being employed as a positive control. But you still cant tell whether this is a true fold change because of differences in sample input, and this is where the endogenous control comes in. A simple function between PCR positives to Covid19 could be a linear function (Eq. Purify the RNA from all your samples across different test conditions using the same method. Arachidonic acid lipoxygenases (ALOX) have been implicated in the pathogenesis of inflammatory, hyperproliferative, neurodegenerative, and metabolic diseases, but the physiological function of ALOX15 still remains a matter of discussion. The PKeye mobile operations monitor provides researchers with around the clock access to their automated liquid handling workstation through integration of on-deck cameras with the PKeyecloud based platform. This standard 96-well plate includes triplicates of 32 stably expressed human genes known to be good control candidates; you are likely to find a control among these that is appropriate for your applications. For example, DNAs with known concentrated and sequences added to samples as controls. Here D(t) is the number of deaths at time t (or a given day) and P(t*) is the number of PCR positives at an earlier time t*=t-t0, where t0 is the time between the number of deaths D recorded and the number of PCR Positives recorded (typically days to weeks as shown in Figure 5). Not for use in diagnostic procedures. A positive control is expected to have amplification of the assay specific SARS-CoV-2 target regions. Benign paroxysmal positional vertigo (BPPV) is an inner- ear disorder that is the most common cause of vertigo, a very specific kind of dizziness that makes you feel as if the room is spinning . In practice, zero variation is very rare and endogenous control genes are allowed small differences in Ct values of up to 0.5 Ct. Endogenous positive controls refer to the use of a native target that is present in the experimental sample (s) of interest, but is different from the target under study. Ayakannu T, Taylor AH, Willets JM et al. Outside of economics, other fields use models with endogenous variables including meteorology and agriculture. Watch video: False Positives and Rapid Tests Explained. They involve adding an outside source of encapsulated RNA to each sample before extraction. Search The issue of potentially endogenous control variables in causal studies based on the assumption of no selection bias conditional on observables (conditional independence assumption, CIA) is discussed. PKamp Respiratory SARS-CoV-2 RT-PCR Panel 1 EUA, PerkinElmer COVID-19 Antigen Test CE-IVD, SARS-CoV-2 Plus RT-qPCR Reagent kit CE-IVD, Respiratory SARS-CoV-2 RT-PCR Panel CE-IVD, PerkinElmer GSP/DELFIA Anti-SARS-CoV-2 IgG Kit CE-IVD, Coviscreen SARS- CoV-2 Lateral Flow Kit CE-IVD, PKamp VariantDetect SARS-CoV-2 RT-PCR Assay, JANUS G3 Workstations for SARS-CoV-2 Testing, explorer Integrated Workstations for SARS-CoV-2 Testing, Solutions for Labs Performing miRNA Services, Labchip GXII Touch Protein Characterization System, IMPROVING THE EFFICIENCY OF SARS-COV-2 TESTING, How to Handle Inconclusive Samples with SARS-COV-2 Real-time PCR Tests, Reducing Errors From Low-throughput Library Prep, Single cell Sequencing Services Leveraging the HIVE scRNAseq Solution, Respiratory Testing during the 2022 Flu Season, Tips on Establishing a Reliable Cell-Free DNA Workflow from Plasma Samples. We might argue that labelled deaths are not in agreement with the true number of deaths by Covid19. Quantitative PCR is the method of choice for studying how a change in the conditions under which a gene is expressedsuch as the addition of a treatmentaffects the amount of mRNA it produces. Remove swab and repeat the same process in the other nostril with the same swab. As part of quality control measures for COVID-19 tests, "control" samples are included in batches to help to detect any faults. Thank you for your explanation. 50% off on PowerUp SYBR Green Master Mix. Unfortunately relating PCR POSITIVE to infectivity is not easy if we consider the whole population. It might not do anything to your cells (virulence), and it might also lack the capacity to move into another person (infectivity) when you speak or sneeze. But this is not the only possibility. That is, it is possible that the population was infected already long before deciding to test and PCR positives would therefore not speak of an advancing pandemic. Exogenous positive controls refer to the use of external DNA or RNA carrying a target of interest. There is no time delay between PCR tests and excess deaths as shown in Figure 7 and it could be argued that this could explain the lack of correlation. %PDF-1.6 % The paper shows that the standard formulation of the CIA obscures the endogeneity problem. We warmly welcome you to come and meet our certified instructors at our Applied Genomics Center of Excellence in Hamburg, Germany. For example, if 20% of a population are PCR positive, the number of PCR positives will depend on the size of the sample. Sample may be stored at 2-8C for up to 72 hours of collection. Endogenous variables are variables in a statistical model that are changed or determined by their relationship with other variables. The Hologic Emergency Use Authorization (EUA) SARS-CoV-2 Real-time RT-PCR assay targets two conserved regions of the SARS-CoV-2 (the causative agent for COVID-19) ORF1ab gene. Choosing and validating an endogenous control. In cases where BAL and sputum are available, they should be sent as they have the highest positivity rates. What antibody tests can provide is a broader understanding of the progression of an outbreak. That a PCR test gives positive or negative depends on how the experiment is conducted. So, the two target DNAs (your target + control sequence) compete for the primers. A positive PCR test does not yield any information about potential immunity. Figure 9. endogenous control detected. It is impossible to predict exactly how any gene will behave under a given range of conditions. Tentang Kol ; Pelajari lebih lanjut tentang teknologi kami dan seberapa banyak universitas, organisasi penelitian, dan perusahaan di semua industri menggunakan data kami untuk menurunkan biaya mereka. Covid19 labelled deaths depend on subjective parameters whether excess deaths have the advantage of being a standard relative to a reference, namely, the number of deaths in previous years. The success of coronavirus disease 2019 (COVID-19) mRNA vaccines (6, 7) has begun to foster the development of mRNA vaccines against other infectious diseases and different types of cancer.Various mRNA vaccine platforms have been developed that use either non-replicating (nr) or self-amplifying (sa) mRNA (8, 9). A positive control lysate is a lysate from a cell line or tissue sample known to express the protein you are detecting. The two regions are not differentiated; amplification of either or both regions is a presumptive positive (detectable) test result and amplification of neither target results a negative (non-detectable) test result. Regression is a statistical measurement that attempts to determine the strength of the relationship between one dependent variable and a series of other variables. The implication is that PCR positives lack predictive power in terms of telling whether people will die in the future. Estimating mortality from COVID-19. Exogenous internal control systems are a bit more complex. Endogenous variables are important in econometrics and economic modeling because they show whether a variable causes a particular effect. Test your candidate endogenous control genes in your qPCR reaction using the same volume of cDNA in each reaction. But then the virus is still present many days after. Therefore, any light increase/decrease in deaths should be contrasted to the temperature. For human studies, the TaqMan Array Human Endogenous Control Panel is an excellent place to start. We can add a time delay indicating that it takes time for people to die after being infected (Figures 3 and 4). L! si*a`[p&Q@H+20lG]$1g w Rate it: RPPV: Resultant Peak Particle Velocity. Although endogenous variables are the dependent variables that correlate with each other, knowing to what extent exogenous variables impact a model is important to consider. For example, assume a model is examining the relationship between employee commute times and fuel consumption. Positive percent agreement: 100%. (2004) Guideline to reference gene selection for quantitative real-time PCR. But calling PCR positives cases does not specify whether the persons have carried the virus for long or whether it is active. 5 qLGPP"e`&%0ftI Copyright | PerkinElmer Inc. All rights reserved. We want to focus on the CEBM argument that depends on viral culture. This sort of control is mostly used in real-time PCR to normalize for different cDNA loading amounts. If collection to receipt in the lab will exceed 72 hours freeze at -10C or colder and ship on dry ice. Predicting infectious SARS-CoV-2 from diagnostic samples. A positive result for this test can indicate either a past infection or it may indicate vaccination against the virus. If so, there should be correlation. 3563 0 obj <>/Filter/FlateDecode/ID[<759A88C7709C3047AF92B5809AF2A20C>]/Index[3544 41]/Info 3543 0 R/Length 94/Prev 1356891/Root 3545 0 R/Size 3585/Type/XRef/W[1 3 1]>>stream An endogenous positive control is important to validate the results, as well as to . In a few months it might not do anything to you anymore. Positive Detected Contact patient with result and confirm continuation of home isolation. There is some evidence of a relationship between the time from collection of a specimen to test, symptom severity and the chances that someone is infectious. 2. Comparison of the C T value of a target gene with that of the endogenous control gene allows the gene expression level of the target gene to be normalized to the amount of input RNA or cDNA. page 5, PCR kits for SARS Cov2 (manufacturers and asymptomatic) page 6, Conclusion in relation to PCR positives and an advancing pandemic. you want to control if a PCR reaction happened in your tube to exclude false negatives. Time from symptom onset to RT-PCR, or symptoms to test (STT), was calculated based on laboratory records. Check the CT between samples for each candidate endogenous control gene. Note: Due to supply chain variables and logistical workflows to minimize turn-around time, orders may be substituted for medically equivalent qualitative assays at an equivalent or cheaper cost. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020; ciaa638. The Abbott Alinity m Emergency Use Authorization (EUA) SARS-CoV-2 Real-time RT-PCR assay targets two regions of the SARS-CoV-2 (the causative agent for COVID-19) genome, the RdRp gene and N gene. Thromb Haemost 2019;119:1084-1093. He previously held senior editorial roles at Investopedia and Kapitall Wire and holds a MA in Economics from The New School for Social Research and Doctor of Philosophy in English literature from NYU. cold winters or heat waves (Figure10). Instructions for Sputum: obtain specimen from deep cough (usually in AM), induction or intubation; do not send saliva. above. An endogenous control gene must have stable expression in all samples tested, i.e. Systematic review. Ship immediately to lab at 2-8C (ice pack). Is the PCR test sensitive enough?. In this respect, the CEBM writes: Viral culture [acts] as reference test against which any diagnostic index test for viruses must be measured and calibrated, to understand the predictive properties of that test.. This is even when the PCR tests or the antibody tests are positive. In the previous example: delta delta Ct = (28.5-27.5) (19.5-18.5) = 0. because inactivated RNA degrades slowly over time it may still be detected many weeks after infectiousness has dissipated.. matteo.chiesa@uit.no Amplification of both targets results in a presumptive positive (detectable) test result, while amplification of one of two targets results in an inconclusive result, and amplification of neither target results a negative (non-detectable) test result. This could result in PCR positive but it does not mean that the virous is virulent or infectious, rather it means that residues and non active viral RNA is still detectable by PCR. The relationship makes sense since the longer a persons commute, the more fuel it takes to reach the destination. 1). endogenous or infused FVIII activity FVIII activity: chromogenic human reagents No Responsive to Hemlibra, but may overestimate clinical hemostatic potential of Hemlibra 1. 3544 0 obj <> endobj This is because one might be PCR Positive long after the virus is no longer active. These types of controls are often referred to as normalizers, and are typically used to correct for quantity and quality differences between samples. The paper shows that the standard formulation of the CIA obscures the endogeneity problem. Fortunately, this problem has a solution. For example, in the months of July to September positive cases in Europe are said to have risen, but we find no evidence of excess deaths in the countries in Europe reported by euromomo.eu (Figure 10). If the positive control works, then samples that come up negative are expected to be negative instead of falsely negative from inhibition or incorrect set-up. A ratio between infections and deaths is the typical way in which mortality is considered[5]. In. this is commonly termed as a "housekeeping gene". In these cases, it adds additional confidence that the likewise encapsulated SARS-CoV-2 was also successfully extracted, and that its genetic material in the form of RNA was also properly transcribed if present. . It is widely used for crop improvement, propagation of valuable varieties and generation of chimeric plants. Differences at the top end of this range will introduce imprecisions. Normalization to endogenous control genes is currently the most . Exogenous variables can have an impact on endogenous factors, however. These control reactions assess whether the samples contain any components that inhibit reverse transcription and/or PCR. The x axis stands for the days of delay from the number of PCR positive recorded to the number of excess deaths. Explanation of the experiment that shows whether a virus is still infective (2003) Validation of endogenous controls for gene expression analysis in microdissected human renal biopsies. This is determined by measuring the SD of the replicate Ct values. 0 The implication is that the number of positive PCR cases is proportional to the excess deaths reported that day, i.e. PCR positives on asymptomatic people should be treated with care since it is possible that the asymptomatic people are not infectious. Khadija Khartit is a strategy, investment, and funding expert, and an educator of fintech and strategic finance in top universities. Care must be taken to avoid contamination of reagents with genetic material from samples, kit controls, the environment, or amplicons from previous reactions. For example Actin RNA in a RNA sample. Copyright and Disclaimer, Department of Laboratory Medicine & Pathology, https://www.cdc.gov/coronavirus/2019-ncov/lab/rt-pcr-detection-instructions.html, https://www.cdc.gov/coronavirus/2019-ncov/index.html, SARS CoV 2 (COVID 19) Qual PCR Specimen Type, SARS CoV 2 (COVID 19) Qual PCR Interpretation, COVID-19 Testing Frequently Asked Questions For Patients, Frequently Asked Questions About COVID-19 Testing for Providers & Clients, Guidance for long term care facilities sending samples for COVID-19 screening, https://depts.washington.edu/uwviro/order/. Figure 7. Scatter plot showing PCR positives versus excess deaths from may to the end of August. It was sensitive to . Ideally and accordingly, if the PCR tests were performed during the very first days of infection, Eq. Interestingly, there are few published studies of gene expression in kidney tissues that used either of these genes as a control. Positive results are indicative of active infection. For example, a high starting amount of an endogenous IC template can impair assay sensitivity. For a wider variety of assays involving other species, go to taqmancontrolsto select Gene Expression, Controls and your species of interest (or All), and then click 'Search'. CPT/PLA codes may differ. In this work we have dedicated most attention to the Spanish data but more curves providing Positive PCR cases versus deaths (not excess but Covid19 as reported by each country) can be found at worldometers.info (https://www.worldometers.info/coronavirus/), John Hopkins, and other sources. Regards, Primer sets are validated for use with most 3412 0 obj <> endobj Quantify and use the same amount of RNA from each sample of your RT reaction. Comparison of the C, Tagged Protein Expression, Purification, Detection, Reverse Transcription & cDNA Synthesis for qPCR, SYBR Green- or Dye-Based One-Step qRT-PCR, Commercial Partner and Distributor Solutions, Relative Expression Levels of Commonly Used Human Housekeeping Genes, Relative Expression Levels of Commonly Used Mouse Housekeeping Genes, Relative expression levels of commonly used human housekeeping genes, Relative expression levels of commonly usedmouse housekeeping genes, Peptidylprolyl isomerase A (cyclophilin A), Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide, Hypoxanthine guanine phosphoribosyl transferase, Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide. There are two different approaches in RT-PCR assay design for internal controls: endogenous and exogenous. Radonic A, Thulke S, Mackay IM et al. Conclusion: A TRUE POSITIVE in PCR does not always mean that the person presents any danger to society. Rate it: RPPV: Revenue Per Page View. TaqMan Endogenous Control Assays. The CEBM explains why culturing the virus is needed to answer this question: In viral culture, viruses are injected in the laboratory cell lines to see if they cause cell damage and death, thus releasing a whole set of new viruses that can go on to infect other cells.. A possible explanation could be that the PCR positives simply measure the number of PCR tests taken on a given day, i.e. The two regions are not differentiated; amplification of either or both regions is a presumptive positive (detectable) test result and amplification of neither target results a negative (non-detectable) test result. After the second swab is completed, immediately place into the sterile vial containing media (UTM is preferred). Find the right products for every step of your experiment effortlessly. A later study by Ayakannu et al. Two, the reverse transcription worked. The coefficient of determination R2 is 0.3 and is highest when plotting the PCR positives recorded on the same day that excess deaths are recorded. It is possible that no single endogenous gene will fit your requirements; in this case, use two or more genes in parallel for best results. You could then conclude that the expression level in the treated sample was twice that in the untreated sample. PCR true positives versus infectivity and virulence Figure 1. I favor using several of the. Kartheek, Exogenous control - A control that is spiked in the sample. medRxiv 2020; 2020.2008.2004.20167932. The UW Clinical Virology Laboratory in the Department of Laboratory Medicine and Pathology incorporates six assays for the detection of the COVID-19 virus (SARS-CoV-2) RNA. A positive control is expected to have amplification of the assay specific SARS-CoV-2 target regions. fsdataanalysis@gmail.com The FDA developed an experiment to precisely compare the performance of the nucleic acid-based SARS-CoV-2 assays which have received EUA authorization and published acomparative performance analysis. What did Tom Jefferson et al. 275 years of forestry meets genomics in Pinus sylvestris. The negative control is expected to result in no amplification of the target regions. Covid19 labelled death versus TRUE death by Covid19 Negative results: With a high likelihood, the results state you were not infected with Sars-CoV-2 at the time of testing. that viral culture is required as a reference to test for infectivity, and other similar ones such as that by Jared Bullard et al[6]., i.e. Send to UW Virology Central Lab (Renton) via courier. A genome-wide association study explores the genetic determinism of host resistance to Salmonella pullorum infection in chickens. This is a common method of disease treatment. The relationship is also referred to as dependent and is seen as predictable in nature. page 3, Explanation of the experiment that shows whether a virus is still infective. Ultimately, this means PCR positives cannot be used to tell if the pandemic is advancing if for that we understand that deaths are to increase or decrease. Positive result of the equine virus indicate proper extraction and PCR. Figure 2. Boyd C. The coronavirus death lag explained: How it can take three weeks between catching the disease and being hospitalised (and three days for the NHS to record the fatality). Other Locations (eg, reference laboratory client), Send all samples with the COVID-19 Test Requisition (form is a fillable pdf - please download and enter information before printing). Here is the effective mortality rate, i.e. Ingenium Biologicals Biotech (IBB) Colorectal Adenomas-Genetics and Searching for New Molecular Screening Biomarkers. The gene fragment might be detected and the virus positively found. endstream endobj 3413 0 obj <. Try the Workflow Configurator. The highest values correspond to the proportionality between excess deaths today and PCR positives today implying that PCR tests lack any predictive power by being redundant at most. The issue of potentially endogenous control variables in causal studies based on the assumption of no selection bias conditional on observables (conditional independence assumption, CIA) is discussed. Lossos et al. In the case of a negative endogenous The Roche cobas Emergency Use Authorization (EUA) SARS-CoV-2 Real-time RT-PCR assay (Fact Sheet) targets two regions of the SARS-CoV-2 (the causative agent for COVID-19) genome, the E gene and ORF1ab gene. Figure 8. We believe the rise in deaths toward August and September corresponds to the heat wave. Multiple Regression: What's the Difference? An endogenous control is basically a control that is already present in your DNA sample. Endogenous control - A control that is present in the sample. Place order in ORCA, Epic, or Sorian using "COVID-19 Coronavirus Qualitative PCR" per routine. That is, does the detected viral RNA have the capacity to reproduce or infect the person (virulence) or get transmitted to other people (infectivity)? What Do Correlation Coefficients Positive, Negative, and Zero Mean? You basically use the endogenous control to normalize the amount of DNA template in all your samples. Testing is limited to the high complexity CLIA clinical laboratory at UW Virology in Seattle, WA. In the example above, we assume that the endogenous control gene is expressed at a consistent level in all studied conditions, so any change in control gene expression between the treated and untreated samples will be measured in that genes delta Ct value, and will contribute to the calculated delta delta Ct. For reliable results, you need to select the correct control. This means that 1) either we do not have the true infection fatality ratio (IFR) but a (CFR), 3) the cases in March-April correspond to different phenomena to those in July-September, or 3) the virus has mutated so rapidly that the true IFR has changed already and dramatically.
Where Is Michelle Tuzee Today, Articles W