|Year : 2022 | Volume
| Issue : 1 | Page : 24-31
Postmortem nasopharyngeal swabs performed during the COVID-19 infection: Analysis of preliminary clinical records by the genoa institute of legal medicine (North-West Italy)
Martina Drommi1, Rosario Barranco1, Arianna Balbo1, Stefano Errico1, Francesca Maria Elena Frigiolini1, Manuela Mangioni1, Giulia Molinari1, Alessandra Zappi1, Patrizia Caligiuri2, Francesco De Stefano1, Francesco Ventura1
1 Department of Forensic and Legal Medicine, University of Genova, Genova, Italy
2 Department of Health Sciences, University of Genova; Department of Hygiene, San Martino Polyclinic Hospital, Genova, Italy
|Date of Submission||16-Jan-2021|
|Date of Decision||31-May-2021|
|Date of Acceptance||12-Aug-2021|
|Date of Web Publication||17-Mar-2022|
Department of Legal Medicine, University of Genova, via De' Toni 12, 16132 Genova
Source of Support: None, Conflict of Interest: None
COVID-19, the disease caused by the SARS-CoV-2 virus, is highly contagious. The persistence of the virus after infected individuals die remains unclear. This article reports the findings taken from postmortem nasopharyngeal swabs performed to investigate the presence of SARS-CoV-2 in the corpses transferred to the Genoa District Mortuary from the outset of the Italian lockdown (March 9) to the end of the first emergency phase (July 13). One hundred and eighty swabs were carried out: 13 corpses resulted positive for the virus, with the diagnosis being reached only after death. Seven were male and 6 female with an average age of 73.5 years old. The most frequent comorbidities recorded were arterial hypertension, diabetes, Alzheimer's, and pulmonary disease. In two cases, the swab tested positive at a distance of 125 h and 165 h from actual death. The nasopharyngeal swab results a useful way to screen corpses for COVID-19 and to handle bodies in Legal Medicine Centers where safe autoptic rooms are not available. Swabs are also a means of safeguarding forensic pathologists, identifying the presence of breeding grounds in the community and providing information for the Public Prosecutor's Office in legal cases. They are able to produce reliable results up to at least 7 days following death, provided that the corpse is correctly preserved.
Keywords: Autopsy, forensic pathology, legal medicine, managing of the corpses, naso-pharyngeal swab, SARS-CoV-2
|How to cite this article:|
Drommi M, Barranco R, Balbo A, Errico S, Elena Frigiolini FM, Mangioni M, Molinari G, Zappi A, Caligiuri P, Stefano FD, Ventura F. Postmortem nasopharyngeal swabs performed during the COVID-19 infection: Analysis of preliminary clinical records by the genoa institute of legal medicine (North-West Italy). J Forensic Sci Med 2022;8:24-31
|How to cite this URL:|
Drommi M, Barranco R, Balbo A, Errico S, Elena Frigiolini FM, Mangioni M, Molinari G, Zappi A, Caligiuri P, Stefano FD, Ventura F. Postmortem nasopharyngeal swabs performed during the COVID-19 infection: Analysis of preliminary clinical records by the genoa institute of legal medicine (North-West Italy). J Forensic Sci Med [serial online] 2022 [cited 2022 May 16];8:24-31. Available from: https://www.jfsmonline.com/text.asp?2022/8/1/24/339793
| Introduction|| |
The recent spread of the disease, caused by the coronavirus 2019 (known as COVID-19), which is potentially capable of causing acute respiratory distress in humans leading to death, has attracted worldwide attention. In China, it was first detected in December 2019, in the city of Wuhan, the capital of China's Hubei province.
In regard to Italy, on February 20, 2020, the first case of a patient affected by COVID-19 was registered in Lombardy, a region in Northern Italy, and by the middle of October 2020, the Supreme Health Authority had already reported 360,000 infected people in the country.
The incubation period of COVID-19 is generally considered to be about 5 days and the period from the onset of symptoms to death varies from 6 to 41 days, with a median of 14 days. It would also seem that the transmission of the disease is possible for approximately 8 days from the first signs of symptoms. The most common symptoms observed at the initial onset of the disease are a cough, fever, fatigue, difficulty in breathing, sore throat, headaches, conjunctivitis, and gastrointestinal/stomach upsets.
In regard to its transmission, human-to-human SARS-CoV2 infection is known to occur through close contact, in particular through respiratory droplets in the air. While this particular means of transmission obviously does not apply to postmortem procedures, it is postulated that transmission may also occur via the contamination of inanimate surfaces from the activated virus. However, the persistence of SARS-CoV-2 after the death of infected individuals, still remains unclear. Interestingly, a study conducted by Skok et al. on consecutive throat swabs (125 infected individuals) revealed positive results up to 128 h after death.
Centers for Disease Control and Preventions recommend collecting nasopharyngeal swabs as a standard for the diagnosis of the active SARS-CoV-2 infection, also before an autopsy is performed.
In fact, according to scientific studies, swabs of the oropharynx (generally carried out on the corpse within 2 h after death) is also advisable in order to determine the presence of a SARS-CoV-2 infection,, the main obligation being to safeguard the health of forensic pathology staff (i.e., pathologists, technicians, and biologists).
In this article, we report the clinical records of nasopharyngeal swabs carried out on all deceased subjects brought to the Genoa District Mortuary. In fact, from the date of the national lockdown (March 9), all the corpses brought to the morgue from the Genoa district and province underwent nasopharyngeal swabs to ascertain the presence of SARS-CoV-2: We have analyzed not only epidemiological data but also the time intervals between death and diagnostic testing, and the presence of comorbidity and symptoms.
Our protocol consisted of performing a nasopharyngeal swab in the upper airways on the corpse's arrival at the Genoa District Mortuary of the University of Genoa, allowing us to identify the presence of the SARS-Cov-2 virus in the corpses to ensure a safe environment in which to perform autopsies before undergoing routine postmortem tests.
| Materials and Methods|| |
We performed nasopharyngeal swabs on all corpses brought to the morgue before being moved into the cold stores. The testing of the presence of SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) required: 1 synthetic fiber swab with plastic shafts, 1 sterile tube (e.g., BD Vacutainer® 5 mL volume) containing 2–3 mL of viral transport medium or sterile saline and 1 transparent plastic bag with an adhesive closure., The sterile tubes and the transparent plastic bag were marked up with the corpse's identification information, together with the type of sample, the date of collection, and a barcode for the lab's own records. To carry out the swab, healthcare professionals used the recommended personal protective equipment.
The presence of SARS-CoV 2 RNA in the nasopharyngeal swab was investigated using Allplex™ 2019 n-CoV, a reverse-transcriptase multiplex-quantitative real-time PCR (Seegene Inc., Seule, Korea). Three target genes of SARS-CoV-2 were detected: The RdRP, N and E gene. The isolation of RNA was performed by an automated extraction on an automated Nimbus IVD platform (Hamilton, USA), using the STARMag Universal Cartridge Kit (Seegene). Real-time PCR was performed by a CFX96 Instrument (Bio-Rad Laboratories). The results were automatically analyzed using Seegene software (2019-nCoV Viewer for Real-Time Instrument V3).
Following the analysis of the deceased's circumstantial data and after an accurate external examination, a thanato-chronological examination was conducted to ascertain the time which had passed between the subject's passing and the carrying-out of the postmortem swab.
First, the deceased's medical history was inspected to assess any preexisting pathological conditions or symptoms relating to SARS-CoV-2 and known contact within the family.
In the case of a positive postmortem swab, the Local Health Authorities were informed, whereas in the case of a negative result, the corpse underwent its routine autoptic checks of a health or judicial nature. Instead, in the absence of Airborne Infection Isolation Rooms (AIIRs) the autopsies of corpses infected with SARS-CoV-2 were not carried out in our territory.
As mentioned above, the samples herein described were taken from corpses that had been brought to the Genoa District Mortuary from March 9 (the start date of the national lockdown) to July 31, 2020 (the end of the first health emergency phase).
| Results|| |
One hundred and eighty postmortem nasopharyngeal swabs were taken to ascertain the presence of SARS-CoV-2 in subjects brought to the Genoa District Mortuary. The average age of the samples taken was 66 years old (minimum 1 - maximum 98 years) with a median of 69.5 years. It was apparent from the results that there was a clear prevalence of men (69%, 124 subjects) compared to women (31%, 56 subjects).
Thirteen of the corpses (7.2%) resulted positive for the presence of the virus in the upper airways, and among these, 7 were men (54%) and 6 were women (46%), with an average age of 73.5 years old and a median age of 78 (age range of 19–95 years old).
Two cases were found in March (15.4%), seven (53.8%) in April (in line with the peak spread of the virus in Italy) followed by three cases found in May (23.1%) and finally, just one case found at the beginning of June (7.7%) [Table 1].
|Table 1: Time interval between the discovery of the corpse and the execution of the nasopharyngeal swab|
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Six corpses (46%) were discovered in their own homes, five (38%) came from nursing homes for the elderly, one discovered on the sea-bed of the Liguria sea (8%), and one other (case no. 1) had been brought to the morgue by order of the Judicial Authorities following a hypothesis of medical malpractice (8%).
Among the 167 corpses that proved negative for the virus, the average age was 65.5 years (minimum 1 - maximum 98), with a median age of 66 years old, among which 50 (30%) were female while 117 (70%) were male. Half of these (86 subjects) had been found in their own homes (52%), 40 (24%) in public areas (i.e., in the street, on the beach, in public buildings, etc.,), 32 had been brought into the mortuary from various local hospitals (19%), and finally, 9 (5%) came from nursing homes for the elderly.
Postmortem intervals between death and swabs taken
From our complete clinical records, the postmortem swabs were conducted between a minimum of 2 h from the subject's death to a maximum of about 15–20 days.
In fact, nasopharyngeal swabs, performed to ascertain the presence of SARS-CoV-2, were also carried out on seven corpses in conditions of colliquative putrefaction, covered with dipterous larva, with difficulties in measuring the postmortem interval (PMI) and limited circumstantial data of up to a maximum of 2–3 weeks.
In the 13 COVID-19-positive cases, the time interval between death and the carrying-out of the swab was 8–165 h [Table 1]. However, the time interval between the arrival of the corpse in the morgue and the moment of carrying out the swab test was between a minimum of 65 min and a maximum of 22 h and 30 min.
In 11 of the cases (85%), in line with data coming from transformative phenomena examinations and from the analysis of circumstantial data, we observed that the nasopharyngeal swab was performed within 72 h from the subject's death (3 days).
In two of the cases, a positive postmortem nasopharyngeal swab was carried out at a distance of 125 h from death (case no. 1) and 165 h from death (case no. 8).
Anamnestic and postmortem data in SARS-CoV-2 negative and positive cases
Amongst the corpses resulted negative to COVID-19 (167 cases) following a postmortem swab, respiratory symptoms obtained from clinical records were apparent in only 7 subjects (4.2%): The autopsies, however, showed no signs of pneumonia. Instead, in two cases with negative history for respiratory symptoms and postmortem nasopharyngeal swab negative for SARS-CoV-2, autopsy and histological examination showed areas of bacterial pneumonia. In no case, postmortem investigations showed interstitial pneumonia.
In regard to the corpses that tested positive [Table 2], we had the clinical records in 10 of the 13 cases (77%): In one case (case no. 13), the anamnestic data showed no previous pathologies However, in 3 cases, the clinical records were not known (23%).
From clinical records, the following resulted: At least two chronic pathologies in 9 cases (of which, at least one, was of a cardio-vascular nature): Specifically, cases no. 7, 8, 11, and 12 presented two pathologies observed from clinical records, cases no. 2, 4 and 9 presented 3 pathologies and in cases no. 3 and no. 6, a number of pathologies ≥4. In regards to those pathologies that were more common, arterial hypertension resulted in 8 subjects (80%), diabetes mellitus type II in 3 subjects (30%), Alzheimer's in 3 subjects (30%), chronic obstructive pulmonary disease and/or pulmonary emphysema in 2 subjects (20%), dyslipidemia, obesity and metabolic syndrome in 2 subjects (20%) and the effects of brain strokes in 2 subjects (20%). Atrial fibrillation emerged only in case no. 9 and heart ischemia in case no. 11.
The main COVID-19-related respiratory symptoms (i.e., a cough, fever, and difficulty in breathing), obtained from clinical records, were apparent in 6 subjects out of 13 (46%): The diagnosis in these cases, where the subjects had already been suspected as SARS-CoV-2-positive when alive, was only confirmed by way of a postmortem swab. In case no. 13, the relatives of the subjects reported no respiratory issues, while in the remaining 6 cases, no information could be obtained in this regard.
| Discussion|| |
In addition to the immense problems and pressures experienced by clinics and public health services, the pandemic COVID-19 has also had huge repercussions on the Forensic Pathology sector. To help in abating this crisis, numerous national and international advisory notices were published,,,,, as to how the corpses infected with COVID-19 should be handled and how to carry out autopsies during the pandemic period.
They stated that pathologists must use disposable headgear, a double pair of disposable gloves, cut-resistant protective gloves, respiratory filter face coverings, namely FFP2 or FFP3 (the latter recommended in the procedures that produce an aerosol effect), face protection (goggles or protective visors), disposable long-sleeved gowns or waterproof suits and disposable overshoes.
In addition, the autopsies of corpses, infected with SARS-CoV-2 (that is, Category Hazard Group 3), must be carried out in AIIRs, with negative pressure and a minimum of 6–12 air renewals per hour with the expulsion of the air directly outside or through a high efficiency particulate air filter. In the absence of AIIRs, autoptic investigations must be conducted in rooms at negative pressure without air re-circulation into adjacent rooms. Finally, autopsies should be restricted to only well-motivated cases and performed in accordance with strict bio-safety rules.
However, the need to implement these measures often encounters severe problems related to the fact that there is a lack of autoptic rooms AIIRs in many of the Legal Medicine Institutes (not only in Italy, but also in other countries); the resulting restrictions means that the number of autopsies is considerably reduced and as a result, the pathological research, aimed at better understanding the physio-pathological mechanisms of SARS-CoV-2,, has been greatly held back. On the other hand, many cases of COVID-19 are, in fact, asymptomatic, and therefore, circumstantial data are somewhat limited. In some cases, nothing is even known about the corpse. Moreover, many people are not aware of having become infected with the virus and can die of other causes. For this reason, all autopsies carried out have the potential risk of being SARS-CoV-2 positive, thus causing a high risk of contamination for technicians.
As a consequence, it is of the utmost importance to ascertain, by way of an effective screening process, whether the corpse is positive or negative for COVID-19 before the autopsy. Only in this way, if the corpse is free from the SARS-CoV-2 infection, can the autopsy be performed in a standard autopsy room (non-AIIRs). This simplifies the handling of autoptic cases, especially within Legal Medicine centers which are more than often not provided with safe autopsy rooms. Therefore, the implementation of a nasopharyngeal swab before the autopsy could be a useful tool in order to understand whether the corpse is infected or not.
In our particular study of case reports, we have reported a total of 180 corpses that underwent a nasopharyngeal swab with 13 (7.2%) being found COVID-19 positive. In spring 2020, in fact, Sars-CoV-2 has hit very hard the Italian population, much more than other European countries.
For example, a report by the Institute of Legal Medicine of the Federal State of Hamburg showed that on 1231 cadavers arrived at the morgue and subjected to postmortem nasopharyngeal swab, only 29 (2.4%) were positive for the virus.
In line with the literature, the average age of the positive cases (73.5 years with a median of 78 years) is higher than the negative cases (65.5 years), leading to the conclusion that patients who are elderly are more susceptible to the infection. In fact, the SARS-CoV-2 virus has caused serious illnesses and death mainly in the older category of people, in particular, those who have had preexisting conditions, such as diabetes and heart problems, probably due to a weakened immune-system which means that the progression of the viral infection is quicker. In no cases (diagnosed via postmortem swab) the diagnosis of SARS-CoV-2 infection was made while the person was alive. Six cases presented symptoms (cough, dyspnea and fever), but none of these patients had undergone a nasopharyngeal swab or a serological test before their deaths. This was because, in the initial stages of the pandemic, the Health Service found itself totally unprepared and as a consequence, faced numerous difficulties in handling the suspected cases, as well as not being able to meet the demand of the large numbers of swabs and serological tests needed.
In 9 out of the 13 cases, the deceased presented important comorbidity (mainly cardiovascular, neurodegenerative, and pulmonary symptoms). In fact, patients with COVID-19, who also showed signs of comorbidity, like hypertension or diabetes type II, had the highest probability of developing a serious prognosis.
On the basis of our clinical records, 6 cases presented ante-mortem respiratory symptoms (probably correlated with the SARS-CoV-2 infection), but they had not undergone diagnostic tests (neither swabs or serological tests) before dying, whereas, in the other 6 cases, the clinical records and medical history showed no respiratory symptoms or infections in the days leading up to their deaths. Only in one case were the findings of COVID-19 coincidental and this concerned a young man of 19 years old who had drowned in high coastal seas in Liguria. The day after the accidental drowning, his body was found on the sea-bed at about 100 m from the shore. The external examination showed signs of skin maceration from having remained stagnant for some time in the sea, an abundance of froth coming from the mouth and liquid seeping from the nostrils. From circumstantial data, the man had not been affected by any previous pathologies and had been completely asymptomatic and therefore, totally unaware of having been COVID-19 positive. However, after his death, molecular tests with COVID-19 genetic (RNA) amplification showed a positive result for SARS-Cov-2. After ascertaining the infection, the autopsy was not immediately performed for safety reasons, but it was apparent that, from circumstantial data and the site where the young man's body was found (under the sea), drowning attributed to his death.
One of the main focus points of this study was also to investigate the forensic aspect and to analyze the period between the presumed death and the carrying out of nasopharyngeal swabs.
It is a fact that the first articles published on COVID-19 autopsies are often limited to particular organs and tissues, or have used minimally invasive techniques. Moreover, whilst several scientific articles describe complete autopsies in the case of SARS-CoV-2,,, very few papers contain details on any microbiological studies.
In forensic reports, the diagnoses are generally made ante-mortem and are based on routine samples taken during the clinical practice and used for clinical diagnoses; in addition, in many cases, it is not specified when exactly the samples were taken.
For example, in a study conducted by Plenzig et al., they described SARS-CoV-2 isolation in tissue samples and swabs of four deceased patients already tested positive for the virus before death. The aim of the study was to assess the persistence of the virus with cell culture and RT- quantitative PCR from tissue samples and swabs of individuals whose positivity was already known and not to determine the reliability of postmortem nasopharyngeal swab of bodies in different putrefactive stages and unknown positivity or negativity, as in our study.
The authors came to the interesting result that, despite beginning signs of putrefaction (marbling of the vessels, bloating of the body, mold infestation in the perioral and neck regions) slowed down by the corpse remaining in the cooling chamber at 4°C, a body can remain infective also 17 days after death.
Moreover, there are very few reports that describe a microbiological postmortem diagnosis (PCR, being the technique used).,, In most of these case studies, the sample analyzed was a pharyngeal swab, whereas, in other cases, the Authors used samples taken from the lower airways, such as a tracheo-bronchial swab or pulmonary parenchyma.
In fact, as of today, we still do not know with certainty if there is the possibility of obtaining a false negative result with postmortem swabs. Neither do we know if there is a time limit to when nasopharyngeal swabs can be considered completely reliable. In addition, literature,, cannot affirm, with any level of precision, if a PMI with too-long a time-lapse could, in fact, alter the results of such a test.
However, in line with our current knowledge, this study is one of the very first studies that has analyzed the results from nasopharyngeal swabs that have been performed before the necroscopy examination (as a screening method) in relationship with PMI.
By obtaining information from complete clinical records, we observed that nasopharyngeal swabs were performed between 2 h and 2–3 weeks after death. More specifically, the time ranged from 8 h to 165 h in the case of a positive result for SARS-CoV-2. Furthermore, we observed that the swab resulted positive also after 165 h after death.
This case concerned an elderly man of 89 years old, affected by arterial hypertension and vascular dementia, who had been resident in a nursing home. In this case, the corpse was kept in a refrigerated chamber within the nursing home but then, due to a lack of space, transferred to the morgue 6 days after his passing, with a swab being performed 7 days after his death. The external examination only revealed a green discoloration that had spread all over his abdomen; once, it was established that the corpse was infected with SARS-Cov-2, the nursing home was immediately informed with the consequent carrying-out of swabs on all the nursing home patients and staff.
These results determine a longer time-frame range (that of the time that lapses between the assumed time of death and the performing of the nasopharyngeal swab) compared to that described in the literature.
For example, Heinrich et al. showed the lacking of a time-dependent effect on SARS-CoV-2 viral loads in a series of 9 sequential pharyngeal swab samples (11 corpses). They also determined that SARS-CoV-2 RNA can persist at constantly high titers up to 35 h after death. On the other hand, according to Skok et al., in a case study of 125 postmortem swabs, viral RNA was found up to 128 h from the time of death. While according to Edler et al. postmortem evidence of COVID-19 using a naso- or oropharyngeal swabs was found up to a maximum PMI of 12 days.
However, our preliminary data indicate that nasopharyngeal swabs can be considered reliable also up to 7 days (about 165 h) from the time of death, even in corpses that are in the early putrefaction phase. In our particular clinical record case study, 7 cases presented an emphysema-colliquative putrefied state with negative swab results. In these cases, no report of any infection or flu-like symptoms prior to death had been found, and therefore, it is quite impossible to assess such cases.
We know neither if, or when, putrefaction can change the viral genome and as a consequence, alter the results of the test. In addition, the environmental conditions and temperature could also interfere with such results. In our study, we performed naso-pharyngeal swabs on the corpses brought to the morgue from the city's territory, found in the houses, in structures for the elderly or on the street, at different temperatures and stages of decomposition.
Moreover, performing the nasopharyngeal swabs before the postmortem examination has an important purpose in terms of bio-safety in the Forensic Pathology Unit. The screening enabled the staff to trace the positive COVID-19 cases, and in such cases, for safety reasons, the autopsy was then not carried out, whereas for the corpses that proved negative for the virus, the autopsy could be performed in a standard autopsy room. In our particular Legal Medicine Institute, we consider the postmortem nasopharyngeal swabs to have had an essential role in the screening of the corpses. In fact, there were no positive cases of SARS-CoV-2 amongst the forensic staff who had been involved in the handling of corpses and the performing of autopsies, even though they had been actively involved in examining both the nostrils and oral cavities of the corpses during external examinations.
Based on the fact that our studies were admittedly somewhat limited in that there was a reduced number of COVID-19 positive cases, it will be necessary to carry out further studies in the future aimed at investigating the PMI and the corpse's putrefaction state to confirm and implement our results on the true reliability of postmortem swab testing.
Another limitation to our study is the lack of autoptic and histological findings in cases of positive SARS-CoV-2 readings, which would have been useful to complete the postmortem analysis and evaluate the macroscopic and microscopic aspects. In addition, unfortunately, we are, as yet, unable to formulate what could be the possibility of a false negative connected to postdeath phenomena (above all, in a decomposed corpse). Nevertheless, the autopsies and histological results did show signs of phlogosis or interstitial pneumonia in only two cases up to 167 (1.2%) where the nasopharyngeal swab gave a negative reading following an autopsy.
| Conclusion|| |
According to our results, a nasopharyngeal swab is a valid and useful screening tool to use before conducting an autopsy. This test enables us to evaluate a positive or negative COVID-19 reading and therefore, to handle all the postmortem tests based on the results, which are particularly important in Legal Medicine Centers that do not have a safe AIIR room available. In addition, the swab test has proven to be reliable in terms of not only safeguarding the bio-safety of forensic pathologists but also for the protection of the community at large.
Moreover, nasopharyngeal swabs performed on corpses have proved to be useful both clinically and epidemiologically for the intercepting and monitoring also of subjects who are asymptomatic or had shown only slight respiratory symptoms when alive, but without a diagnosis of the SARS-CoV-2 virus; as described in literature, PCR-based monitoring of the bodies transferred to the distrectual morgue can allow the detection of positive cases, which would remain otherwise unacknowledged.
From a forensic point of view, postmortem swabs also provide the Judicial authorities with invaluable help in evaluating cases of hypothetical medical malpractice (as long as the corpse is transferred to a localized AIIR room), as well as enabling the important investigation of nursing and care homes for the elderly. In fact, such homes, at the peak of the pandemic, experienced a marked spread of the virus and an increase in the mortality of those patients, many of which, due to the lack of effective monitoring using nasopharyngeal swabs, had not been diagnosed with the COVID-19 infection when alive.
Furthermore, according to our results, postmortem nasopharyngeal swabs can be considered reliable in giving accurate results up to almost 7 days (165 h) from the time of death.
Finally, it is true that whilst our study presents some limitations, due to its preliminary nature, we are convinced that further scientific research and more in-depth study will confirm our data and prove to be most useful for future reference.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]