EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Due to the emergency nature of the pandemic, many anti-COVID-19 vaccines were rushed ahead into testing through emergency-use authorization, leading to questionable accuracy of data with regard to the short- and long-term efficacy and safety and time span of immune protection of these vaccines. Several scientifically founded concerns, along with many questions, have been raised with no clear answers as to whether these vaccines will have the same efficacy across different populations, among distinct regions, and for any emerging new variants. These concerns are coupled with the variable levels of preventive, therapeutic, and protective measures, such as the recent imposition of the sanitary pass in some but not all countries. Given the lack of a universal policy in its application, the recently reported short-lived vaccine-induced protective immunity of a few months duration, the consequent growing number of newly diagnosed COVID-19 cases in the most vaccinated countries, the equal spread of the Delta variant among vaccinated and unvaccinated individuals, the significantly lesser virulence of the Delta variant as reflected by the lower rate of hospitalization and death, and the recent admission by the US Centers of Disease Control and Prevention of the poor specificity of the COVID-19 polymerase chain reaction diagnostic panel in detection of SARS-CoV-2, this scientifically unfounded sanitary pass, based on recently emerging data from the most vaccinated countries, not only seems obsolete but can also be regarded as a tool of indirect coercion, forcing vaccination on those who may be vaccine prudent, therefore jeopardizing the essence of an individual’s freedom of choice that is guaranteed by all international laws. In the presence of these concerns and many unanswered questions, it becomes evident that the informed consent rather than the sanitary pass should be enforced and should become not only a necessity but also mandatory.

Key words : Adverse effects, COVID-19 vaccines, Delta variant, Informed consent

Many of the anti-COVID-19 vaccines were quickly rushed into testing, bypassing animal experimenta-tions, and have been adopted for use before complete regulatory acceptance. This is happening through emergency-use authorization, which helps accelerate vaccine deployment due to the emergency nature of the pandemic. This process can lead to less than optimal collection of the usually broad data on safety, immunogenicity, effectiveness, and time span of protection, as well as to a short-term follow-up of only a few months.^1,2 The vital need for COVID-19 vaccines must be taken into consideration while also guaranteeing the respect of recognized clinical safety testing protocols during vaccine development and roll out, both before and after deployment. Only this will allow for the public trust of vaccine safety.³ None of the original studies from Pfizer and Moderna^1,2 were designed to look at degrees of prevention of hospitalization, severe disease, or death or on prevention of infection and transmission potential. Thus, there are questions on whether the vaccine policies should remain as they are with current COVID-19 vaccines and whether we should mandate the sanitary pass in public and private domains despite the many raised valid concerns regarding the short-term and long-term safety of these vaccines.⁴ This review was designed to conduct a critical appraisal of the scientific validity behind the imposition of the sanitary pass in some but not all countries with variable policies in its application. Recently emerging postvaccination data within the context of these concerns were reviewed in some of the minimally and maximally vaccinated countries to help understand the justification and true need for its application.

Concerns and Unanswered Questions

Today, many provocative questions have been raised regarding the imposition of the sanitary pass with no clear answers regarding these genuine concerns.⁴ These concerns are described in each of the subsections sections shown below.

1: Short duration of efficacy and safety follow-up
There have been important limitations in both the Pfizer-BioNTech and Moderna original trials, recognized by the investigators themselves, which confirm the experimental nature of these vaccines.^1,2 Most importantly, there was great concern regarding the pending loss on the long-term follow-up of control patients in both trials who were offered vaccines on a compassionate basis before the trials were completed. As recently stated in an editorial in the British Medical Journal, “It is already concerning that full approval by the Food and Drug Administration (FDA) is being based on 6 months’ worth of data despite the clinical trials designed for two years.”⁵

2: Lack of an identified correlate of protection and time span of immunity
This concern, confirmed among other investigators^2,6,7 and reflected in the Moderna trial, will be discussed below (Subsections 6, 7, 10, and 12).

3: Newly reported morbidity and mortality cases shortly after vaccination
Many deaths had occurred between 5 and 30 days after vaccination, as shown by the American (vaccine adverse events reporting system [VAERS]) and European (EudraVigilance) pharmacovigilance reporting systems.^8-10 Of importance, the 2 organiza-tions found a considerable increase in the number of deaths in 2020 and 2021, the year of anti-COVID-19 vaccination, compared with the numbers shown in previous years (Figure 1). Moreover, the use of voluntary reporting of adverse events through a 30-year-old electronic platforms like VAERS to monitor long-term adverse events and assess vaccine safety, as currently practiced, is of questionable accuracy and would certainly underestimate real data. Adverse events from drugs and vaccines are common but underreported. For example, although 25% of ambulatory patients experience adverse drug events, less than 0.3% of all adverse drug events and only 1% to 13% of serious events are reported to the FDA.¹¹

4: Uncertainty regarding the risk of enhanced disease on exposure to the virus in the long-term
A number of reports^4,12-15 have clearly highlighted this risk as a key limitation point in the Moderna vaccine phase 3 interim trial.² Antibody-dependent enhancement is a well-known phenomenon by which subneutralizing antibodies promote infection and viral replication by enhancing the entry of the virus into host cells. Laboratory cultures have shown that antibody-dependent enhancement was responsible for increasing the infectivity of severe acute respiratory syndrome (SARS) coronavirus¹²; this immune enhancement led to inflammatory processes and tissue damage in organs of animal models that resembled those shown in organs of individuals infected with SARS virus who died from the disease.

5: Continuous possibility of viral shedding and transmission despite vaccination
The United States, as reported by the US Centers for Disease Control and Prevention (CDC),¹⁶ and other countries such as the United Kingdom and Israel had closed their borders even to fully vaccinated travelers following the eruption of the Delta variant.^17-21 With the possible decline in short-lived vaccine-induced immunity, authorities in different countries enforced protective measures such as distancing and indoor or outdoor masking even in vaccinated individuals.

6: Recently reported reduced efficacy of vaccines with the emergence of new variants
New variants (Alpha B1.1.7, Beta B1.351) and efficacy against the new dominant Delta B1.617.2 variant from 95% to 65%¹⁸ have been observed in countries that undertook mass vaccination of their population like Israel. This resulted in a relatively sharper increase in the daily reported new cases, reaching more than 700/million population among all age groups,¹⁹ and in the daily reported COVID-19-related deaths per million population, amounting to 3 times those reported in a neighboring country like Lebanon (Figure 2, A and B).¹⁹ Lebanon, which had significantly lower vaccination rates (Figure 3), has a precarious socio-economic situation and a degrading health care system. In addition, both Israel and Lebanon have similar numbers of hospital beds per capita (2.9/1000 capita), a similar Mediterranean diet, and a similar median age (~30 years) and life expectancy (79 vs 83 years), with significantly higher population density in Lebanon (594 vs 402 people/km2) and lower annual GDP per capita ($US 13 300 vs $US 33 130),¹⁹ which are all important factors that impact outcomes. The rate of hospitalizations and deaths associated with the Delta variant seem to be so far significantly lower compared with the previous wave caused by the wild-type, suggesting high infectivity rate but lower virulence.¹⁹ Despite a lower fatality rate, as reported by the Public Health England (PHE)²⁰ by vaccination status among all sequenced and genotyped Delta cases in England from February 1, 2021 to July 19, 2021, the derived probability of death (deaths per case) appears to be higher in those who are vaccinated (0.3%) versus those not vaccinated (0.1%) as shown in Table 1. Moreover, 40% of the 204 266 screened cases received at least 1 dose of the vaccine; most importantly, death occurred predominantly among those >50 years of age (90%), with vaccinated individuals representing nearly two-thirds of the cases (279/410, 68%) compared with unvaccinated individuals (131/410, 32%). In their latest COVID-19 update, PHE experts also warned that people who have been inoculated may be able to transmit the Delta strain as easily as those who have not been inoculated. Hundreds of fully vaccinated people in England have been hospitalized with the highly contagious Delta coronavirus variant. From July 19 to August 2, 512 (35%) of the 1467 people hospitalized with the Delta variant had received 2 doses.²¹ These findings imply that not only are vaccinated individuals from all ages not protected against the Delta variant, and hence can transmit the disease to others, but also that they are even more vulnerable, especially those older than 50 years of age, to develop severe disease and have equal or higher risk of dying compared with their unvaccinated counterparts. Moreover, according to recent data from the Israeli Health Ministry, patients with COVID-19 who have recovered from the virus were far less likely to become infected during the latest wave of the pandemic than people who were vaccinated against COVID-19. More than 7700 new cases of the virus have been detected during the most recent wave starting in May 2021, but just 72 of the confirmed cases were reported in people who have been infected previously, that is, less than 1% of the new cases. Roughly 40% of new cases, or more than 3000 patients, involved people who had been infected despite being vaccinated. These data suggest that natural immunity seems to provide a more robust and protective immunity against the Delta variant than the Pfizer mRNA vaccine.²² These recent findings from 2 predominantly vaccinated countries put into question the true efficacy and hence the utility of the AstraZeneca and Pfizer vaccines in combating the new Delta variant.

7: Efficacy and safety of these vaccines in the previously excluded subgroups
Subgroups excluded from vaccine trials have included children, pregnant women, frail elderly patients, and high-risk and immunocompromised individuals, such as cancer patients and solid-organ transplant recipients. Recent data from Israel have revealed that COVID-19 vaccine protection seems to decline after 6 months. In 397 fully vaccinated patients hospitalized in Israel by April 26, 2021 who had polymerase chain reaction (PCR)-proven COVID-19 after their second vaccine dose, 234 (59%) had severe COVID-19 and 90 (38%) of those who were hospitalized had died.^23,24 In fact, a recent Israeli study reported on 152 breakthrough fully vaccinated patients,²⁴ in which most were frail, elderly patients (median age of 75 years) and 40% were immunocompromised (such as cancer patients or solid-organ transplant recipients with multiple comorbidities). More specifically, the patient outcomes were comparable to those shown for nonvaccinated hospitalized COVID-19 patients. As suggested by the author, these findings may be because of either lower vaccine effectiveness in patients with comorbidities or higher risk of comorbidity exacerbation after breakthrough infection or because of both. Since June 21, 2021, the number of COVID-19-related hospitalizations (Figure 4A) has been sharply increasing in Israel, with nearly half in intensive care units (Figure 4B).¹⁹These data^18,19,22-24 seem to be in agreement with those emerging from the United Kingdom^20,21 regarding the significant lack of immunological protection against the Delta variant provided by all COVID-19 vaccines and the consequent increased risks of transmission, severe disease development, and death mainly in the frail population, which is supposed to be protected by vaccination, similar to risks observed in unvaccinated individuals. This is probably what prompted Pfizer to propose a third booster for frail elderly immunocompromised individuals.²³

Data on COVID-19 vaccination in terms of safety, immunogenicity, and clinical efficacy in children are also currently lacking. In fact, at the end of the second week of June 2021, more than 1200 cases of myocarditis or pericarditis have been reported to the US VAERS. The findings were notably higher in males and mainly occurred during the week after the second vaccine dose. Teenagers and people in their early 20s accounted for more than half of cases despite representing a fraction of people who have received the mRNA vaccines. This prompted the FDA to add heart inflammation warnings to Pfizer and Moderna vaccines,²⁵ although with no direct comment.

With the average life expectancy of 80 to 84 years in most industrialized countries. the average age of death from COVID-19 is 85 years. The mean case fatality rate (~2%) varies according to country and ranges from 0.000% in children to 0.02% in people <50 years old, increasing with the number of associated comorbidities and age and reaching 13% to 20% in those >80 years of age.¹⁹ Most importantly, the mean estimated infection fatality rate is ~0.13% (number of confirmed death divided by the estimated total number of infected people). Should we take the risk of serious side effects or even the death of a child or even young person to save the life of someone over 85 with less than 1-year life expectancy who seems to benefit the least from vaccination according to these new emerging data?^19,20,24 This is an important ethical and philosophical question specifically in the absence of long-term efficacy and safety follow-up and with the presence of potential risk of a genome alteration that may be associated with the vaccines that was not addressed in any of the main trials.

Many important and relevant questions remain with no clear and definite answers on the design and conduct of the COVID-19 vaccines trials. These include why children, immunocompromised patients, and pregnant women have been excluded from most trials, whether long-term safety was adequately evaluated, and whether the definition of an accurate correlate of protective immunity, the lifespan of this immunity, and the risk of genome alteration are being adequately addressed.

8: Unknown risk of immunogenicity
These risks may cause any of the following: autoimmune diseases, cancer, and chronic inflammation. An early onset of vascular thrombosis was observed shortly after vaccination with the adenovirus DNA vaccines. Most of these thrombotic adverse events were associated with an immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4, which clinically mimics autoimmune heparin-induced thrombocytopenia.^26-30 Other cases of similar serious thrombosis were reported after use of the Johnson & Johnson anti-COVID-19 vaccine in the United States. The roll out of the AstraZeneca vaccine was thus paused in many European countries, with final annulation of the contract between the European Union and AstraZeneca starting in June 2021. Moreover, evidence has been increasing on a link between the mRNA vaccines and increased risk of heart inflammation affecting either the heart muscle (myocarditis) or the tissue surrounding the heart (pericarditis). As reported by the CDC and FDA, this has led to hospital admissions in more than 20% of affected cases and seems to occur mainly in young male patients within 1 week after the second dose of the mRNA vaccines.²⁵ These severe cardiovascular adverse events with unknown long-term consequences may be linked to the established cytopathogenic effect of the spike protein as shown recently.^31,32

9: Risk of genome alteration
There are risks that may occur in the presence of the reverse transcriptase enzyme. A potential risk for genetic modification of the host (risk of DNA being reverse-transcribed from the vaccine mRNA and being incorporated into the host genome) could not be completely excluded as trials specifically excluded genetic analyses.^33,34 Recently, SARS-CoV-2 RNA was shown to be reverse-transcribed and integrated into the genome of infected cells, with transcription of the integrated DNA copies perhaps responsible for positive PCR tests long after the initial infection was cleared.³³

10: Systematic vaccination of naturally immunized individuals
In naturally immunized individuals, the use of any of the currently available COVID-19 vaccines is not supported by any solid scientific evidence; this was highlighted in the Moderna trial.² A more recent study even stated that vaccination probably is not beneficial.³⁵ The progression of the pandemic in the 2 neighboring countries of Lebanon (Figure 5A) and Israel (Figure 5B) revealed similar curves, with a peak in the cases around mid-January 2021 in both countries. By that time, 25% of the Israeli population were fully vaccinated with none in Lebanon. In the beginning of March 2021, nearly 60% of Israel population had received at least 1 vaccine dose in contrast to only 1% in Lebanon. With the near ending of the cases by the end of June 2021 in both countries, Israel had already fully vaccinated 60% of its population versus 5.4% in Lebanon (Figure 3 and Figure 5, A and B).¹⁹ Of note, both countries had one of the toughest lockdowns, which is well known to slow down the entry to hospitals but not the number of cases. Most importantly, many of the protective measures, including the lockdown, were not followed in many regions of Lebanon, as was the case in many countries around the world. These data together suggested that, in the absence of meaningful vaccination of the Lebanese population during the pandemic combined with poor compliance with protective measures, a poor socio-economic situation, and a demolished health care system, herd immunity more likely may have been the main factor responsible for the ending of the third wave and not the vaccination as claimed by the Israeli sources.

With more than 563 000 PCR-positive COVID-19 cases in Lebanon reported as of August 3, 2021 by the Lebanese Ministry of Health, it is estimated today that nearly 3.4 million (563 000 × 6 = 3 384 000) Lebanese had been infected with the SARS-CoV-2 and therefore acquired the herd immunity, amounting for 50% to 60% of the Lebanese population. It is well known that 70% to 80% of people who get infected by SARS-CoV-2 remain asymptomatic; currently, there is no clear correlate of immunity,² which appears to be cellular and humoral lasting for at least 11 months after the infection.^6,7 It is well established that simple serological tests for SARS-CoV-2 antibodies do not reflect the richness and durability of immune memory for this virus.⁶ In contrast, the 2 arms of humoral immune memory (long-living bone marrow plasma cells and memory B cells) are most likely responsible for long-lasting robust immunity⁶ against the whole virus and not a selective one as provided by a short-lived vaccine and that is against one specific component of the virus, the spike protein. Moreover, as recently observed in massively vaccinated countries, vaccination today of the population using a vaccine directed against the wild-type SARS-CoV-2, which has been replaced by new variants and a likely change in the conformational structure of the spike protein, raises serious questions regarding the efficacy of these vaccines against these variants.^19-21 These data again put into question the utility of the current COVID-19 vaccines as an efficacious therapeutic tool against the new variants.

11: Fear of a potential hidden coercion
These fears may have been formed by the imposition by either public or private sectors on citizens to receive the vaccine despite divided opinions, including among different scientific experts, and despite no clear and convincing answers to the many above-mentioned relevant concerns. Mandating the sanitary pass as practiced in some countries and as planned to be implemented by some governments is an indirect form of coercion to enforce vaccination despite newly emerging scientific data on the considerable breakthrough cases in already fully vaccinated people in countries with massive vaccination policies of their population. This was recently reported in a study from Israel published in the prestigious journal Nature³⁶ and by the PHE in the United Kingdom.^20,21 The recently reported declines in the short-lived protective immunity duration of a few months,^21-24 the consequent reduction in vaccine efficacy with increased rates of breakthrough,37,38 the risk of transmission among all ages,¹⁹ and the increased risk for disease severity and death in frail immunocompromised vaccinated individuals^20,21,23,24 render the sanitary pass obsolete, since those vaccinated are becoming potential carriers and transmitters of the virus and remain at risk to develop the disease. As recently highlighted by Prof Luc Montagnier (Nobel Prize Laureate for his discovery of the HIV): “Pfizer, Moderna, and Astra Zeneca vaccines do not prevent person-to-person transmission of the virus, and the vaccinated are just as transmissive as the unvaccinated and the hope of a ‘collective immunity’ by an increase in the number of vaccinated is totally futile.”³⁹ He made an appeal to all leaders to reconsider the policy of massive vaccination for the prevention of the spread of the COVID-19. Therefore, in the absence of solid scientific proof to support such policies and with the current limited evidence discussed above, such an approach is considered to be a major breach to the code of medico-legal ethics and in complete contradiction to many of the international laws and declarations that protect individual freedom of choice to receive any form of therapy. This is well highlighted in the Nuremberg code, Helsinki declaration, Belmont report, the United Nation Chart for Human Rights, and the recent Resolution 2361 (adopted on January 28, 2021) from the Council of Europe in Articles 7.3.1 7.3.2: “Vaccination should NOT be compulsory” and “no one should be pressured political, social, or other, to be vaccinated, if he or she does not wish to do it personally.”⁴⁰

12: Risk of sanitary pass in solid-organ transplant patients
None of the recently rolled out vaccines has been tested in solid-organ transplant recipients. Similarly, safety, immunogenicity, and clinical efficacy data on COVID-19 vaccination for potential recipients and recipients of pediatric solid-organ transplant are currently lacking. In addition, immunocompromised hosts, such as solid-organ transplant recipients, may serve as a source for development of SARS-CoV-2 variants, as recently shown by an Israeli study. In that study, 40% of breakthrough cases in double vaccinated patients were immunocompromised, including cancer patients and solid-organ transplant recipients with multiple comorbidities.²⁴In the absence of any well-defined correlate of humoral or cellular protective immunity, assessments of immunogenicity of COVID-19 vaccines remain an important challenge in solid-organ transplant recipients irrespective of their age.⁶ Among solid-organ transplant recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies.⁴¹ In solid-organ transplant recipients, quantitative antibody titers directed against different components of SARS-CoV-2, such as spike protein S, nucleocapsid protein, and the receptor binding domain, are frequently below the median titer observed in immunocompetent patients. Moreover, only half of patients in different organ transplant settings have shown detectable antibody levels after both doses of the vaccine and relatively infrequent detectable levels after the first dose. Transplant-related variables, including age, renal function level, and nature of immunosuppression, were important predictors.^41-44

A recent report from a single Spanish kidney transplant center described 21 kidney transplant recipients (20 kidney transplant recipients and 1 simultaneous pancreas-kidney transplant recipient) who developed a PCR-proven COVID-19 after being fully vaccinated. Only 1 patient (5%) developed SARS-CoV-2 immunoglobulin G antibodies after vaccination (which were assessed >15 days after the second dose). All patients were diagnosed with COVID-19 through a nasopharyngeal swab after a mean time of 84.71 ± 27.43 days from the second vaccine dose. Two patients were infected with the Alpha variant and 3 with the Delta one. Half of the patients required hospital admission, and one-third required intensive care unit admission, with need for mechanical ventilation in 6 patients. Among the 21 patients, 1 (5%) died.⁴⁵

This information along with other information shown above reinforce the apparently less efficient immunization effect that COVID-19 vaccines provide in kidney transplant recipients and the need to maintain precautions against COVID-19 in this population (especially against the Delta variant), even after full vaccination. This was further confirmed by the recent resurgence of SARS-CoV-2 infection in an immunocompetent highly vaccinated health system workforce at the University of California San Diego Health. The workforce experienced a dramatic increase in SARS-CoV-2 infections,⁴⁶ which coincided with the rapid dominance of the B.1.617.² (Delta) variant that first emerged in mid-April and accounted for over 95% of isolates at this health center by the end of July. Consequently, vaccine effectiveness fell from 90% to 65.5% (95% CI, 48.9-76.9) in July 2021. According to the authors, this dramatic change in vaccine effectiveness from June to July could be due to both the emergence of the Delta variant and waning immunity over time, compounded by the end of masking requirements in California and the resulting greater risk of exposure in the community.

Interestingly, a team from Japan reported that the SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines through the complete escape from anti-N-terminal domain neutralizing antibodies, while increasing responsiveness to anti-N-terminal domain infectivity-enhancing antibodies.⁴⁷ They have elegantly demonstrated that, when 4 common mutations were introduced into the receptor binding domain of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity, mimicking the so-called antibody-dependent enhancement of immunity responsible for exaggerated disease. The Delta variant with 3 similar receptor binding domain mutations has already emerged according to the Global Initiative on Sharing All Influenza Data (GISAID) Database, suggesting a possible near acquisition of complete vaccine resistance, which should make it necessary to develop new vaccines that protect against the newly emerging variants. This raises a serious question regarding the ongoing scientifically unfounded governmental recommendation of a third booster. In fact, this important matter is triggering an ongoing debate regarding the validity and the safety and efficacy of the third booster among pharma companies, experts from the World Health Organization, the FDA, and other independent experts.^48,49

Serious concerns have been raised regarding the vaccine confidence and public health messaging on the value of getting vaccinated, particularly if boosters are only used for 1 type of vaccine. Philip Krause and Marion Gruber, two FDA researchers responsible for the case, stepped down in August, unofficially amid pressure from their line managers and the Biden administration in the United States to approve a vaccine booster. The 2 researchers published in the Lancet, along with 16 other colleagues, a vitriolic article against a vaccine booster based on the examination of the epidemiological data, which stated, “To date, none of these studies have provided credible data proving a substantial drop in protection against the severe form of the disease.” Furthermore, boosters could pose “risks” if they are “introduced too early or too frequently.”^49,50

Circulating antibody titers are not predictive of T-cell memory, and simple serological tests for SARS-CoV-2 antibodies do not reflect the richness and durability of immune memory to SARS-CoV-2.⁶ No study has looked at frequency of postvaccine cellular responses in immunocompromised patients. Likewise, the rate of breakthrough and the severity of breakthrough infections have not been fully studied to assess clinical efficacy and safety of the vaccine in the transplant population.^42-44 Given the new information on the emergence of the new Delta variant and potential newer variants in the future, the noticeably lower immunogenicity provided by all anti-COVID-19 vaccines, the consequent increased risk of breakthrough disease despite full vaccination (mainly in immunocompromised patients), and the potential risk of carrying and transmitting the new variants in an asymptomatic way similar to the unvaccinated population should together raise concerns on the false reassurance of protection through the possession of vaccine passports in ensuring a COVID-19-free environment. This might endanger the transplant recipient because it gives a false sense of secure protection that is not constantly present and will certainly endanger others when the patient is a carrier and namely a silent one.

As shown in the currently available scientific data, there are many unanswered questions as to whether a vaccine will have the same efficacy across different populations and in distinct regions and whether new variants will have a similar response and what level of variable protective, preventive, and therapeutic measures should be implemented. None of the original studies from Pfizer and Moderna^1,2 were designed to look at degrees of prevention of hospitalization, severe disease, or death or on prevention of infection and transmission potential. This should all play an important role on whether we should widely apply a vaccine as planned with current COVID-19 vaccines^51,52 and therefore whether the sanitary pass should be mandated in public and private domains. Moreover, the efficacy of a given vaccine in the evaluation of clinical trial data is usually reported as a relative risk ratio using relative risk (the ratio of disease rates with and without a vaccine) rather than absolute risk ratio (ARR). However, health professionals and the public have a poor understanding of relative risk reduction and absolute risk reduction measures. To consider risk in whole populations, an ARR would be a more representative parameter to assess COVID-19 vaccine efficacy and is essential to the prevention of outcome reporting bias.⁵³ However, ARRs tend to be ignored because they give a much less impressive effect size than relative risk ratios (ie, 1.3% vs 67% for the AstraZeneca-Oxford, 1.2% vs 94% for the Moderna-NIH, and 0.84% vs 95% for the Pfizer-BioNTech vaccines).⁵² Absolute risk ratios are also used to determine the number needed to vaccinate. This calculation shows how many people need to be vaccinated to prevent 1 case of COVID-19 (Figure 6).⁵³ In a recent study,¹⁰ risks and benefits of the mRNA COVID-19 vaccines were assessed using data from a large Israeli field study and from the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register. It was estimated that 16 serious side effects would occur with 4.11 fatalities per 100 000 vaccinations and that for every 3 deaths prevented by vaccination 2 would be inflicted by vaccination. The authors concluded that this lack of clear benefit should cause governments to rethink their vaccination policies. This study was retracted after publication as a result of pressure on the journal editorial board from scientists known to have a pro-vaccine stand. The reason given for the decision is that the side effect data recorded in the Dutch pharmacovigilance database could not be attributed with certainty to the vaccination despite the well-documented suspicion discussed above of a causal link between vaccination and side effects. However, the authors have maintained support of their findings.

Thus, there are valid concerns^4,54,55 and divisions in opinions within the scientific community and the world population regarding one or more of the numbered elements described here.

First is the experimental nature of the vaccination process. Second and third are the limited short-term and absent long-term follow-up in the main trials, and the lack of a well-identified correlate of immune protection.^2,6,7

Fourth is the recently reported considerable reduction in vaccine efficacy and the consequent risk of transmission by fully vaccinated individuals similar to that shown in unvaccinated individuals with the emergence of the new variants.

Fifth is the consequent rapid increase in the number of breakthrough cases with the emergence of the new Delta variant in highly vaccinated countries with enhanced disease severity and increased probability of death mainly in frail vaccinated individuals, rendering questions on the utility and safety of vaccination in this particular subgroup of the population.

Sixth is the questionable accuracy of the PCR test, well reflected by the recent decision of the CDC requesting the FDA to withdraw the Use for Emergency Utilization Authorization of the 2019-Novel Coronavirus PCR Diagnostic Panel for detection of SARS-CoV-2 because it cannot distinguish between COVID-19 and flu.⁵⁶ This questions not only the relevance of the sanitary pass using this test but also the validity of the whole COVID-19 pandemic that was and is still mainly based on the utilization of the PCR for case definition and clinical diagnosis.

The seventh, eighth, and ninth concerns are the well-recognized short-term and long-term safety issues, including serious adverse events and death, the potential risk of genome alteration, and the risk of vaccination in individuals during the incubation period.

Tenth is the absence of scientific evidence supporting the safety of systematic vaccination without prior knowledge of the immunity status in the vaccine recipient.^2,35

Eleventh is the systematic vaccination of children who are at no or extremely minimal risk of developing severe disease in the absence of long-term follow-up and with the presence of potential risk of genome alteration.

Twelfth is the occurrence of herd immunity and the natural progression of the pandemic, with the third wave seeming to end in the absence of vaccination and despite the coexistence of several determinants of poor outcomes as discussed above. This ending also included a lack of compliance by many with most of the protective measures, as was observed in Lebanon.

Thirteenth is the emerging scientific evidence regarding the availability of alternative prophylactic and curative therapy in animal⁵⁷ and human models provided by such a cheap, old, and safe drug like ivermectin.^58-60 Slovakia became the first nation in the European Union to formally approve ivermectin (January 28, 2021) for both prophylaxis and treatment of patients with COVID-19. There was a total decline of cases in the absence of meaningful vaccination of the population,^19,61 as well as in many other countries around the world like India, Panama, Mexico, and Paraguay with remarkable reduction in the new cases.

Fourteen are the serious concerns regarding the potential hidden coercion under different forms, like adopting the sanitary pass and indirectly imposing mandatory vaccination, as currently practiced by the some governments and private organizations despite the low case fatality rate (1.4%),^19,62 the even lower infection fatality rate (0.13% to 0.2%) associated with previous wild-type COVID-19 according to the Lebanese Ministry of Health, and the even lower case fatality rate reported by the PHE (0.2%) (Table 1) associated with the new Delta variant.²⁰ These new findings in addition to the recently emerging data on the efficacy of ivermectin and other well-known therapeutic tools in the prophylaxis and/or the treatment of COVID-19 cases put into question the real existence of an emergency situation that justifies the utilization of these experimental vaccines as sole forms of therapy against SARS-CoV-2.

The final point of concern is the dismissal by law of pharma companies and health care providers from any medico-legal responsibilities despite the speculative assurances to the public about the short- and long-term safety and efficacy of the vaccines.⁴

These concerns should put a halt on the application and enforcement of the vaccine sanitary pass. The ongoing debate today between the pro-vaccination supporters and the vaccine-prudent individuals is driven by a state of fear and panic on both sides: the fear of dying from COVID-19 for the former and the distress of vaccine-associated serious adverse events for the latter. This debate is fueled by the media in all its forms and by the continuously emerging contradictory scientific information. This has created a state of stigmatization that is leading to the alienation and division of societies worldwide. This scientifically unfounded sanitary pass is a form of coercion to supposedly maintain theoretically a COVID-19-free environment by forcing into vaccination those who are currently vaccine objectors (representing at least 50% of the population in most countries). In Lebanon, only one-third of the Lebanese are registered on the vaccination platform and only 14% are fully vaccinated as of August 15, 2021 (Figure 3).^19,62 As discussed above, the absence of any solid scientific evidence for such an approach, as reflected by the lack of universal policies in its application resulting in a wide range of strategies enforced by different European countries,^17,61,63-66 the recent growing number of newly diagnosed COVID-19 cases in the most vaccinated countries (Figures 2A and 3),^19,20,67-69 the equal spread of the Delta variant among vaccinated and unvaccinated people,^16-21,67,68 the relatively higher rates of intensive care unit admissions¹⁹ (Figure 4B) and death (Figure 2B, Table 1)^19,20 in vaccinated countries compared with those with limited vaccination¹⁹(Figure 3) despite significantly overall lesser virulence of the Delta variant (as reflected by lower rates of hospitalization and death in both maximally and minimally vaccinated populations),¹⁹ and the recent admission by the CDC of the poor specificity of the 2019-Novel Coronavirus PCR Diagnostic Panel in the detection of SARS-CoV-256 together suggest that the sanitary pass should be obsolete. Unfortunately, any insistence on imposing the sanitary pass would be certainly contradicting and jeopardizing the essence of an individual’s freedom of choice that is guaranteed by all international laws.

In the presence of the scientifically based concerns described here, the contradictory medical information, and the many unanswered questions,⁴ an informed consent^54,55 rather than the sanitary pass should be enforced. It should become not only a necessity but also mandatory. This should be done in accordance with all international laws and declarations on human rights as done for any other medical procedure so that the most fundamental principle of the individual freedom of choice can be protected. Such information should be universal and provided to every potential vaccine recipient in the form of an official digital written informed consent before registration on the COVID-19 platform or prior to receiving the vaccine, as done for any medical procedure.

As for physicians, our sacred role, according to the Hippocrates Oath, is first to do no harm “primum, non nocere.” Our duty is certainly not to convince people in one way or another but rather to enlighten and empower society the best we can by offering them to the best of our knowledge all available information regarding all forms of preventive and curative therapeutic tools in an unbiased way that allows them to make the most appropriate decision regarding the vaccine. This could be guaranteed through the mandatory application of informed consent.^54,55

Volume: 20 Issue: 4 April 2022

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