What’s in the web for family physicians - The COVID pandemic aftermath

Sio-pan Chan 陳少斌，Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩

On 28th February, 2023, our Chief Executive announced the end of the mask mandate and proclaimed Hong Kong was back to “normalcy”. Since then, people are free to choose whether to wear a mask or not except in special places such as hospitals. People are no longer required to report COVID cases to the health authority and can get back to their workplaces even if they are tested positive for COVID-19. In May 2023, the World Health Organization WHO chief declared “end to COVID-19 as a global health emergency”. However, he also said “Last week, COVID-19 claimed a life every three minutes– and that’s just the deaths we know about”.

Since March 2023, frontline doctors have seen an unprecedented rise in cases of COVID-19 infections. The number of cases were likely to exceed most previous waves, such drastic increase was clearly shown in Singapore where they are still reporting cases to the Worldometer database. Fortunately, we were much better prepared to manage COVID-19 infection than before and most cases were relatively mild. According to the Government data, by March 2023, we had about 84% of the population who have at least 4 doses of COVID vaccine, together with the huge number of people who had contracted COVID-19 since the beginning of the pandemic, supposedly we should have a good herd immunity against COVID-19 as predicted by many specialists. So why are we still having so many new and repeated COVID-19 infections, many of the patients have 4 to 5 vaccines including the newer bivalent mRNA vaccine. Apparently, the traditional concept of herd immunity by vaccination or infection does not apply to COVID-19, as in so many other coronavirus infections like common cold.

Another important issue is the real world efficacy of mRNA vaccines versus their adverse side effects. A recently published paper cast doubts on the effectiveness of the bivalent vaccine on the newer XBB variant and showed that there is no significant risk reduction during the XBB-dominant phase. Furthermore, there are observational studies in Israel and in the United States showing that, paradoxically, the more number of vaccines may result in a higher chance of getting COVID-19 infections or reinfections. Studies also showed the presence of residual spike protein in many organs and tissues after mRNA vaccination and thus raised the concern on its long term effect on the body's immune system. There are numerous studies showing that mRNA vaccines resulted in much higher adverse effects or “vaccine injuries” than previously thought. In fact, most European countries have long stopped their mass vaccination program except for the high risk groups.

The “Excess deaths” phenomenon, from 2020 to 2023, various studies including the WHO have reported significant increase in mortality worldwide that cannot be explained by deaths from COVID-19. This phenomenon is more obvious in the United Kingdom, South Africa and most European countries which have good death registry statistics. Excess deaths are the extra number of deaths compared with the expected average mortality of that particular country over the past five years. The excess deaths in the United Kingdom at the time of writing this article is over 20% above the expected mortality whereas similar or lower figures were reported in the United States and other European countries. Such excess deaths are still persistent and that they cannot be accounted for by COVID-19 infection. Cardiovascular disease (CVD) deaths including acute myocardial infarct, heart failure and strokes are the major causes of excessive deaths.

COVID-19 infection may cause T-cell dysfunction which may lead to reactivation of some latent viral infections. Reactivation of latent Epstein-Barr virus and Cytomegalovirus (CMV) is postulated to be one of the possible causes of Long COVID infection. COVID-19 per se or treatment of COVID-19 with dexamethasone and tocilizumab may potentially cause reactivation of latent tuberculosis, hepatitis B and hepatitis C. A more commonly encountered complication we see in family practice is the increase in Herpes Zoster infections, the rate of which, according to recent studies, is up to 15% for people over the age of 50.

The problem of “Long COVID”, which is also known by many other names such as long-haul COVID, post-COVID-19 syndrome, post-COVID-19 condition, post-acute sequelae of COVID-19 (PASC), or chronic COVID syndrome (CCS), is by itself a complication issue. We shall discuss Long COVID in a separate article.

COVID-19 herd immunity - the concept of classical herd immunity may not apply to COVID-19

Since the time when COVID-19 vaccines were available, the official narrative was that when 70% of the population got vaccinated, we were able to build up a herb immunity. Subsequently, the narrative had kept on changing, that vaccines would not protect people from infection, but would protect those vaccinated from hospitalisation and deaths. In this paper, the authors, including Dr. Antony Fauci himself, commented that the concept of classical herd immunity may not apply to COVID-19.

Vaccine efficacy, real world data (including XBB data)

The narrative on vaccine efficacy has always been changing – primarily because of the frequent emergence of new variants with immune escape that reduce the effectiveness of the original COVID vaccines. This article from Cleveland Clinic has demonstrated the race between more boosters and the rate of variant mutation is probably a futile effort. It has shown that there is little extra protection you can get from having an extra booster, and there is a likelihood of a paradoxical increase in chance of infection shortly after a booster dose. Also the bivalent mRNA vaccine did not show any significant additional protection against the XBB variant.

Estimation of Vaccine Effectiveness (VE) of CoronaVac and BNT162b2 against severe outcomes

In this Hong Kong study, the authors concluded that there is no significant difference against severe outcomes of either vaccine. The actual VE figures against hospitalisation for CoronaVac was 84.5% (95% CI, 82.4%-86.2%) at the third dose and BNT162b2 85.8% (95% CI, 83.3%-88.3%) at the third dose. The VE against death was also similar. Mixing doses of CoronaVac and BNT162b2 were as effective against hospitalisation or death. The authors also mentioned that in several studies have found that CoronaVac was less effective against severe outcomes than BNT162b2, but this study suggested that both CoronaVac and BNT162b2 provide protection against severe outcomes caused by the Omicron variant and the VE waned consistently after the second dose. In fact, a national study in Chile found that CoronaVac was 86% effective against death in early 2021, when the Gamma and Alpha variants were circulating.

Vaccine injuries

A Hong Kong study has shown definite risk of myocarditis/pericarditis of mRNA vaccine. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38－12.53) and 37.32 (95% CI, 26.98－51.25) per 100000 persons vaccinated and 84% of those required hospitalisation. They concluded that there is a significant increase in the risk of acute myocarditis/pericarditis following mRNA vaccination among Chinese male adolescents, especially after the second dose. Myocarditis/pericarditis is probably the most serious and noticeable vaccine injuries, according to other studies, they only rank third in in the adverse effects list including thrombosis, stroke, myocarditis, myocardial infarction, pulmonary embolism, and arrhythmia, thrombocytopenia etc. A very recent paper from Switzerland has shown that 1 in 35 healthy persons demonstrate an increase in troponin levels troponin levels a few days after receiving the second Moderna mRNA vaccine. Raised troponin level is a biomarker of myocardial damage. Therefore, the risk/ benefit ratio and the need-to-harm issue has to be fully evaluated before the Government recommends the future vaccination campaign.

Excess mortality

Excess mortality is measured as the difference between the reported number of deaths in a given week or month (depending on the country) in 2020 – 2023 and an estimate of the expected deaths for that period had the COVID-19 pandemic not occurred. Up to the first quarter of 2023, the excess death rate in the United Kingdom and United States were up to 20% above the expected deaths. Somewhat lower figures were reported in most other countries. The excess deaths cover the entire age groups including many younger individuals. Further analysis showed that the leading cause of excess deaths were CVD related conditions. Surprisingly the actual number of deaths from respiratory conditions was not a cause of excess deaths.

Spike protein presence in tissue after mRNA vaccine and potential implication

A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he was tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for Immunoglobulin G (IgG), while nucleocapsid IgG/ IgM was not elicited. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results suggested that the first vaccination induces immunogenicity but not sterile immunity. This study confirmed that spike protein can present in multiple organs/tissue after a single dose of mRNA vaccine, subsequent vaccination is likely to increase its presence in other unintended sites and may remain for an unknown period of time. As with any foreign proteins, how our immune system responds to this foreign protein in different tissues remains unknown. Myocarditis/pericarditis is likely to be one of such local responses.

Reactivation of latent diseases

This meta-analysis has shown that post severe COVID-19 disease is associated with significant risk of reactivation of latent herpes viruses. The pooled cumulative incidence estimate was 38% for herpes simplex virus (HSV), 19% for CMV, 45% for Epstein- Barr virus (EBV), 18% for human herpesvirus 6 (HHV- 6), 44% for human herpesvirus 7 (HHV-7), and 19% for human herpesvirus 8 (HHV-8), all figure with 95% CI. Reactivation of EBV and CMV was implicated as a causative factor in Long COVID infection. While reactivation of HSV and HHV implies that we shall encounter more cold sores and herpes zoster infection. The second reference above concluded that there is a 15% increased risk of having herpes zoster infection for those who have contracted COVID-19. Perhaps this is an additional incentive of those over 50 years old who had COVID-19 infection to receive herpes zoster vaccination.