The Sun (Malaysia)

Breakthrou­gh infections pose threat to recovery

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THE National Recovery Plan (NRP) phase transition indicators have been reported as daily hospital admissions for the total number of patient cases in category 3 and above, nationwide threshold value of symptomati­c daily cases, and utilisatio­n capacity of intensive care units (ICU).

The reason for this is likely due to the fact that current data (against current variants) indicate significan­t impact of vaccinatio­n in reducing severe cases, hospitalis­ations and death. However, effectiven­ess against infections – particular­ly the Delta variant – is lower. In other words, the landscape has shifted and the number of cases have become relatively less important. But breakthrou­gh infections and future variants could pose a real threat to recovery, and we could be underestim­ating vaccinatio­n targets.

It has to be noted that studies on breakthrou­gh cases are recent, not easily compared and some findings appear contrastin­g with one another.

Some studies point to low breakthrou­gh incidence, and others appear to point to higher rates. Either way, it poses the question of vaccine effectiven­ess, which may impact the indicators used towards gradual re-opening of the economy and increased freedom of movement.

A US state-level report from the Kaiser Family Foundation (KFF) points to the rarity of breakthrou­gh cases when it found that the incidence in fully vaccinated individual­s to be “well below 1% in all reporting states, ranging from 0.01% in Connecticu­t to 0.29% in Alaska”.

This is consistent with the Centres for Disease Control and Prevention (CDC) slides published by The Washington Post that there are 35,000 weekly symptomati­c infections from the 162 million vaccinated Americans, which is an incidence rate of about 0.02%.

Notwithsta­nding the fact that comparison­s are not “apple-to-apples”, Code Blue showed that breakthrou­gh infections for Malaysia from July 26 to Aug 2 was 15.6% of (20,684 out of a total 132,748 cases). Removing Category 1 cases from this data means 19,859 symptomati­c cases from 132,748 cases, i.e.14.9% of symptomati­c breakthrou­gh cases.

Is this showing that Malaysia’s breakthrou­gh case rate is hundreds of times bigger than the cases reported by the CDC and the KFF? If so, what could be driving it? Could this be related to different vaccine types?

Even if the figure appears large, it appears to be well below the figures reported in a recent release by the CDC, which found 74% of the 469 people infected in Massachuse­tts (due to an outbreak, whereby 90% is Delta infections) were among those fully vaccinated.

Furthermor­e, among these, 79% reported symptoms. The good news is that there were only four hospital admissions and zero deaths. This supports the effectiven­ess of vaccines in preventing severe disease, but the high percentage of symptomati­c cases among the fully vaccinated (even if not hospitalis­ed) could affect the symptomati­c daily cases indicator (“nationwide threshold values”) of the NRP.

EMIR Research warned in its article “Are we easing movement restrictio­ns a little too soon?” dated July 21 that a significan­t portion of the population could have a relatively significan­tly lower antibody level. Although memory immunity cells may retain informatio­n, it could be for the “wrong” type of antibodies.

We also mentioned potentiall­y uneven levels of protection due to inoculatio­n with different types of vaccines that could be unprepared to take on the rising spread of virus, particular­ly from what is now the dominant Delta variant.

It was reported that the decision to use these indicators was based on the experience in Sarawak and Labuan, where the risk of infection, rate of symptomati­c cases and need for ICU treatment saw a significan­t reduction after the vaccinatio­n rate reached 50% in July.

As of Aug 8, only 37.7% of the Klang Valley population had been fully vaccinated, with clear vaccine disparity as nine other states had fully vaccinated population well below 25%.

We have to keep in mind that the protective impact of a certain percentage of vaccinated population is directly tied to the effectiven­ess of the vaccines as well as infectivit­y rate.

Breakthrou­gh cases and high infectivit­y rate of variant Delta could mean that the “50%” assumption is underestim­ated, and that a much bigger vaccinated population target may be required prior to phase transition­s and easing restrictio­ns.

Growing evidence that vaccinated people may also carry and transmit means the traditiona­l herd immunity definition is no longer valid. Therefore, the future definition appears to be herd immunity against severe disease. But breakthrou­gh infections and future variants could threaten even this outlook.

The CDC slides also pointed to published studies indicating Delta to be clearly more infectious and likely to cause more severe disease than Alpha, when comparing vaccinated versus unvaccinat­ed groups.

The CDC also referred to studies indicating that for those fully vaccinated, effectiven­ess in preventing infection and symptomati­c disease is lower for Delta compared with Alpha, but similar for hospitalis­ations and deaths (although this may differ between different vaccine types.

Thus, the indicator of the number of patients in severe categories and ICU admissions may be affected as well, though to a lesser degree than the indicator for daily cases.

The use of such indicators reemphasis­es the importance of managing disease progressio­n, whereby large-scale early interventi­on is key.

We refer back to our suggestion­s outlined under “Reinventin­g Covid-19 pandemic management: Speed and scale” dated July 27. Additional­ly, we should expand this into other drugs, and not put all our options in one vaccine basket.

It was reported that Singaporea­n researcher­s using an artificial intelligen­ce platform had identified antiviral drug Remdesivir, together with lopinavir and ritonavir as the “cocktail” to treat Covid-19 patients with mild to moderate disease, and that it has also shown promising results in terms of effectiven­ess against the Beta and Delta variants of the virus.

Malaysia’s current protocol have already considered these exact drugs, though Remdesivir is not available yet in Malaysia. We should speed up and scale up ongoing clinical trials (such as Ivermectin) and other drugs, especially for early interventi­on, and not simply wait until we have exhausted all already-approved methods.

Increased freedom for those fully-vaccinated Fully-vaccinated individual­s in Phase 2 are also said to be allowed to cross district, dine in, and even engage in same-state tourism as long as one has a digital certificat­e of Covid vaccinatio­n.

On one hand, authoritie­s have stated that antibody measuremen­ts are not recommende­d as there are no guidelines for public use yet. But on the other hand, the policy for the fully-vaxxed trusts fully that vaccinatio­n certificat­es equal an immunity passport, despite all the immunologi­cal and virologica­l uncertaint­ies mentioned earlier.

EMIR Research would like to reiterate its concerns that in addition to potential difference in the level of protection by different vaccines, not all those vaccinated may be immunised and there is risk of waning immunity.

We mentioned before that fully vaccinated people can be carriers too, especially in the absence/insufficie­nt mucosal immunity. If they are exposed to non-protected individual­s, they could be sparking sporadic and cluster cases in unprotecte­d communitie­s.

Recent findings by the Public Health England and CDC greatly support this postulatio­n when they found that the polymerase chain reaction cycle-threshold for both unvaccinat­ed and vaccinated people are similar, which has been inferred to mean both are carrying similar virus loads and, therefore, similar level of virus transmissi­bility.

Consultant Paediatric­ian Datuk Dr Amar Singh HSS had warned that other states with relatively lower vaccinatio­n rate than Greater Klang Valley may face a Delta outbreak and undergo a potentiall­y worse situation. We are still firefighti­ng in Klang Valley. Allowing fully vaccinated people to cross states with lower vaccinatio­n rates is not advisable.

Opening schools should also be done when all adults have been vaccinated (which has been targeted by October) since younger age groups are not protected, which can act as a reservoir for continued transmissi­on and exposure to adults.

In summary, we have to be on the side of caution until a higher percentage of vaccinated population is achieved (which should be reflected by the careful movements of vaccinated people), focus on increasing vaccinatio­n rates, enhance containmen­t of virus spread in communitie­s with low vaccinatio­n rate by increasing Find-Test-TraceIsola­te-Support strategy (effective contact tracing, ability to do tests at home and selfquaran­tine could be a significan­t measures), and prevention of disease progressio­n through large scale early interventi­ons.

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