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The Long Haul, Part 4: The Cost of Long COVID In Terms Of Individual Health And Quality Of Life

Surviving COVID-19 is one thing, recovering is another.

My frustration with those who would minimize the impact of COVID-19 is reaching an apex. I constantly have to deal with their baseless rationalizations that “it is just a cold,” or “it only kills 0.01% of people” (actually the number is 2% around the world), etc. And I constantly reply to these iconoclasts that COVID has become, by far, the leading killer in the US. I also explain over and over that treating simple mortality percentage as the only relevant statistic to consider is falderal. For example, the Spanish flu also killed “only” 2% of those infected, but in just 24 weeks, that virus killed more people around the world than were killed in WWI AND WWII together! The percent figure is meaningless without considering the percent of what. Why do they continue to ignore the devisor and, hence, the total number of deaths?

A small percentage of a very large number is, in fact, another large number.

Those who wish to downplay the significance of the pandemic only focus on this mortality percent, but mortality is NEVER the whole story for any pandemic. A serious person will also consider the morbidity caused by the disease. In fact, the major CDC publication on health in the US is called the Morbidity and Mortality Weekly Report. Notice that it considers both morbidity and mortality, and further notice that morbidity is listed first in the title. I have made three prior posts in this series on Long COVID, about the significant lasting morbidity of COVID-19. You can see these posts here, here, and here. In those posts, I shared data showing that some ~10-30% of COVID survivors suffer serious health problems that last months.

In those posts, I mentioned the cases of a young, healthy MD, and of a young, healthy journalist, both of whom struggled with long COVID, and how it affected their careers and cost them thousands of dollars in out-of-pocket expenses for the dozens of tests and doctors they needed. In an article in Maclean’s magazine, a reporter interviewed many Canadian long COVID patients and heard how their lives have been turned upside down. They reported that they are unable to live like they used to and care for their families, do anything mildly strenuous, or even cook their meals. They spend long stretches of time in bed. Many of those interviewed had not returned to work several weeks after recovering from the acute disease.

Anecdotes like these have been repeated millions of times around a world that, according to the Johns Hopkins University COVID tracker, has seen more than 330 million cases of COVID (and this is a significant undercount since many countries do not record these data well). Research has corroborated these anecdotes.

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Common long-term symptoms include debilitating fatigue; respiratory problems; and “brain fog.”  Other common symptoms include compromised function of the heart, and kidneys, which sometimes require transplantation. Wide-spread clotting problems can cause significant illness and even limb amputation. There also are frequent neurological and neuropsychiatric symptoms as highlighted in Part 3 of this series. Surprising manifestations continue to emerge, such as new-onset diabetes.

Lung scarring often occurs in patients who experienced COVID-caused acute respiratory distress syndrome (ARDS), a common problem seen in acute COVID patients who required ICU care. ARDS is a serious respiratory problem that can be caused by different respiratory viruses and other things. About a third of patients with ARDS arising from any cause were unemployed 5-years later because of their lung damage. It is fully expected that patients with COVID-related ARDS will be found to fare similarly.

There also is the dysfunctional immune response common in many moderate to severe COVID cases that can cause long-term multi-organ damage, particularly in the liver and kidneys. It can also disrupt coagulation control of the blood, sometimes leading to amputations, mostly in patients in their 30s and 40s. It was reported that amputations due to vascular problems have doubled since the CoV-2 virus arrived. Compromised coagulation control in COVID patients can also precipitate adverse cardiovascular events such as heart failure, or hemiplegia due to strokes. Data from the COVID Infection Survey on long-COVID suggest that the risk of major adverse cardiovascular events and long-term illness is about ten times higher in COVID patients (even after mild COVID) compared to non-COVID matched controls. A Dutch study found that 31% of COVID ICU patients suffered thrombotic complications. These problems can unexpectedly pop up in people who had completely recovered from COVID.

A global survey tallied 205 different symptoms across 10 different organ systems that can persist after COVID infection has cleared. Typically, these manifold long COVID symptoms do not appear in isolation, but in multi-symptom clusters. A long hauler typically has several of these problems at a time.

While it is estimated that overall, 10-30% of COVID patients become long haulers, reports on the number of people suffering long COVID vary widely. Depending on the report, anywhere from 30-90% of COVID survivors suffer long term health problems. And even at the lower end of that range, 30% of over 330 million people world-wide who have been infected is a very large number. It represents an enormous personal toll in terms of lost health and diminished quality of life. Some of these reports are summarized below.

  • Half of 70,000 hospitalized UK COVID-19 patients experienced long-term complications, according to a study published in July. Complications occurred regardless of age group: For instance, 25% of adults aged 19-29 developed complications, as did 33% of those aged 30-39. Complications affecting the kidneys and respiratory system, liver injury, anemia, and arrhythmia were the most common.
  • Many COVID-19 survivors require extensive and prolonged rehabilitation. An European study found about one-third of 1,837 non-hospitalized COVID patients (i.e., those with mild disease) needed a caregiver three months after their symptoms started.
  • In April the CDC reported in its Morbidity and Mortality Weekly Report that 69 percent of nonhospitalized adult COVID patients in Georgia required
  • one or more outpatient visits 28 to 180 days after their diagnosis.
  • A study published last February in the Journal of the American Medical Association found that roughly one-third of 177 people who had mild COVID disease not requiring hospitalization reported persistent symptoms and a decline in quality of life up to nine months after illness.
  • 70% of people hospitalized for COVID-19 in the UK had not fully recovered five months after hospital discharge. They averaged nine long COVID symptoms requiring continued medical care.
  • A study in South Korea found that 90% of patients who recovered from acute COVID experienced long-term side effects.
  • According to a report in the journal, Lancet, 75% of people hospitalized with COVID-19 in Wuhan early in the pandemic, reported continued problems with fatigue, weakness, sleep problems, anxiety and depression six months after being diagnosed with the disease. More than half also had persistent lung abnormalities.

Data like these have been commonly reported around the world, pointing to a more chronic and expensive health problem than seen with the flu or common cold, which often is caused by different coronaviruses. A July 2021 article in Scientific American talked about how all of this indicates that long COVID will cause a “tsunami of disability” that will affect individual lives as well as create enormous strain on the health system. Consider the numbers: More than 60 million Americans (this is an underestimate since many COVID cases are not reported) have been infected with the CoV-2 virus. Therefore, if only 30% of these suffer long COVID, we are talking about 20 million long haulers and counting.

The related health care and disability costs of all of this are also still being calculated. How many “long haulers” will not be able to return to work for months, or at all? How many will need short-term disability payments, and how many will become permanently dependent on disability programs? As increasing numbers of younger people become infected, will we see a generation of chronically ill? This then moves us to consider the economic and financial cost of long COVID, which will be the topic of the next installation in this series.

Stay tuned.

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Naturally Immune? You Still Better Get A Vaccine

Over 43 million Americans have reported cases of COVID-19. Many of them likely have some level of immunity that can be quite protective, even without vaccination. Even before vaccines were available, individuals who recovered from COVID-19 had detectable T-cell responses, and reinfections were rare, at least prior to the emergence of the more contagious Delta variant. This is what people refer to colloquially as “natural immunity,” to distinguish it from immunity conferred by vaccination. Some people claim that natural immunity is better and preferable to vaccine immunity and that a history of infection should count as much as being vaccinated when considering vaccine mandates. Is all this true? Well, like what we have seen and heard during the pandemic, a lot of truths have been spread, same with lies and disinformation. The story around natural immunity follows this pattern. Let me try to sort all this out here with a focus on whether previously infected people should consider getting vaccinated.

Natural infection can confer immunity to COVID. Like most viruses, previous infection with SARS-CoV-2 does confer immune protection against future re-exposure to the virus. Several peer-reviewed studies conducted in the early months of the pandemic, before vaccines were available, found that people previously infected were around 80% less likely to test positive for the virus during the next viral surge. These included studies of healthcare workers in the UK, the Danish population, and patients at the Cleveland Clinic, a large health system in Ohio and Florida.

Other data from the UK Office for National Statistics showed that between May and August 2021, a prior infection offered around the same level of protection against the Delta variant as vaccination. (Note that very recent and preliminary observations in South Africa suggest that infection with the new Omicron variant is high in people previously infected with other CoV-2 variants. However, since Omicron is so new and data on it are very sketchy at this time, this review will not further comment on this variant.)

A recent large Israeli study found that people who had been fully vaccinated with two Pfizer shots were 13 times more likely to later get infected with CoV-2 than those who had a prior infection. It also suggested that immunity from infection was longer lasting than that from vaccination. The study also showed that natural immunity plus the vaccine offered protection that was even stronger than either natural or vaccine immunity alone. This is one of the very few studies suggesting that natural immunity is better than vaccine immunity and has not been peer-reviewed. Furthermore, the subsequent rise of Delta since the end of this study confounds the issue a bit since Delta has been shown to be more infectious than the viruses the study subjects were exposed to. 

In the most recent review of the current scientific evidence by the CDC, they concluded that both fully vaccinated and those previously infected with the virus have a low risk of re-infection for at least six months, but that the two forms of immunity appear to have different strengths. Vaccination with mRNA vaccines produced higher concentrations of neutralizing antibodies—the type that prevent the virus from entering cells—than natural infection, although, over time, the antibody levels waned in both groups. However, long lasting immune memory conferred by natural infection appeared to be stronger than that conferred by vaccination.

Over time, immune B cells typically evolve to produce antibodies that better recognize an antigen, and an earlier study published in Nature found that antibodies produced by naturally immune memory B cells continued to evolve at least a year after infection. In contrast, antibodies produced by memory B cells in vaccinated people did not change much over time. This would suggest that over time, antibodies produced by natural immunity gain greater ability to respond to re-infection with the virus than antibodies produced by vaccination. One possible reason for this difference in the evolution of the anti-viral antibodies was that pieces of virus remain in the body for weeks after infection and continue to engage the immune cells, whereas vaccine lipid nanoparticles quickly fade away providing less immune stimulation. 

On the other hand, vaccine immunity might be better. So, as we have seen, a few reports suggest that natural immunity is superior to vaccine immunity. However, more studies suggest the opposite and even show that not everyone who catches COVID-19 will have effective immunity to re-infection. A CDC study reported that 36% of previously infected people did not form any antibodies against the virus. This is in stark contrast to antibody formation reported in 100% of people who received just one dose of an mRNA vaccine. Furthermore, the CDC reported in August that COVID survivors who went unvaxed were more than twice as likely as vaccinated people to get infected again contrasting with the Israeli study I mentioned earlier. Yet another CDC study looking at data from ~190 hospitals in nine states confirmed that unvaccinated people who survived an infection several months earlier were more than five times more likely to get COVID again than vaccinated people.

The reason that natural immunity might not always be effective is because the natural exposure to the virus is highly variable. People naturally infected are exposed to widely different doses of virus via different routes and possibly to different viral strains, all of which conspire to confer different degrees of protection. In contrast, vaccinated people receive standardized doses of the same viral antigen via the same route of exposure, making them more likely to develop a uniform degree of immunity. Researchers found that some people who had been infected had high antibody levels to the virus, while others had low levels, reflecting this variability in natural infection. This was substantiated by a new study from the University of Pittsburgh that also found that in many cases antibody levels from a prior infection are not high enough to protect people from getting sick again. Then, an Oxford study found that both long term T and B cell immune responses were highly variable in naturally immune people. The investigators took monthly samples of blood from infected subjects and measured their T and B cell responses over time. Interestingly, the variability in their responses was clearly identified as early as one-month post infection. Those with the weakest immunity at one month (25% of the subjects) had no detectable antibodies after six months. This contrasts to vaccine immunity, which does fade a bit over six months, but still remains consistently strong months after full vaccination. 

Finally, new evidence from an NIH-supported study from the Fred Hutchinson Cancer Research Center, Seattle showed that antibodies from vaccinated people better recognized the mutated spike proteins from viral variants than antibodies from naturally immune people who had not been vaccinated. In other words, vaccinated people seem better able to respond to mutated spike proteins present in new viral variants.

The bottom line. In sum, while natural immunity can be effective, most evidence shows that vaccines typically give rise to consistently better antibody and long term T and B cell responses.

Having made this point, it is important to further note that a combination of both types of immunity, or so-called hybrid immunity, appears to be stronger than either alone. Researchers found that vaccination of naturally infected people boosted antibody and memory B cells to levels higher than seen in those with just either type of immunity. People with prior COVID-19 who received even one vaccine dose had half the risk of a breakthrough infection than unvaccinated people with prior COVID-19. Another study from researchers at the Icahn School of Medicine in New York found that a single dose of either the Pfizer or Moderna vaccines produced more antibodies in people who had previously had COVID-19 than two vax doses did in those who had never encountered the virus. It also found that people with prior infection report more unpleasant, but not serious side effects from vaccination. Vaccinating previously infected people also elicits important cross-variant neutralizing antibodies that better protect them against the known viral variants. Hybrid immunity also appears to work in the other direction: A study of vaccinated people who were then infected during a July 4 holiday weekend outbreak on Cape Cod found that they produced higher levels of antibodies and T-cells directed against the virus. In sum, vaccination helps those with natural immunity (and everyone they interact with) and vice versa

For these reasons, the CDC now recommends that people who have had COVID-19 be vaccinated because the shots plus natural immunity have been shown to offer better protection than natural immunity alone.


Unvaccinated People Are 11 Times More Likely To Die Of COVID-19

People who were not fully vaccinated this spring and summer were ~10 times more likely to be hospitalized, and 11 times more likely to die of COVID-19, than those who were fully vaccinated, according to one of three major studies published mid-September by the CDC.

That study did not distinguish between which vaccine the vaccinated cohort received. But, a second study compared the different vaccines and found that the Moderna vax was somewhat more effective in preventing hospitalizations than the Pfizer and J&J vaccines. This assessment was based on the largest US study to date of the real-world effectiveness of all three vaccines, involving about 32,000 patients seen in hospitals, emergency departments and urgent-care clinics across nine states from June through early August. While the three vaccines were collectively 86 percent effective in preventing hospitalization, protection was higher among Moderna vaccine recipients (95 percent) than among those who got the Pfizer (80 percent) or J&J vaccines (60 percent). That finding echoes a smaller study by the Mayo Clinic Health System in August, which showed the Moderna vaccine to be more effective than the Pfizer vax at preventing infections from the Delta variant.

Vaccine effectiveness against infection dropped from 90 percent last Spring, when Delta had not yet gained significant traction, to less than 80 percent from mid-June to mid-July, when Delta began out-competing other viral variants. Importantly, effectiveness against hospitalization and death showed barely any decline during the entire period. Thus, all vaccines remain quite effective and useful in protecting against illness.

Get one!

Why there is a difference in preventing infection between the Pfizer and Moderna mRNA vaccines was discussed earlier in these pages.