The Covid Pandemic Has Been Terrible, but We Do Not Yet Know How Terrible

 Most of the world seems to have decided that they can live with the covid virus and its multiple variants.  Infection rates rise and fall as new variants appear, people continue to die, but at a relatively low rate, and vaccines appear to provide considerable protection from severe illness for the infections that do occur.  The issue of whether to wear a mask is mostly left to the individual to decide.  Many people feel comfortable returning to their pre-pandemic lifestyles.  The assumption seems to be that while the virus is not going away, we will learn to live with it, much like we live with flu viruses or those of the common cold.  A combination of vaccines and improved natural immunity that will follow from multiple infections over years will reduce the virus to a nuisance not a threat.  Basically, the conclusion is that if we are not likely to die or be severely sick during an infection, then why worry? However, there is at least one country that has decided to follow a different path: China.  China seems to have decided to worry—about something.

The initial outbreak occurred in China.  Severe measures were taken to suppress the epidemic with considerable success.  For a long time, China was smug about how it had controlled the situation.  Similar measures also worked well whenever new cases were encountered.  China appeared to have an effective approach, but one that less powerful governments would have difficulty imposing on their citizens.  As a result, many countries would impose restrictions until lower infection rates were attained but reimpose them when inevitably a resurgence would occur.  These less intrusive tactics were deemed justified by the appearance of effective vaccines that brought us to where we are today.  China’s approach became more complicated as newer variants became more transmissible and containment of an outbreak required even more draconian restrictions.  At present China is placing entire populous cities into a complete lockdown with citizens unable to leave their homes while the virus is causing infections.

People question China’s strategy because it is extremely stressing to its own people and to its economy.  Shock waves to China’s productivity propagate throughout the world.  Most pundits question the wisdom of the approach and suggest a failure of leadership.  Xi Jinping is accused being unwilling to admit that his “zero-covid” policy was overkill, so he stubbornly continues to stick with a failed policy.  That contention may prove correct, but just because most experts disagree with China does not demonstrate that China is wrong.  Perhaps experts’ time might be better spent wondering if there could possibly be reasons why China’s strict approach might be the appropriate solution in the longer term.

Let us consider some of the data finally being released.  And let us also consider that China, with its intrusive policies, might have been just as aggressive in evaluating the virus and its consequences much earlier in the pandemic.  Could China have discovered something to worry about?

Before the covid virus spread worldwide and became a pandemic, much could have been deduced about the threat it was becoming from previous experiences with other versions such as the SARS and MERS coronaviruses.  Consider the article Here’s what coronavirus does to the body published early on in February, 2020.  It clearly warns that the virus would threaten the respiratory system of a patient and would also likely spread widely to other organs where it would be able to reproduce and cause damages.  This claim was based on observations with the earlier versions as well as data from early covid-19 patients. 

“Such has been the nature of past zoonotic coronaviruses, ones that hopped from animals to humans like SARS and MERS. Unlike their common-cold-causing cousins, these emergent coronaviruses can spark a viral-induced fire throughout many of a person’s organs, and the new disease—dubbed ‘COVID-19’ by the World Health Organization—is no exception…”

Covid is foremost a respiratory disease.  So much so that the standard test for the disease is to search for evidence of the virus in the sinus passages.  One worries about infection if symptoms appear in the respiratory system.  If the symptoms disappear and the virus is not found with a nasal swab, the patient is assumed cured and returns to normal life, or at least tries to.  Medical personnel observe non-respiratory symptoms in covid patients, as one would expect if the virus is capable of spreading to organs throughout the body.  Occasionally these symptoms are severe, but usually they are minor compared to issues with the lungs and receive relatively little attention.  It soon became evident that many “cured” patients were complaining about lingering health conditions.  These cases have been dubbed incidences of “long covid” and the invasion of multiple body organs by the virus is the prime suspect.  It has also been learned that the incidence of long covid is unrelated to the severity of the covid infection.  One can suffer from the condition without even realizing one had been infected with covid.

The UK seems to be the country most interested in tracking the long-covid issue.  The Economist reported on findings in April 2021: Researchers are closing in on long covid: The results are alarming.  The condition is difficult to identify with precision because the symptoms are many with sufferers often claiming multiple conditions.

“There are, indeed, many of them. A survey of almost 3,800 people around the world reported 205. A sufferer typically has several at a time, with the most debilitating usually being one of three: severe breathlessness, fatigue or ‘brain fog’.”

Many sufferers become patients demanding relief as their ability to function properly damages their lifestyles and diminishes their capability to perform at work.  The indication is that these patients could be a severe long-term burden on healthcare systems in addition to the normal pandemic burden.

“Britain’s Office for National Statistics (ONS) estimates that 14% of people who have tested positive for covid-19 have symptoms which subsequently linger for more than three months…In more than 90% of those cases the original symptoms were not severe enough to warrant admission to hospital.”

“At the time when the ONS collected those data, at least 1.1% of Britain’s population, including 1.5% of working-age adults, reported symptoms dragging on for three months or longer. Multiply that by the hundreds of millions around the world who have been infected at some point by SARS-COV-2, the virus that causes covid-19, and a public-health catastrophe may be in the making. In the short term, it was only right that effort focused on dealing with the acute disease. Today covid-19’s chronic after-effects also need to be considered.”

These early studies relied on patient-reported symptoms causing many to wonder if the reporting was accurate.  Could these figures be an exaggeration of reality?  The UK recently came out with another study: Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study.  This was essentially a survey of people who were hospitalized and recovered from their initial covid infection   At five months and at one year, these people were asked about their recovery.  This approach suggested that the count of people claiming lingering symptoms was vastly underestimated with only about a quarter of the people claiming full recovery.  Apparently, many people feel lingering effects but not all request medical assistance.

“2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35·6% were female, mean age 58·7 (SD 12·5) years, and 27·8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/1965 (25·5%) and one year 232/804 (28·9%).” 

“The sequelae [consequences] of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission.” 

Much of the data accumulated is from the pre-vaccine era.  This source suggests that while vaccines limit infections somewhat, the incidence of long covid seems to persist at a similar rate.

“Vaccines reduce the risk of long COVID by lowering the chances of contracting COVID-19 in the first place. But for those who do experience a breakthrough infection, studies suggest that vaccination might only halve the risk of long COVID — or have no effect on it at all.”

One might also wonder if children are safe from long covid.  They are not.  Consider this article from Bloomberg Businessweek: The Children Left Behind by Long Covid.

 “The U.S. and the world are trying to move on from Covid-19. Everyone is tired of even thinking about it. The Centers for Disease Control and Prevention has effectively given up on trying to impose collective measures to control the virus. Even people who’ve been vigilant are ditching their masks. And, yet again, cases are rising in the U.S.”

“More cases will mean more long Covid, including pediatric long Covid. Estimates of the number of children who face long-term symptoms are far from precise, but they probably range from 5% to 10% of those infected with the virus, says Daniel Griffin, an infectious diseases expert at Columbia University… Even at the lower end of the estimates, that translates to more than a half-million children of the 13 million so far infected. (Studies of infected adults indicate that an estimated 10% to 30% may have long Covid.)”

There is a report from the National Institutes of Health providing detailed information on how the virus distributes itself through the body of infected people and can persist for long periods: SARS-CoV-2 infection and persistence throughout the human body and brain.  This was determined by performing autopsies on people who died from covid or were infected by covid while dying from some other cause.  It demonstrates that while the virus may not always appear active in the various organs, it remains capable of reproducing itself, suggesting it is active at a lower level than in the respiratory system or it is latent and could become active at a later time.

“COVID-19 is known to cause multi-organ dysfunction in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARSCoV-2 (PASC). However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple pulmonary and extrapulmonary tissues early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.”

“Overall, SARS-CoV-2 RNA was detected in respiratory tissue of 43/44 cases (97.7%); cardiovascular tissue of 35/44 cases (79.5%); lymphoid tissue of 38/44 cases (86.4%); gastrointestinal tissue of 32/44 (72.7%); renal and endocrine tissue of 28/44 cases (63.6%); reproductive tissue in 17/40 cases (42.5%); muscle, skin, adipose, and peripheral nervous tissue in 30/44 cases (68.2%); ocular tissue and humors of 22/28 cases (57.9%); and brain tissue in 10/11 cases (90.9%).”

“Finally, a major contribution of our work is a greater understanding of the duration and locations at which SARS-CoV-2 can persist. While the respiratory tract was the most common location in which SARS-CoV-2 RNA tends to linger, ≥50% of late cases also had persistence in the myocardium, thoracic cavity lymph nodes, tongue, peripheral nerves, ocular tissue, and in all sampled areas of the brain, except the dura mater.”

And then the authors leave the reader with this thought over which to ponder. 

“Interestingly, despite having much lower levels of SARS-CoV-2 in early cases compared to respiratory tissues, we found similar levels between pulmonary and the extrapulmonary tissue categories in late cases. This less efficient viral clearance in extrapulmonary tissues is perhaps related to a less robust innate and adaptive immune response outside the respiratory tract.” 

What do these various sources tell us?  The vaccines at our disposal do not eliminate infections.  Consequently, the number of vaccinated who become infected will continue to be significant no matter how high the vaccination rate is.  With current relaxed restrictions, eventually everyone would be infected at least once with many infected multiple times.  If 10 to 30 percent of those having been infected now have long-term aftereffects, that number could rise beyond 100 million in the US.  A significant fraction of these would be seeking medical attention and unable to perform in our economy.  This would be a catastrophe.

What do these sources not tell us?  We should be doing autopsies of people who contracted covid and recovered and then went on to die from some other condition.  We should be particularly interested in long-covid sufferers to evaluate the viral load that might persist in multiple organs and how it varies with time.  We don’t yet know for sure if long covid is caused by damages caused by the initial infection or by the persistence of the virus in parts of out bodies, or both.  Could the virus find areas in our bodies where it can lie dormant for long periods and then be reactivated at some time in the future.  We older people are well aware that a chicken pox infection as a child can reappear as a nasty case of shingles in our senior years.

If China’s response is considered extreme in terms of excess restrictions on life, ours in the US is also extreme in the lack of restrictions and in the willingness to let infections propagate to the entire population.  How can we relax restrictions before we know what is going on?

You can learn a little about a lot of things or you can learn a lot about a very few things. Guess which is the most fun.