As we reach the tenth month of the pandemic, the COVID-19 crisis only seems to be worsening in the United States. At the time of writing, about 40,000 to 70,000 more Americans are testing positive each day, with infection rates gradually increasing. It is no secret that SARS-CoV-2 is exceedingly contagious: according to the CDC, it spreads much more quickly than other viruses, such as influenza (2020a). Luckily, however, the disease has a relatively low fatality rate of about 1%, including both reported cases and estimates of unreported cases (Mallapaty, 2020). In other words, most people seem to recover after a couple weeks of battling SARS-CoV-2, able to continue their lives without permanent complications.
Yet, is this really true? Recently, scientists have been studying patients after their supposed recovery time, examining their immune systems, their symptoms, their mental health, and more factors, all to answer the question: When it comes to coronavirus, what happens after recovery?
Firstly, researchers are particularly interested in the immunity of COVID-19 survivors. Theoretically, if enough individuals develop an immunity to the virus, the virus will be unable to infect enough individuals to remain wide-spread, and gradually decline (Randolph & Barreiro, 2020). This type of resistance to the disease is called herd immunity. Scientists study how the body becomes immune to viruses, in part to understand under which conditions herd immunity will develop.
After an infection, the immune system identifies the invading pathogen by scanning its surface. By doing so, it finds unique external molecules (called antigens) that it can use to distinguish the foreign germ from other cells. With this information, the immune system’s plasma cells get to work, mass-producing antibodies to target the specific viral or bacterial strain. Antibodies are tiny chemicals that bind to the antigens of the virus, either neutralizing the cells by themselves, or marking the pathogenic cells for destruction by other immune responses. Through these mechanisms, antibodies are the body’s most powerful weapons in the fight against disease. (Ghose, 2020)
After an infection has been fought off, antibodies remain in the bloodstream, ready to defend the body against any cells that display the antigen it was designed for. In addition, “memory B” cells are produced, which are able to manufacture antibodies quickly in case of a reinfection. In this way, the individual theoretically develops an immunity to the pathogen: numerous antibodies swarm and eliminate any of the same viruses before they can multiply. (Ghose, 2020)
This is the traditional view of how we become immune to a disease after infection. However, not all diseases leave antibodies in the bloodstream. Furthermore, these antibodies can diminish over time. (Schimelpfening, 2020)
Recently, researchers have studied how coronavirus survivors have specifically exhibited immune characteristics. One study published in the journal Immunity on October 5th analyzed the antibodies of 5,882 Arizona citizens who had recovered from the virus (Ripperger et al., 2020). They estimated the antibody levels in the blood of subjects using a serology (antibody) test (Ackerman & Von Eisenburg, 2020). In this process, researchers exposed participants’ blood samples to SARS-CoV-2 antigens. The reaction between the blood and the antigens revealed the concentration of antibodies in the sample. From this data, scientists concluded that while intense cases of the coronavirus led to greater antibody production, even mild cases confer COVID-19 resistance for at least 5-7 months. They also suggest that immunity can last for longer, but do not yet have much evidence to back this claim. This study is good news for herd immunity, because it proves that individuals are most likely protected from further infection and transmission after recovering from an initial COVID-19 sickness.
However, other recently published evidence calls these conclusions into question. As of October 19th, 2020, there have been two confirmed cases of coronavirus reinfection in the United States. One twenty-five year old Nevada man became stricken with the virus in mid-April, and tested positive on April 18th. He quickly recovered in a few weeks and tested negative in early May. However, he returned to his urgent care facility on May 31st, with a self-reported fever, headache, dizziness, cough, nausea, and diarrhea. He was later found to be hypoxic (inadequately receiving oxygen), and sent to the hospital, where he again tested positive for the virus on June 5th. Worryingly, his second bout with coronavirus had much more intense symptoms than his first, although he survived to test negative once again. (Tillet et al., 2020)
The second instance of reinfection follows much the same pattern. A forty-two year old man from Virginia tested positive for COVID-19 on March 21st and June 1st, with a negative test in-between. Furthermore, in both of these cases, comparisons of viral RNA sequences between the two infections revealed that the strains belonged to separate viral clades, thus confirming that the two men both had two cases of reinfection, and not one prolonged case. (Larson et al., 2020)
While these are only two anecdotes, they are extremely worrying for a coronavirus prognosis. 49 and 72 days between reinfections are far removed from the predicted 5-7 months that Ripperger, et al. calculated. And, there are other reported reinfections outside of the United States (Goodman, 2020). Unfortunately, it is impossible to know the true number of these double-contractions, since many cases may be asymptomatic. Quick-succession infections may be extreme outliers, or they could be more common than we think. More research must be done to confirm or deny such claims. For now, even those who have recovered from the virus must not fall into a false sense of security. And, policymakers need to consider the possibility that herd immunity may be an impossible goal, if most individuals are vulnerable to reinfections.
However, the problem of reinfection only arises in those who have recovered from COVID-19. Frighteningly, some individuals have reported cases of the virus that have lasted much longer than the one to two week average recovery time. These individuals experience long-term side effects, including fever, shortness of breath, nausea, chest pain, headache, fatigue, and others, that can continue for months (Couzin-Frankel, 2020). Symptoms also often jump between body system to body system, moving from respiratory, cardiovascular, neurological, and digestive systems one after another. This type of COVID-19 is referred to as “ongoing COVID-19” or “long COVID.”
It is unclear how many people live with ongoing COVID-19. One United Kingdom study found that more than one in ten patients experienced characteristic symptoms (e.g. fatigue, headaches, coughs, sore throats, delirium, and chest pain) after three weeks of diagnosis (COVID: UK Data, 2020). A study in Italy took a more liberal view on COVID-19 symptoms, and concluded that 87% of individuals had at least minor symptoms two months after the onset of the disease, with 40% of patients claiming that the disease’s aftereffects still reduced their quality of life (Carfì et al., 2020). Other studies have returned statistics of 10%, 20%, and 45% of coronavirus cases with continuing symptoms after a month (NIHR, 2020).
Regardless of the exact proportion, long COVID definitely exists. There are endless testimonials from those who claim to experience intense symptoms for months after diagnosis. These individuals’ symptoms are also verifiable with empirical evidence and coronavirus tests, meaning that this is not a mental phenomenon. Many sufferers of long COVID have also experienced distrust from health professionals who are skeptical that COVID-19 can last for these long periods of time, leading to unnecessary hardship and psychological strain. This problem is intensified by the fact that there is currently no code for the diagnosis of ongoing COVID-19 (NIHR, 2020).
Urgent research is needed into ongoing COVID-19. This subset of the virus potentially affects millions, yet it has not been adequately studied to even have a scientific name. Beyond the health of these millions, it is important to fully understand how long those affected remain contagious to others, and how these cases should influence policies surrounding the pandemic.
Besides ongoing COVID-19, perhaps even more worrying is the uncertainty about the long-term effects of the disease even in those who have made a full recovery. Luckily, COVID-19 seems to follow a lytic cycle, in which viruses invade a cell, reproduce using the cell’s machinery, and then burst outwards into the environment to infect other cells. This is in contrast to the lysogenic cycle, in which viruses incorporate their genome into a host cell’s DNA (Doss et al., 2017). This viral genetic information then remains in the body, as cells with contaminated DNA replicate many times over. After many years, certain environmental stimuli can trigger the cell to express the hidden viral genome and construct new viruses, restarting the infection. A real-world example of this is the varicella-zoster virus, which causes chicken pox (Zerboni et al., 2014). After the initial disease, the virus often lies inactive until adulthood, when the same individual contracts shingles. For now, evidence points to SARS-CoV-2 following only a lytic cycle in nature, and not a lysogenic cycle. However, the research is still young and incomplete, and the small chance of a viral resurgence in millions of COVID-19 survivors decades later is something to consider.
Even still, the coronavirus is known to sometimes cause permanent damage to tissue. There are many cases of stroke, brain hemorrhage, and memory loss due to the virus (Marshall, 2020). These symptoms are caused by both encephalitis (neural inflammation), lack of oxygen, and direct attacks to brain tissue by SARS-CoV-2. Although it is not known how many are affected in these ways, it is clear that the coronavirus can damage neurons and the central nervous system as a whole in irreversible ways, especially towards the elderly (Budson, 2020).
The disease also poses other risks of permanent damage, including kidney failure, myocarditis (heart damage), scar tissue in the lungs, and increased risk for Alzheimer’s and Parkinson’s (e.g. Long et al., 2020). For example, the American Heart Association reported that 78% of recovering coronavirus patients possessed heart abnormalities detected with cardiac MRIs (2020). These abnormalities were mostly due to cardiac inflammation; it is feared that this widespread damage will lead to increased heart failure in these patients later in life. In addition, a common complication of the virus, Acute Respiratory Distress Syndrome (ARDS), leaves lasting pulmonary scarring in its victims (Galiatsatos, 2020). The scientific name for this is pulmonary fibrosis, and it leaves the normally thin, lacy walls of the lungs thick and stiff, permanently reducing the ability to dissolve oxygen in the blood. Concerning the excretory system, one estimate places about 30% of COVID-19 victims showing signs of kidney damage (Sperati, 2020). However, the cause of these injuries is unknown; some theories include targeting of kidney cells by the virus itself, complications reducing blood flow to the kidneys, and excessive inflammation due to cytokine storms, an aggressive immune response by the body.
While the CDC states they are “actively working to learn more about the whole range of short- and long-term health effects associated with COVID-19,” at the present, there just isn’t adequate research about the disease’s lasting effects on our health (2020b). There may even be enduring symptoms that haven’t been identified yet, and may only present themselves years after the pandemic is over.
Cycles of reinfections, the prevalence of long-COVID, and permanent damage to our bodies after COVID recovery are all aspects of the disease that have the potential to be just as influential as the base infection itself. Unfortunately, these developments are presently all dangerously under-researched (a common theme of the coronavirus). It can be difficult for scientists to create new treatments and lawmakers to support new policies without all of the relevant knowledge. It often seems impossible to look towards the future, when the present is full of such difficult challenges. However, researchers need to make these three subjects’ close examination a priority, to ensure the safety of our society in the long-term, and not just in the short-term.
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Article written by Alex Borengasser
Article edited by Devanandh Murugesan
Graphics by Tiya Shah
Group advised by Lakshmi Sriram