COVID-19: Why is it mild for some, deadly for others?
Among the confounding aspects of the novel coronavirus is the wide range of disease severity听patients听experience. While听a minority of COVID-19 patients听require听丑辞蝉辫颈迟补濒颈锄补迟颈辞苍, the effects of infection for these people are dramatic and in some cases life threatening.听听
Why do some people get severe and life-threatening COVID-19, while others suffer no symptoms or just mild ones?听听
Older听vs. Younger听
Age is听one听risk factor.听Compared to younger patients, middle-aged and older ones are far more likely to听suffer symptoms, to听be hospitalized, and to die. One recent听听of Chinese data estimated听the chance of death in confirmed COVID-19听cases听at听more than 13 percent for patients 80 and older,听compared to听about 0.15 percent for patients in their 30s, and听virtually听zero听percent听for patients under 20.听A听听of early U.S.听cases by the Centers for Disease Control and Prevention (CDC)听had similar findings.听
Partly this may be explained by the fact that older immune systems tend to be听听at clearing听viral听infections. However, that鈥檚 probably not the full story. 鈥淧eople in their听40s, 50s, and 60s听generally aren鈥檛 hit by other viral infections, such as flu, the way they鈥檙e hit by COVID-19,鈥 said听Dr. Fred听Pelzman, associate professor of clinical medicine at 日本av色情片 and associate attending physician at听NewYork-Presbyterian/日本av色情片 Medical Center.听
Severe COVID-19 is driven not just by viral damage to cells but by a听reactive听鈥渟torm鈥澨of inflammation听that harms the lungs and other organs. There may be changes in different parts of the immune system听from听aging that make the middle-aged more vulnerable to this storm听than younger patients, even if they are healthy and have no underlying medical conditions.听There may also be听lifestyle factors, such as听a听greater听likelihood of听encountering the virus听in social and work settings听that middle-aged people听frequent,听that听contribute to their听vulnerability, Dr.听Pelzman听said.听
Children听,听but are听听听severe听illness.听Again, the reason isn鈥檛 clear.听One听suggestion from听studies of other viruses, including the听听that caused the 2002-04 SARS epidemic,听is that children and younger animals听may be听听to听develop听an inflammatory storm听when infected.听
Men vs. Women听
Men and women appear to get COVID-19 at roughly equal rates, but in most countries men are听听of it. In Italy and Ireland, for example, males account for听about 70听percent of COVID-19 deaths.听
There is no shortage of hypotheses for this difference.听One is that there are听听in the immune response鈥攕tudies of听influenza, for example,听have found that older men tend to have听听outcomes than older women.听Men听also听are听, which听听the immune system听and听. Men听are听听to smoke tobacco, which听听immunity and听overall听lung function,听primes听the lungs and other vital organs听for greater inflammation, and leads to听greater susceptibility to听respiratory infections and听pneumonia.听Chinese clinicians treating COVID-19 cases early听this year听听that a history of cigarette smoking was a very strong risk factor听in听predicting worse disease outcomes.听
Even so, the studies needed to听determine听the factors underlying men鈥檚听extra听vulnerability just haven鈥檛 been done yet, Dr.听Pelzman听emphasized.听
Underlying听Medical Conditions听
Patients听who听develop serious or fatal听COVID-19听are听听to have听at least one major underlying health condition, such as diabetes, hypertension, obesity,听cardiovascular disease,听asthma, kidney disease, or chronic obstructive pulmonary disorder.听
In some cases,听the possible explanations for these links are obvious.听听and听听are听associated with a听weaker resistance to infections; a听听from 日本av色情片 physicians published on April 17 in NEJM suggested that obesity, particularly in men, was associated with treatment requiring mechanical ventilation.听听and chronic obstructive pulmonary disorder involve reduced lung function, and a greater susceptibility to lung inflammation; moreover, patients with these disorders often use听听immune-suppressing drugs, which reduce immunity to respiratory infections. In general, any听serious听underlying medical condition can make a听听less able to withstand听the biological stresses caused by听an听infection and resulting inflammation.听
Some researchers have听听that common treatments for high blood pressure and diabetes may worsen COVID-19 risk, based on the fact that听these drugs听can boost听the levels of ACE2, a cell-surface enzyme that the COVID-19 coronavirus uses to get into cells. However, there is no clinical evidence that these drugs worsen risk, and doctors generally have not advised patients to stop taking them.听
Many people take non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for chronic conditions such as arthritis. These drugs are known to stress the kidneys when taken long-term and may even cause听chronic kidney disease.听That is potentially a problem in the context of COVID-19 because the infection often attacks the kidneys.听Some intensive care specialists have observed unexpectedly severe cases of COVID-19 in people with histories of long-term NSAID use, Dr.听Pelzman听said.听
Having an unusually听weakened immune system,听for example due to听,听organ transplants, or other conditions requiring patients to take immune-suppressing drugs,听is another factor that听may greatly increase the susceptibility to听serious COVID-19 infection听鈥听and听make people听听during infection.听Doctors have been advising those with听suppressed immune systems to听be extra careful听to听avoid potential exposure to the virus, for example by staying home, and washing hands frequently..听
Race听
There is emerging evidence that African Americans are disproportionately likely to develop severe COVID-19. Currently in Louisiana, for example, this group accounts for about 70 percent of COVID-19 deaths, although they make up only a third of the state population. Similar discrepancies are found in many other states. It is simply too early to know what accounts for this apparent vulnerability, but possible factors include African Americans鈥 relatively high rates of听听already linked to severe COVID-19, including hypertension, kidney disease, obesity, and diabetes. Socioeconomic factors, such as poverty, access to healthcare and health insurance may also play a role.听
Immune system 鈥済aps鈥听
Some people who听seem听perfectly healthy and听are听not considered immune-deficient may nevertheless have inherited immune system features that leave them more vulnerable than average听to certain viral infections. This may be due to random genetic variation as well as听鈥攊n principle,听populations听with less historical exposure to coronaviruses could be more vulnerable to COVID-19.听听linking immune听system听gene variants to COVID-19 susceptibility is just beginning, however.听听
Viral dose听
Doctors have long known that the amount, or 鈥渄ose,鈥 of exposure to an infectious agent can be an important determinant of disease severity. Researchers now are looking at this as a factor that possibly explains why some otherwise healthy people are hit so hard by COVID-19.听
鈥Catching a low dose from someone who was mildly symptomatic on the subway may involve a lower risk of severe illness, compared to catching a high dose from a very sick and highly contagious patient,鈥 Dr.听Pelzman听said.听
Viral strain听
SARS-CoV-2, which causes COVID-19,听is a single-stranded RNA virus that has the听ability听to mutate quickly. Over time, and as it spreads around the world, it will develop genetically distinct strains. Some of these听strains听may听spread more easily, or听cause听more听severe disease. However, to date there is no evidence听that the听SARS-CoV-2听viruses听circulating now听are clinically very different from each other听or听that their minor genetic differences听explain the range of symptom severity patients are experiencing.听
Unknowns听
Ultimately,听researchers will need听time听to听analyze听the coronavirus that causes听COVID-19听and evaluate the characteristics of patients who become听infected听in order听to tease听out听the听complex听factors that explain why听some听people get听mortally sick while听others听get听only听a听brief听fever and听cough听鈥听or no symptoms at all.听
鈥While听we wish we had all the answers, we clearly don鈥檛 yet,鈥听Dr.听Pelzman听said.听