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 severitypatientsexperience. Whilea minority of COVID-19 patientsrequireDz辱ٲپDz, the effects of infection for these people are dramatic and in some cases life threatening.
Why do some people get severe and life-threatening COVID-19, while others suffer no symptoms or just mild ones?
Oldervs. Younger
Age isonerisk factor.Compared to younger patients, middle-aged and older ones are far more likely tosuffer symptoms, tobe hospitalized, and to die. One recentof Chinese data estimatedthe chance of death in confirmed COVID-19casesatmore than 13 percent for patients 80 and older,compared toabout 0.15 percent for patients in their 30s, andvirtuallyzeropercentfor patients under 20.Aof early U.S.cases by the Centers for Disease Control and Prevention (CDC)had similar findings.
Partly this may be explained by the fact that older immune systems tend to beat clearingviralinfections. However, that’s probably not the full story. “People in their40s, 50s, and 60sgenerally aren’t hit by other viral infections, such as flu, the way they’re hit by COVID-19,” saidDr. FredPelzman, associate professor of clinical medicine at ͼ and associate attending physician atNewYork-Presbyterian/Weill Cornell Medical Center.
Severe COVID-19 is driven not just by viral damage to cells but by areactive“storm”of inflammationthat harms the lungs and other organs. There may be changes in different parts of the immune systemfromaging that make the middle-aged more vulnerable to this stormthan younger patients, even if they are healthy and have no underlying medical conditions.There may also belifestyle factors, such asagreaterlikelihood ofencountering the virusin social and work settingsthat middle-aged peoplefrequent,thatcontribute to theirvulnerability, Dr.Pelzmansaid.
Children,but aresevereillness.Again, the reason isn’t clear.Onesuggestion fromstudies of other viruses, including thethat caused the 2002-04 SARS epidemic,is that children and younger animalsmay betodevelopan inflammatory stormwhen infected.
Men vs. Women
Men and women appear to get COVID-19 at roughly equal rates, but in most countries men areof it. In Italy and Ireland, for example, males account forabout 70percent of COVID-19 deaths.
There is no shortage of hypotheses for this difference.One is that there arein the immune response—studies ofinfluenza, for example,have found that older men tend to haveoutcomes than older women.Menalsoare, whichthe immune systemand. Menareto smoke tobacco, whichimmunity andoveralllung function,primesthe lungs and other vital organsfor greater inflammation, and leads togreater susceptibility torespiratory infections andpneumonia.Chinese clinicians treating COVID-19 cases earlythis yearthat a history of cigarette smoking was a very strong risk factorinpredicting worse disease outcomes.
Even so, the studies needed todeterminethe factors underlying men’sextravulnerability just haven’t been done yet, Dr.Pelzmanemphasized.
UnderlyingMedical Conditions
Patientswhodevelop serious or fatalCOVID-19areto haveat least one major underlying health condition, such as diabetes, hypertension, obesity,cardiovascular disease,asthma, kidney disease, or chronic obstructive pulmonary disorder.
In some cases,the possible explanations for these links are obvious.andareassociated with aweaker resistance to infections; afrom ͼ physicians published on April 17 in NEJM suggested that obesity, particularly in men, was associated with treatment requiring mechanical ventilation.and chronic obstructive pulmonary disorder involve reduced lung function, and a greater susceptibility to lung inflammation; moreover, patients with these disorders often useimmune-suppressing drugs, which reduce immunity to respiratory infections. In general, anyseriousunderlying medical condition can make aless able to withstandthe biological stresses caused byaninfection and resulting inflammation.
Some researchers havethat common treatments for high blood pressure and diabetes may worsen COVID-19 risk, based on the fact thatthese drugscan boostthe 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.
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 causechronic kidney disease.That is potentially a problem in the context of COVID-19 because the infection often attacks the kidneys.Some intensive care specialists have observed unexpectedly severe cases of COVID-19 in people with histories of long-term NSAID use, Dr.Pelzmansaid.
Having an unusuallyweakened immune system,for example due to,organ transplants, or other conditions requiring patients to take immune-suppressing drugs,is another factor thatmay greatly increase the susceptibility toserious COVID-19 infection–andmake peopleduring infection.Doctors have been advising those withsuppressed immune systems tobe extra carefultoavoid potential exposure to the virus, for example by staying home, and washing hands frequently..
Race
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’ relatively high rates ofalready 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.
Immune system “gaps”
Some people whoseemperfectly healthy andarenot considered immune-deficient may nevertheless have inherited immune system features that leave them more vulnerable than averageto certain viral infections. This may be due to random genetic variation as well as—in principle,populationswith less historical exposure to coronaviruses could be more vulnerable to COVID-19.linking immunesystemgene variants to COVID-19 susceptibility is just beginning, however.
Viral dose
Doctors have long known that the amount, or “dose,” 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.
“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,” Dr.Pelzmansaid.
Viral strain
SARS-CoV-2, which causes COVID-19,is a single-stranded RNA virus that has theabilityto mutate quickly. Over time, and as it spreads around the world, it will develop genetically distinct strains. Some of thesestrainsmayspread more easily, orcausemoresevere disease. However, to date there is no evidencethat theSARS-CoV-2virusescirculating noware clinically very different from each otherorthat their minor genetic differencesexplain the range of symptom severity patients are experiencing.
Unknowns
Ultimately,researchers will needtimetoanalyzethe coronavirus that causesCOVID-19and evaluate the characteristics of patients who becomeinfectedin orderto teaseoutthecomplexfactors that explain whysomepeople getmortally sick whileothersgetonlyabrieffever andcough–or no symptoms at all.
“Whilewe wish we had all the answers, we clearly don’t yet,”Dr.Pelzmansaid.