By LAU­RA UN­GAR and LIND­SEY TAN­NER-As­so­ci­at­ed Press

More than a year af­ter a bout with COVID-19, Re­bekah Hogan still suf­fers from se­vere brain fog, pain and fa­tigue that leave her un­able to do her nurs­ing job or han­dle house­hold ac­tiv­i­ties.

Long COVID has her ques­tion­ing her worth as a wife and moth­er.

“Is this per­ma­nent? Is this the new norm?” said the 41-year-old Lath­am, New York, woman, whose three chil­dren and hus­band al­so have signs of the con­di­tion. “I want my life back.’’

More than a third of COVID-19 sur­vivors by some es­ti­mates will de­vel­op such lin­ger­ing prob­lems. Now, with omi­cron sweep­ing across the globe, sci­en­tists are rac­ing to pin­point the cause of the be­dev­il­ing con­di­tion and find treat­ments be­fore a po­ten­tial ex­plo­sion in long COVID cas­es.

Could it be an au­toim­mune dis­or­der? That could help ex­plain why long COVID-19 dis­pro­por­tion­ate­ly af­fects women, who are more like­ly than men to de­vel­op au­toim­mune dis­eases. Could mi­cro­clots be the cause of symp­toms rang­ing from mem­o­ry laps­es to dis­col­ored toes? That could make sense, since ab­nor­mal blood clot­ting can oc­cur in COVID-19.

As these the­o­ries and oth­ers are test­ed, there is fresh ev­i­dence that vac­ci­na­tion may re­duce the chances of de­vel­op­ing long COVID.

It’s too soon to know whether peo­ple in­fect­ed with the high­ly con­ta­gious omi­cron vari­ant will de­vel­op the mys­te­ri­ous con­stel­la­tion of symp­toms, usu­al­ly di­ag­nosed many weeks af­ter the ini­tial ill­ness. But some ex­perts think a wave of long COVID is like­ly and say doc­tors need to be pre­pared for it.

With $1 bil­lion from Con­gress, the Na­tion­al In­sti­tutes of Health is fund­ing a vast ar­ray of re­search on the con­di­tion. And clin­ics de­vot­ed to study­ing and treat­ing it are pop­ping up around the world, af­fil­i­at­ed with places such as Stan­ford Uni­ver­si­ty in Cal­i­for­nia and Uni­ver­si­ty Col­lege Lon­don.

WHY DOES IT HAP­PEN?

Mo­men­tum is build­ing around a few key the­o­ries.

One is that the in­fec­tion or rem­nants of the virus per­sist past the ini­tial ill­ness, trig­ger­ing in­flam­ma­tion that leads to long COVID.

An­oth­er is that la­tent virus­es in the body, such as the Ep­stein-Barr virus that caus­es mononu­cle­o­sis, are re­ac­ti­vat­ed. A re­cent study in the jour­nal Cell point­ed to Ep­stein-Barr in the blood as one of four pos­si­ble risk fac­tors, which al­so in­clude pre-ex­ist­ing Type 2 di­a­betes and the lev­els of coro­n­avirus RNA and cer­tain an­ti­bod­ies in the blood. Those find­ings must be con­firmed with more re­search.

A third the­o­ry is that au­toim­mune re­spons­es de­vel­op af­ter acute COVID-19.

In a nor­mal im­mune re­sponse, vi­ral in­fec­tions ac­ti­vate an­ti­bod­ies that fight in­vad­ing virus pro­teins. But some­times in the af­ter­math, an­ti­bod­ies re­main revved up and mis­tak­en­ly at­tack nor­mal cells. That phe­nom­e­non is thought to play a role in au­toim­mune dis­eases such as lu­pus and mul­ti­ple scle­ro­sis.

Justy­na Fert-Bober and Dr. Su­san Cheng were among re­searchers at Cedars-Sinai Med­ical Cen­ter in Los An­ge­les who found that some peo­ple who have had COVID-19, in­clud­ing cas­es with­out symp­toms, have a va­ri­ety of these el­e­vat­ed “au­toan­ti­bod­ies” up to six months af­ter re­cov­er­ing. Some are the same ones found in peo­ple with au­toim­mune dis­eases.

An­oth­er pos­si­bil­i­ty is that tiny clots play a role in long COVID. Many COVID-19 pa­tients de­vel­op el­e­vat­ed lev­els of in­flam­ma­to­ry mol­e­cules that pro­mote ab­nor­mal clot­ting. That can lead to blood clots through­out the body that can cause strokes, heart at­tacks and dan­ger­ous block­ages in the legs and arms.

In her lab at Stel­len­bosch Uni­ver­si­ty in South Africa, sci­en­tist Re­sia Pre­to­rius has found mi­cro­clots in blood sam­ples from pa­tients with COVID-19 and in those who lat­er de­vel­oped long COVID. She al­so found el­e­vat­ed lev­els of pro­teins in blood plas­ma that pre­vent­ed the nor­mal break­down of these clots.

She be­lieves that these clot­ting ab­nor­mal­i­ties per­sist in many pa­tients af­ter an ini­tial coro­n­avirus in­fec­tion and that they re­duce oxy­gen dis­tri­b­u­tion to cells and tis­sue through­out the body, lead­ing to most if not all symp­toms that have been linked to long COVID.

IT CAN HIT NEAR­LY ANY­ONE

While there’s no firm list of symp­toms that de­fine the con­di­tion, the most com­mon in­clude fa­tigue, prob­lems with mem­o­ry and think­ing, loss of taste and smell, short­ness of breath, in­som­nia, anx­i­ety and de­pres­sion.

Some of these symp­toms may first ap­pear dur­ing an ini­tial in­fec­tion but linger or re­cur a month or more lat­er. Or new ones may de­vel­op, last­ing for weeks, months or over a year.

Be­cause so many of the symp­toms oc­cur with oth­er ill­ness­es, some sci­en­tists ques­tion whether the coro­n­avirus is al­ways the trig­ger. Re­searchers hope their work will pro­vide de­fin­i­tive an­swers.

Long COVID af­fects adults of all ages as well as chil­dren. Re­search shows it is more preva­lent among those who were hos­pi­tal­ized, but al­so strikes a sig­nif­i­cant por­tion who weren’t.

Re­tired flight at­ten­dant Jac­ki Gra­ham’s bout with COVID-19 at the be­gin­ning of the pan­dem­ic wasn’t bad enough to put her in the hos­pi­tal. But months lat­er, she ex­pe­ri­enced breath­less­ness and a rac­ing heart. She couldn’t taste or smell. Her blood pres­sure shot up.

In the fall of 2020, she be­came so fa­tigued that her morn­ing yo­ga would send her back to bed.

“I’m an ear­ly ris­er, so I’d get up and push my­self, but then I was done for the day,” said Gra­ham, 64, of Stu­dio City, Cal­i­for­nia. “Six months ago, I would have told you COVID has ru­ined my life.”

Hogan, the New York nurse, al­so wasn’t hos­pi­tal­ized with COVID-19 but has been de­bil­i­tat­ed since her di­ag­no­sis. Her hus­band, a dis­abled vet­er­an, and chil­dren ages 9, 13 and 15 fell ill soon af­ter and were sick with fever, stom­ach pains and weak­ness for about a month. Then all seemed to get a lit­tle bet­ter un­til new symp­toms ap­peared.

Hogan’s doc­tors think au­toim­mune ab­nor­mal­i­ties and a pre-ex­ist­ing con­nec­tive tis­sue dis­or­der that caus­es joint pain may have made her prone to de­vel­op­ing the con­di­tion.

PO­TEN­TIAL AN­SWERS

There are no treat­ments specif­i­cal­ly ap­proved for long COVID, though some pa­tients get re­lief from painkillers, drugs used for oth­er con­di­tions, and phys­i­cal ther­a­py. But more help may be on the hori­zon.

Im­muno­bi­ol­o­gist Akiko Iwasa­ki is study­ing the tan­ta­liz­ing pos­si­bil­i­ty that COVID-19 vac­ci­na­tion might re­duce long COVID symp­toms. Her team at Yale Uni­ver­si­ty is col­lab­o­rat­ing with a pa­tient group called Sur­vivor Corps on a study that in­volves vac­ci­nat­ing pre­vi­ous­ly un­vac­ci­nat­ed long COVID pa­tients as a pos­si­ble treat­ment.

Iwasa­ki, who is al­so an in­ves­ti­ga­tor with the Howard Hugh­es Med­ical In­sti­tute, which sup­ports The As­so­ci­at­ed Press’ Health and Sci­ence De­part­ment, said she is do­ing this study be­cause pa­tient groups have re­port­ed im­prove­ment in some peo­ple’s long COVID symp­toms af­ter they got their shots.

Study par­tic­i­pant Nan­cy Rose, 67, of Port Jef­fer­son, New York, said many of her symp­toms waned af­ter she got vac­ci­nat­ed, though she still has bouts of fa­tigue and mem­o­ry loss.

Two re­cent­ly re­leased stud­ies, one from the U.S. and one from Is­rael, of­fer pre­lim­i­nary ev­i­dence that be­ing vac­ci­nat­ed be­fore get­ting COVID-19 could help pre­vent the lin­ger­ing ill­ness or at least re­duce its sever­i­ty. Both were done be­fore omi­cron emerged.

Nei­ther has been pub­lished in a peer-re­viewed jour­nal, but out­side ex­perts say the re­sults are en­cour­ag­ing.

In the Is­raeli study, about two-thirds of par­tic­i­pants re­ceived one or two Pfiz­er shots; the oth­ers were un­vac­ci­nat­ed. Those who had re­ceived two shots were at least half as like­ly to re­port fa­tigue, headache, mus­cle weak­ness or pain and oth­er com­mon long COVID symp­toms as the un­vac­ci­nat­ed group.

UN­CER­TAIN FU­TURE

With few clear an­swers yet, the fu­ture is murky for pa­tients.

Many, like Gra­ham, see im­prove­ment over time. She sought help through a long COVID pro­gram at Cedars-Sinai, en­rolled in a study there in April 2021, and was vac­ci­nat­ed and boost­ed.

To­day, she said, her blood pres­sure is nor­mal, and her sense of smell and en­er­gy lev­el are get­ting clos­er to pre-COVID lev­els. Still, she wound up re­tir­ing ear­ly be­cause of her or­deal.

Hogan still strug­gles with symp­toms that in­clude ag­o­niz­ing nerve pain and “spaghet­ti legs,” or limbs that sud­den­ly be­come limp and un­able to bear weight, a con­di­tion that al­so af­fects her 13-year-old son.

Some sci­en­tists wor­ry that long COVID in cer­tain pa­tients might be­come a form of chron­ic fa­tigue syn­drome, a poor­ly un­der­stood, long-last­ing con­di­tion that has no cure or ap­proved treat­ment.

One thing’s for sure, some ex­perts say: Long COVID will have a huge ef­fect on in­di­vid­u­als, health care sys­tems and economies around the world, cost­ing many bil­lions of dol­lars.

Even with in­sur­ance, pa­tients can be out thou­sands of dol­lars at a time when they’re too sick to work. Gra­ham, for ex­am­ple, said she paid about $6,000 out of pock­et for things like scans, labs, doc­tor vis­its and chi­ro­prac­tic care.

Pre­to­rius, the sci­en­tist in South Africa, said there is re­al wor­ry things could get worse.

“So many peo­ple are los­ing their liveli­hoods, their homes. They can’t work any­more,” she said. “Long COVID will prob­a­bly have a more se­vere im­pact on our econ­o­my than acute COVID.”