On the long road to understanding long Covid, this UCSF initiative leads

In the earliest days of the pandemic, critical care doctors tried their best to rescue patients from the worst of a disease that was only narrowly understood. In the spring of 2020, even as the medical community was struggling to figure out the basics of the novel coronavirus, reports of lengthy and life-altering Covid hangovers began to emerge.

Soon, there was a name for the condition: Long Covid.

Now, as the country transitions into the era of endemic Covid, a growing medical infrastructure is being developed to help guide patients through the often-severe lingering impacts of infection. At the heart of that effort is UCSF’s OPTIMAL Clinic, which opened in May 2020 as one of the first clinics specifically dedicated to providing follow-up care for patients who have recovered from the acute symptoms of Covid.

The initiative started as an ad hoc effort, bringing in ICU doctors, a furloughed trauma psychologist, pharmacy students and volunteer specialists in what the clinic’s medical director and founder Dr. Lekshmi Santhosh called “a startup, bootstrapped operation.” 

From the outset, OPTIMAL sought to find effective treatments for those suffering from Long Covid. In the quest to root out its causes and develop therapies, the OPTIMAL team ended up recruiting a multidisciplinary corps of medical professionals. Today, two years into the pandemic, the clinic employs specialists in pulmonology, geriatrics, psychology, physical therapy and social work—all of them working to better understand the complex and intersectional factors that contribute to Long Covid and help patients find their way to recovery.

In the process, the OPTIMAL Clinic has learned a lot about this sometimes-devastating condition, compiled a playbook for others in the nascent field of Long Covid treatment and unearthed clues that may ultimately help battle other mysterious maladies.

Last March, Santhosh co-authored a paper in the medical journal Chest. The paper laid out a framework for others to rapidly design and implement their own clinics to treat patients suffering from Long Covid—or Post-acute Sequelae of Covid-19 (PASC) to those who study the syndrome.

While estimates vary on the number of patients suffering from PASC, the condition is likely to affect millions in the United States.

With a dizzying array of symptoms that range from fatigue to gastrointestinal issues to cognitive impairment or “brain fog,” the holistic approach taken by UCSF’s post-Covid clinic is meant to provide a broad approach to help patients regain overall physical function while improving their mental health and connecting them with resources meant to help with rehabilitation. 

There’s much to be discovered about the causes and physiological mechanisms associated with long Covid, but some answers are becoming clearer. For one, a consensus is growing that an atypical or overbearing immune response to the virus is one of the root causes of the disease.

Additionally, work done at post-Covid clinics like OPTIMAL has provided more detail on the trajectory of recovery, how to design rehabilitation programs to avoid major setbacks and what type of testing is more effective.

While many basic questions remain, and the Long Covid treatment space is still mired in what Santhosh called “snake oil salesmen,” she says the work that she and her team are doing is yielding results.

Some clinical models have provided a working model for patients suffering from lingering Covid symptoms, particularly work done in the post-ICU Syndrome (PICS) space. PICS often impacts those who are critically ill for a prolonged time and hooked up to life support devices, like Covid patients who are put on ventilation while hospitalized.  

One important role the clinic plays, according to Dr. Brian Block, a UCSF pulmonologist and one of OPTIMAL’s founding clinicians, is helping to parse out which symptoms are direct results of a patient’s Covid infection versus those caused by long-term hospitalization or unrelated to their Covid diagnosis. 

“Oftentimes, when we're meeting people who have (PASC), it has nothing to do with Covid specifically, but instead has something to do with the treatment and the effects of being critically ill,” Block said. “That’s where the terminology gets complicated, I think patients are right and that Long Covid is the best descriptor for issues that are Covid-specific.”

Block said a common conversation he has with patients explores that distinction. According to World Health Organization, for example, patients should not be diagnosed with Long Covid until they are experiencing symptoms at least three months after their initial infection. 

In some cases, Block and his colleagues have found alternative explanations for patient symptoms, including respiratory muscle weakness, autoimmune lung disease or even asthma, which lead them down different treatment routes.  

Dissecting these distinctions can help hone the research questions necessary to effectively tackle the condition long term.

Clinicians have also drawn a connection between Long Covid and Chronic Fatigue Syndrome which appears to have similar post-viral origins and overlap in the kinds of symptoms experienced by patients—but Santhosh stressed the variety of disease presentations mean an individualized approach is key.

"The mind and the body are connected. Your physical health impacts your pulmonary health, your mental health impacts your pulmonary health,” Santhosh said. “Oftentimes when [patients] get to us, we’re the first people to say, ‘We do believe you, we do believe your symptoms and know they’re not just in your head.’”

Block, who splits his time between the OPTIMAL clinic and working with Covid patients the ICU, said his work in the post-Covid clinic has also critically informed how he can advise and help guide his patients who end up in the hospital with the virus.

The experience has also underscored the connection between mental and physical health and how they both inform overall recovery. 

Maryam Moody, who works as a social worker with the OPTIMAL clinic, counsels patients through the stress and emotional toll of living with their symptoms, as well as managing the PTSD that can result from the experience of going through the ICU—an ordeal that often leaves patients with a loss of motor or cognitive function.

“Going from an able-bodied person to a disabled person leads to a huge loss of identity,” Moody said.

Another role Moody says she plays is being an understanding ear for patients dealing with the ramifications of suffering from a disease that is not well understood. 

“There's this question they have of how do I recover from this when the rest of the world has kind of moved on?” Moody said.

Kathy Bonacini, a physical therapist with the OPTIMAL Clinic has guided patients’ rehabilitation process with an emphasis on helping them regain their function. Some of the typical issues Bonacini sees is a weakness in core muscles, which impact balance and regular movement, as well as restrictive breathing that can be caused by long-term ICU stays. 

“There's so much about long-haul Covid that we don't know, but people do get better,” Bonacini said, though it can take a very long time.

In order to keep patients motivated and progressing, Bonacini often recommends they keep an activity journal to write down the small daily victories of recovery: eating a meal at the kitchen table, emptying the dishwasher or being able to sit up for a prolonged period without being overly fatigued.

“What's so hard is that you compare yourself how you are today to how you were before you had Covid. That comparison pays a big toll on your psyche,” Bonacini said. “So if you start with a baseline of where you are today and then you fast forward and you have two weeks worth of journaling of what you're able to do, then you start seeing the progress.”

She used the example of one patient who presented as extremely frail and struggled with shallow breathing issues worsened by anxiety. Along with the individual's social worker and pulmonologist, Bonacini helped start the patient on gentle breathing and movement exercises and eventually a more extensive regimen. 

“Part of the interview process was what are your goals and what do you want to get back to being able to do?” Bonacini said. “And we remind them of that. ‘Look you said that you were really wanting to help with your grandkids. Now you're upright all day and helping them with their homework.’ It's very rewarding to be able to see people get back to their regular lives, but the progress can be fast or slow.”

For many Long Covid patients, securing social and medical benefits often requires navigating complex bureaucratic systems—a difficult enough task without shortness of breath, persistent fatigue and brain fog.

For younger patients, Moody said she has seen myriad difficulties in applying for and receiving longer-term disability benefits through Social Security, because of their age.
“Some of the patients we see survive in part because they were a little bit younger a little bit healthier, but that ends up making it even harder to get long-term disability benefits,” Moody said.

In a similar vein, Santhosh says she and her team have had to battle with the business side of the medical industry to justify their existence.

Last month, Santhosh published a paper in the Annals of the American Thoracic Society where she laid out the challenges in selling a business case for a clinic model like OPTIMAL, which relies on upfront investment without necessarily clear-cut returns. 

Ultimately, Santhosh argues that in order to effectively tackle the challenges of a new widespread chronic disease like long Covid, the medical system should respond by shifting its focus to a management model that can prove its worth by protecting patients from bad outcomes that can lead back costly hospital visits.

“Ours is but one example of how post-Covid clinics across the country are fighting to sustain themselves in the face of this novel chronic disease,” she wrote. “While the financial ledger may still be ‘in the red’ for now, some of the benefits that we have described remain to be studied, and some benefits—like clinician well-being and prevention of readmissions—are indeed priceless.”