What the Future May Hold for Covid-19 Survivors
More than 3 million Americans1 have been hospitalized with Covid-19, and 770,000 of them have died. 2 As of this writing, 49,000 Americans are hospitalized, with 12,000 remaining in intensive care units.3 With growing numbers of patients being discharged from extensive stays in the ICU for severe Covid, it remains to be seen what the long-term impact will be on these patients, their families and on society writ large.
And these are just the patients with severe Covid: those who were never hospitalized are also showing deleterious effects from the effects of their illness.
Covid in the ICU
What we know is that prior to Covid, 10% of all patients were admitted to ICU with acute respiratory distress syndrome4 (ARDS), despite receiving such life-saving measures as mechanical ventilation, medication, and supportive nutrition. Those who do survive face a long journey.4 Besides the specific respiratory recovery needed in those with ARDS, patients who have spent time in the ICU can develop multiple non-respiratory complications, including muscle wasting, generalized weakness, and delirium. The physical, cognitive, and psychological impairments that follow an ICU stay are termed postintensive care syndrome (PICS). PICS is an underrecognized phenomenon that describes the immense complications of an ICU stay for any reason. Recognition of this entity, and education of patients, is particularly important now as we face an ongoing pandemic which is creating a burgeoning number of ICU graduates.
Cognitive dysfunction is one hallmark of PICS. Delirium is a common complication of any hospitalization, with critically ill patients particularly susceptible given the severity of their illness and their exposure to medications such as sedatives. However, persistent global cognitive impairment is unique to PICS. Up to 40% 4 of ICU survivors have been found to have cognitive test results similar to those with moderate traumatic brain injury 3 months after discharge; approximately 34% were still affected at 1 year. Similar findings were seen in a different study of ARDS patients.5 Hopkins et al. found that in these patients the rate of neurocognitive deficit persisted in 47% of patients at their 2-year follow-up. Patients describe being unable to re-enter their prior lives, troubled by difficulties with complex thinking and activities of daily living.
The second aspect of PICS is its psychological component. In the Hopkins study,5 23% ultimately reported persistent symptoms of depression and/or anxiety two years afterwards. Some patients have described intrusive distorted memories from their time in ICU; one patient detailed a recurring memory of an hallucination in which the nurses were transformed into demons hovering over his bed. Others have described feelings akin to depression, anxiety, and posttraumatic stress syndrome (PTSD).
The final component of PICS is physical impairment. Those who are critically ill commonly suffer intensive care unit-acquired weakness,6 which is a term to describe generalized limb and diaphragmatic weakness with no other medical cause. Risk factors for this entity include sepsis, multi-organ failure, mechanical ventilation, hyperglycemia, extensive immobilization, and exposure to steroids and neuromuscular blocking agents. ICU-acquired weakness can resolve within weeks to months but in some studies can persist for years. It has been observed that survivors of ARDS experience persistent physical limitations, even 5 years later.
Covid in the ICU
Estimates of the incidence of PICS due to Covid are evolving. A report on 1700 Covid hospitalized patients in Wuhan, China demonstrated a large prevalence of residual symptoms at 6 months. The most common symptoms were fatigue and weakness (63%), insomnia (26%), and anxiety or depression (23%).7 Furthermore, one-fourth to one-third of those with severe illness fell below the lower limit of normal for a 6-minute walk test. An Italian study demonstrated decreased global quality of life indices for Covid ICU survivors8 3 months from discharge, particularly with mobility, eating, and resuming usual activities. In a Michigan observational9 study, which included all hospitalized patients with Covid including those never in ICU, one-third of respondents said they continued to cough or have shortness of breath. Only one-fourth had returned to work, with many of them having to modify activities or reduce hours due to their health. Nearly half reported being negatively emotionally impacted by their health issues. Last, a single French hospital10 discovered that Covid patients 4 months after hospital discharge experienced numerous, persistent symptoms. 38% of patients confirmed some form of cognitive impairment, with 17% reporting memory difficulties, 10% mental slowness, and 10% concentration problems. Of patients who were intubated, one-third still reported subjective dyspnea. Nearly a third still struggled with weakness.
As more centers track the progress of their ICU graduates over time, we can better understand the profound impact of critical illness on our Covid patients and better educate our patients and families on what to expect. One might be able to gain some clues from what is known regarding the prior coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In these diseases, a meta-analysis showed significant rates of lung function abnormalities,11 physical deconditioning, and mental health disorders during the 6 months after discharge. It might be that the impact of SARS-CoV2 is even more profound on survivors; additional studies need to be done.
What is particularly unique to Covid is the prevalence of long-term symptoms in those who were never hospitalized for Covid. Recent estimates of non-hospitalized patients who had Covid are showing at least 25% of them have had long-lasting effects, including stomach pain and respiratory issues.12 We are continuing to learn more about what is described as “long-haul syndrome.” It has been described in both hospitalized and non-hospitalized patients, and therefore it can be hard to distinguish which symptoms are attributable to long-term effects of Covid infection versus the critical illness/PICS itself. These long-haul symptoms range from persistent lack of smell and taste, cognitive dysfunction, fatigue, decreased exercise endurance, and an increase in mental health disorders. The prognosis and spectrum of disease, as well as treatment, have yet to be determined, and the NIH is initiating a multicenter research study, RECOVER, to better characterize this syndrome.13 Patients who are interested in enrolling can fill out an interest form at recoverCovid.org.
Financially 1/314 of patients were impacted by their hospitalization for Covid, with nearly 10% using most or all their savings, despite many being covered by cost-sharing waivers for Covid care. A study reviewing Medicare data noted that the mean cost of a hospitalization for Covid is $21,752,15 increasing to nearly $50,000 if mechanical ventilation is needed. This does not account for the cost of rehabilitative care, as 40%16 of patients are discharged either to home with additional services or to other facilities (skilled nursing facility, hospice). As insurance companies increasingly lift the cost-sharing waivers and patients assume more responsibility for paying more of this cost, the financial burden on individual patients will increase. Furthermore, given a prolonged course of mental and physical disabilities after severe Covid, patients may lose their ability to return to work, their medical insurance, or their ability to provide childcare, further compounding their family’s financial woes.
The long-term effects of hospitalization from Covid argues further for continued work on increasing the vaccination rate of our population. Even with Delta variant, vaccines decrease the risk of hospitalization and death by more than a factor of 10.17 The profound medical and financial effects of severe Covid, and the repercussions on their family, should compel us as health care practitioners to inform those who are vaccine hesitant and to inform patients that they are eligible for vaccine boosters. The combination of colder weather and loosening of social distancing has already led to another surge of Covid infections and makes expedient vaccination the priority.