COVID-19 patients at risk of sequelae after acute phase of SARS-CoV-2 infection

Patients with COVID-19 appear to have an increased risk of developing new clinical sequelae after the acute phase of SARS-CoV-2 infection, including specific types of sequelae less commonly seen in other viral illnesses, a study has found.

Older patients, those with pre-existing conditions, or those who are hospitalized due to COVID-19 are at greatest excess risk, but younger adults (aged ≤50 years), those without pre-existing conditions, or those not admitted to a hospital are also at high risk of developing new clinical sequelae.

“We found that 14 percent of individuals with SARS-CoV-2 infection developed a new type of clinical sequelae that required medical care after the acute phase of the illness, which was 4.95-percent higher than the 2020 comparator group,” the researchers said.

“An increased and sustained risk for clinical sequelae was seen during the 4 months after the acute illness, particularly, but not exclusively, in individuals with pre-existing conditions or admitted to [a] hospital for COVID-19,” they added.

This retrospective cohort study used three merged data sources from a large US health plan: a large national administrative claims database, an outpatient laboratory testing database, and an inpatient hospital admission database. Individuals aged 18–65 years with continuous enrolment in the health plan from January 2019 to the date of a SARS-CoV-2 infection diagnosis were included.

Using propensity score, the researchers matched patients with COVID-19 to three comparator groups: a 2020 comparator group, a historical 2019 comparator group, and a historical comparator group with viral lower respiratory tract illness. Using ICD-10, more than 50 clinical sequelae were identified after the acute phase of SARS-CoV-2 infection, defined as the date of first diagnosis (index date) plus 21 days.

Of the patients, 14 percent (27,074 of 193,113) had at least one new type of clinical sequelae requiring medical care after the acute phase of the disease, which was 4.95-percent higher than in the 2020 comparator group. [BMJ 2021;373:n1098]

A significantly higher risk for specific new sequelae attributable to SARS-CoV-2 infection after the acute phase—including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia, diabetes, liver test abnormalities, myocarditis, anxiety, and fatigue—was noted in comparison to the three comparator groups (2020, 2019, and viral lower respiratory tract illness groups; p<0.001 for all).

Significant risk differences due to SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people (p<0.001 for all). Compared with the 2020 comparator group, hazard ratios ranged from 1.24 to 25.65.

“Many of these outcomes have been previously reported in case studies or observational studies during the acute phase of COVID-19, including tachycardia, hypercoagulability, mental health outcomes, encephalopathy, diabetes, and amnesia),” the researchers said. [EClinicalMedicine 2020;29:100639; Heart Rhythm 2020;17:1439-1444; Brain Behav Immun 2020;89:531-542; Brain Behav Immun 2020;88:945-946; N Engl J Med 2020;382:2268-2270; Diabetes Obes Metab 2021;23:870-874]

“A few studies have also highlighted persistent symptoms or new clinical diagnoses after the acute infection, although few have reported on a full range of new clinical diagnoses across multiple organ systems in such a large population,” they added. [J Infect 2020;81:e4-6; J Infect 2021;82:378-383; Blood Adv 2020;4:5373-5377; Lancet 2021;397:220-232; JAMA Netw Open 2021;4:e210830]

In a linked editorial, scientific adviser Elaine Maxwell from the National Institute for Health Research in London, UK, believed that it is “too early to predict how long clinical sequalae will persist after COVID-19.” However, the symptoms were clearly a major burden for many people, with some having difficulty returning to work or unable to care for dependents. [BMJ 2021;373:n1173]

“Long COVID is also putting a strain on healthcare services, which have been already decimated by the pandemic. Identifying risk factors would facilitate triage and faster access to specialist care,” Maxwell said. “However, one of the peculiarities of long COVID is its nonlinear progression, hampering attempts to predict who will develop particular symptoms and when.”

As such, healthcare professionals should watch out for the possibility of long COVID in anyone with confirmed or suspected COVID-19, according to Maxwell, adding that treatment of these longer-term consequences is now an urgent research priority.