Long COVID, or postacute sequelae of SARS-CoV-2 infection, refers to persistent, relapsing-remitting, or new symptoms of COVID-19 lasting longer than 3 months after initial SARS-CoV-2 infection.¹ Common symptoms include fatigue, dyspnea, and cognitive impairment.¹ Anxiety and depression are common, with prevalence rates ranging from 16% to 37% for anxiety and 15% to 32% for depression.^2–4 Over 22 months, adults with long COVID experienced persistently higher rates of depressive symptoms and less improvement in anxiety compared with adults who fully recovered from SARS-CoV-2 infection.⁵ Mental health sequelae in patients with long COVID are shaped by complex factors, including biologic (eg, systemic inflammation), social (eg, health care access, isolation), and psychological (eg, psychiatric history) contributors.⁶ Consequently, the biopsychosocial model is important for addressing mental health symptoms and avoiding implications that symptoms are psychogenic.^7–9

Risk factors for anxiety and depression in long COVID include COVID-related factors (eg, self-perceived illness severity, hospitalization for COVID-19, bereavement), female sex, prior psychiatric history, and clinical and biologic factors (eg, comorbidities, higher circulating inflammatory cytokines, disrupted serotonin production).¹⁰ Anxiety and depression may also reflect adjustment disorders in response to long COVID. Additionally, adults from underrepresented minority groups (eg, racial and ethnic minorities, transgender and gender-diverse populations) face higher risk for long COVID and associated mental health sequelae due to systemic inequities and barriers to care.^11,12

Best practices in caring for adults with long COVID include a trauma-informed biopsychosocial approach to screening, assessment, and treatment.^7–9,13 Adults with long COVID often report that their symptoms are dismissed or attributed to psychogenic rather than physiologic causes.¹³ Trauma-informed care cultivates physical and emotional safety, trust, empowerment, collaboration, and mutuality. It aims to mitigate the impact of cultural, racial, and gender-based biases and promote peer support.¹³ Clinicians should validate and integrate knowledge of long COVID–related trauma (eg, symptom dismissal, job loss) and prevent further traumatization by fostering therapeutic rapport built on safety and trust, while providing care and care coordination across symptom and biopsychosocial domains.¹³ This approach can reduce distress, enhance self-efficacy for symptom management, and improve engagement in care.

Routine screening for anxiety and depression is recommended for adults with long COVID.¹⁴ Common screening tools include the Generalized Anxiety Disorder measure (2- or 7-item) and the Patient Health Questionnaire (2- or 9-item).^15,16 Given the potential for score inflation from somatic symptom overlap, 2-item screeners may be preferable for initial screening.¹⁷ A multidisciplinary consensus statement recommends standard psychiatric protocols for anxiety and depression, with careful consideration to avoid medications that could exacerbate long COVID fatigue and postexertional malaise (ie, sedative-hypnotics, anticholinergics, first-generation antihistamines, and antidepressants or antipsychotics with anticholinergic activity).¹⁴ First-line anxiolytics include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.¹⁴ Escitalopram especially shows promise for treating depression in patients with long COVID, and additional evidence supports the use of sertraline, citalopram, paroxetine, fluvoxamine, and fluoxetine.^18,19

Nonpharmacologic psychological interventions are another therapeutic component in long COVID, although they are not a substitute for medical treatment.^14,20,21 Cognitive behavior therapy, an evidence-based approach for treating anxiety and depression, improves symptom management in chronic conditions with symptoms similar to long COVID, such as myalgic encephalomyelitis and multiple sclerosis. Fatigue, cognitive difficulties, neuropathic symptoms, and dysautonomia are common with these conditions.^14,22,23 Emerging evidence shows cognitive behavior therapy can improve long COVID fatigue.²⁴ Mindfulness- and acceptance-based treatments, such as acceptance and commitment therapy, reduce anxiety and depression and may improve functioning and symptoms in people with chronic health conditions.²⁵ Preliminary evidence indicates that psychological treatments (eg, cognitive behavior therapy, acceptance and commitment therapy) improve mental health outcomes in long COVID.²⁶ These evidence-based, manualized psychotherapies are effective when using telemedicine, improving access despite ongoing affordability barriers. Long COVID–informed therapists can be found through resources such as the COVID-Conscious Therapist Directory.

Based in cognitive behavior therapy, diaphragmatic breathing and goal setting with pacing are evidence-informed strategies (ie, adapted from the best available evidence, theory, and clinical expertise in related conditions) that can be administered by family physicians to improve management of anxiety, depression, and other long COVID symptoms (eg, pain).²⁷ Clinicians should introduce their physiologic benefits to promote engagement and can guide patients through practice using resources such as the CAReS (COVID Aftercare Recovery and Support) Program.

Goal setting with pacing for energy management can improve depression by increasing sustainable engagement in rewarding activities. Long COVID symptoms often impede daily activities and lower quality of life.²⁶ Clinicians should validate these challenges and briefly explain the adverse reinforcing cycle of depression in long COVID (symptoms can cause disengagement from meaningful activities, which can cause or exacerbate depression).²⁸ If indicated, clinicians can assist patients in setting SMART goals that integrate pacing.²⁹ SMART goals are specific (clearly defined), measurable (progress is trackable), achievable (patient is confident in attainment), relevant (aligns with priorities), and timebound (within a clear time frame). To ensure achievability, clinicians can emphasize pacing goal-oriented activities by scheduling breaks and setting goals within a short, manageable time frame. For example, a person with long COVID fatigue could set a SMART goal to walk for 10 minutes, then rest for 10 minutes, twice per week, gradually increasing exertion as tolerated (eg, increasing walking time by 10%, adding another walking and rest period, increasing the number of weekly walks). The aim is to break the symptom-disengagement-depression cycle by starting small and building momentum to support euthymic mood by fostering sustainable engagement in valued activities.

Anecdotally, many patients with long COVID use apps such as Visible to help with pacing. Online directories such as the Solve M.E. resource list offer additional guidance for long COVID care. Clinicians may begin these conversations and refer patients to behavioral health specialists in managing chronic health conditions (eg, rehabilitation and health psychologists).

Adults with long COVID face increased risk of anxiety and depression due to complex factors and benefit from a trauma-informed biopsychosocial approach to screening, assessment, and treatment. Primary care physicians can use pharmacologic and nonpharmacologic treatments, including cognitive behavior therapy–based strategies, to manage anxiety and depression in people living with long COVID.