An Overview of Long Covid

Background:

COVID-19 (coronavirus disease 2019) is a respiratory disease caused by the SARS-CoV-2 virus. As of June 1, 2024 nearly 1.2 million people have died of COVID-19 in the U.S. The Infectious Diseases Society of America (IDSA) has developed evidence-based, frequently updated guidelines for the treatment and management of COVID-19. Recommendations are categorized as strong or conditional based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.

Diagnosis
Outpatient Treatment
Pre-Exposure Prophylaxis
Post-Exposure Prophylaxis
Antiviral Therapies
Other Therapies
Primary Sources

Diagnosis:

Symptoms are wide ranging from mild to severe illness and generally appear 2-14 days after exposure to the virus and may include: Fever or chills | Cough | Dyspnea or Tachypnea | Odynophagia | Congestion or rhinorrhea | Anosmia or Dysguesia | Fatigue | Myalgias | Headache | Nausea or Vomiting | Diarrhea
Testing is helpful for guiding management and to distinguish from other respiratory viruses with overlapping symptoms. There are two main types of test:
- Nucleic Acid Amplifications Test (NAAT) or Polymerase Chain Reaction (PCR)
  - Considered gold standard with high sensitivity and specificity
  - Takes several hours to result
- Antigen tests:
  - Takes 15-30 minutes to result and can be done at home or in office
  - Less sensitive than NAAT and may result in false negative
  - Repeat testing indicated in 24-48 hours if clinical suspicion high

Definitions of COVID-19 Severity
- Mild to moderate COVID-19 (SpO2 ³ 94% on RA and no need for supplemental O2)
- Severe COVID-19 (Sp < 94% on RA or needing low-flow supplemental oxygen)
- Critical COVID-19 needing high-flow oxygen | non-invasive ventilation | ECMO

Outpatient Treatment

Clinical evaluation should consider patient and pathogen specific factors that can influence choice of COVID-19 treatments.

Pre-Exposure Prophylaxis

Pemivibart: Suggested for moderately or severely immunocompromised individuals aged 12+ when regional variants are susceptible (Conditional; Low certainty)
- Benefits are higher in severely immunocompromised adults but lower in adolescents.
- Risks include a 0.6% chance of anaphylaxis.
Evusheld (Tixagevimab/Cilgavimab): No longer authorized in the U.S. due to inactivity against circulating variants.

Post-Exposure Prophylaxis

Neutralizing antibody combinations (e.g., Bamlanivimab/Etesevimab, Casirivimab/Imdevimab) are no longer authorized due to inactivity against Omicron variants.

Antiviral Therapies: Recommended for ambulatory mild-moderate disease with high risk for progression to severe disease (see above) | hospitalization| death and can be considered inpatients with mild-moderate COVID-19 hospitalized for other reasons.

Remdesivir:
- Suggested for mild-to-moderate cases at high risk of severe disease if initiated within seven days of symptom onset (Conditional; Low certainty).
- Reduced risk of hospitalization and death by 87% in unvaccinated outpatients at high risk of severe disease
- Administered via IV for 3 days
- Caution when CrCl< 30 mL/min

Nirmatrelvir/Ritonavir
- Suggested for mild-to -moderate cases at high risk of severe disease if initiated within five days of symptom onset (Conditional recommendation, Low certainty of evidence)
- Reduced risk of hospitalization and death by 87% in unvaccinated outpatients with COVID-19 at higher risk of severe disease
- 5-day oral course
- Reduced dosage for eGFR £60 mL/min and ³30mL/min
- Not recommended for eGFR £30 mL/min
- Viral Rebound i.e., Recurrence of symptoms after improvement and negative test results has been estimated to occur in 0.8% to 6.6% treated with Nirmatrelvir/Ritonavir. Repeated course of anti-viral is not recommended and no known negative outcome from viral rebound.
- Several drug interactions due to the ritonavir component and clinicians evaluate these e.g., Liverpool COVID-19 Interaction (see more “Learn More)
Molnupiravir
- In ambulatory patients (≥18 years) with mild-to-moderate COVID-19 at high risk for progression to severe disease who have no other treatment options, the IDSA guideline panel suggests molnupiravir initiated within five days of symptom onset rather than no molnupiravir. (Conditional recommendation†, Low certainty of evidence)
- Molnupiravir was shown to have low efficacy against severe outcomes in clinical trials and has little evidence of effectiveness particularly among vaccinated individuals.
- 5-day oral course
- Avoid in pregnant women and advise contraception during treatment and for four days after treatment for women
- Men of reproductive potential who are sexually active with females of childbearing potential should use a reliable method of contraception during treatment and for at least three months after the last dose of molnupiravir
- Viral Rebound has also been described with molnupiravir and a repeated anti-viral course is not recommended nor are there any known negative outcomes from viral rebound

Other Therapies

Hydroxychloroquine/Chloroquine: Strongly discouraged for treatment or prophylaxis at all severity levels.
Convalescent Plasma:
- Conditional use suggested for immunocompromised patients or ambulatory high-risk individuals with no other options.
Inhaled Corticosteroids: Advised against in ambulatory mild-to-moderate cases unless prescribed for other conditions.
Famotidine: Suggested against its use in both ambulatory and hospitalized severe cases.