What is the latest standard care for Covid-19 (Coronavirus disease 2019) positive patients?

From the Guidelines

The standard care for COVID-19 positive patients depends on disease severity, with the most recent and highest quality evidence recommending glucocorticoids therapy as the standard of care for hospitalized patients with COVID-19 who require oxygen therapy 1. For mild to moderate cases, treatment typically involves:

• Rest
• Hydration
• Over-the-counter medications like acetaminophen or ibuprofen to manage symptoms such as fever and pain Antiviral medications like nirmatrelvir/ritonavir (Paxlovid) may be prescribed for high-risk patients within 5 days of symptom onset, typically as a 5-day course of 300mg nirmatrelvir with 100mg ritonavir twice daily. For severe cases requiring hospitalization, treatment may include:
• Oxygen therapy
• Dexamethasone (6mg daily for up to 10 days)
• Potentially immunomodulators like tocilizumab or baricitinib
• Anticoagulation therapy to prevent blood clots Supportive care remains essential, including prone positioning for patients with respiratory difficulties. These treatments aim to reduce viral replication, manage inflammatory responses, and support organ function while the body fights the infection. Vaccination remains the most effective preventive measure, and patients should isolate according to current guidelines to prevent transmission, as recommended by various studies, including those published in the European Respiratory Journal 1 and Clinical Nutrition 1.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Efficacy in Subjects at High Risk of Progression to Severe COVID-19 (EPIC-HR)

EPIC-HR (NCT04960202) was a Phase 2/3, randomized, double-blind, placebo-controlled trial in non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection Eligible subjects were 18 years of age and older with at least 1 of the following risk factors for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically-related technological dependence, or were 60 years of age and older regardless of comorbidities. The primary efficacy endpoint was the proportion of subjects with COVID-19 related hospitalization or death from any cause through Day 28 The analysis was conducted in the modified intent-to-treat (mITT) analysis set [all treated subjects with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic monoclonal antibody (mAb) treatment], the mITT1 analysis set (all treated subjects with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated subjects with onset of symptoms ≤5 days). A total of 2,113 subjects were randomized to receive either PAXLOVID or placebo At baseline, mean age was 45 years; 51% were male; 71% were White, 15% were Asian, 9% were American Indian or Alaska Native, 4% were Black or African American, and 1% was missing or unknown; 41% were Hispanic or Latino; 67% of subjects had onset of symptoms ≤3 days before initiation of study treatment; 49% of subjects were serological negative at baseline; the mean (SD) baseline viral RNA in nasopharyngeal samples was 4.71 log10 copies/mL (2. 89); 27% of subjects had a baseline viral RNA of ≥10^7 (log10 copies/mL); 6% of subjects either received or were expected to receive COVID-19 therapeutic monoclonal antibody treatment at the time of randomization and were excluded from the mITT and mITT1 analyses. The proportions of subjects who discontinued treatment due to an adverse event were 2. 0% in the PAXLOVID group and 4. 2% in the placebo group. Table 8 provides results of the primary endpoint in mITT1 analysis population. For the primary endpoint, the relative risk reduction in the mITT1 analysis population for PAXLOVID compared to placebo was 86% (95% CI: 72%, 93%) The estimated cumulative proportion of subjects hospitalized or death by Day 28 was calculated for each treatment group using the Kaplan-Meier method, where subjects without hospitalization and death status through Day 28 were censored at the time of study discontinuation COVID-19 Related Hospitalization or Death from Any Cause Through Day 28 n (%) 9 (0.9%) 64 (6.5%) Reduction Relative to Placebo* (95% CI), % -5.6 (-7.3, -4.0) COVID-19 Related Hospitalization Through Day 28, % 9 (0.9%) 63 (6. 4%) All-cause Mortality Through Day 28†, % 0 12 (1. 2%)

The latest standard care for Covid-19 positive patients, as per the provided drug label 2, includes the use of PAXLOVID (nirmatrelvir/ritonavir) for non-hospitalized symptomatic adult subjects with a laboratory confirmed diagnosis of SARS-CoV-2 infection and at least one risk factor for progression to severe disease.

• The treatment consists of PAXLOVID 300 mg/100 mg orally every 12 hours for 5 days.
• The primary efficacy endpoint was the proportion of subjects with COVID-19 related hospitalization or death from any cause through Day 28.
• The results showed a relative risk reduction of 86% in the mITT1 analysis population for PAXLOVID compared to placebo.
• The estimated cumulative proportion of subjects hospitalized or death by Day 28 was 9 (0.9%) in the PAXLOVID group and 64 (6.5%) in the placebo group. Key points:
• PAXLOVID is indicated for the treatment of COVID-19 in patients with at least one risk factor for progression to severe COVID-19.
• The treatment should be initiated as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset.
• The patient should be monitored for adverse events and the treatment should be discontinued if any adverse event occurs.

From the Research

Latest Standard Care for Covid-19 Positive Patients

The latest standard care for Covid-19 positive patients involves a combination of treatments, including:

• Multimodal approach: A study published in 2021 3 found that a multi-mechanism approach, which includes immunomodulation, anticoagulation, viral suppression, and oxygenation, can reduce the length of stay in the ICU for severe Covid-19 patients.
• Antiviral medications: Nirmatrelvir plus ritonavir (Paxlovid) has been shown to be effective in reducing the risk of progression to severe Covid-19 in symptomatic, unvaccinated, non-hospitalized adults with mild-to-moderate Covid-19 at high risk for progression to severe disease 4, 5.
• Combination therapy: A prospective single-centre study published in 2025 6 found that early combination of sotrovimab with nirmatrelvir/ritonavir or remdesivir is associated with a low rate of persisting SARS CoV-2 infection in immunocompromised outpatients with mild-to-moderate Covid-19.
• Sequential multidrug therapy: A study published in 2020 7 suggested that prompt early initiation of sequenced multidrug therapy (SMDT) can stem the tide of hospitalizations and death in Covid-19 patients.

Key Considerations

• Early treatment: Early administration of combination therapy with a direct antiviral and sotrovimab seems to be effective in preventing hospitalization, progression to severe Covid-19, and development of prolonged/persisting SARS-CoV-2 infection in immunocompromised patients 6.
• Patient population: The efficacy and safety of nirmatrelvir/ritonavir have been demonstrated in unvaccinated, high-risk patients with symptom onset of no more than five days 5.
• Equity aspects: Subgroup analyses for equity have identified differences in effect size and direction for ethnicity, but not for age or comorbidity status 5.