What are the management and treatment options for COVID-19, particularly in relation to spike proteins, in eligible individuals?

Management and Treatment of COVID-19 in Relation to Spike Proteins

Primary Treatment Approach

For hospitalized COVID-19 patients requiring supplemental oxygen, non-invasive ventilation, or mechanical ventilation, the combination of systemic glucocorticoids (primarily dexamethasone) plus tocilizumab should be administered, as this reduces disease progression and mortality. 1

Understanding Spike Protein Pathophysiology

The SARS-CoV-2 virus enters human cells through binding of viral spike proteins (S-protein) to the angiotensin converting enzyme-2 (ACE2) receptor, which is abundant in lung, heart, kidney, adipose tissue, esophagus, stomach, bladder, ileum, and colon. 1 After receptor binding, lysosomal proteases cleave the spike protein, releasing the signal peptide that facilitates viral entry into cells. 1

Treatment Algorithm by Disease Severity

Non-Hospitalized or Hospitalized Without Oxygen Requirements

• No immunomodulatory therapy is indicated for patients who are either non-hospitalized or hospitalized but not requiring oxygen therapy. 1

Early Disease (Symptom Onset <5 Days)

Monoclonal antibodies against SARS-CoV-2 spike protein should be considered in patients at risk of severe COVID-19 course with symptom onset less than 5 days or who are still seronegative. 1

• Combinations such as bamlanivimab plus etesevimab, or casirivimab plus imdevimab, significantly reduce viral load when administered within the first week after symptom onset. 1
• Casirivimab and imdevimab are effective only in patients seronegative at baseline. 1
• Critical caveat: Regional prevalence of SARS-CoV-2 variants must be considered, as specific monoclonal antibodies have different activities against variants. 1

Antiviral treatment with remdesivir should be initiated as soon as possible after diagnosis of symptomatic COVID-19. 2

• For hospitalized patients requiring invasive mechanical ventilation and/or ECMO: 10-day treatment course 2
• For hospitalized patients not requiring invasive mechanical ventilation and/or ECMO: 5-day treatment course, extendable to 10 days if no clinical improvement 2
• Dosing: 200 mg loading dose on Day 1, followed by 100 mg daily maintenance doses (for adults and pediatric patients ≥40 kg) 2

Moderate to Severe Disease (Requiring Oxygen)

Systemic glucocorticoids (dexamethasone) are mandatory in patients requiring supplemental oxygen, non-invasive ventilation, or mechanical ventilation, as they decrease mortality. 1

Add tocilizumab to glucocorticoids in this population, as the combination reduces disease progression and mortality more effectively than glucocorticoids alone. 1

Baricitinib or tofacitinib combined with glucocorticoids could be considered in patients requiring oxygen therapy, non-invasive ventilation, or high-flow oxygen, as this combination may decrease disease progression and mortality. 1

• Tofacitinib plus standard of care (where 90% received glucocorticoids) showed significant improvement in the composite outcome of respiratory failure or mortality at day 28 (RR 0.63,95% CI 0.41-0.97). 1

Drug-Drug Interactions with Spike Protein-Targeted Therapies

When using nirmatrelvir/ritonavir in patients on BTK or BCL-2 inhibitors, either switch to remdesivir (which has no drug-drug interactions) or discontinue/reduce the dose of ibrutinib/venetoclax until 3 days after completing nirmatrelvir/ritonavir therapy, as ritonavir significantly increases concentrations of these agents through CYP3A4 inhibition. 1

Treatments to Avoid

Hydroxychloroquine should be avoided for treating any stage of SARS-CoV-2 infection, as it provides no additional benefit to standard of care and could worsen prognosis in severe patients, particularly when co-prescribed with azithromycin. 1

Convalescent plasma should not be used in patients without hypogammaglobulinemia with symptom onset greater than 5 days, as large RCTs showed no benefit (RR 0.99,95% CI 0.93-1.05 for progression to mechanical ventilation or death at day 28). 1

Insufficient Evidence

There is currently insufficient evidence to recommend GM-CSF inhibitors (mavrilimumab, otilimab, lenzilumab), anakinra, canakinumab, low-dose colchicine, or various interferons for COVID-19 treatment. 1

Special Considerations for Immunocompromised Patients

In patients with chronic lymphocytic leukemia or hematological malignancies, vaccine response to spike protein-based vaccines is significantly diminished (5-90% seroconversion rate compared to general population), with particularly poor responses in those recently treated with anti-CD20 antibodies (0-14% response rate). 1