Real life experience of molnupiravir as a treatment of SARS-CoV-2 infection in vaccinated and unvaccinated patients: a letter on its effectiveness at preventing hospitalization

Abstract

Background

The SARS-CoV-2 pandemic has prompted clinicians to develop an early and effective treatment of viral infections. To date, vaccines, monoclonal antibodies, and antivirals are the cornerstone of therapy for SARS-CoV-2. AIFA approved the prescription of molnupiravir on 30/12/2021. Molnupiravir is a prodrug that causes the accumulation of errors in the viral genome.

Methods

We prescribed molnupiravir to a total of 74 patients in a range between 26 and 96 years old and followed-up them for 30 days. 10 patients affected by idiopathic pulmonary fibrosis (IPF) were treated.

Results

The follow-up showed that all of the treated patients presented a regression of symptoms. No patients were hospitalized and/or showed sequelae after the infection by SARS-CoV-2, even though the examined population was older and with more co-morbidities than other patients treated with different antivirals.

Conclusion

Molnupiravir is safe and well-tolerated by patients with high-risk of progression to severe COVID. No patients were hospitalized or showed sequelae, including all patients affected by IPF.

Introduction

The SARS-CoV-2 pandemic has prompted clinicians to develop an early and effective treatment of viral infections.

To date, vaccines, monoclonal antibodies, and antivirals are the cornerstone of therapy for SARS-CoV-2.

AIFA, the Italian Medicines Agency, approved the prescription of molnupiravir [1, 2] on 30/12/2021. Molnupiravir is a prodrug metabolized to the ribonucleoside analog N-hydroxycytidine (NHC). NHC spreads into cells, where it is phosphorylated to form the pharmacologically active ribonucleoside triphosphate (N-hydroxycytidine triphosphate, NHC-TP). Incorporating NHC-TP into viral RNA by the use of viral RNA polymerase causes an accumulation of errors in the viral genome, which inhibits its replication.

The prescribed dosage is 4 tablets (200 mg each) every 12 h for 5 days. The treatment has to be started within 5 days after the onset of symptoms.

AIFA laid out indications when prescribing the antiviral. Molnupiravir may be prescribed to patients with mild to moderate symptoms who do not need oxygen supplementation nor an increase in oxygen demand in the event of at-home baseline oxygen therapy due to chronic conditions. Patients cannot be already hospitalized for COVID-19. Patients also must have at least one of the following risk factors associated with the evolution into severe disease:

• Severe pulmonary and/or cardiovascular disease

• Oncological or onco-hematological disease in active phase

• Primary or acquired immunodeficiency

• Obesity (BMI ≥ 30)

• Chronic renal failure

• Uncontrolled diabetes mellitus

No dose adjustments are required in case of renal or hepatic impairment.

Molnupiravir should not be used in dialysis patients or in patients with eGFR < 30 ml/min/1.73 m².

Molnupiravir should not be prescribed during pregnancy. Women of childbearing potential must use contraceptive methods for the duration of treatment and for at least four additional days after the end of treatment; men who are partners of women of childbearing potential must use contraceptive methods for the entire duration of treatment and for at least three months after the end of treatment with molnupiravir.

Possible side effects [3] are dizziness, headache, diarrhea, nausea, vomiting, rash, and urticaria.

To our knowledge, there are few real-life studies about molnupiravir [4] and no reports about at-home treatment in European population.

Our experience

We prescribed molnupiravir to a total of 74 patients (39 male, 35 female) with an average age of 72.3 (ds 14.5) in a range between 26 and 96 and followed-up for 30 days. The most frequent symptoms in these patients were fever, coughing, and pharyngodynia.

70 patients were vaccinated in the six months before positivity to SARS-CoV-2. Among vaccinated patients, only 65 had underwent a complete vaccination course of three doses.

5 treated patients were under 55; four of them had indication to antiviral therapy for immunodeficiency, and one had indication to oxygen therapy and home ventilation for severe chronic respiratory failure.

Only one patient had an indication for an oncological condition. He had been vaccinated with three doses in the previous six months.

3 patients were treated with the indication for chronic kidney disease associated with cardiovascular disease.

17 patients were eligible for being treated with molnupiravir due to severe pulmonary disease (10 of these patients were diagnosed with idiopathic pulmonary fibrosis (IPF)), 10 patients due to severe pulmonary disease associated with cardiovascular disease (of which one was diagnosed with IPF), and one patient due to severe pulmonary disease associated with cardiovascular disease and obesity.

9 patients were treated with the indication for immunodeficiency; one of them underwent lung transplantation 5 years prior to being treated with molnupiravir.

Obesity was the risk factor to determine eligibility in 7 patients. In two cases, obesity was associated with cardiovascular diseases, in one more case with cardiovascular severe pulmonary diseases, and in a further one with diabetes mellitus.

8 patients were treated with the indication for uncontrolled diabetes mellitus (of which one was associated with obesity, 3 with cardiovascular diseases, and one with both cardiovascular disease and chronic renal failure).

39 patients were treated due to risks associated with severe cardiovascular disease (22 of them had only this indication with no other co-morbidities) (Table 1).

Table 1.

Characteristics of population

Number of patients	74
Gender	39 male, 35 female
Age	AV 72,3 (SD 14,5)
Vaccinated	70
Oncological disease	1
Chronic renal disease	3
Severe pulmonary disease	17 (10 affected by IPF)
Immunodeficiency	9
Obesity	7
Uncontrolled diabetes mellitus	8
Severe cardiovascular disease	39

We observed an average negative result of nasopharyngeal control swab on day 12. This is due to the fact that regional follow-up protocol allows control tests to be carried at least 7 days after the first positive result, with more flexible further calendar, i.e., the test can be performed on resolution of symptoms.

The most remarkable result of this study is that all of the treated patients presented a regression of symptoms during follow-up. No patients were hospitalized and/or showed sequelae after the infection by SARS-CoV-2, even though the examined population was older and presented more co-morbidities than other patients who underwent treatment with other available antivirals.

No patients complained about side effects related to the assumption of Molnupiravir. Furthermore, experience shows that molnupiravir is easier to access when compared to other approved antiviral drug, due to lack of significant restrictions (e.g., drug interactions and dose adjustment).

Finally, to the best of our knowledge, this is the first report about the use of molnupiravir in patients affected by IPF, with extremely positive results.

In conclusion, molnupiravir is safe and well-tolerated by patients with high-risk of progression to severe COVID. According to these results, molnupiravir can lead to a potential risk reduction of 100%, especially when associated with vaccination.

Larger studies may shed brighter light on the actual effectiveness of early treatment at home.

Funding

The authors declare that they have not received funding for this work.

Data Availability

All data are available contacting the corresponding author.

Declarations

Conflict of Interests

The authors declare no competing interests.