The target patients who had quantifiable RNAs in the nasopharyngeal sample took Molnupiravir orally for 5 days according to the standard protocol. Fever is one of the most common symptoms of COVID-19. However, people with COVID-19 sometimes have a low-grade fever or no fever at all. In general, a fever is a temperature of above 100.4°F (38°C) ([℃(Celsius)×1.8] + 32=℉[Fahrenheit]). Patients were grouped according to the presence of a fever of 38 ℃ one time (Group A), two times (Group B), and three or more times (Group C) at 10 days after oral administration (Fig. 1). There were no significant differences in the Ct values of the A group, the B group, or the C group. However, there were differences in symptoms during and after oral administration (Table 2). No deaths were observed during the observation period. No exacerbation of the risk factor was observed in patients with at least one risk factor. Compared to before administration, there was no myelosuppression, such as thrombocytopenia, during the observation after administration, and no hepatic dysfunction or renal dysfunction was observed. No significant changes in blood pressure or pulse were observed. Patients in the A group had a fever of 38 ℃ or higher that was then reduced to 36 ℃ or lower and did not had a subsequent fever. Nausea and anaphylaxis were observed in 1 patient, each occurring within 14 days after the start of oral administration. Two patients experienced substantial disturbances: one had hypoglycemic symptoms, and one tube-fed patient required sputum aspiration for 12 days but improved with the use of antiemetics and antihistamines. Two patients with tube feeding resumed rehabilitation without any adverse events. Patients in the B Group had a fever of 38 ℃ or higher that then decreased to 36 ℃ or lower and had only one fever of 38℃ or higher during the 10 days after administration. No fever occurred after the administration of acetaminophen. During oral administration, one patient developed nausea, and another developed vomiting. It improved with the use of antiemetics. In the 14 days after the start of oral administration, 2 people discharged a large amount of sputum, and suction was needed. One of them was a patient who experienced vomiting. Aspiration was suspected. Two patients had poor appetites, and one had nausea. In addition to these patients, one patient had an SaO2 (Arterial oxygen saturation) of 90% or less and required oxygen administration (0.5-1 L/min). No increase in white blood cells (WBCs) or C-reactive protein (CRP) was observed. X-ray examinations and computerized tomography (CT) scan examinations could not be performed due to the spread of infection. After administration, one tube-fed patient could eat without fever and resumed rehabilitation without accidents. Patients in the C group had a fever of 38 ℃ or higher that then decreased to 36 degrees or lower and also had a fever of 38 ℃ or higher two or more times within 10 days. No fever occurred after the administration of acetaminophen. However, symptoms were noted in seven patients who did not have a fever. 1. During oral administration, one person felt dizzy, but no numbness, paralysis, nystagmus, or pupil abnormalities were observed in the extremities, and their condition improved without medication. 2. During oral administration, one person had headaches, which improved with the use of acetaminophen. The CT scan showed no abnormalities. 3. One patient had diarrhea after the oral administration but they improved without antidiarrheal or other drugs to relieve intestinal ailments. 4. One of the two patients with diarrhea, experienced nausea during administration, discharged a large amount of sputum, and was given oxygen. The patient was unable to eat orally but improved with a one-week-long infusion and regained the ability to eat orally. 5. One patient with chronic obstructive pulmonary disease discharged more sputum after infection and was given oxygen. After dosing, nausea and vomiting were observed but improved with the use of antiemetics. However, the patient developed difficulty eating and received nutrition from a nasogastric tube. 6. One patient with chronic interstitial pneumonia had a large discharge of sputum during the oral administration and was given oxygen. This patient then vomited and developed difficulty eating and was fed from a nasogastric tube. 7. One patient had melena during oral administration, but there was a possibility of colorectal cancer, and a colonoscopic examination was planned.
Table 2
Incidence of Adverse Events
Patients over 80 years (n = 29) | < 5 d1 | < 7 d | < 14 d | < 21 d | < 28 d | Actual number of patients |
A (n = 13) | | | | | | |
nausea | 0 | 1 | 0 | 0 | 0 | 1 |
anaphylaxis | 0 | 1 | 0 | 0 | 0 | 1 with facial rash |
disturbance | 1 | 1 | 0 | 0 | 0 | 2 with disturbances |
IGT2 | 1 | 0 | 0 | 0 | 0 | 1 with hypoglycemia |
sputum | 1 | 1 | 1 | 0 | 0 | 1 with sputum suction |
B (n = 9) | | | | | | |
nausea | 1 | 0 | 0 | 0 | 0 | 1 |
vomiting | 1 | 0 | 0 | 0 | 0 | 1 |
substantial amount of sputum | 2 | 1 | 0 | 0 | 0 | 2 with sputum suction |
poor appetite | 1 | 2 | 1 | 0 | 0 | 2 with difficulty eating |
hypoxia | 1 | 1 | 0 | 0 | 0 | 1 with oxygen administration |
C (n = 7) | | | | | | |
feeling dizzy | 1 | 0 | 0 | 0 | 0 | 1 |
headaches | 1 | 0 | 0 | 0 | 0 | 1 |
diarrhea | 1 | 1 | 0 | 0 | 0 | 2 with diarrhea |
nausea | 1 | 1 | 0 | 0 | 0 | 2 with nausea |
vomiting | 0 | 2 | 0 | 0 | 0 | 2 with vomiting |
substantial amount of sputum | 3 | 3 | 3 | 1 | 0 | 3 with sputum suction |
inedia | 0 | 3 | 2 | 2 | 2 | 2 with tube feeding management |
hypoxia | 3 | 3 | 3 | 2 | 2 | 3 with oxygen administration |
melena | 1 | 0 | 0 | 0 | 0 | 1 |
1 d: days |
2 IGT: impaired glucose tolerance |
In the 14 days after the start of administration, 3 patients discharged a large amount of sputum, and suction was needed. Two of them were patients who experienced vomiting and aspiration was suspected. These two patients became unable to eat orally due to difficulty swallowing and underwent tube feeding management. At the same time, swallowing training was conducted, and as a result, the patients were able to eat. Oxygen was administered (1–3 L/min) to 3 patients who had an SaO2 of 87% or lower. Two of them were patients who required sputum aspiration. These two patients had elevated WBC and CRP levels, had a history of sepsis, suspected bacterial pneumonia, received a loxoprofen antipyretic, and were administered meropenem antibiotics for improvement. One patient ended oxygen administration, and the other continued to receive oxygen due to a history of brainstem infarction. One patient had a history of interstitial pneumonia, which was improved by steroid administration for 3 days, and the oxygen dose was reduced (0.5-1 L/min). They had an SaO2 of 95% or higher. If it worsened, we planned to manage the ventilator considering the need for endotracheal intubation. Rehabilitation was resumed for all patients except for these 3 patients.