April 22, 2020

Two antiviral treatments present "little benefit" for mild or moderate COVID-19, diarrhoea linked to prolonged COVID-19 symptoms

By Denise Baez

NEW YORK -- April 22, 2020 -- In today’s DG Alert, we cover the effectiveness of lopinavir/ritonavir and arbidol for mild or moderate cases of coronavirus disease 2019 (COVID-19) in adults, and the link between diarrhoea and symptom duration and viral carriage in patients with COVID-19.

Compared with standard supportive care, neither lopinavir/ritonavir nor arbidol improved outcomes for patients with mild or moderate COVID-19, according to a randomised controlled study published in Med.

From February 1, 2020, to March 28, 2020, Linghua Li, Guangzhou Eighth People’s Hospital, Guangzhou, China, and colleagues randomised 86 patients (mean age, 49.4 years) with mild or moderate COVID-19 to receive lopinavir/ritonavir 200 mg/50 mg (n = 34), arbidol (n = 35), or no antiviral medication (n = 17). 

Baseline characteristics were comparable between groups and none of the patients complained of dyspnoea, diarrhoea, palpitation or headache on admission.

The lopinavir/ritonavir group received treatment twice daily for 7 to 14 days, arbidol group), 35 patients were given arbidol 200 mg 3 times daily for 7 to 14 days. All 3 groups were treated with supportive care and effective oxygen therapy if in need. Antiviral treatment was discontinued for patients who (1) had been treated for more than 7 days and tested negative for SARS-CoV-2 nucleic acid in 2 consecutive tests separated by more than 24 hours, or (2) were discharged from hospital, or (3) had intolerable side effects.

The mean time for positive-to-negative conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid -- the primary endpoint -- was 9 days in the lopinavir/ritonavir arm, 9.1 days in the arbidol arm, and 9.3 days in the control group. 

After 7 days of treatment, the positive-to-negative conversion rates of SARS-CoV-2 nucleic acid in pharyngeal swab in the lopinavir/ritonavir group was 35.3%, compared with 37.1% in the arbidol group, and 41.2% in the control group. After 14 days of treatment, the positive-to-negative conversion of SARS-CoV-2 nucleic acid was 85.3%, 91.4%, and 76.5%, respectively.

There were no differences between groups in rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (P> 0.05 for all). At day 7, 8 (23.5%) patients in the lopinavir/ritonavir group showed deterioration in clinical status (from moderate to severe/critical), compared with 3 (8.6%) patients in the arbidol group and 2 (11.8%) patients in the control group.

In order to rule out the influence of the time from onset to treatment on clinical status, the authors compared the time from onset to treatment in patients who deteriorated to severe/critical clinical status (mean, 5 days) with those who did not (mean, 4 days), and did not find any significant difference between them (P = 0.619).
 

Overall, 12 (35.3%) patients in the lopinavir/ritonavir group and 5 (14.3%) patients in the arbidol group experienced adverse events during the follow-up period. 

“Lopinavir/ritonavir or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalised with mild/moderate COVID-19 over supportive care,” the authors concluded.

They noted several limitations to their study, including the small sample size, the fact that critically ill patients were not included, and that the study was not completely blinded. 

Another study, published in Clinical Gastroenterology and Hepatology, showed that, among patients with SARS-CoV-2, fever and dyspnoea lasted longer in patients with diarrhoea compared with those without. 

In addition, stool samples from a higher proportion of patients with diarrhoea tested positive for virus RNA (69%) than from patients without diarrhoea (17%; P< 0.001) and of 76 patients with a negative result from their latest throat swab test during hospitalisation, a significantly higher proportion of patients with diarrhoea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhoea (20%; P = 0.039).
 

Xiao-Shan Wei, MD, Union Hospital, Wuhan, China, and colleagues retrospectively analysed 84 hospitalised healthcare workers aged 24 to 74 years (33% male) with laboratory-confirmed COVID-19 at Wuhan Union Hospital from January 19, 2020, to February 7, 2020. There were 17 doctors, 66 nurses, and 1 allied health worker. All patients received antibiotics and antiviral agents during hospitalisation.

Several clinical symptoms were more common among patients with diarrhoea compared with patients without, including headache (58% vs 22%; P = 0.003), myalgia or fatigue (65% vs 34%; P = 0.010), cough (85% vs 45%; P< 0.001), sputum production (54% vs 21%; P = 0.004), nausea (38% vs 10%; P = 0.005), and vomiting (19% vs 2%; P = 0.010). The duration of fever (10.5 ± 4.7 vs 7.6 ± 3.4 days; P = 0.005) and dyspnoea (8.1 ± 3.2 vs 4.7 ± 2.3 days; P = 0.002) in patients with diarrhoea was significantly longer than those without diarrhoea. 

Hospital stays were longer among patients with diarrhoea compared with patients without diarrhoea (16.5 ± 5.2 vs 11.8 ± 5.6 days; P< 0.001).

As of February 19, none of the patients had died or were admitted to the intensive care unit and 63 patients had been discharged. Of the patients without diarrhoea, 83% were discharged compared with 58% of those with diarrhoea (P = 0.028). 

By the end of February 19, a lower proportion of patients with diarrhoea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhoea (97%) (P = 0.010) during hospitalisation. The mean time of SARS-CoV-2 in throat swab turning to be negative was longer in diarrhoea group, compared with patients without diarrhoea (12.5 ± 4.0 vs 9.2 ± 3.9 days; P = 0.002).

“In this single-centre case series of 84 patients with confirmed COVID-19 in Wuhan,  31% had diarrhoea,” the authors wrote. “Patients with COVID-19 with diarrhoea suffered discomfort longer compared with patients without diarrhoea. In patients with diarrhoea, stool specimens testing to SARS-CoV-2 may persist positive, even after the throat swab testing to SARS-CoV-2 has turn to be negative.”

SOURCE: Med, and Clinical Gastroenterology and Hepatology