An Alternative to Nirmatrelvir-Ritonavir Shows Efficacy, Two-Dose Vaccine Regimen Protects Pregnant Women, Infants Against COVID-19 Variants, and More

Oral Antivrial Agent Effective in Treating COVID-19¹

VV116—an oral antiviral agent—is an alternative option to nirmatrelvir-ritonavir in treating patients with mild-to-moderate COVID-19, according to a recent study.

Due to its high demand, nirmatrelvir-rionavir’s supply falls short globally, leaving few alternative options for mild-to-moderate COVID-19 treatment on a global scale. In a phase 3, noninferiority, observer-blinded, randomized trial during the COVID-19 outbreak, participants (n = 822) received either nirmatrelvir-ritonavir (n = 387) or VV116 (n = 384) over a 5-day course. The primary endpoint of their research was the “time from randomization to sustained clinical recovery … through day 28.”

Upon the team’s final analysis, they found “the time to sustained symptom resolution and to a first negative SARS-CoV-2 test did not differ substantially between the two groups.” Further, in either group, no participants died or progressed to a severe case of COVID-19 by day 28. In the VV116 group, the incidence of adverse events was 67.4% compared to the nirmatrelvir-ritonavir group with 77.3%.

Given the results, the researchers concluded that VV116 is a safe and effective option in the treatment of mild-to-moderate COVID-19.

Two Doses of COVID-19 Vaccine Protects Women, Infants Against Delta, Omicron Infections²

Women who are pregnant and receive two doses of an mRNA COVID-19 vaccine are protected against the delta and omicron strains of infection, according to a recent study. Further, the risk for infants being admitted into the hospital during their first 6 weeks of life was lower.

“COVID-19 vaccines are highly effective against severe infection,” the researchers wrote. “However, these vaccines are not yet licensed for infants younger 6 months of age and the immunogenicity provided by new vaccine technologies in this age group is unknown.”

Using the knowledge that passive immunity is effective for infants in preventing diseases such as pertussis and influenza, the researchers conducted a population-based, test-negative design study. In total, 8809 infants aged 6 months or younger participated in the study (99 delta cases, compared with 4365 controls, and 1501 omicron cases compared with 4847 controls).

The researchers found that infant vaccine effectiveness from two doses of mRNA from the mother was 95% against delta infection and 97% against infant hospital admission due to delta, and 45% against omicron infection and 53% against hospital admission due to omicron.

Further, the researchers found that a second dose of the vaccine in the third trimester of pregnancy allowed for the highest vaccine effectiveness (53%) when compared to women receiving the vaccine in the first (47%) or second (37%) trimester.

“In this population-based study, maternal vaccination with the primary mRNA covid-19 vaccine series was highly effective against delta and moderately effective against omicron infection and admission to hospital in infants during the first six months of life,” the researchers concluded. “Three vaccine doses improved protection against omicron infection and admission to hospital. Vaccination during the third trimester of pregnancy provided the greatest protection, and effectiveness was highest in infants between birth and eight weeks of age.”

Pegylated Interferon Lambda and its Use for Treating COVID-19³

A single dose of pegylated interferon lambda effectively lowers the incidence of hospitalization or an emergency department visit for COVID-19 in people predominately vaccinated for the virus, according to a randomized, controlled study.

Researchers compared the effects of a single dose of pegylated interferon lambda to placebo in people who presented with symptoms consistent with COVID-19 within 7 days after the onset of symptoms. In total, 933 patients received an injection of pegylated interferon lambda, and 1018 patients received placebo, 83% of the patients being vaccinated.

Of the total, 25 patients (2.7%) in the interferon group were either hospitalized or visited an emergency department, compared with 57 (5.6%) in the placebo group. Further, the researchers found that the results were consistent “across dominant variants and independent of vaccine status.”

“In this trial involving largely vaccinated outpatients who presented with acute symptomatic COVID-19, the incidence of hospitalization or an emergency department visit due to COVID-19 was significantly lower among patients who received a single dose of pegylated interferon lambda than among those who received placebo,” the researchers concluded. “These results, which were observed regardless of viral variant, offer the possibility that a single-dose regimen can play a role in the response to COVID-19.”

Prescence of Prolonged Symptoms in Patients With Pre-Delta COVID-19 Infection⁴

People infected with COVID-19 pre-delta are more likely to experience COVID-19 symptoms post-infection when compared with those infected with delta and omicron, according to a recent study.

“However, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms,” the researchers of the study continued.

The multicenter prospective cohort study included 2402 adults positive for COVID-19 and 821 adults that tested negative for COVID-19. Among the participants who test positive for the infection, 463 (19.3%) were pre-delta, 1198 (49.9%) delta, and 741 (30.8%) omicron.

Prolonged severe fatigue and three or more prolonged symptoms were observed in patients who were pre-delta COVID-positive, compared to those in the delta and omicron cohorts.

Further, in multivariable models adjusted for vaccination, the researchers observed a lack of fatigue and odds of having three or more symptoms were not significant across variants.

“Our study demonstrated that post-COVID conditions differed across SARS-CoV-2 variants,” the researchers concluded. “While higher rates of prolonged severe fatigue and multiple symptoms during pre-Delta compared with Delta and Omicron were found, these differences disappeared after accounting for sociodemographics and vaccination status.”

References:

1. Cao Z, Gao W, Bao H, et al. VV 116 versus nirmatrelvir-rionavir for oral treatment of COVID-19. N Engl J Med. 2023;388:406-417. doi:10.1056/NEJMoa2208822
2. Jorgenson SC, Hernandez A, Fell DB, et al. Maternal mRNA COVID-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study. BMJ. Published online February 8, 2023. doi:10.1136/bmj-2022-074035
3. Reis F, Moreira Silva EAS, Medeiros Silva DC, et al. Early treatment with pegylated interferon lambda for COVID-19. N Engl J Med. 2023;388:518-528. doi: 10.1056/NEJMoa2209760
4. Gottlieb M, Wang RC, Yu H, et al. Severe fatigue and persistent symptoms at 3 months following severe acute respiratory syndrome coronavirus 2 infections during the pre-delta, delta, and omicron time periods: a multicenter prospective cohort study. Clin Infect Dis. Published online January 27, 2023. doi:10.1093/cid/ciad045