Virus World

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals.

Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6–89.6) and 642.8 (95% CI: 596.9–689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9–31.0%) and 21.3% (18.2–24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection. Analysis of data from the US Department of Veterans Affairs showed that 2 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, risk for most postacute sequelae remained elevated in people who were hospitalized with COVID-19 but was attenuated in nonhospitalized individuals.

Publisjed August 1, 2o23) Nature Med.:

https://doi.org/10.1038/s41591-023-02521-2 

In a new study, both messenger RNA vaccines available in the U.S. demonstrated high effectiveness against COVID-19, although the Moderna vaccine was associated with a lower risk for infection and hospitalization than the Pfizer-BioNTech vaccine. The trial is the “first head-to-head comparison of the effectiveness” of each vaccine, according to a press release.  “Given the high effectiveness of both the Moderna and Pfizer vaccines, confirmed by our study, either one is recommended to any individual offered a choice between the two,” Barbra A. Dickerman, PhD, a study author and an epidemiology instructor with the Harvard T.H. Chan School of Public Health, said in a press release. “While the estimated differences in effectiveness were small on an absolute scale, they may be meaningful when considering the large population scale at which these vaccines are deployed.” For the study, Dickerman and colleagues analyzed the electronic health records of nearly 440,000 U.S. veterans who were administered either vaccine (219,842 in each group) between Jan. 4 and May 14. The participants were matched in a 1:1 ratio based on their risk factors and followed for up to 24 weeks. “The two vaccine groups were extremely similar in terms of variables with respect to an extensive set of demographic, geographic and health-related attributes,” Dickerman said in the release.

The results, published in The New England Journal of Medicine, showed that the estimated risk for documented SARS-CoV-2 infection was 5.75 events per 1,000 persons (95% CI, 5.39-6.23) in the Pfizer-BioNTech cohort and 4.52 events per 1,000 persons (95% CI, 4.17-4.84) in the Moderna cohort. During a period in which alpha was the predominant variant, the excess number of events per 1,000 persons for Pfizer compared with Moderna was 1.23 (95% CI, 0.72-1.81) for documented infection, 0.44 (95% CI, 0.25-0.7) for symptomatic infection, 0.55 (95% CI, 0.36-0.83) for COVID-19-related hospitalization, 0.1 (95% CI, 0-0.26) for COVID-19-related ICU admission and 0.02 (95% CI, 0.06 to 0.12) for death from COVID-19. The corresponding excess risk with Pfizer vs. Moderna for documented infection during a 12-week period in which delta was the predominant variant was 6.54 events per 1,000 persons (95% CI, 2.58 to 11.82). J.P. Casas, MD, PhD, a study co-author and associate epidemiologist at Brigham and Women's Hospital, noted in the press release that the findings were consistent “regardless of the predominant strain.”

In a related editorial, Eric J. Rubin, MD, PhD, the editor-in-chief of The New England Journal of Medicine, and Dan L. Longo, MD, a professor of medicine at Harvard Medical School, said the take-home message “is not about differences — it’s about similarities.” “We are lucky to have such good options,” they wrote. “Vaccination with any vaccine is far better than remaining unprotected. The message is that the best vaccine is the one that’s available.”

Original findings published in New England  J. Medicine (Dec. 1, 2021):

https://www.nejm.org/doi/full/10.1056/NEJMoa2115463 

Paxlovid, the antiviral pill that reduces the risk of hospitalization and death from Covid-19, also reduces the risk of long Covid, according to a new study by researchers at the US Department of Veterans Affairs. The study, posted online as a preprint on Saturday, analyzed electronic records for more than 56,000 veterans with Covid-19, including more than 9,000 who were treated with Paxlovid within the first five days of their infection. The analysis showed people treated with Paxlovid had a 26% reduced risk of developing several long Covid conditions, including heart disease, blood disorders, fatigue, liver disease, kidney disease, muscle pain, neurocognitive impairment and shortness of breath. That corresponded to 2.3 fewer cases of long Covid conditions per 100 people three months after their diagnosis. Paxlovid also reduced the risk of hospitalization or death following acute Covid-19.  In the analysis, there wasn’t a statistically significant link between taking Paxlovid and risk of two long Covid conditions: cough and new diabetes diagnosis. The study was posted to the preprint server medRxiv and hasn’t been peer-reviewed or published in a medical journal. Patients included in the study had an average age of 65 and were diagnosed with Covid-19 between March 1 and June 30, 2022. They all had at least one risk factor for progression to severe Covid-19, such as older age, diabetes or being a current smoker. Paxlovid reduced the risk of long Covid in people who were unvaccinated, vaccinated and boosted, and in people experiencing their first Covid-19 infection or a reinfection, the study said.

“Paxlovid reduces the risk of severe COVID-19 in the acute phase, and now, we have evidence that it can help reduce the risk of long COVID,” Dr. Ziyad Al-Aly, chief of research and development at the VA St. Louis Health Care System and leader of the study, said in a news release. “This treatment could be an important asset to address the serious issue of long COVID.” The study has several limitations, including that the majority of people included were White and male, which might limit its relevance more generally. The analysis captured Paxlovid use only through the VA system and considered only 12 long Covid conditions, although many people with long Covid describe a wide variety of symptoms.

Millions of people who had Covid-19 face a range of lasting symptoms since their initial illness, but there is no specific treatment for long Covid. Paxlovid is an antiviral treatment for Covid-19 that combines a newer antiviral, nirmatrelvir, with an older drug, ritonavir. It’s available for people as young as 12 and has been shown to sharply reduce risk of hospitalization and death in people at risk of severe Covid-19.   The drug is made by Pfizer and comes as pills taken over five days. It works best if started within five days of symptom onset; researchers noted it’s not clear whether longer duration or higher dose or both might reduce risk of long Covid conditions even more, or whether starting Paxlovid after acute illness from Covid-19 would reduce risk of long Covid. The National Institutes of Health said last month it would launch a study of Paxlovid as a treatment for patients already experiencing long Covid. “The totality of evidence suggests the need to improve uptake and utilization of nirmatrelvir in the acute phase as a means of not only preventing progression to severe acute disease, but to also reduce the risk of post-acute adverse health outcomes,” authors of the VA study wrote.

Study cited in medRxiv (Nov. 5, 2022):

https://doi.org/10.1101/2022.11.03.22281783 

A malaria drug widely touted by President Donald Trump for treating the new coronavirus showed no benefit in a large analysis of its use in U.S. veterans hospitals. There were more deaths among those given hydroxychloroquine versus standard care, researchers reported.

The nationwide study was not a rigorous experiment. But with 368 patients, it's the largest look so far of hydroxychloroquine with or without the antibiotic azithromycin for COVID-19, which has killed more than 171,000 people as of Tuesday. The study was posted on an online site for researchers and has been submitted to the New England Journal of Medicine, but has not been reviewed by other scientists. Grants from the National Institutes of Health and the University of Virginia paid for the work. Researchers analyzed medical records of 368 male veterans hospitalized with confirmed coronavirus infection at Veterans Health Administration medical centers who died or were discharged by April 11.

About 28% who were given hydroxychloroquine plus usual care died, versus 11% of those getting routine care alone. About 22% of those getting the drug plus azithromycin died too, but the difference between that group and usual care was not considered large enough to rule out other factors that could have affected survival. Hydroxychloroquine made no difference in the need for a breathing machine, either. 

Preprint Available at medRxiv (April 21, 2020)

https://doi.org/10.1101/2020.04.16.20065920