Viruses cannot replicate by themselves. Instead, they rely on the host for almost all their replicative functions. Similarly, many viruses are unable to cause damage without the host immune system. ...Because of this, two strategies can often ameliorate disease — antivirals, which block replication, and antiinflammatories, which can limit the damage induced by infection. In the lung, this latter strategy is exemplified by the treatment of
Pneumocystis jiroveci
, in which treatment with glucocorticoids reduces the severity of disease and the risk of death.
1,2
However, because blocking inflammatory pathways raises the possibility of diminishing the host response and increasing replication of . . .
Covid-19 — The Search for Effective Therapy Baden, Lindsey R; Rubin, Eric J
New England journal of medicine/The New England journal of medicine,
05/2020, Volume:
382, Issue:
19
Journal Article
Peer reviewed
Open access
Covid-19 is spreading rapidly through Europe and North America, but we have few specific tools to control the growing epidemic and treat those who are sick. We rely on quarantine, isolation, and ...infection-control measures to prevent disease spread and on supportive care for those who become ill. What we lack is a specific antiviral agent to treat the infected and, optimally, decrease viral shedding and subsequent transmission. One antiviral-drug candidate is a combination of the HIV protease inhibitors lopinavir and ritonavir. Lopinavir, which acts against the viral 3CL protease, has modest antiviral activity against SARS-CoV-2.
1
Together with ritonavir, which increases . . .
Lindsey Baden and Eric Rubin comment on the findings of an urgent randomized clinical trial of a possible treatment for Covid-19 in Wuhan, China. They note that whether the findings of such trials are positive or negative, they will be central to clinical care as the pandemic continues.
Two injections of mRNA-1273, a lipid nanoparticle–encapsulated mRNA-based vaccine produced in collaboration with the NIAID that encodes the SARS-CoV-2 spike protein, conferred protection against ...Covid-19 illness in 94% of vaccinated patients. Adverse effects of the vaccine were mild, transient local reactions, and the incidence of systemic effects such as fever, headache, and fatigue was low.
In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of ...protection. These immune markers were measured at the time of second vaccination and 4 weeks later, with values reported in standardized World Health Organization international units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. Vaccine recipients with postvaccination 50% neutralization titers 10, 100, and 1000 had estimated vaccine efficacies of 78% (95% confidence interval, 54 to 89%), 91% (87 to 94%), and 96% (94 to 98%), respectively. These results help define immune marker correlates of protection and may guide approval decisions for messenger RNA (mRNA) COVID-19 vaccines and other COVID-19 vaccines.
Neutralization of the omicron variant was assessed in serum samples obtained from persons who had received an mRNA-1273 booster. After the standard two-dose vaccine regimen, these titers were ...approximately 35 times lower than those against the D614G variant. However, boosters increased omicron neutralization by a factor of 20 — to levels that correlate with clinical resistance to infection.
This letter describes an immunocompromised patient who had persistent infection with SARS-CoV-2 over a period of months, despite several courses of remdesivir. Phylogenetic analysis showed ...accelerated viral evolution.
Medical Journals and the 2019-nCoV Outbreak Rubin, Eric J; Baden, Lindsey R; Morrissey, Stephen ...
New England journal of medicine/The New England journal of medicine,
02/2020, Volume:
382, Issue:
9
Journal Article
Peer reviewed
Open access
The editors announce expedited handling for submitted manuscripts describing the 2019-nCoV outbreak and make broad recommendations for speed, transparency, and data sharing.
When given as a second booster, a bivalent vaccine including sequences from the Wuhan-Hu-1 and omicron BA.1 viral strains induced higher levels of neutralizing antibodies against BA.4/5 subtypes than ...a Wuhan-Hu-1 booster.
Objective
To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID‐19) pandemic.
Methods
A task force, ...including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by email and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1–9‐point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7–9, 4–6, and 1–3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus.
Results
Draft guidance statements approved by the task force have been combined to form final guidance.
Conclusion
These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a “living document,” and future updates are anticipated.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons.
To evaluate antinucleocapsid antibody ...(anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.
Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial. (ClinicalTrials.gov: NCT04470427).
99 sites in the United States, July 2020 through March 2021.
Participants were aged 18 years or older, had no known history of SARS-CoV-2 infection, and were at risk for SARS-CoV-2 infection or severe COVID-19. Substudy participants were diagnosed with SARS-CoV-2 infection during the trial's blinded phase.
2 mRNA-1273 or placebo injections 28 days apart.
Nasopharyngeal swabs from days 1 and 29 (vaccination days) and from symptom-prompted illness visits were tested for SARS-CoV-2 via polymerase chain reaction (PCR). Serum samples from days 1, 29, and 57 and the participant decision visit (PDV, when participants were informed of treatment assignment; median day 149) were tested for anti-N Abs by the Elecsys immunoassay.
Among 812 participants with PCR-confirmed COVID-19 illness during the blinded phase of the trial (through March 2021), seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% 95% CI, 27% to 54%) versus 605 of 648 placebo recipients (93% CI, 92% to 95%). Each 1-log increase in SARS-CoV-2 viral copies at diagnosis was associated with 90% higher odds of anti-N Ab seroconversion (odds ratio, 1.90 CI, 1.59 to 2.28).
The scope was restricted to mRNA-1273 vaccinees and the Elecsys assay, the sample size was small, data on Delta and Omicron infections were lacking, and the analysis did not address a prespecified objective of the trial.
Vaccination status should be considered when interpreting seroprevalence and seropositivity data based solely on anti-N Ab testing.
National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
PDF
