Tag: convalescent plasma

Categories : COVIDTags :

Convalescent Plasma was Effective in Early Pandemic

On By ModernMedia

Convalescent plasma from COVID patients was likely of benefit to patients early on in the pandemic, before the introduction of remdesivir and corticosteroids as treatments, according to results of a landmark study published in JAMA Internal Medicine.

The randomised clinical trial, CONTAIN COVID-19, was established to evaluate the safety and efficacy of convalescent plasma in hospitalised coronavirus patients. Overall, the trial showed that convalescent plasma was safe and well tolerated. It worked best in the early days of the pandemic, when plasma had higher antibody levels, when it was given early in the disease, and particularly for immunosuppressed people.

“This landmark study shows once and for all that convalescent plasma is an important countermeasure early in a pandemic when no other therapies are available. It was an important finding that lays the foundation for the rapid response to future pandemics,” said Luis Ostrosky, MD, professor and director of the Division of Infectious Diseases at McGovern Medical School at UTHealth Houston. “This trial, the largest of its kind, also showed that with proper funding and structure, researchers across the country were able to come together quickly in the middle of a global crisis to explore this therapeutic intervention.”

Trial results also showed a drop in efficacy after the introduction of remdesivir and corticosteroids, and by the end of the 11-month trial, there was no difference in outcome between plasma and placebo in patients at 14 and 28 days. However, patients on corticosteroids, but not remdesivir, appeared to benefit from convalescent plasma at day 14.

Since the patient characteristics, available treatments, and the virus, all changed over time, subgroup analyses were done, which showed a possible benefit for patients in the first quarter of the trial, a period from April to June 2020.

Participants in that first quarter were older, less severely ill, had a longer duration of symptoms, and received high-titer plasma. Shorter symptom duration can indicate a more severe case of the viral infection.

“Convalescent plasma could be an important early treatment tool in places that don’t have access to monoclonal antibodies, corticosteroids, remdesivir, or other therapies,” said the study’s co-investigator, Professor Bela Patel, MD. “It should also be considered for patients who are immunosuppressed and those whose B cell function is compromised.”

The researchers also suggested that, in addition to the introduction of corticosteroids and remdesivir, the decrease in efficacy over time may have been due to using convalescent plasma that originated from New York City before the emergence of other SARS-Co-V-2 variants .

Source: University of Texas Health Science Center at Houston

Categories : COVIDTags :

SARS-CoV-2 Mutation Evolved in Immunocompromised Patient

On By ModernMedia

The discovery of SARS-CoV-2 mutations evolving in an immunocompromised patient treated with convalescent plasma has been revealed by Ravindra Gupta, MD, PhD, of University of Cambridge in England, and team.

“We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the authors wrote.

Previous research has shown that immunosuppressed patients could serve as reservoirs for norovirus variants.

Although they did not claim the UK variant was created by that particular case, Gupta’s group speculated that the plasma therapy could have unleashed the resistant variants, and could do so in other immunosuppressed patients too.

They wrote that, in such patients, “the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations.” 

They cautioned that convalescent plasma use should be limited, and only with appropriate infection control in monitoring in immunosuppressed patients.

A man in his 70s, who had received immunotoxic chemotherapy to treat lymphoma eight years previously, was initially hospitalised in May with neutropenic sepsis, and, about a week later, tested positive for SARS-CoV-2. He was discharged later in May, but in late June was readmitted with cough and breathlessness.

His condition worsened and he received dexamethasone and two 10-day courses of remdesivir 5 days apart. On two days around July 20, convalescent plasma was administered; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.

Gupta and team took viral samples from this patient on 23 occasions, and over the first 57 days, they observed little change in viral population upon treatment with remdesivir, but after the July round of convalescent plasma, a shift in viral genotype occurred.

Initially the patient’s viral serotype showed a mutation first reported in China. However, in late July, a variant was observed with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant. Testing showed a twofold reduced susceptibility to the antibodies in the convalescent plasma.

The team wrote that this sort of evolution is unlikely to emerge in immunocompetent patients. They cautioned against using convalescent plasma in severe COVID patients, and especially those who were immunosuppressed.

The study’s limitations included being only a single case, and samples were taken from the upper respiratory tract and not the lower respiratory tract. 
Given South Africa’s large HIV positive population, if viral evolution is driven by convalescent plasma in immunosuppressed patients, this raises questions for the country’s COVID strategy.

Source: MedPage Today

Journal information: Kemp SA, et al “SARS-CoV-2 evolution during treatment of chronic infection” Nature 2021; DOI: 10.1038/s41586-021-03291-y.