A Mayo Clinic–led meta-analysis suggests that transfusion of COVID-19 convalescent plasma improves survival in hospitalized, infected patients who have impaired immune systems.

The antibody-rich plasma, donated by COVID-19 survivors, may help prevent the reinfections to which these high-risk patients are susceptible, the researchers said. The study was published yesterday in JAMA Network Open.

On Aug 12, 2022, the team analyzed 3 randomized clinical trials (RCTs), 5 matched-cohort studies, 13 uncontrolled case series, and 125 case-report series on the use of convalescent plasma in immune-impaired COVID-19 patients.

A 37% risk reduction

In the primary meta-analysis of 8 controlled trials involving 469 intervention patients, COVID-19 convalescent plasma was tied to a lower all-cause death rate than observed in 1,305 control patients in a combination of randomized clinical trials and matched-cohort studies (risk ratio [RR], 0.63; 95% confidence interval, 0.50 to 0.79).

In an individual-level analysis of the 125 case reports or case series involving 265 patients, the median time from symptom onset to receipt of convalescent plasma was 17 days, and the median time from hospitalization to plasma therapy was 11 days. Fifty-one of 218 patients (23.4%) received mechanical ventilation, and 31 of 265 (11.6%) died.

The authors noted that interest in convalescent plasma was renewed when monoclonal antibodies, which had been widely used, were found to be ineffective against the new immune-evasive SARS-CoV-2 variants. Since then, several scientific groups have revised their guidelines to recommend convalescent plasma for immune-impaired patients.

"COVID-19 convalescent plasma appears to have maintained clinical efficacy over time with emerging SARS-CoV-2 variants due to heterogeneous, broad spectrum of neutralizing antibodies and widespread availability," they wrote, "…particularly for patients who are immunocompromised, who are not able to mount a sufficiently protective antibody response against the virus, and who have contraindications or adverse effects from small molecule antivirals."

COVID-19 convalescent plasma appears to have maintained clinical efficacy over time with emerging SARS-CoV-2 variants.

The authors pointed out that while most studies included in their meta-analysis used convalescent plasma from unvaccinated donors, "it is noteworthy that Vax-Plasma is now widely available from regular donors and retains higher neutralizing antibody titers and efficacy against most SARS-CoV-2 variants."

The Sabin Vaccine Institute announced yesterday that it has been awarded a multiyear contract from the US government to advance the development and production of vaccine candidates for the Ebola Sudan and Marburg viruses.

Under the agreement, the US Department of Health and Human Services' Biomedical Advanced Research and Development Authority (BARDA) will initially invest approximately $35 million to produce up to 100,000 doses of Sabin's Ebola Sudan virus vaccine (ChAd3-SUDV).

ChAd3-SUDV is one of three vaccine candidates being evaluated in a World Health Organization trial launched in Uganda in December 2022 amid the recent Ebola Sudan outbreak, which caused 55 deaths before the Ugandan government declared the outbreak over on Jan 11.

The Ebola Sudan outbreak in Uganda underscored the critical need for readily available solutions.

Sabin has also initiated planning for a phase 2 clinical trial to be conducted in Uganda and Kenya. Previous clinical trials and nonhuman primate studies indicate the vaccine is safe, immunogenic, provides rapid protection, and is durable for up to 12 months.

"The Ebola Sudan outbreak in Uganda underscored the critical need for readily available solutions," Sabin CEO Amy Finan said in a press release. "We'll now have ample material to respond quickly to such an outbreak in the future."

The contract, which has a funding potential of up to $214 million, will also support the manufacture of doses of Sabin's Marburg virus vaccine (ChAd3-MARV) for future trials and outbreak response. There are currently no licensed vaccines for Ebola Sudan or Marburg viruses, both of which cause hemorrhagic fever and kill roughly half the people infected.

An observational study of hospitalized adults with complicated urinary tract infection (cUTI) suggests that 7 days of antibiotics appears effective when antibiotics with comparable intravenous (IV) and oral bioavailability are administered, US researchers reported yesterday in Clinical Infectious Diseases.

While several studies have examined the optimal duration of antibiotic therapy for common bacterial infections in hospitalized patients, few have investigated the duration of therapy for cUTI. The study authors say identifying the shortest but still effective antibiotic therapy is critical for patients who are prone to cUTI, because they may remain at risk for recurrent UTI for the rest of their lives, and future infections may be increasingly antibiotic resistant.

The retrospective cohort study, led by researchers from Johns Hopkins University, looked at 1,099 patients treated at 24 US hospitals in 2019 who had gram-negative cUTIs and associated bloodstream infections and received either 7 (265 patients), 10 (382), or 14 (452) days of antibiotic exposure. The primary outcome was recurrent infection up to 30 days after the discontinuation of antibiotic therapy.

There was no difference in the odds of recurrent infection for patients receiving 10 days of therapy compared with 14 days of therapy (adjusted odd ratio [OR], 0.99; 95% confidence interval [CI], 0.52 to 1.87), while a 2.5-fold increase in the odds of recurrence was observed in patients receiving 7 days versus 14 days of treatment (aOR 2.54; 95% CI, 1.40 to 4.60). But when limiting the 7-day versus 14-day analysis to the 627 patients who remained on IV beta-lactam therapy or were transitioned to highly bioavailable oral agents (mainly fluoroquinolones and trimethoprim/sulfamethoxazole), differences in outcomes no longer persisted (aOR 0.76; 95% CI, 0.38 to 1.52).

Of 76 patients who had recurrent infections, 11%, 10%, and 36% in the 7, 10, and 14-day groups, respectively, had drug-resistant infections.

"Our study suggests that for patients receiving IV beta-lactams or fluoroquinolones/trimethoprim-sulfamethoxazole for the entire treatment course, 7 days of antibiotic therapy is likely sufficient; 10 days may be needed for other patients," the authors concluded. 

Our study suggests that for patients receiving IV beta-lactams or fluoroquinolones / trimethoprim-sulfamethoxazole for the entire treatment course, 7 days of antibiotic therapy is likely sufficient.

Two African nations reported more polio cases this week, all involving vaccine-derived strains, according to the latest weekly update from the Global Polio Eradication Initiative (GPEI).

The Democratic Republic of the Congo reported 17 more circulating vaccine-derived poliovirus type 1 (cVDPV1) cases, mostly from Haut Lomami province, bringing its total for 2022 to 68. The country also reported 15 more circulating vaccine-derived poliovirus type 2 (cVDPV2) cases in five provinces, including Haut Lomami, boosting the country's number for 2022 to 236.

Elsewhere, Niger reported 1 more cVDPV2 case, which involves a patient from Tahoua, lifting its 2022 total to 14.

Details on Sudan cases

In related developments, the World Health Organization (WHO) provided more details about Sudan's first cVDPV2 case of 2022, which was first reported in late December.

The patient is a 4-year-old boy from West Darfur whose acute flaccid paralysis (AFP) began on Oct 31. A genetic analysis of the virus isolate suggests that it is closely related to a strain circulating in Nigeria's Borno state and is not related to the cVDPV2 strain involved in Sudan's 2020 outbreak, which was just declared over in August 2022.

The WHO said the re-emergence of the virus in Sudan points to gaps in routine immunization. It added that the country's health ministry in late November launched a polio vaccination campaign for children younger than 13 years in affected areas. Two more campaigns are planned, with a goal of reaching children younger than 5 years old.