Brazilian trial finds no COVID-19 benefit from hydroxychloroquine, azithromycin
A randomized controlled trial of hospitalized COVID-19 patients in Brazil found that the use of hydroxychloroquine, with or without azithromycin, did not improve clinical status at 15 days compared with standard care, researchers reported today in the New England Journal of Medicine.
The multicenter trial, conducted at 55 hospitals in Brazil, included 667 patients with suspected or confirmed COVID-19 and mild-to-moderate illness. Participants were randomly assigned 1:1:1 to receive standard of care, standard of care plus 400 milligrams of hydroxychloroquine twice daily, or standard of care plus hydroxychloroquine and azithromycin (500 mg once daily for 7 days).
Standard of care included the use of glucocorticoids, other immunomodulators, antibiotics, and antivirals. The primary outcome was clinical status at 15 days based on the use of a seven-level ordinal scale, with a score of 1 indicating not hospitalized and 7 indicating death.
A total of 504 patients had confirmed COVID-19 and were included in the intention-to-treat analysis. Compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days were not affected by being treated with hydroxychloroquine alone (odds ratio [OR], 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (OR, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). There was also no effect on secondary outcomes.
In addition, more adverse events, including prolongation of the corrected QT interval and elevation of liver-enzyme levels, occurred in patients receiving hydroxychloroquine plus azithromycin (39.3%) and hydroxychloroquine alone (33.7%) than in patients receiving standard care (22.6%).
Jul 23 N Engl J Med study
Study reveals risk factors for COVID-19 deaths in nursing homes
COVID-19 infections passed from staff members to residents at 627 long-term care (LTC) facilities in Ontario, Canada, by early April were strongly associated with resident deaths from the novel coronavirus, according to a study published yesterday in JAMA Network Open.
By Apr 10, 198 of 401 [49%] of Canada's COVID-19 deaths had occurred in residents of LTC facilities, prompting researchers at the University of Toronto to conduct a cohort study comparing community-living Ontarians older than 69 years who died of coronavirus by Apr 11 with nursing home residents who died by Apr 7.
Of the 627 nursing homes, 272 (43.4%) reported COVID-19 infections in residents or employees. Of 1,731,315 community-living Ontarians older than 69 years, 229 (<0.1%) died, as did 83 (0.1%) of an estimated 79,498 nursing home residents.
Thus, the incident rate ratio (IRR) for coronavirus deaths in LTC residents was 13.1 (95% CI, 9.9 to 17.3) versus their community-living counterparts. The IRR rose dramatically over time, to 87.3 (95% credible interval, 6.4 to 769.8) by Apr 11. Staff member infections were linked to resident deaths after a 6-day lag (adjusted IRR for death per infected employee, 1.17; 95% CI, 1.11 to 1.26).
The authors said that the study adds another risk factor to the list of long-recognized drivers of nursing home deaths, such as advanced resident age, lack of access to testing, difficulty maintaining physical distance among mobile residents with dementia, crowding, low staff-to-resident ratios, staff movement among different nursing home sites, and care needs that necessitate close contact between staff and residents.
It also shows that staff are more likely to infect residents than vice versa. The authors noted that, in addition to staff-to-resident infection, fear of COVID-19 could have kept some employees home, increasing the risk of resident death from dehydration or other means.
As of Jun 10, 1,766 nursing home residents have died of COVID-19 in Ontario, constituting 71% of all deaths in the province.
"Early identification of risk requires a focus on testing, providing personal protective equipment to staff, and restructuring the LTC workforce to prevent the movement of COVID-19 between facilities," the authors wrote.
Jul 22 JAMA Netw Open study
Live COVID-19 virus isolated from human nose-throat, saliva specimens
A small study published yesterday in Clinical Microbiology and Infection found live SARS-CoV-2, the virus that causes COVID-19, in one nose-throat swab and two saliva specimens of five infected hospital patients in Korea 11 to 15 days after symptom onset.
Researchers collected nose-throat swabs, saliva, urine, and stool samples from the patients hospitalized from Feb 25 to Mar 5 on days 8, 11, 13, 15, and 30 after study enrollment. They performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to detect SARS-CoV-2 RNA and cell culture to detect viable virus.
No live virus—only viral RNA—was isolated on cell culture from five urine, two saliva, four nose-throat, and three fecal specimens.
The researchers also inoculated two groups of ferrets intranasally with two patient urine specimens and one fecal specimen found to contain SARS-CoV-2 RNA on qRT-PCR. Nasal washes were collected from the ferrets every 2 days until 8 days after infection. Live virus was isolated from the nasal washes of one feces-treated ferret and two urine-treated ferrets. All treated ferrets showed moderate increases in temperature and nasal discharge and decreased activity at days 4 and 6.
Median patient age was 63 years, and three patients were men. One patient had mild illness, three had severe disease and needed supplementary oxygen, and one patient was critically ill with respiratory failure and septic shock. Four of the five patients had recovered by the time of specimen sampling, while the fifth still required mechanical ventilation.
The authors noted that, because of the lack of collection of specimens from coronavirus patients over time, the study couldn't provide information about changing viral loads. Also, the findings in ferrets may not apply to humans for several reasons, one of them being that the viral dose that can infect a ferret might be different than that in humans.
Jul 22 Clin Microbiol Infect study