Recommendations and research negative on hydroxychloroquine, early testing after exposure

New ACP practice points say not to use chloroquine or hydroxychloroquine alone or in combination with azithromycin for COVID-19 except in trials, and a new study finds that testing for the novel coronavirus is most accurate one to three days after symptom onset.


ACP issued a set of practice points addressing whether clinicians should use chloroquine or hydroxychloroquine alone or in combination with azithromycin for prophylaxis or treatment of COVID-19. The conclusion, based on a systematic evidence review, was that they should not, due to known harms and no available evidence of benefit. However, the guidance said that in the context of a clinical trial, clinicians may use the drugs to treat hospitalized COVID-19-positive patients, using shared and informed decision making with patients (and their families). The points were approved by the ACP Board of Regents on May 4 and published by Annals of Internal Medicine on May 13. They will be updated as new evidence becomes available. A new edition of Annals Consult Guys also focuses on hydroxychloroquine.

Several studies published in the past week failed to find benefit from hydroxychloroquine in COVID-19. A retrospective analysis of 1,438 patients hospitalized in New York, published by JAMA on May 11, found no significant differences in inpatient mortality among patients receiving hydroxychloroquine, azithromycin, both drugs together, or neither drug. Cardiac arrest was significantly more likely in patients receiving both drugs together than those receiving neither. A trial of hydroxychloroquine in hospitalized Chinese patients with persistent but mostly mild to moderate cases of COVID-19 did not find any significant difference in the rate of negative conversion between 75 patients randomized to the drug and 75 who didn't receive it, according to results published by The BMJ on May 14. Similarly, no differences in outcomes were found in a retrospective study of French patients with COVID-19 who required oxygen but not intensive care, also published by The BMJ on May 14. Rates of ICU transfer and survival were similar in the 84 patients who received hydroxychloroquine within 48 hours of admission and the 89 patients who did not receive it.

Highlighting another challenge in combating COVID-19, testing for SARS-CoV-2 soon after exposure results in a high false-negative rate, according to an analysis published by Annals of Internal Medicine on May 13. It included seven studies with 1,330 patients (some hospitalized, some not) that provided data on reverse transcriptase polymerase chain reaction (RT-PCR) test performance by time since symptom onset or exposure. The study found that with a typical time of symptom onset on day 5, the probability of a false-negative result in an infected person decreases from 100% on day 1 to 67% on day 4, 38% on day 5, and 20% on day 8. It then increases from 21% on day 9 to 66% on day 21. Given that the false-negative rate was lowest on day 8, the results suggest clinicians “should consider waiting 1 to 3 days after symptom onset to minimize the probability of a false-negative result,” the study authors said.

They noted that “if testing is done immediately after exposure, the pretest probability is equal to the negative posttest probability, meaning that the test provides no additional information about the likelihood of infection” and that “if clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered.” The latest edition of Annals On Call also addressed testing for COVID-19, as did a recent Q&A in ACP Hospitalist Weekly.

Finally, another recent study, published by Clinical Infectious Diseases on May 15, looked at COVID-19 infections and outcomes among health care workers in China. Out of a total of 2,457 health care worker cases, 52.06% were nurses, 33.62% were doctors, and 14.33% were other staff. The case infection rate was 2.22% among nurses and 1.92% among doctors. Although the case infection rate of health care workers was significantly higher than that of non-health care workers (2.10% vs. 0.43%), their case fatality rate was significantly lower (0.69% vs. 5.30%). The results should spur protective measures for health care workers beyond an adequate supply of personal protective equipment, the authors said. “Other measures should be considered, including nutritious food supply, adequate rest time, and societal, familial, and psychological support.”