COVID-19 research briefs: Persistent fatigue, dyspnea common following hospitalization; promising vaccine developed in China

Daily POEMs

Published: 2020-08-23 © 2020 John Wiley & Sons, Inc.

Clinical question
What longer term symptoms follow hospitalization for COVID-19? Is a vaccine developed in China a possible solution?

Bottom line
Persistent fatigue, dyspnea, and other symptoms commonly follow hospitalization for COVID-19. Chinese researchers report a successful Phase 2 trial of a COVID-19 vaccine. (LOE = 2c)

Reference
Carfi A, Bernabei R, Landi F, et al. Persistent symptoms in patients after acute COVID-19. JAMA 2020; doi:10.1001/jama.2020.12603

Study design: Not applicable

Funding source: Unknown/not stated

Setting: Not applicable

Synopsis
Research Brief #49: In this study set in Rome, patients who had been hospitalized but now met criteria for discontinuing quarantine (afebrile for 3 days, symptoms improved, and 2 negative polymerase chain reaction [PCR] test results 24 hours apart) were invited to attend a COVID-19 follow-up clinic. Of the 179 eligible patients, 165 agreed to participate, but 22 had a positive PCR result and were excluded. Their mean age was 57 years and 63% were men. Patients were post symptom onset by a mean of 60 days, and 87% still reported symptoms, with 32% reporting 1 or 2 symptoms and 55% reporting 3 or more persistent symptoms. A total of 44% reported a clinically significant 10-point decline on a 100-point quality of life scale compared with their pre-COVID-19 state. The most common post-COVID-19 symptoms at follow-up were fatigue (53%), dyspnea (43%), joint pain (27%), chest pain (22%), cough (17%), and anosmia (16%). Strengths of this study include a standard protocol for data collection and a good response rate among invited patients. This is important prognostic information for patients who were sick enough to be hospitalized; longer term follow-up in these patients, as well as in patients who were less symptomatic, will be important. Comparison with patients who have survived other serious pulmonary infections, such as community acquired pneumonia and acute respiratory distress syndrome, are also needed to provide context. Carfi A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. Published online July 9, 2020. doi:10.1001/jama.2020.12603. Research Brief #50: These researchers identified 508 healthy volunteers and randomized them to receive a low-dose vaccine (5 x 10^10 viral particles), a high-dose vaccine (1 x 10^11 viral particles), or a placebo vaccine in a 2:1:1 ratio. The vaccines were adenovirus type-5 vectored vaccines. Allocation was concealed and patients and outcome assessors were masked. Patients' mean age was 40 years, with a range of 18 years to 83 years, but only 13% of recipients were 55 years or older. Seroconversion of the binding antibody was very high (96% to 97%) in the 2 vaccine groups at 28 days. Seroconversion of the neutralizing antibodies to SARS-CoV-2 occurred in 59% who received the high-dose vaccine and 49% who received the low-dose vaccine at 28 days. Note that binding antibodies bind to the viral antigen, but do not prevent infection of the host cell, while neutralizing antibodies prevent infection. Evidence of humoral (T-cell–mediated) immunity was detected at 28 days in 90% of patients who received the high-dose vaccine and 88% who had the low-dose vaccine. Older patients and patients with high pre-existing titers to adenovirus type 5 had less vigorous immune responses and would likely require a second immunization. Severe adverse events (most commonly fever, but also induration, headache, fatigue, dyspnea, and myalgia/arthralgia) occurred in 9% of the high-dose group and only 1% of the low-dose group. There were no serious or life-threatening adverse effects in either group. Zhu F-C, Guan X-H, Li Y-H, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. Published online July 20, 2020. https://doi.org/10.1016/S0140-6736(20)31605-6.

Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA

Copyright © 2020 John Wiley & Sons, Inc.