Nayagam JS, Jeyaraj R, Mitchell T, et al. Persistent cholestasis in survivors of SARS-CoV-2. J Infection April 03, 2021. DOI: https://doi.org/10.1016/j.jinf.2021.03.029
A considerable proportion of patients with SARS-CoV-2 infection do not normalize their liver blood tests during follow-up, particularly those with highly elevated GGT. Of 397 patients who survived to 60 days, 216 had abnormal liver blood tests. Repeat blood tests at day 60 were performed in 43 of these patients, and a persistent abnormality in liver blood tests was detected in 24/43 patients (55.8%), predominantly in a cholestatic pattern: 3/38 (7.9%) AST abnormal; 12/43 (27.9%) ALP abnormal; and 23/43 (53.5%) GGT abnormal.
Havervall S, Rosell A, Phillipson M, et al. Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers. JAMA April 7, 2021, https://jamanetwork.com/journals/jama/fullarticle/2778528?resultClick=1
Probably one of the best longitudinal studies on long COVID-19 to date, comparing 323 seropositive (with mild disease) vs 1072 seronegative HCW. At 8 months, 15% vs 3% (at 2 months: 26% vs 9%) reported at least one moderate to severe symptom. Symptoms disrupted work, social, and home life.
Taquet M, Geddes JR, Husain M, et al. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry April 06, 2021. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00084-5/fulltext
Did we ever mention that COVID-19 is not the flu? Among 236,379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 34%, with 13% receiving their first such diagnosis. Most diagnostic categories were more common in patients who had COVID-19 than in those who had influenza (hazard ratio 1.44 for any diagnosis; 1.78 for any first diagnosis) and those who had other respiratory tract infections (1.16 and 1.32). Risks were greatest in, but not limited to, patients who had severe COVID-19.
Hosp JA, Dressing A, Blazhenets G, et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain April 3, 2021, awab009, https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab009/6209743?searchresult=1
Cognitive deficits are present in many COVID-19 patients requiring in-patient treatment. Of 15 patients undergoing extended neuropsychological testing, only two patients performed entirely normally. Orientation and language abilities were in the range of healthy subjects, while memory and executive items were most severely affected, making general deterioration unlikely. There was no decline in general attention or speed of processing. This specific pattern can hardly be explained by non-specific factors like fatigue. It also differs from cognitive impairment post-sepsis. Many patients displayed frontoparietal cognitive dysfunctions and 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism.
Ayoubkhani D, Khunti K, Nafilyan V, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ 2021;372: n693. 31 March 2021. https://www.bmj.com/content/372/bmj.n693
47,780 hospitalized patients (mean age 65) discharged alive by 31 August 2020 were exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics. Over a mean follow-up of 140 days, nearly a third were readmitted and more than 1 in 10 died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of multi-organ dysfunction after discharge were raised compared to the matched control group, suggesting extrapulmonary pathophysiology. As shown in the Figure, diabetes and major adverse cardiovascular event were particularly common.
Arnold DT, Milne A, Samms E, et al. Are vaccines safe in patients with Long COVID? A prospective observational study. bioRxiv 2021, posted 14 March. Full text: https://doi.org/10.1101/2021.03.11.21253225
Observational study of 44 vaccinated participants and 22 matched unvaccinated participants. Most were highly symptomatic of Long COVID at 8 months (82% in both groups had at least 1 persistent symptom), with fatigue (61%), breathlessness (50%) and insomnia (38%) predominating. When compared to matched unvaccinated participants from the same cohort, those who had received a vaccine had a small overall improvement in Long COVID symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated) (p = 0.035). Placebo effect? Hopefully not.
Paper of the Day
Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med 2021, published 22 March. Full-text: https://doi.org/10.1038/s41591-021-01283-z
The authors provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae, and discuss relevant considerations for the multidisciplinary care of COVID-19 survivors.
The Writing Committee for the COMEBAC Study Group. Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19. JAMA. March 17, 2021. https://jamanetwork.com/journals/jama/article-abstract/2777787
How is it going after four months? Not so well. This study included 142 of 172 ICU patients and 336 of 662 non-ICU patients from Paris. During a telephone interview, 244/478 patients (51%) declared at least one symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. CT lung scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 (19%).
Perlis RH, Ognyanova K, Santillana M, et al. Association of Acute Symptoms of COVID-19 and Symptoms of Depression in Adults. JAMA Netw Open. 2021; 4(3):e213223. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777421?resultClick=1
Depression may be considered as potential neuropsychiatric sequelae. Among more than 3900 individuals with prior COVID-19 surveyed between May 2020 and January 2021, 52.4% met criteria for moderate or greater symptoms of major depression. Symptoms were more prevalent in younger and in male patients.
Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med March 10, 2021. https://www.nature.com/articles/s41591-021-01292-y
Is it possible to predict long COVID-19? Among 4182 people who self-reported their symptoms prospectively in the COVID Symptom Study app, a total of 558 (13.3%) reported symptoms lasting ≥ 28 days, 189 (4.5%) for ≥ 8 weeks and 95 (2.3%) for ≥ 12 weeks. Experiencing more than five symptoms during the first week of illness was associated with long COVID in all sexes and age groups (odds ratio = 3.5). Main caveat: the population was limited by being confined to app contributors (disproportionately female patients). May not be generalizable.
Weng J, Li Y, Li J, et al. Gastrointestinal sequelae 90 days after discharge for COVID-19. Lancet Gastroenterology Hepatology March 9, 2021. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00076-5/fulltext
In this retrospective study from Hubei and Guangdong provinces, 52 (44%) of 117 patients reported gastrointestinal symptoms after discharge at a 90 day telephone interview: loss of appetite (24%), nausea (18%), acid reflux (18%), and diarrhoea (15%). Of note, severe illness during hospitalisation was not associated with post-discharge gastrointestinal sequelae.
Subbaraman N. US health agency will invest $1 billion to investigate ‘long COVID’. Nature News 04 March 2021. https://www.nature.com/articles/d41586-021-00586-y
Nidhi Subbaraman reports that the US will spend big on research into ‘long COVID’ — the long-lasting health effects of a SARS-CoV-2 infection (see our recent review) for which experts have coined a new term: post-acute sequelae SARS-CoV-2 infection (PASC).
Gacci M, Coppi M, Baldi E, et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Human Reproduction March 1, 2021. Full-text: https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deab026/6125160
Mauro Gacci from Florence, Italy, and colleagues performed a large prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV-2 (3-6 weeks after negative swab). One patient had a positive PCR in semen (21 days after the second negative swab). Of note, 11/43 were oligo-crypto-azoospermic and all azoospermic patients reported a previous unimpaired fertility status suggesting that semen impairment was due to COVID-19. However, a main limitation of the study is the lack of samples obtained prior to COVID-19.
Klein H, Asseo K, Karni N, et al. Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infections. A cohort study in Israeli patients. Clin Microbiol Infect. 2021 Feb 16:S1198-743X(21)00083-5. PubMed: https://pubmed.gov/33607252. Full-text: https://doi.org/10.1016/j.cmi.2021.02.008
Of 103 patients with mild COVID-19, 46% had at least one unresolved symptom at six months, most commonly fatigue (22%), smell and taste changes (15% and 8%, respectively), and breathing difficulties (8%).
Logue JK, Franko NM, McCulloch D, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open, February 19, 2021;4(2):e210830. Full-text: https://doi.org/10.1001/jamanetworkopen.2021.0830
A longitudinal prospective cohort of adults with COVID-19 (11 asymptomatic, 150 outpatients with mild disease, 16 with severe illness) was compared with a concurrent cohort of healthy patients. Between 3 and 9 months after onset of illness, the most common persistent symptoms were fatigue (14%) and loss of sense of smell or taste (14%). Notably, 14 participants, including 9 non-hospitalized individuals, reported negative impacts on activity of daily living after infection. With > 60 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.
Zhou M, Wong CK, Un KC, et al. Cardiovascular sequalae in uncomplicated COVID-19 survivors. PLoS One. 2021 Feb 11;16(2):e0246732. PubMed: https://pubmed.gov/33571321. Full-text: https://doi.org/10.1371/journal.pone.0246732
Cardiac abnormality is common (but mostly self-limiting) among COVID survivors with mild disease: a systematic cardiac screening was performed among 97 consecutive COVID-19 survivors (mean age 46 years, all with non-severe disease), including treadmill exercise test and cardiac magnetic resonance imaging (CMR). Median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%) and elevated troponin level (6.2%). For COVID-19 survivors with persistent elevation of troponin levels after discharge or newly detected T wave abnormalities, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.
Raven K. Long-COVID – the nightmare that won’t end – a researcher’s first hand perspective. Peacock Lab 2021, published 6 February. Full-text: https://professorsharonpeacock.co.uk/long-covid-the-nightmare-that-wont-end-a-first-hand-perspective
“I’ve given an account of my own experience with long COVID, which I hope will help to raise awareness of this debilitating illness, but it’s estimated there could be 300.000 other sufferers in the UK (3), with more joining those ranks every day. Some features are shared with others, others differ. But I think for all of us recognition, help, and research are key. And we need them desperately.”