++ Long COVID ++

24 November

Li P, Zhao W, Kaatz S, et al. Factors Associated With Risk of Postdischarge Thrombosis in Patients With COVID-19. JAMA Netw Open November 22, 2021;4(11):e2135397. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786413?resultClick=1

Among 2832 patients hospitalized with COVID-19, 36 (1.3%) had postdischarge venous thromboembolic events. These events occurred 3-4 times more often in those with a history of venous thromboembolism, peak D-dimer level greater than 3 μg/mL, and predischarge CRP level greater than 10 mg/dL.


15 November

Petek BJ, Moulson N, Baggish AL, et al. Prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms following SARS-CoV-2 infection in 3597 collegiate athletes: a study from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). Br J Sports Med. 2021 Nov 1:bjsports-2021-104644. Full text: https://doi.org/10.1136/bjsports-2021-104644

In this large registry, persistent symptoms > 3 weeks were present in 44/3529 (1.2%) athletes with 2/3529 (0.06%) reporting symptoms > 12 weeks. Exertional cardiopulmonary symptoms were present in 137/3393 (4.0%) of athletes.


13 November

Xie Y, Bowe B, Al-Aly Z. Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status. Nat Commun November 11, 2021, 12, 6571. https://www.nature.com/articles/s41467-021-26513-3

Using the healthcare databases of the US Department of Veterans Affairs to build a cohort of 181,384 people with COVID-19 and 4,397,509 non-infected controls, the authors estimate that post-acute sequelae – defined as at least one sequela in excess of a non-infected control group—was 73 per 1000 persons at 6 months. The burden of PASC increased as a function of the severity of the acute infection at 45, 217, and 360 per 1000 persons at 6 months among non-hospitalized, hospitalized, and those who were admitted to intensive care during the first 30 days of infection, respectively.


10 November

Matta K, Wiernik E, Robineau O, et al. Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic. JAMA Intern Med November 8, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785832?resultClick=1

The results of this cross-sectional analysis of a large, population-based French cohort suggest that physical symptoms persisting 10 to 12 months after the COVID-19 pandemic first wave may be associated more with the belief in having experienced COVID-19 infection than with actually being infected with the SARS-CoV-2 virus.


1 November

Van Hattum JC, Spies JL, Verwijs SM. Cardiac abnormalities in athletes after SARS-CoV-2 infection: a systematic review. BMJ Open Sport Exerc Med 2021, October 12;7(4):e001164. https://pubmed.ncbi.nlm.nih.gov/34691762/

According to this review, rates of pericardial/myocardial abnormalities in athletes are highly variable and dependent on study quality. “Prospective athlete studies, with pre-SARS-CoV-2 imaging (CMR), including structured follow-up and arrhythmia monitoring, are urgently needed”. (Joshua, why not now consider a “pre-SARS-CoV-2 CMR”?)


26 October

Becker JH, Lin JJ, Doernberg M, et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Netw Open October 22, 2021;4(10):e2130645. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785388?resultClick=1

A cohort of 740 patients with COVID-19, indicating a relatively high frequency of cognitive impairment several months later. The most prominent deficits were in processing speed (18%), executive functioning (16%), phonemic (initial letter) fluency (15%) and category fluency (20%), memory encoding (24%), and memory recall (23%).


Wenzel J, Lampe J, Müller-Fielitz H, et al. The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells. Nat Neurosci October 21, 2021). https://www.nature.com/articles/s41593-021-00926-1

Is this the explanation? Jan Wenzel and colleagues from Germany show microvascular pathology in the brains of SARS-CoV-2-infected patients that likely explains signs and symptoms. They propose a mechanism by which SARS-CoV-2 infection compromises brain endothelial function, damages the brain blood barrier and reduces CNS perfusion.


18 October

Al-Aly Z. The WHO is letting down long Covid patients. The Guardian 2021, published 17 October. Full text: https://www.theguardian.com/commentisfree/2021/oct/17/who-long-covid-patients

“Failure to recognize the scope of the illness will harm countless people around the globe.”


15 October

Groff D, Sun A, Ssentongo AE, et al. Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review. JAMA Netw Open. 2021 Oct 1;4(10):e2128568. PubMed: https://pubmed.gov/34643720. Full text: https://doi.org/10.1001/jamanetworkopen.2021.28568

In this review of 57 studies comprising more than 250,000 survivors of COVID-19, the most common sequelae involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. The authors warn that these long-term effects “occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.”


1 October

Zhang X, Wang F, Shen Y, et al. Symptoms and Health Outcomes Among Survivors of COVID-19 Infection 1 Year After Discharge From Hospitals in Wuhan, China. JAMA Netw Open September 29, 2021; 4(9):e2127403. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784558

Long-term follow up from Wuhan. Of 2433 patients with a 1 year follow-up, 1095 (45%) reported at least one symptom. The most common symptoms included fatigue, sweating, chest tightness, anxiety, and myalgia. Older age, female sex, and severe disease during hospital stay were associated with higher risks of fatigue. Of note, 4.2% of patients reported palpitations, which may point to long-term damage of COVID-19 to the cardiovascular system.


1 September

Huang L, Yao Q, Gu X, et al. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet August 28, 2021. Volume 398, ISSUE 10302, P747-758. https://doi.org/10.1016/S0140-6736(21)01755-4

The largest cohort study by far, on 1276 COVID-19 survivors who had been hospitalized and who had a follow up of one year. The proportion of patients with at least one sequelae symptom decreased from 68% at 6 months to 49% at 12 months. 88% of patients who were employed before COVID-19 had returned to their original work at 12 months. However, 12% did not (see below). Fatigue or muscle weakness was still present in 20%.


Auwaerter PG. The Race to Understand Post–COVID-19. Ann Int Med August 31, 2021. https://www.acpjournals.org/doi/10.7326/M21-3072

Some thoughts and ideas. “Even if only 10% of patients experience persistent symptoms after COVID-19, the number afflicted will easily be tens of millions.” And, “If science does not move with dispatch in addressing post–COVID-19 care in a multidisciplinary manner, the vacuum will be quickly filled by pseudoscience and quackery.”


31 July

Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021 Jul 26;374:n1648. PubMed: https://pubmed.gov/34312178. Full-text: https://doi.org/10.1136/bmj.n1648

The day after COVID-19: fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, etc. A state-of-the-art review of long COVID, discussing risk factors and possible therapeutic options.


Alwan NA. The road to addressing Long Covid. Science 2021, published 30 July. Full text: https://doi.org/10.1126/science.abg7113

“The road to properly addressing Long Covid is long and must be traveled with humility, open mindedness, compassion, and scientific rigor.”


17 July

Radtke T, Ulyte A, Puhan MA, et al. Long-term Symptoms After SARS-CoV-2 Infection in Children and Adolescents. JAMA July 15, 2021. https://jamanetwork.com/journals/jama/fullarticle/2782164?resultClick=1

Best study title. “Ciao Corona” is a longitudinal cohort study investigating SARS-CoV-2 seroprevalence in 55 randomly selected schools in the canton of Zurich in Switzerland. Prevalence of symptoms compatible with long COVID was low. Between October and November 2020 and March and April 2021, 4 of 109 seropositive children (4%) versus 28 of 1246 seronegative ones (2%) reported at least 1 symptom lasting beyond 12 weeks.


14 July

Barizien N, Le Guen M, Russel S, et al. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep July 7, 2021, 11, 14042. https://www.nature.com/articles/s41598-021-93546-5

A small study, indicating that dysautonomia (the failure or the increase of the sympathetic or para-sympathetic components activities in the autonomic nervous system) may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia.


11 July

Nehme M, Braillard O, Chappuis F, et al. Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting. Annals Int Med July 6, 2021. https://www.acpjournals.org/doi/10.7326/M21-0878

Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. Of the 629 participants who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%) and dyspnea (11.7%).


Radin JM, Quer G, Ramos E, et al. Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection. JAMA Netw Open July 7, 2021;4(7):e2115959. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781687?resultClick=1

Huge study, indicating a prolonged physiological impact of COVID-19 infection, lasting approximately 2 to 3 months, on average, but with substantial intraindividual variability, which may reflect various levels of autonomic nervous system dysfunction or potentially ongoing inflammation.


7 July

Seeßle J, Waterboer T, Hippchen T, et al. Persistent symptoms in adult patients one year after COVID-19: a prospective cohort study. Clinical Infectious Diseases July 5, 2021, ciab611, https://doi.org/10.1093/cid/ciab611

Is autoimmunity a co-factor in the etiology of long COVID? Of 96 patients who were included 5 months after acute COVID-19 in this prospective, non-interventional study, only 23% of patients were completely free of symptoms at 12 months. The most frequent symptoms were reduced exercise capacity (56%) and fatigue (53%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥ 1:160 in 44% of patients at 12 months, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥ 1:160 compared to < 1:160.


27 June

Amin-Chowdhury Z, Ladhani SN. Causation or confounding: why controls are critical for characterizing long COVID. Nat Med June 17, 2021. https://doi.org/10.1038/s41591-021-01402-w

Read this first, in order to understand the limitations, biases and caveats in the following studies.


Blomberg B, Mohn KG, Brokstad KA, et al. Long COVID in a prospective cohort of home-isolated patients. Nat Med June 22, 2021. https://www.nature.com/articles/s41591-021-01433-3

In this study from Norway, 32/61 of home-isolated young adults aged 16–30 years had symptoms at 6 months, including loss of taste and/or smell (28%), fatigue (21%), dyspnea (13%), impaired concentration (13%) and memory problems (11%).

Pratt J, Lester E, Parker R. Could SARS-CoV-2 cause tauopathy? Lancet Neurology, July, 2021. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00168-X/fulltext
James Pratt, Evan Lester and Roy Parker believe that follow-up studies of neurological dysfunction in survivors of COVID-19 should be done, particularly in people who showed acute or subacute neurological symptoms. Such studies should continue for at least a decade and focus on young individuals in order to reduce the proportion of participants who develop tauopathies due to age.


Menezes AMB, Victora CG, Hartwig FP, et al. High prevalence of symptoms among Brazilian subjects with antibodies against SARS-CoV-2. Sci Rep June 24, 2021, 11, 13279. https://www.nature.com/articles/s41598-021-92775-y

Out of 849 (2.7%) participants positive for SARS-CoV-2 antibodies, only 12.1% reported no symptoms, compared to 42.2% among those negative. The main limitation: the information was collected after the individual had learned about the test result.


Bliddal S, Banasik K, Pedersen OB, et al. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients. Sci Rep June 23, 2021, 11, 13153. https://www.nature.com/articles/s41598-021-92045-x

Among non-hospitalized PCR-confirmed COVID-19 patients, one third were asymptomatic while one third of symptomatic participants had persistent symptoms illustrating the heterogeneity of disease presentation. The most common persistent symptoms were fatigue and memory and concentration difficulties, reported by 36% of 198 symptomatic participants with follow-up > 4 weeks. Risk factors for persistent symptoms included female sex (women 44% vs. men 24%) and BMI.


Renaud M, Thibault C, LeNormand F, et al. Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis. JAMA Netw Open June 24, 2021;4(6):e2115352. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781319?resultClick=1

At 8 months, objective olfactory assessment confirmed full recovery in 49 of 51 patients (96%). Two patients remained hyposmic at 1 year. Findings suggest that an additional 10% gain in recovery can be expected at 12 months, compared to studies with 6 months of follow-up.


25 June

Amin-Chowdhury Z, Ladhani SN. Causation or confounding: why controls are critical for characterizing long COVID. Nat Med June 17, 2021. https://doi.org/10.1038/s41591-021-01402-w

Zahin Amin-Chowdhury and Shamez N. Ladhani discuss the limitations, biases and caveats studies on long COVID studies. More robust, well-conducted longitudinal studies are urgently needed for proper characterization of this syndrome.


14 June

Komaroff AL, Lipkin WI. Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome. Trends in Molecular Medicine June 07, 2021. https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00134-9

Post-COVID-19 syndrome is similar to post-infectious fatigue syndromes triggered by other infectious agents, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is associated with underlying abnormalities of the central and autonomic nervous system, immune dysregulation, disordered energy metabolism and redox imbalance. This summary of current knowledge concludes that it is still unclear if the same abnormalities will be identified in post-COVID-19 syndrome.


Després JP. Severe COVID-19 outcomes — the role of physical activity. Nature Reviews Endocrinology 10 June 2021. https://www.nature.com/articles/s41574-021-00521-1

It’s not only obesity: according to this nice review, current sedentary behaviors and lack of physical activity are also contributing to morbidity and mortality associated with COVID-19.


Perlis RH, Santillana M, Ognyanova K, et al. Factors Associated With Self-reported Symptoms of Depression Among Adults With and Without a Previous COVID-19 Diagnosis. JAMA Netw Open June 11, 2021;4:e2116612. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780928?resultClick=1

Some differences in phenomenology and risk factors of depression between individuals with and without prior COVID-19 illness.


Komaroff AL, Lipkin WI. Insights from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome. Trends in Molecular Medicine June 07, 2021. https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(21)00134-9

Post-COVID-19 syndrome is similar to post-infectious fatigue syndromes triggered by other infectious agents, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is associated with underlying abnormalities of the central and autonomic nervous system, immune dysregulation, disordered energy metabolism and redox imbalance. This summary of current knowledge concludes that it is still unclear if the same abnormalities will be identified in post-COVID-19 syndrome.


2 June

Arnold DT, Milne A, Samms E, et al. Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series. Ann Int Med, 25 May 2021. https://www.acpjournals.org/doi/10.7326/M21-1976

In total, 36 patients who reported at least 1 persistent symptom 8 months after acute infection were vaccinated with Astra Zeneca or the BionTech vaccine. There was some improvement and no decrease in quality of life or worsening of symptoms.


29 May

Daniels CJ, Rajpal S, Greenshields JT, et al. Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection. JAMA Cardiol May 27, 2021. https://jamanetwork.com/journals/jamacardiology/fullarticle/2780548?resultClick=1

In this study of aggregate data from 13 Big Ten universities, 1597 athletes who tested positive by PCR underwent comprehensive cardiac evaluation including ECG, echocardiogram, troponin, and CMR imaging. Of these, 2.3% had either clinical or subclinical myocarditis that restricted them from training and competitive play. The authors believe that the role of CMR imaging in routine screening for athletes’ safe return to play should be explored further.


28 May

Nasserie T, Hittle M, Goodman SN, et al. Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19A Systematic Review. JAMA Netw Open May 26 2021. 2021;4(5):e2111417. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780376?resultClick=24

This systematic review found that symptoms commonly persisted beyond the acute phase of infection. However, current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.


23 May

Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ May 19, 2021; 373. doi: https://doi.org/10.1136/bmj.n1098

This retrospective study, conducted in a large administrative database, evaluated the excess risk of developing a wide range of clinical sequelae after the acute phase of SARS-CoV-2 infection in commercially insured adults aged 18-65. Around 14% developed at least one new type of clinical sequelae that required medical care after the acute phase of SARS-CoV-2 infection, which was 4.95% higher than the 2020 comparator group and 1.65% higher than individuals diagnosed as having viral lower respiratory tract illness. The risk for incident sequelae increased with age, pre-existing conditions, and admission to hospital for COVID-19, and in adults aged ≤ 50 and those with no pre-existing conditions or not admitted to hospital, the risk for some clinical sequelae was still elevated.


12 May

Lund LC, Hallas J, Nielsen H, et al. Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study. Lancet Inf Dis May 10, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00211-5/fulltext

This nationwide cohort study investigated the occurrence of post-acute effects of SARS-CoV-2 infection in individuals who were not admitted to hospital for primary infection. The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission was low. There was no increased risk of delayed severe acute complications and new onset of chronic disease, except for a slightly increased absolute risk of venous thromboembolism.There was also an increased risk of healthcare encounters caused by dyspnea.


Huang L, Cao B. Post-acute conditions of patients with COVID-19 not requiring hospital admission. Lancet Inf Dis May 10, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00225-5/fulltext

In their comment, Lixue Huang and Bin Cao argue that there is the possibility of greatly underestimating the real prevalence, due to so many reasons that patients with persistent symptoms might not visit a healthcare service, such as symptoms being mild, not having health insurance or access to healthcare, and the risk of re-infection when visiting a health-care facility during the COVID-19 pandemic.


8 May

Wu X, Liu X, Zhou Y, et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Resp Med May 05, 2021. https://doi.org/10.1016/S2213-2600(21)00174-0

One year later. In 135 patients who recovered from severe COVID-19, dyspnea scores and exercise capacity improved over time; however, at 12 months, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide, DLCO) remained impaired at 12% and radiographic changes were found in 24%.


24 April

Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequalae of COVID-19. Nature April 22, 2021. https://www.nature.com/articles/s41586-021-03553-9

High-dimensional is correct. This incredible work, the largest post-acute COVID-19 study to date, included 73,435 non-hospitalized and 13,654 hospitalized patients with COVID-19, 4,990,835 controls, and 13,997 patients hospitalized with seasonal influenza. The results suggest that beyond the first 30 days of illness, people with COVID-19 are at higher risk of death, health care resource utilization, and exhibit a broad array of incident pulmonary and extrapulmonary clinical manifestations.


19 April

Moulson N, Petek BJ, Drezner JA, et al. SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes. Circulation 17 Apr 2021. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054824

Cardiac involvement is rare among young competitive athletes. Among 3018 athletes who tested positive for SARS-CoV-2 infection (mean age 20 years, 32% female), abnormal findings suggestive of cardiac involvement were detected by ECG (0.7%), cardiac troponin (0.9%), and TTE (0.9%). Clinical predictors of cardiac involvement included cardiopulmonary symptoms (such as chest pain or shortness of breath) during acute infection or upon return to exercise and any abnormality on triad testing. Findings suggest that asymptomatic or mildly symptomatic athletes who have fully recovered from SARS-CoV-2 infection may return to sport without cardiac testing.


14 April

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.


10 April

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.


9 April

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.


6 April

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.


3 April

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.


24 March

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.

23 March

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.


19 March

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%).


16 March

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.


13 March

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.

12 March

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.


9 March

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).


3 March

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.


24 February

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.


9 February

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.”