Different SARS-CoV-2 variants may give rise to different long COVID symptoms, study suggests

Italian study of long-COVID patients suggests those infected with the Alpha variant experienced different neurological and emotional symptoms compared to those who contracted the original form of SARS-CoV-2

Authors: EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES

24-MAR-2022

New research to be presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal (23-26 April), suggests that the symptoms connected to long COVID could be different in people who are infected with different variants. The study is by Dr Michele Spinicci and colleagues from the University of Florence and Careggi University Hospital in Italy.

Estimates suggest that over half of survivors of SARS-CoV-2 infection experience post-acute sequelae of COVID-19 (PASC), more commonly known as ‘long COVID’ [1]. The condition can affect anyone—old and young, otherwise healthy, and those with underlying conditions. It has been seen in people who were hospitalised with COVID-19 and those with mild symptoms. But despite an increasing body of literature, long COVID remains poorly understood.

In this study, researchers did a retrospective observational study of 428 patients—254 (59%) men and 174 (41%) women—treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2 and the Alpha variant were circulating in the population. The patients had been hospitalised with COVID-19 and discharged 4-12 weeks before attending a clinical visit at the outpatient service and completing a questionnaire on persistent symptoms (an average [median] of 53 days after hospital discharge). In addition, data on medical history, microbiological and clinical COVID-19 course, and patient demographics were obtained from electronic medical records.

At least three-quarters 325/428 (76%) of patients reported at least one persistent symptom. The most common reported symptoms were shortness of breath (157/428; 37%) and chronic fatigue (156/428; 36%) followed by sleep problems (68/428; 16%), visual problems (55/428; 13%), and brain fog (54/428; 13%).

Analyses suggest that people with more severe forms, who required immunosuppressant drugs such as tocilizumab, were six times as likely to report long COVID symptoms, while those who received high flow oxygen support were 40% more likely to experience ongoing problems. Women were almost twice as likely to report symptoms of long COVID compared with men. However, patients with type 2 diabetes seemed to have a lower risk of developing long COVID symptoms. The authors say that further studies are needed to better understand this unexpected finding.

Researchers performed a more detailed evaluation comparing the symptoms reported by patients infected between March and December 2020 (when the original SARS-COV-2 was dominant) with those reported by patients infected between January and April 2021 (when Alpha was the dominant variant) and discovered a substantial change in the pattern of neurological and cognitive/emotional problems.

They found that when the Alpha variant was the dominant strain, the prevalence of myalgia (muscle aches and pain), insomnia, brain fog and anxiety/depression significantly increased, while anosmia (loss of smell), dysgeusia (difficulty in swallowing), ad impaired hearing were less common (figure 2 in notes to editors).

“Many of the symptoms reported in this study have been measured, but this is the first time they have been linked to different COVID-19 variants”, says Dr Spinicci. “The long duration and broad range of symptoms reminds us that the problem is not going away, and we need to do more to support and protect these patients in the long term. Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms.”

The authors acknowledge that the study was observational and does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients—which may limit the conclusions that can be drawn.

Long COVID Could Be Linked to the Effects of SARS-CoV-2 on the Vagus Nerve

SciTechDaily

Authors: EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES FEBRUARY 11, 2022

New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2022, Lisbon, April 23-26) suggests that many of the symptoms connected to post-COVID syndrome (PCC, also known as long COVID) could be linked to the effect of the virus on the vagus nerve – one of the most important multi-functional nerves in the body. The study is by Dr. Gemma Lladós and Dr. Lourdes Mateu, University Hospital Germans Trias i Pujol, Badalona, Spain, and colleagues.

The vagus nerve extends from the brain down into the torso and into the heart, lungs, and intestines, as well as several muscles including those involved in swallowing. As such, this nerve is responsible for a wide variety of bodily functions including controlling heart rate, speech, the gag reflex, transferring food from the mouth to the stomach, moving food through the intestines, sweating, and many others.

Long COVID is a potentially disabling syndrome affecting an estimated 10-15% of subjects who survive COVID-19. The authors propose that SARS-CoV-2-mediated vagus nerve dysfunction (VND) could explain some long COVID symptoms, including dysphonia (persistent voice problems), dysphagia (difficulty in swallowing), dizziness, tachycardia (abnormally high heart rate), orthostatic hypotension (low blood pressure) and diarrhea.

The authors performed a pilot, extensive morphological and functional evaluation of the vagus nerve, using imaging and functional tests in a prospective observational cohort of long COVID subjects with symptoms suggestive of VND. In their total cohort of 348 patients, 228 (66%) had at least one symptom suggestive of VND. The current evaluation was performed in the first 22 subjects with VND symptoms (10% of the total) seen in the Long COVID Clinic of University Hospital Germans Trias i Pujol between March and June 2021. The study is ongoing and continues to recruit patients.

Of the 22 subjects analyzed, 20 (91%) were women with a median age of 44 years. The most frequent VND-related symptoms were: diarrhea (73%), tachycardia (59%), dizziness, dysphagia and dysphonia (45% each), and orthostatic hypotension (14%). Almost all (19 subjects, 86%) had at least 3 VND-related symptoms. The median prior duration of symptoms was 14 months. Six of 22 patients (27%) displayed alteration of the vagus nerve in the neck shown by ultrasound – including both thickening of the nerve and increased ‘echogenicity’ which indicates mild inflammatory reactive changes.

A thoracic ultrasound showed flattened ‘diaphragmatic curves’ in 10 out of 22 (46%) subjects (which translates a decrease in diaphragmatic mobility during breathing, or more simply abnormal breathing). A total of 10 of 16 (63%) assessed individuals showed reduced maximum inspiration pressures, showing weakness of breathing muscles.

Eating and digestive function was also affected in some patients, with 13 of 18 assessed (72%) having a positive screen for self-perceived oropharyngeal dysphagia (trouble swallowing). An assessment of gastric and bowel function performed in 19 patients revealed 8 (42%) had their ability to deliver food to the stomach (via the esophagus) impaired, with 2 of these 8 (25%) reporting difficulty in swallowing. Gastroesophageal reflux (acid reflux) was observed in 9 of 19 (47%) individuals; with 4 of these 9 (44%) again having difficulty delivering food to the stomach and 3 of these 9 (33%) with hiatal hernia – which occurs when the upper part of the stomach bulges through the diaphragm into the chest cavity.

A Voice Handicap Index 30 test (a standard way to measure voice function) was abnormal in 8/17 (47%) cases, with 7 of these 8 cases (88%) suffering dysphonia.

The authors say: “In this pilot evaluation, most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically-relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing. Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

Meeting: The European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022)

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19A Systematic Review

Authors: Tahmina Nasserie, MPH1Michael Hittle, BS1Steven N. Goodman, MD, MHS, PhD1 JAMA Netw Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417 May 26, 2021

Key Points

Question  What are the frequency and variety of persistent symptoms after COVID-19 infection?

Findings  In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%; symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia. However, the studies were highly heterogeneous and needed longer follow-up and more standardized designs.

Meaning  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life; however, methodological improvements are needed to reliably quantify these risks.Abstract

Importance  Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy.

Objective  To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection.

Evidence Review  A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19SARS-CoV-2coronavirus2019-nCoVlong-termafter recoverylong-haulpersistentoutcomesymptomfollow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality.

Findings  A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity.

Conclusions and Relevance  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. 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.

For More Information: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780376

COVID-19 vaccines and thrombosis with thrombocytopenia syndrome

Authors: Chih-Cheng Lai 1Wen-Chien Ko 2Chih-Jung Chen 3Po-Yen Chen 4Yhu-Chering Huang 3Ping-Ing Lee 5Po-Ren Hsueh 6 7

Abstract

Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain language summary: What is the context? Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines. TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality. What is new? TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated. What is the impact? TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.

For More Information: https://pubmed.ncbi.nlm.nih.gov/34176415/

Predictors of COVID-19 severity: A literature review

Authors: Benjamin Gallo Marin,1Ghazal Aghagoli,1Katya Lavine,1Lanbo Yang,1Emily J. Siff,2Silvia S. Chiang,3,4Thais P. Salazar-Mather,1,5Luba Dumenco,1,5Michael C Savaria,1Su N. Aung,6Timothy Flanigan,6 and Ian C. Michelow3,4

Summary

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient factors—including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings—that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.

1. INTRODUCTION

The newly described coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has strained healthcare systems around the world. The viral spread has been amplified not only by the occurrence of asymptomatic infections but also by limited widespread testing and personal protective equipment (PPE) for healthcare providers across the world.1 The overwhelming influx of COVID19-infected patients to many hospitals presents a need to thoroughly understand the clinical, radiological, and laboratory findings associated with greater disease severity and mortality. Here, we synthesize the current literature to describe early demographic, clinical, virologic, immunologic, hematological, biochemical, and radiographic factors that may correlate with COVID-19 disease severity. In this paper, we will use the World Health Organization’s (WHO) definition of severe pneumonia to categorize severe disease. As of 27 May 2020, the WHO’s most recent clinical guidelines define “severe disease” as adults with clinical signs of pneumonia (fever, dyspnea, cough, and fast breathing) accompanied by one of the following: respiratory rate > 30 breaths/min; severe respiratory distress; or oxygen saturation (SpO2) ≤ 90% on room air.2 The precise determinants of severe disease are not known, but it appears that primarily host factors rather than viral genetic mutations drive the pathogenesis.3 However, emerging data from a non-peer-reviewed paper suggest that a D614G mutation in the viral spike (S) protein of strains from Europe and the United States, but not China, is associated with more efficient transmission.4 Identification of potential risk factors that predict the disease course may be of great utility for healthcare professionals to efficiently triage patients, personalize treatment, monitor clinical progress, and allocate proper resources at all levels of care to mitigate morbidity and mortality. Here, we present a review of the current literature on patient factors that have been proposed as predictors for COVID-19 severity and mortality.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855377/

Long-Term Neurologic Symptoms Emerge in COVID-19

— Hospitalized patients show deficits including cognitive impairment 6 months later

Authors: by Judy George, Senior Staff Writer, MedPage Today January 7, 2021share to facebookshare to twittershare to linkedinemail article

Long-term neurologic manifestations were seen in more than a third of patients hospitalized with SARS-CoV-2 infection, a prospective study in Italy showed.

In a group of hospitalized COVID-19 patients with no prior neurologic disease, 37.4% showed abnormalities on neurologic exam 6 months later — most commonly cognitive deficits, hyposmia, and postural tremor — according to Alessandro Padovani, MD, PhD, of the University of Brescia, and co-authors. The findings were reported in a medRxiv preprint and have not undergone peer review.

Patients also noted fatigue, memory impairment, and sleep disorders, Padovani said. “The severity of SARS-CoV-2 infection was an important predictor, together with age and premorbid condition, of long-term neurological symptoms and features in the cohort.”

The findings are important for long-term management of COVID-19 patients, he told MedPage Today. “They showed that the severity of SARS-CoV-2 infection may impact on neurological sequelae, but also that the symptoms reported do not always reflect neurological features at examination.”

The study is one of the first to look specifically for new long-term neurologic manifestations in COVID-19 patients who were hospitalized. Earlier research showed that 87% of patients hospitalized with COVID-19 reported persistence of at least one lingering symptom, notably fatigue and dyspnea, 60 days after discharge. Fatigue and dyspnea also were the most prevalent symptoms reported during infection and at 3-month follow-up in an analysis of both hospitalized and non-hospitalized COVID-19 patients.

For More Information: https://www.medpagetoday.com/infectiousdisease/covid19/90587