Long covid: Damage to multiple organs presents in young, low risk patients

Authors: Gareth Iacobucci BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4470 (Published 17 November 2020)Cite this as: BMJ 2020;371:m4470

Young, low risk patients with ongoing symptoms of covid-19 had signs of damage to multiple organs four months after initially being infected, a preprint study has suggested.1

Initial data from 201 patients suggest that almost 70% had impairments in one or more organs four months after their initial symptoms of SARS-CoV-2 infection.

The results emerged as the NHS announced plans to establish a network of more than 40 long covid specialist clinics across England this month to help patients with long term symptoms of infection.

The prospective Coverscan study examined the impact of long covid (persistent symptoms three months post infection) across multiple organs in low risk people who are relatively young and had no major underlying health problems. Assessment was done using results from magnetic resonance image scans, blood tests, and online questionnaires.

The research has not yet been peer reviewed and could not establish a causal link between organ impairment and infection. But the authors said the results had “implications not only for [the] burden of long covid but also public health approaches which have assumed low risk in young people with no comorbidities.”

The study enrolled participants at two UK sites in Oxford and London between April and August 2020. Two hundred and one individuals (mean age 44 (standard deviation 11.0) years) completed assessments after SARS-CoV-2 infection a median of 140 days after initial symptoms.

Participants were eligible if they tested positive for SARS-CoV-2 by random polymerase chain reaction swab (n=62), a positive antibody test (n=63), or had typical symptoms and were determined to have covid-19 by two independent clinicians (n=73).

The prevalence of pre-existing conditions was low (obesity: 20%, hypertension: 6%, diabetes: 2%, heart disease: 4%), and less than a fifth (18%) of individuals had been hospitalised with covid-19.

The most commonly reported ongoing symptoms—regardless of hospitalization status—were fatigue (98%), muscle ache (88%), shortness of breath (87%), and headache (83%). There was evidence of mild organ impairment in the heart (32% of patients), lungs (33%), kidneys (12%), liver (10%), pancreas (17%), and spleen (6%).

For More Information: https://www.bmj.com/content/371/bmj.m4470

Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines

Authors: Johanna Chapin-Bardales, PhD, MPH1Julianne Gee, MPH1Tanya Myers, PhD, MSc1

In December 2020, 2 mRNA-based COVID-19 vaccines (Pfizer-BioNTech and Moderna) were granted Emergency Use Authorization by the US Food and Drug Administration as 2-dose series and recommended for use by the Advisory Committee on Immunization Practices.13 In late February 2021, the US Food and Drug Administration granted Emergency Use Authorization for a third COVID-19 vaccine, a single-dose adenovirus vector-based vaccine from Janssen (Johnson & Johnson).

In clinical trials of the mRNA-based 2-dose vaccines, participants reported local and systemic reactions (reactogenicity).4,5 Frequently reported reactions included injection site pain, fatigue, and headache; greater reactogenicity was reported following the second dose.4,5 Continued monitoring of reactogenicity of COVID-19 vaccines outside of clinical trial settings may provide additional information for health care practitioners and the public about transient local and systemic reactions following COVID-19 vaccination.

V-safe Active Surveillance System

To facilitate rapid assessment of COVID-19 vaccines, in 2020, the Centers for Disease Control and Prevention (CDC) established v-safe, a new active surveillance system for collecting near–real-time data from COVID-19 vaccine recipients in the US. V-safe participants voluntarily self-enroll and receive periodic smartphone text messages to initiate web-based health surveys from the day of vaccination (day 0) through 12 months after the final dose of a COVID-19 vaccine.6 From day 0 through day 7 after each vaccine dose, participants are asked questions about solicited local and systemic reactions (eg, injection site pain, fatigue, headache). These solicited reactions do not include allergic reactions or anaphylaxis; however, v-safe does allow participants to enter free-text information about their postvaccination experience and asks about adverse health events (eg, received medical care). Medically attended events are followed up on through active telephone outreach; future analyses will address these adverse vaccine experiences. This report describes information on solicited local and systemic reactogenicity reported to v-safe on days 0 to 7 after each dose of vaccine from December 14, 2020, through February 28, 2021. Responses were limited to individuals who were vaccinated by February 21, 2021, to allow a 7-day reporting period after the day of vaccination. Preliminary data from v-safe through January 13, 2021, have been previously reported.7 This activity was reviewed by the CDC and was conducted consistent with applicable federal law and CDC policy (see Additional Information).

Self-reported Local and Systemic Reactions Among V-safe Participants

By February 21, 2021, more than 46 million persons received at least 1 dose of an mRNA-based COVID-19 vaccine.8 A total of 3 643 918 persons were enrolled in v-safe and completed at least 1 health survey within 7 days following their first vaccine dose; 1 920 872 v-safe participants reported receiving a second vaccine dose and completed at least 1 daily health survey within 7 days following the second dose. Solicited local and systemic reactions during days 0 to 7 after each dose were assessed.

Most v-safe participants reported an injection site reaction (dose 1: 70.0%; dose 2: 75.2%) or a systemic reaction (dose 1: 50.0%; dose 2: 69.4%) during days 0 to 7 after vaccination (Table). The most frequently reported solicited local and systemic reactions after the first dose of COVID-19 vaccine were injection site pain (67.8%), fatigue (30.9%), headache (25.9%), and myalgia (19.4%). Reactogenicity was substantially greater after the second dose for both vaccines, particularly for systemic reactions, including fatigue (53.9%), headache (46.7%), myalgia (44.0%), chills (31.3%), fever (29.5%), and joint pain (25.6%).Table.  Solicited Local and Systemic Reactionsa to mRNA-Based COVID-19 Vaccines Reported 0 to 7 Days After Vaccination—Centers for Disease Control and Prevention V-safe Surveillance System, December 14, 2020, to February 28, 2021 View LargeDownload

Solicited Local and Systemic Reactionsa to mRNA-Based COVID-19 Vaccines Reported 0 to 7 Days After Vaccination—Centers for Disease Control and Prevention V-safe Surveillance System, December 14, 2020, to February 28, 2021

A greater percentage of participants who received the Moderna vaccine, compared with the Pfizer-BioNTech vaccine, reported reactogenicity; this pattern was more pronounced after the second dose (Table). When stratified by age (<65 vs ≥65 years), differences in reactogenicity by vaccine remained consistent with overall findings (data not shown). Local and systemic reactions were less commonly reported by v-safe participants 65 years and older compared with those younger than 65 years, but greater reactogenicity after the second dose was observed for both age groups (eFigure in the Supplement). For both doses of both vaccines, the percentage of v-safe participants who reported local and systemic reactions was highest on day 1 after vaccination and declined markedly through day 7.

For More Information: https://jamanetwork.com/journals/jama/fullarticle/2778441

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Authors:

  1. Jonathan P Rogers1,2, Cameron J Watson3, et.al

Abstract

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.

We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.

13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.

Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic’s early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

For More Information: https://jnnp.bmj.com/content/92/9/932

Virology, transmission, and pathogenesis of SARS-CoV-2

Authors: Muge Cevik, clinical lecturer2,  Krutika Kuppalli, assistant professor3,  Jason Kindrachuk, assistant professor of virology4,  Malik Peiris, professor of virology5

What you need to know

  • SARS-CoV-2 is genetically similar to SARS-CoV-1, but characteristics of SARS-CoV-2—eg, structural differences in its surface proteins and viral load kinetics—may help explain its enhanced rate of transmission
  • In the respiratory tract, peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness, with subsequent decline thereafter, indicating the highest infectiousness potential just before or within the first five days of symptom onset
  • Reverse transcription polymerase chain reaction (RT-PCR) tests can detect viral SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days; however, detection of viral RNA does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness
  • Symptomatic and pre-symptomatic transmission (1-2 days before symptom onset), is likely to play a greater role in the spread of SARS-CoV-2 than asymptomatic transmission
  • A wide range of virus-neutralizing antibodies have been reported, and emerging evidence suggests that these may correlate with severity of illness but wane over time.

Since the emergence of SARS-CoV-2 in December 2019, there has been an unparalleled global effort to characterize the virus and the clinical course of disease. Coronavirus disease 2019 (covid-19), caused by SARS-CoV-2, follows a biphasic pattern of illness that likely results from the combination of an early viral response phase and an inflammatory second phase. Most clinical presentations are mild, and the typical pattern of covid-19 more resembles an influenza-like illness—which includes fever, cough, malaise, myalgia, headache, and taste and smell disturbance—rather than severe pneumonia (although emerging evidence about long term consequences is yet to be understood in detail).1 In this review, we provide a broad update on the emerging understanding of SARS-CoV-2 pathophysiology, including virology, transmission dynamics, and the immune response to the virus. Any of the mechanisms and assumptions discussed in the article and in our understanding of covid-19 may be revised as further evidence emerges.

For More Information: https://www.bmj.com/content/371/bmj.m3862