Clinical determinants of the severity of COVID-19: A systematic review and meta-analysis

PLOS

Abstract

Objective


We aimed to systematically identify the possible risk factors responsible for severe cases.


Methods

We searched PubMed, Embase, Web of science and Cochrane Library for epidemiological studies of confirmed COVID-19, which include information about clinical characteristics and severity of patients’ disease. We analyzed the potential associations between clinical characteristics and severe cases.


Results

We identified a total of 41 eligible studies including 21060 patients with COVID-19. Severe cases were potentially associated with advanced age (Standard Mean Difference (SMD) = 1.73, 95% CI: 1.34–2.12), male gender (Odds Ratio (OR) = 1.51, 95% CI:1.33–1.71), obesity (OR = 1.89, 95% CI: 1.44–2.46), history of smoking (OR = 1.40, 95% CI:1.06–1.85), hypertension (OR = 2.42, 95% CI: 2.03–2.88), diabetes (OR = 2.40, 95% CI: 1.98–2.91), coronary heart disease (OR: 2.87, 95% CI: 2.22–3.71), chronic kidney disease (CKD) (OR = 2.97, 95% CI: 1.63–5.41), cerebrovascular disease (OR = 2.47, 95% CI: 1.54–3.97), chronic obstructive pulmonary disease (COPD) (OR = 2.88, 95% CI: 1.89–4.38), malignancy (OR = 2.60, 95% CI: 2.00–3.40), and chronic liver disease (OR = 1.51, 95% CI: 1.06–2.17). Acute respiratory distress syndrome (ARDS) (OR = 39.59, 95% CI: 19.99–78.41), shock (OR = 21.50, 95% CI: 10.49–44.06) and acute kidney injury (AKI) (OR = 8.84, 95% CI: 4.34–18.00) were most likely to prevent recovery. In summary, patients with severe conditions had a higher rate of comorbidities and complications than patients with non-severe conditions.

Conclusion

Patients who were male, with advanced age, obesity, a history of smoking, hypertension, diabetes, malignancy, coronary heart disease, hypertension, chronic liver disease, COPD, or CKD are more likely to develop severe COVID-19 symptoms. ARDS, shock and AKI were thought to be the main hinderances to recovery.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250602

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

Authors: Sasha Peiris 1 2Hector Mesa 3Agnes Aysola 4Juan Manivel 5Joao Toledo 1 2Marcio Borges-Sa 6Sylvain Aldighieri 1 2Ludovic Reveiz 2 7

Abstract

Background: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33909679/

Elevated level of C‐reactive protein may be an early marker to predict risk for severity of COVID‐19

Authors: Nurshad Ali 1

The outbreak of coronavirus disease‐2019 (COVID‐19) is an emerging global health threat. The healthcare workers are facing challenges in reducing the severity and mortality of COVID‐19 across the world. Severe patients with COVID‐19 are generally treated in the intensive care unit, while mild or non‐severe patients treated in the usual isolation ward of the hospital. However, there is an emerging challenge that a small subset of mild or non‐severe COVID‐19 patients develops into a severe disease course. Therefore, it is important to early identify and give the treatment of this subset of patients to reduce the disease severity and improve the outcomes of COVID‐19. Clinical studies demonstrated that altered levels of some blood markers might be linked with the degree of severity and mortality of patients with COVID‐19. 1 Of these clinical parameter, serum C‐reactive protein (CRP) has been found as an important marker that changes significantly in severe patients with COVID‐19. 3 CRP is a type of protein produced by the liver that serves as an early marker of infection and inflammation. 6 In blood, the normal concentration of CRP is less than 10 mg/L; however, it rises rapidly within 6 to 8 hours and gives the highest peak in 48 hours from the disease onset. 7 Its half‐life is about 19 hours 8 and its concentration decreases when the inflammatory stages end and the patient is healing. CRP preferably binds to phosphocholine expressed highly on the surface of damaged cells. 9 This binding makes active the classical complement pathway of the immune system and modulates the phagocytic activity to clear microbes and damaged cells from the organism. 7 When the inflammation or tissue damage is resolved, CRP concentration falls, making it a useful marker for monitoring disease severity. 7

The available studies that have determined serum concentration of CRP in patients with COVID‐19 are presented in Table 1. A significant increase of CRP was found with levels on average 20 to 50 mg/L in patients with COVID‐19. 10 12 21 Elevated levels of CRP were observed up to 86% in severe COVID‐19 patients. 10 11 13 Patients with severe disease courses had a far elevated level of CRP than mild or non‐severe patients. For example, a study reported that patients with more severe symptoms had on average CRP concentration of 39.4 mg/L and patients with mild symptoms CRP concentration of 18.8 mg/L. 12 CRP was found at increased levels in the severe group at the initial stage than those in the mild group. 1 In another study, the mean concentration of CRP was significantly higher in severe patients (46 mg/L) than non‐severe patients (23 mg/L). 21 The patients who died from COVID‐19 had about 10 fold higher levels of CRP than the recovered patients (median 100 vs 9.6 mg/L). 16 A recent study showed that about 7.7% of non‐severe COVID‐19 patients were progressed to severe disease courses after hospitalization, 3 and compared to non‐severe cases, the aggravated patients had significantly higher concentrations of CRP (median 43.8 vs 12.1 mg/L). A significant association was observed between CRP concentrations and the aggravation of non‐severe patients with COVID‐19 [1], and the authors proposed CRP as a suitable marker for anticipating the aggravation probability of non‐severe COVID‐19 patients, with an optimal threshold value of 26.9 mg/L. 3 The authors also noted that the risk of developing severe events is increased by 5% for every one‐unit increase in CRP concentration in patients with COVID‐19.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301027/

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

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

  1. Authors: Sasha Peiris, Hector Mesa, Agnes Aysola, Juan Manivel, Joao Toledo, Marcio Borges-Sa, Sylvain Aldighieri, Ludovic Reveiz

Abstract

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250708

What Does COVID Do to Your Blood?

Authors: Panagis Galiatsatos, M.D., M.H.S., Robert Brodsky, M.D.

COVID-19 is a very complex illness. The coronavirus that causes COVID-19 attacks the body in many different ways, ranging from mild to life threatening. Different organs and tissues of the body can be affected, including the blood.

Robert Brodsky, a blood specialist who directs the Division of Hematology, and Panagis Galiatsatos, a specialist in lung diseases and critical care medicine, talk about blood problems linked to SARS-CoV-2 — the coronavirus that causes COVID-19 — and what you should know.

Coronavirus Blood Clots

Blood clots can cause problems ranging from mild to life threatening. If a clot blocks blood flow in a vein or artery, the tissue normally nourished by that blood vessel can be deprived of oxygen, and cells in that area can die.

Some people infected with SARS-CoV-2 develop abnormal blood clotting. “In some people with COVID-19, we’re seeing a massive inflammatory response, the cytokine storm that raises clotting factors in the blood,” says Galiatsatos, who treats patients with COVID-19.

“We are seeing more blood clots in the lungs (pulmonary embolism), legs (deep vein thrombosis) and elsewhere,” he says.

Brodsky notes that other serious illnesses, especially ones that cause inflammation, are associated with blood clots. Research is still exploring if the blood clots seen in severe cases of COVID-19 are unique in some way. 

The Impact of Coronavirus Blood Clots Throughout the Body

In addition to the lungs, blood clots, including those associated with COVID-19, can also harm:

The nervous system. Blood clots in the arteries leading to the brain can cause a stroke. Some previously young, healthy people who have developed COVID-19 have suffered strokes, possibly due to abnormal blood clotting.

The kidneys. Clogging of blood vessels in the kidney with blood clots can lead to kidney failure. It can also complicate dialysis if the clots clog the filter of the machine designed to remove impurities in the blood.

Peripheral blood vessels and “COVID toe.” Small blood clots can become lodged in tiny blood vessels. When this happens close to the skin, it can result in a rash. Some people who test positive for COVID-19 develop tiny blood clots that cause reddish or purple areas on the toes, which can itch or be painful. Sometimes called COVID toe, the rash resembles frostbite.

For More Information: https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/what-does-covid-do-to-your-blood