Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-Analysis

BACKGROUND: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. METHODS: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. FINDINGS: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). INTERPRETATION: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission;and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.

COVID-19 in patients with inflammatory bowel disease.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread world over causing morbidity and mortality in affected patients, especially elderly and those with co-morbidities. Inflammatory Bowel Disease (IBD) patients frequently require immunosuppressive therapy and are known to be at risk of opportunistic infections. AREAS COVERED: We hereby review the available literature pertaining to COVID-19 in IBD based on published consensus guidelines, expert opinions, case series, registries and reports. EXPERT OPINION: Preliminary data suggests no increase in incidence of COVID-19 in IBD patients as compared to general population. Morbidity and mortality rates attributable to COVID-19 are also similar in IBD patients as compared to general population. Though exact reason is unknown, some aspects of COVID-19 pathogenesis may explain this paradox. Medications for IBD need to be carefully reviewed during COVID-19 crisis. Steroids may need dose tapering or substitution to avoid complications based on anecdotal evidence. Endoscopic procedures for IBD maybe deferred unless absolutely necessary. General measures recommended for COVID-19 tailored to specific needs of IBD patients maybe the best way to prevent infection. Our understanding of the disease outcomes and optimal management protocols are likely to evolve as we move ahead in this pandemic.

Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis.

BACKGROUND: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored. OBJECTIVES: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course. METHODS: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome. RESULTS: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3). CONCLUSIONS: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-Analysis.

BACKGROUND: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. METHODS: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. FINDINGS: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). INTERPRETATION: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.