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Table 2 Main findings observed in the systematic reviews obtained

From: Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

Review identification General summary Clinical symptoms Diagnosis Laboratory findings Radiological findings Therapeutic findings Comorbidities evaluated Quality of evidence Overall quality assessment using AMSTAR 2 Review strengths and limitations
Adhikari et al The study presents several categories of findings. Epidemiological findings showed that both the immunosuppressed and normal population appear susceptible to the COVID-19 infection. Biological analysis showed that SARS-CoV-2 is similar to coronaviruses found in bats. The effective reproductive number of SARS-CoV-2 (2.9) is higher than that of SARS (1.77). Virus transmission originated in Wuhan and from there it spread internationally. It is likely to be transmitted from human-to-human contact (via droplets or aerosol) as well as via surface contact. Prevention and control consist of isolation, identification and follow-up of contacts, environmental disinfection, and use of personal protective equipment. The most commonly reported clinical symptoms are fever, cough, myalgia or fatigue, pneumonia, and complicated dyspnea, whereas less commonly reported symptoms include headache, diarrhea, hemoptysis, runny nose, and phlegm producing cough. Patients with mild symptoms were reported to recover after 1 week while severe cases were reported to experience progressive respiratory failure due to alveolar damage from the virus, which may lead to death. Diagnosis of suspected cases used real-time fluorescence (RT-PCR) to detect the positive nucleic acid of SARS-CoV-2 in sputum, throat swabs, and secretions of the lower respiratory tract samples. Decrease in lymphocytes and white blood cells. New pulmonary infiltrates on chest radiography No actual improvement in symptoms after 3 days of antibiotics treatment. Cases resulting in death were primarily middle-aged and elderly patients with pre-existing diseases (tumor surgery, cirrhosis, hypertension, coronary heart disease, diabetes, and Parkinson’s disease). Not available Critically low Early scoping report. Broad range of topics addressed. Narrative presentation of many results.
Borges do Nascimento et al All-cause mortality was 0.3% (95% CI 0.0–1.0%). Epidemiological studies showed that mortality was higher in males and elderly patients The incidence of symptoms were shown as following: Fever 82%, (CI) 56–99%; Cough 61, 95% CI 39–81%; Muscle aches and/or fatigue 36, 95% CI 18–55%; Dyspnea 26, 95% CI 12–41%; Headache 12, 95% CI 4–23%; Sore throat 10, 95% CI 5–17% and gastrointestinal symptoms 9,95% CI 3–17%. Median time from onset of disease to diagnosis was 5 (interquartile ratio 2–9) days. In addition, Artificial intelligence has been recently raised as a potential tool to enhance care, and possibly be used for COVID-19 related cases. Laboratory findings revealed lymphopenia (0.93 × 109/L, 95% CI 0.83–1.03 × 109/L and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL. Radiological findings varied, but mostly described ground-glass opacities and consolidation. Antivirals (oseltamivir, umifenovir, ganciclovir, ritonavir) were reported as the most commonly used agents. Use of antibiotics was also reported (vancomycin, azithromycin, meropenem, cefaclor, cefepime and tazobactam). Other medications used were corticosteroids, alpha-interferon, immunoglobulin and antifungal drugs The most prevalent co-morbidities were hypertension, diabetes, chronic liver disease and smoking. All-cause mortality with a very low quality of evidence using GRADE Critically low Broad range of topics addressed
Cortegiani et al Chloroquine seemed to be effective in limiting the replication of SARS-CoV-2 in vitro, justifying clinical research in patients with COVID-19. However, clinical use should adhere to the Monitored Emergency Use of Unregistered Interventions framework or be ethically approved as a trial Not available Not available Not available Not available Not available Not available Not available Critically low Reviewed early pre-clinical evidence of effectiveness and safety of chloroquine, which justified following clinical research.
Li B et al The median ages were, respectively, 56, 49, 47, 55.5, 34 and 57 years old according to the six studies. Patients with previous cardiovascular metabolic diseases are more likely to have a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19. COVID-19 can also aggravate the damage to the heart. Not available The infection was diagnosed throughout the whole spectrum of age covering from new born to 92 years old. Not available Not available Not available The most prevalent comorbidities among confirmed cases of COVID-19 were hypertension (17.1%), cardiocerebrovascular disease (16.4%) and diabetes (9.7%). Patients with severe disease/in ICU were more likely to have hypertension, cardio-cerebrovascular diseases and diabetes than patients with non-severe disease/not in ICU; 8.0% of patients with COVID-19 suffered acute cardiac injury. Incidence of myocardial injury was ~ 13 times higher in patients with severe disease/in ICU than patients with non-severe disease/not in ICU. Not available Critically low Assessed the prevalence important comorbidities.
Li LQ et al The patients were 60% male (95% CI [0.54, 0.65]), the discharge rate was 42% (95% CI [0.29, 0.55]), and the fatality rate was 7% (95% CI [0.04,0.10]). Clinical symptoms presented were: fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%), headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). Not available Laboratory results showed lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%). Not available Not available Not available Not available Critically low Broad range of topics addressed
Lippi & Henry Overall, in only one study active smoking was found to be a significant predictor of COVID-19 severity, whilst in the other four studies the association was not statistically significant. Not available Not available No significant association was found between active smoking and severity of COVID-19 (OR, 1.69; 95% CI, 0.41–6.92; p = 0.254). Not available Not available Smocking acticity Not available Critically low Addressed the association of COVID-19 with an important comorbidity.
Lippi et al cTnI values are significantly increased in patients with severe SARS-CoV-2 infection compared to those with milder forms of disease. Not available Not available cTnI values were significantly increased in patients with severe COVID-19 compared to those with non-severe disease (SMD, 25.6 ng/L; 95% CI, 6.8–44.5 ng/L). Not available Not available Not available Not available Critically low Addressed biomarker with potential prognostic value.
Lippi & Plebani Procalcitonin measurement may play a role for predicting evolution towards a more severe form of disease. Not available Not available Results suggested that an increased procalcitonin value is associated with a higher risk of severe COVID-19 (OR, 4.76; 95% CI, 2.74–8.29). Not available Not available Not available Not available Critically low Addressed biomarker with potential prognostic value.
Lippi et al Thrombocytopenia is associated with increased risk of severe disease and mortality in patients with COVID-19. Not available Not available Platelet count was significantly lower in patients with more severe COVID-19 (weighted mean difference (WMD(−31 × 109/L; 95% CI −35-29 × 109/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, −48 × 109/L; 95% CI −57 to -39 × 109/L). A low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI 1.8–14.6). Not available Not available Not available Not available Critically low Addressed lab value with potential prognostic value.
Ludvigsson Children account for 1–5% of diagnosed COVID-19 cases and they frequently have milder disease than adults; deaths have been extremely rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission is scarce. Clinical characteristics presented mainly as fever and respiratory symptoms, and fewer children seem to have developed severe pneumonia. Nasal and pharyngeal swabs or blood analysis are adequate samples for RT-PCR. Sequencing of specimens and clinical diagnosis have been used as alternative diagnostic approaches. Elevated inflammatory markers were less common in children than adults and lymphocytopenia seemed rare. Included studies described ground-glass opacities, local or bilateral patchy shadowing, and halo signs Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. Not available Not available Critically low Addressed symptoms and prognosis in children
Lupia et al Most of the patients were male (age range, 8–92). Cardiovascular, digestive and endocrine system diseases were commonly reported. Fever, cough, dyspnea, myalgia and fatigue were the most common symptoms. Not available Case studies reported leukopenia, thrombocytopenia, slightly elevated AST and ALT, and elevated C-reactive protein. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral GGOs were most commonly reported in chest CT findings. Lopinavir, ritonavir, umifenovir and oseltamivir were the most common antivirals used to treat the infection. Supportive intervention (oxygen therapy) was frequently required by patients. Empirical antibiotics have been described. Steroids were also commonly described Not available Not available Critically low Summarizes findings from English-language case reports and case series.
Marasinghe No studies were found investigating the effectiveness of face mask use in limiting the spread of this specific virus. Not available Not available Not available Not available Not available Not available Not available Critically low Addressed an important preventive topic (face mask use).
Mullins et al Study revealed that 7 mothers were asymptomatic (21.8%) and 2 mothers were admitted to the intensive care unit (6.25%). Delivery was by Caesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. Seven patients were asymptomatic at admission while 18 were symptomatic (with viral changes on chest x-ray and chest tomography). Included symptoms were: cough, headache, chills, myalgia, sore throat, and shortness of breath. Not available Not available Among included pregnant patients, evidence of pneumonia, bilateral infiltrates, ground-glass opacities, and consolidation were the most common radiological findings. Not available Included patients with asthma and pulmonary fibrosis. Not available Critically low Addressed COVID-19 in pregnancy, delivery and postnatal.
Pang et al The current diagnostic and therapeutic alternatives, including rapid diagnostics and vaccines are essential to limit transmission of respiratory infectious diseases such as the novel coronavirus. Possible diagnostic approaches are RT-PCR, serological assays and point-of-care testing. The study presented a detailed description of diagnostic methods, such as rapid tests, detection of genetical material and serological testing. Not available Not available Several trials were identified, investigating therapeutics such as hydroxychloroquine, lopinavir and ritonavir, glucocorticoids therapy. Several vaccines are in development. Not available Not available Critically low Review focused on potential new diagnostics and therapeutics.
Rodriguez-Morales et al 20.3% (95% CI 10.0–30.6%) of patients required ICU support, 32.8% presented with acute respiratory distress syndrome (95% CI 13.7–51.8) and 6.2% (95% CI 3.1–9.3) with shock. The case fatality rate was 13.9% (95% CI 6.2–21.5%). Clinical symptoms presented were fever (88.7, 95% CI 84.5–92.9%), cough (57.6, 95% CI 40.8–74.4%) and dyspnea (45.6, 95% CI 10.9–80.4%). Not available Regarding laboratory findings, decreased albumin (75.8, 95% CI 30.5–100.0%), high C-reactive protein (58.3, 95% CI 21.8–94.7%), and high lactate dehydrogenase (57.0, 95% CI 38.0–76.0), lymphopenia (43.1, 95% CI 18.9–67.3), and high erythrocyte sedimentation rate (41.8, 95% CI 0.0–92.8), were the most common laboratory results. Results showed bilateral pneumonia, with associated ground-glass opacities. Not available Patients presented in 36.8% of cases with comorbidities (95% CI 24.7–48.9%), the most significant being hypertension (18.6, 95% CI 8.1–29.0%), cardiovascular disease (14.4, 95% CI 5.7–23.1%), and diabetes (11.9, 95% CI 9.1–14.6%), among others. Not available Critically low Broad range of topics addressed.
Salehi et al Known features of COVID-19 on initial CT include bilateral multilobar ground-glass opacification with a peripheral or posterior distribution, mainly in the lower lobes and less frequently within the right middle lobe. Septal thickening, bronchiectasis, pleural thickening,
and subpleural involvement are some of the less common findings, mainly in the later stages of the disease.
Not available Not available Not available A correlation was found between CT findings and disease severity and mortality. In severely ill patients, the most commonly reported CT findings were bilateral and multilobar involvement and subsegmental consolidative opacities. ARDS was the most common indication for transfer to the ICU, with the majority of COVID-19 mortalities occurring among patients with ARDS in the ICU. Not available Not available Not available Critically low Focused review on radiological imaging.
Sun et al The percentage of severe cases among all infected cases was 0.181 (95% CI: 0.127–0.243), and the case fatality rate was 0.043 (95% CI: 0.027, 0.061). Clinical symptoms presented were fever 0.891 (95% CI: 0.818–0.945), cough 0.722 (95% CI: 0.657–0.782), muscle soreness or fatigue 0.425 (95% CI: 0.213–0.652). ARDS incidence was 0.148 (95% CI: 0.046–0.296). Not available Not available The incidence of abnormal chest computer tomography was 0.966 (95% CI: 0.921–0.993). Not available Not available Not available Critically low Broad range of topics addressed.
Yang et al The symptoms of COVID-19 are similar to those of influenza (e. g, fever, cough or fatigue), and the COVID-19 outbreaks occurred during a year of a high prevalence of respiratory diseases caused by influenza, respiratory syncytial virus, and other respiratory viruses. The most common clinical symptoms were fever (91 ± 3, 95% CI 86–97%), cough (67 ± 7, 95% CI 59–76%), fatigue (51 ± 0, 95% CI 34–68%) and dyspnea (30 ± 4, 95% CI 21–40%). Not available Not available Not available Not available The most common comorbidities were hypertension (17 ± 7, 95% CI 14–22%), diabetes (8 ± 6, 95% CI 6–11%), cardiovascular diseases (5 ± 4, 95% CI 4–7%) and respiratory system diseases (2 ± 0, 95% CI 1–3%). There was a higher likelihood that patients with severe disease had hypertension (OR 2.36, 95% CI: 1.46–3.83), respiratory disease (OR 2.46, 95% CI: 1.76–3.44), or cardiovascular disease (OR 3.42, 95% CI: 1.88–6.22), compared with patients with non-severe disease. Not available Critically low Review published in and early phase of the pandemic, which assessed symptoms and comorbidities.
  1. List of abbreviations: SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2, CI Confidence Interval, RT-PCR Real Time Polymerase Chain Reaction, GRADE Grading of Recommendations, Assessment, Development and Evaluations, ARDS Acute Respiratory Distress Syndrome, ICU Intensive Care Unit, AST Aspartate Transaminase, ALT Alanine Transaminase, cTnI Cardiac Troponin I, GGO Ground-glass opacification