The communicable period corresponds to the interval between the positive clinical diagnosis and the negative tests for COVID-19. The average communicable period was 9.5 days, reaching up to 21 days for asymptomatic cases ¹³. The average COVID-19 symptoms period was 11.5 days in 97.5% of patients, with an interval of 1.2 days between the onset of symptoms and hospitalization. Disease development was also expected after 14 days of active monitoring or quarantine in about 101 cases for every 10,000 ⁹. The viral shedding median was 20 days, reaching up 37 days in cured patients. The viral shedding has also been identified in killed patients. For the treated patients with antivirals, in the severe and in the critical stages, the viral shedding median was 22, 19, and 24 days, respectively ¹⁴. These four-time parameters were mostly researched between March and May 2020, at least 17% of published studies.

The main COVID-19 symptoms were fever, cough, sputum, chills, fatigue, shortness of breath, headache, and olfactory and gustatory disorders. Several asymptomatic cases have also been identified worldwide (Figure 5C). Fever was the most common symptom among patients, and the first identified early in the pandemic ¹⁵, followed by dry cough ⁶, fatigue or myalgia, and headache ^12,16. The onset of fever and cough occurred, respectively, in 5 and 7 days ⁸, being the fever classified as mild (37.3-38.9 °C) or moderate (38.1-39 °C) ¹⁶. The onset of fatigue occurred in 8 days ¹⁷.

Psychosomatic issues, such as anxiety, stress, and depression during the COVID-19 pandemic, were observed, especially in March and April 2020, in at least 10% of the most cited papers. An online survey with more than 1,200 people was conducted in 194 Chinese cities. More than half of the interviewees reported moderate to severe psychological impact, 16.5% depressive symptoms, approximately 29% anxiety, and just over 8% some stress. The survey also found that just over 75% of respondents had concerns about family members’ contamination. The most severe levels of mental health complications have been identified among women, especially students ²⁹.

Some scientific studies estimated the number of cases, mortality rate, and contact tracing (especially the zero case) since the beginning of the COVID-19 pandemic (Figure 5F). The increase of cases worldwide was related to international travel and late social isolation established by countries, leading to an immediate outbreak of COVID-19, as previously seen in Italy and Spain, and after in the USA and Brazil. The mortality rates in China and Italy became identical and equal to 2.3%, with older adults’ predominance. The failure to identify the Italian zero case may have influenced that rate ³⁶. Travel ban measures in Wuhan (China) contributed to the reduction of about 80% of predicted imported cases in mid-February 2020, despite a predicted disease progression delay of only 3 to 5 days. Travel restrictions would only effectively alter the COVID- 19 progress if combined with a reduction of at least 50% in the community transmissions ³⁷. Travel restrictions were also beneficial in reducing the average number of daily reproductions in Wuhan, which dropped from 2.35 to 1.05 a week after adopting these measures ³⁸. All estimates were made using the exponential growth rate from Chinese exported cases for COVID-19, where the necessary number of reproduction (secondary transmission) and the mortality rate could be determined. The COVID-19 pandemic was predicted from two scenarios: from a single case and using the growth rate adjusted with other parameters. Mortality rates ranged from 5.3% to 8.4%, while the number of secondary cases ranged from 2.1 to 3.2 for the scenarios, respectively ³⁹. In May and June 2020, research on the COVID-19 cases’ estimation was not among the most cited papers in the period, possibly due to disease stabilization in many countries and the interest in other more critical disease aspects.

Several antiviral drugs have been investigated (Figure 7). Lopinavir-ritonavir was used to treat HIV (human immunodeficiency virus) and was used to treat COVID-19 since it had previous results in vitro and clinical studies against SARS-CoV. It was prescribed twice a day for 14 days to infected adult patients, and the results were compared to the standard COVID-19 treatment. There was no improvement in patients who used lopinavir-ritonavir ⁴⁰. However, the first case of COVID-19 in Korea was treated with lopinavir-ritonavir, which significantly reduced the viral β- coronavirus loads ⁸.

Nucleotide inhibitors such as Anti-HCV used to fight hepatitis C by inhibiting RNA polymerase ⁴¹, and inhibitors of the Renin-Angiotensin-Aldosterone System (RAAS), considered vasoactive peptides ⁴² were also investigated. Examples of anti-polymerase drugs with positive results for the COVID-19 treatment were sofosbuvir, IDX-184, ribavirin, and Remdesivir ^41,43. The RAAS inhibitors have been indicated in severe clinical cases, especially in patients with comorbidities related to heart disease. However, the real activity of these inhibitors in combating COVID-19 has been researched. The angiotensin-converting enzyme 2 (ACE2) is considered responsible for coronavirus infection since it functions as a receptor. Studies suggested that RAAS inhibition favors ACE2 overexpression, causing viral activity to increase ⁴². Therefore, further studies involving RAAS inhibitors must be carried out to verify their real benefits against COVID- 19.

According to WHO, it will take at least 18 months for a vaccine against the novel coronavirus to be completed, although different research groups and experts are in a real scientific race for its fast development ⁴⁷. Currently, treatments only combat symptoms, acting as anti-inflammatory and antiviral drugs. Experience with immunological studies of SARS-CoV and its similarity to SARS-CoV-2 allowed the tracking and identification of B and T cell epitopes in SARS-CoV immunogenic structural proteins, also identified in SARS-CoV-2. As no epitope mutations were observed in more than 120 SARS-CoV-2 sequences, they were considered useful in researching a new vaccine, with complete and global coverage ⁴⁸. Other vaccines have also been investigated, but not reported in the most cited articles in the first half of 2020, possibly because they are confidential research or in little advanced development stages.

The management of COVID-19 involved control strategies that range from outstanding medical care and personal hygiene to the social isolation measures. Furthermore, the clinical case determination and the disease importation control, either between countries or between regions of the same country, have been necessary measures for the effective control of COVID-19 (Figure 8). Although these strategies have been prioritized differently from February to June 2020, they have all been equally important in reducing the number of cases or stabilizing the COVID-19 and overcoming it in the coming months.

The care for patients admitted to the ICU has involved adopting special medical measures and protocols, which could ensure health professionals’ safety and patients’ well-being. The main procedures included the infection control (risks of SARS-CoV-2 transmission), laboratory tests, supportive care (continuous renal replacement – CRRT, invasive mechanical ventilation ³², extracorporeal membrane oxygenation – ECMO ⁴⁷, hemodynamic support ³), and COVID-19 therapy ³. Some procedures were considered specific and necessary in patients with COVID-19, such as emergency tracheal intubation, predicted or unexpected difficult tracheal intubation, cardiac arrest, anesthetic care, and tracheal extubating ⁵¹ (Figure 9A). Although ventilatory support was mostly reported in April 2020 in 56% of the most cited papers, all measures related to care in the ICU were used equally in May 2020, possibly due to the disease’s peak in many countries in this period.

Social isolation was a measure used to contain viruses such as SARS and COVID-19, by reducing the disease peak and flattening the curve over time, to ensure sufficient time for the government to implement public health care measures ⁵². The main social isolation measures included the closure of schools and workplaces non-essential (non-food and non-health) and people’s reduced movement on the streets ⁵². Countries that took a long time to implement quarantine measures suffered the consequences of the accelerated increase in cases of COVID-19 ⁵³. Although COVID- 19 and SARS differ in terms of transmissibility, infectious period, and disease spread, measures taken to control SARS have helped to control COVID-19, such as syndromic surveillance, immediate isolation of infected patients, and strict application of vertical quarantine (lockdown) ⁴. Mathematical models considering social isolation and contact tracing could predict the positive impacts on the new COVID-19 cases, thus contributing to the outbreak control ¹⁰. The early relaxation of social isolation compromised COVID-19 control. Therefore, it is necessary to have a strict contact control between people and a policy willing to implement social distance measures until the disease stabilizes and decreases ⁵².

A critical study on vulnerability to COVID-19 in developing countries, especially in Africa, was carried out. The COVID-19 importation was related to the recipient country’s ability to respond to the outbreak. Countries such as Egypt, Algeria, and South Africa presented a higher importation risk of the novel coronavirus, but a high capacity to control the disease. Countries such as Ethiopia, Nigeria, Sudan, Angola, Ghana, Tanzania, and Kenya with moderate risk showed high vulnerability to control the outbreak. The same was verified for the provinces of Guangdong, Fujian, and Beijing city ⁵⁷. This study can be used to reference countries with limited preparedness to deal with COVID-19, suggesting the adoption of intensified surveillance and resource allocation. Non-African countries can also use these measures.