key: cord-0744156-3vqw8pwi authors: Ahmad Bhat, Showkat; Singh, Gurjinder; Bhat, Waseem F; Ali Khan, Ashraf; Parvez Azad, Tariq title: Coronavirus Disease-2019 and its current Scenario - A Review date: 2021-12-02 journal: Clinical eHealth DOI: 10.1016/j.ceh.2021.09.002 sha: ebe0e4f4ffefa909d68ae27d27f420a56160696a doc_id: 744156 cord_uid: 3vqw8pwi Coronaviruses are enveloped non-segmented positive-sense RNA viruses belonging to the family Coronaviridae. The human coronavirus infections are mild; the epidemics of the two β-coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have caused more than ten thousand cumulative cases in the past twodecades. There is a new public health crisis threatening the world with the emergence and spread of 2019 novel coronavirus (2019-nCoV). The virus originated in bats and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province in China during the month of December 2019. Till date around 7,823,289 reported cases of coronavirus disease 2019 (COVID-2019) and 431,541 reported deaths till date. The disease is transmitted by inhalation or contact with infected droplets with incubation period of 2 to 14 days. The symptoms are usually fever, sore throat, dry cough, breathlessness, fatigue while many people are asymptomatic. Coronavirus (2019-nCoV) may progress to pneumonia, acute respiratory distress syndrome (ARDS) and can cause multi-organ dysfunction. Currently diagnosis is done by demonstration of the virus in respiratory secretions by special molecular tests like real-time reverse-transcription–polymerase-chain-reaction (RT-PCR), Radiological examinations (chest CT). Common laboratory tests like white cell counts and C-reactive protein (CRP) and measure symptoms can be used as preliminary screening at large scale after lock down the area or country. Treatment is essentially supportive; role of antiviral agents is yet to be established. It is paramount to implement infection control practices by infection source controlling, transmission route blocking, and susceptible population protection. Early preventive measures can be home isolation of suspected cases and those with mild illnesses and strict infection control measures at hospitals that include contact and droplet precautions. The worldwide impact of this Coronavirus new epidemic is yet uncertain. returning from Wuhan. Transmission to healthcare workers caring for patients was described on 20 th Jan, 2020. By 23 rd January, the 11 million population of Wuhan was placed under lock down with restrictions of entry and exit from the region. Soon this lock down was extended to other cities of Hubei province. Cases of COVID-19 in countries outside China were reported in those with no history of travel to China suggesting that local human-to-human transmission was occurring in these countries (11) . Airports in different countries including India put in screening mechanisms to detect symptomatic people returning from China and placed them in isolation and testing them for COVID-19. Soon it was apparent that the infection could be transmitted from asymptomatic people and also before onset of symptoms. Therefore, countries including India who evacuated their citizens from Wuhan through special flights or had travelers returning from China, placed all people symptomatic or otherwise in isolation for 14 d and tested them for the virus. Cases continued to increase exponentially and modelling studies reported an epidemic doubling time of 1.8 d (12) . In fact on the 12 th of February, China changed its definition of confirmed cases to include patients with negative/ pending molecular tests but with clinical, radiologic and epidemiologic features of COVID-19 leading to an increase in cases by 15,000 in a single day (8). 96,000 cases worldwide (80,000 in China) and 87 other countries and 1 international conveyance (696, in the cruise ship Diamond Princess parked off the coast of Japan) have been reported as of 05/03/2020 (2). The measure threat is that while the number of new cases has reduced in China lately, they have increased exponentially in other countries including South Korea, Italy, Iran, Spain, Germany, UK, netherland, India. Of those infected, 20% are in critical condition, 25% have recovered, and 3310 (3013 in China and 297 in other countries) have died (2). India, which had reported only 1100 cases till date, has also seen a sudden increase in cases. These numbers are possibly an underestimate of the infected and dead due to limitations of surveillance and testing. Though the SARS-CoV-2 originated from bats, the intermediary animal through which it crossed over to humans is uncertain. Pangolins and snakes are the current suspects. (12, 13) Symptoms vary from person-to-person with COVID-19. It may produce few or no symptoms. However, it can also lead to severe illness and may be fatal. Data obtainable from reports allow dividing the clinical manifestations of the disease according to the severity of the clinical pictures. The COVID-19 may present with mild, moderate, or severe illness. Among the severe clinical manifestations, there are severe pneumonia, ARDS, sepsis, and septic shock. The clinical course of the disease seems to predict a favorable trend in the majority of patients. In a percentage still to be defined of cases, after about a week there is a sudden worsening of clinical conditions with rapidly worsening respiratory failure and MOD/MOF. As a reference, the criteria of the severity of respiratory insufficiency and the diagnostic criteria of sepsis and septic shock can be used (14). These patients usually present with symptoms of an upper respiratory tract viral infection, including mild fever, cough (dry), sore throat, nasal congestion, malaise, headache, muscle pain, or malaise. Signs and symptoms of a more serious disease, such as dyspnea, are not present. Compared to previous HCoV infections, non-respiratory symptoms such as diarrhea are challenging to find. Respiratory symptoms such as cough and shortness of breath (or tachypnea in children) are present without signs of severe pneumonia. Fever is associated with severe dyspnea, respiratory distress, tachypnea (> 30 breaths/min), and hypoxia (SpO2 < 90% on room air). However, the fever symptom must be interpreted carefully as even in severe forms of the disease, it can be moderate or even absent. Cyanosis can occur in children. In this definition, the diagnosis is clinical, and radiologic imaging is used for excluding complications. When PaO2 is not available, a ratio SpO2/FiO2 ≤ 315 is suggestive of ARDS. Chest imaging utilized includes chest radiograph, CT scan, or lung ultrasound demonstrating bilateral opacities (lung infiltrates > 50%), not fully explained by effusions, lobar, or lung collapse. Although in some cases, the clinical scenario and ventilator data could be suggestive for pulmonary edema, the primary respiratory origin of the edema is proven after the exclusion of cardiac failure or other causes such as fluid overload. Echocardiography can be helpful for this purpose. According to the International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis represents a life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection, with organ dysfunction (15). The clinical pictures of patients with COVID-19 and with sepsis are particularly serious, characterized by a wide range of signs and symptoms of multi-organ involvement. These signs and symptoms include respiratory manifestations such as severe dyspnea and hypoxemia, renal impairment with reduced urine output, tachycardia, altered mental status, and functional alterations of organs expressed as laboratory data of hyperbilirubinemia, acidosis, high lactate, coagulopathy, and thrombocytopenia. The reference for the evaluation of multi-organ damage and the related prognostic significance is the Sequential Organ Failure Assessment (SOFA) score, which predicts ICU mortality based on lab results and clinical data (16). A pediatric version of the score has also received validation (17). In this scenario, which is associated with increased mortality, circulatory, and cellular/metabolic abnormalities such as serum lactate level greater than 2 mmol/L (18 mg/dL) are present. Because The CDC advise that although there have been reports of complications in young children, these are rare. COVID-19 most commonly produces mild symptoms in children. Cold-or flu-like symptoms usually set in from 2-4 days after a coronavirus infection and are typically mild. However, symptoms vary from person-to-person, and some forms of the virus can be fatal.  sneezing  runny nose  fatigue  cough  fever  sore throat  exacerbated asthma Scientists cannot easily cultivate human coronaviruses in the laboratory unlike the rhinovirus, which is another cause of the common cold. This makes it difficult to gauge the impact of the coronavirus on national economies and public health. There is no cure for coronaviruses that cause symptoms resembling the common cold. Treatments include self-care and over-the-counter (OTC) medication. People can take several steps, including:  resting and avoiding overexertion  drinking enough water  avoiding smoking and smoky areas  taking acetaminophen for pain and fever  using a clean humidifier or cool mist vaporizer All ages are susceptible. Infection is transmitted through large droplets generated during coughing and sneezing by symptomatic patients but canal so occur from asymptomatic people and before onset of symptoms (11). Studies have shown higher viral loads in the nasal cavity as compared to the throat with no difference in viral burden between symptomatic and asymptomatic people. Patients can be infectious for as long as the symptoms last and even on clinical recovery. Some people may act as super spreaders; a UK citizen who attended a conference in Singapore infected 11other people while staying in a resort in the French Alps and upon return to the UK (8). These infected droplets can spread 1-2 m and deposit on surfaces. The virus can remain viable on surfaces for days in favorable atmospheric conditions but are destroyed in less than a minute by common disinfectants like sodium hypochlorite, hydrogen peroxide etc (19) . Infection is acquired either by inhalation of these droplets or touching surfaces contaminated by them or then touching the nose, mouth and eyes. The virus is also present in the stool and contamination of the water supply and subsequent transmission via aerosolization/ feco oral route is also hypothesized (8). As per current information, transplacental transmission from pregnant women to their fetus has not been described (20). However, neonatal disease due to post natal transmission is described ( Fatality rate in hospitalized adult patients ranged from 4 to 11%. The overall case fatality rate is estimated to range between 2 and 3% (2). Interestingly, disease in patients outside Hubei province has been reported to be milder than those from Wuhan (22, 23). Similarly, the severity and case fatality rate inpatient outside China has been reported to be milder (8). This may either be due to selection bias wherein the cases reporting from Wuhan included only the severe cases or due to predisposition of the Asian population to the virus due to higher expression of ACE2 receptors on the respiratory mucosa (13). Disease in neonates, infants and children has been also reported to be significantly milder than their adult counterparts. In a series of 34 children admitted to a hospital in Shenzhen, China between January 19th and February 7th, there were 14 males and 20 females. The median age was 8 y 11 moandin 28 children the infection was linked to a family member and 26 children had history of travel/residence to Hubei province in China. All the patients were either asymptomatic (9%) or had mild disease. No severe or critical cases were seen. The most common symptoms were fever (50%) and cough (38%). All patients recovered with symptomatic therapy and there were no deaths. One case of severe pneumonia and multi-organ dysfunction in a child has also been reported (24, 25) . Similarly the neonatal cases that have been reported have been mild (26). A suspect case is defined as one with fever, sore throat and cough who has history of travel to China or other areas of persistent local transmission or contact with patients with similar travel history or those with confirmed COVID-19 infection. However cases may be asymptomatic or even without fever. A confirmed case is a suspect case with a positive molecular test. Specific diagnosis is by specific molecular tests on respiratory samples (throat swab/ nasopharyngeal swab/ sputum/ endotracheal aspirates and broncho alveolar lavage). Virus may also be detected in the stool and in severe cases, the blood. It must be remembered that the multiplex PCR panels currently available do not include the COVID-19. Commercial tests are also not available at present. In a suspect case in India, the appropriate sample has to be sent to designated reference labs in India or the National Institute of Virology in Pune. As the epidemic progresses, commercial tests will become available. Other laboratory investigations are usually non specific. The white cell count is usually normal or low. There may be lymphopenia; a lymphocyte count <1000 has been associated with severe disease. The platelet count is usually normal or mildly low. The CRP and ESR are generally elevated but procalcitonin levels are usually normal. A high procalcitonin level may indicate a bacterial co-infection. The ALT/AST, prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high levels are associated with severe disease. The chest X-ray (CXR) usually shows bilateral infiltrates but may be normal in early disease. The CT is more sensitive and specific. CT imaging generally shows infiltrates, ground glass opacities and sub segmental consolidation. It is also abnormal in asymptomatic patients/ patients with no clinical evidence of lower respiratory tract involvement. In fact, abnormal CTscans have been used to diagnose COVID-19 in suspect cases with negative molecular diagnosis; many of these patients had positive molecular tests on repeat testing (27-29). The differential diagnosis includes all types of respiratory viral infections (influenza, parainfluenza, respiratorysyncytial COVID-19 coronavirus), atypical organisms (mycoplasma, chlamydia) and bacterial infections. It is not possible to differentiate COVID-19 from these infections clinically or through routine lab tests. Therefore travel history becomes important. However, as the epidemic spreads, the travel history will become irrelevant (27). Treatment is essentially supportive and symptomatic. The first step is to ensure adequate isolation (discussed later) to prevent transmission to other contacts, patients and healthcare workers. Mild illness should be managed at home with counseling about danger signs. The usual principles are maintaining hydration and nutrition and controlling fever and cough. In hypoxic patients, provision of oxygen through nasal prongs, face mask, high flow nasal cannula (HFNC) or non-invasive ventilation is indicated (27, 30) . Mechanical ventilation and even extra corporeal membrane oxygen support may be needed. Renal replacement therapy may be needed in some. Since at this time there are no approved treatments for this infection, prevention is crucial. Several properties of this virus make prevention difficult namely, non-specific features of the disease, the infectivity even before onset of symptoms in the incubation period, transmission from asymptomatic people, long incubation period, tropism for mucosal surfaces such as the conjunctiva, prolonged duration of the illness and transmission even after clinical recovery. Isolation of confirmed or suspected cases with mild illness at home is recommended (27, 37) . This new virus outbreak has challenged the economic, medical and public health infrastructure of China and of other countries especially, its neighbours. Time alone will tell how the virus will impact our lives here in India. More so, future outbreaks of viruses and pathogens of zoonotic origin are likely to continue. Therefore, apart from curbing this outbreak, efforts should be made to devise comprehensive measures to prevent future outbreaks of zoonotic origin. Common laboratory tests like white cell counts and C-reactive protein (CRP) and measure symptoms can be used as preliminary screening at large scale. A novel coronavirus outbreak of global health concern Clinical features of patients infected with 2019 novel coronavirus in Wuhan Evaluation and Treatment Coronavirus (COVID-19) Clinical Virology Middle East Respiratory Syndrome Coronavirus China's CDC detects a large number of new coronaviruses in the South China seafood market in Wuhan Clinical features of patients infected with 2019 novel coronavirus in Wuhan Transmission of 2019nCoV infection from an asymptomatic contact in Germany Early transmission dynamics in Wuhan, China, of novel International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children Risk Factors for Fatal Middle East Respiratory Syndrome Coronavirus Infections in Saudi Arabia: Analysis of the WHO Line List Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: are retrospective review of medical records Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumoniain Wuhan, China Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective cases eries Clinical and epidemiological characteristicsof34childrenwith2019novelcoronavirusinfection in Shenzhen First case of severe childhood novel coronavirus pneumonia in China Firstcase of neonate infected with novel coronavirus pneumonia in China A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus A Review of Coronavirus Disease-2019 (COVID-19) Use of chest CT in combination with negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia Clinical management of severe acute respiratory infection when novel coronavirus [nCoV] infection is suspected First case of2019novel coronavirus in the United States Potential interventions for novel coronavirus in China: a systemic review Multicenter Collaboration Group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for Chloroquine in the Treatment of Novel Coronavirus Pneumonia. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia World Health Organization. Coronavirus disease [COVID-19] Technical Guidance: Infection Prevention and Control Game consumption and the 2019 novel coronavirus Coronavirus disease 2019 (COVID-19) Situation Report WHO Emergencies preparedness, response. Pneumonia of unknown origin -China. Disease outbreak news A new virus isolated from the human respiratory tract Treatment of Middle East respiratory syndrome with a combination of lopinavirritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic delta-coronaviruses with a highly divergent RNA dependent RNA polymerase Baricitinib as potential treatment for 2019-nCoV acute respiratory disease