INTRODUCTION:

SARI is the term for serious acute respiratory infections with a history of fever greater than 38°C and more than 10 days of coughing. It needs to be admitted into hospital¹. Most Sari cases require Ventilator Assisting Intensive Care Unit (ICU) admissions. Extreme causes of Sari include serious pneumonia, sepsis, acute respiratory distress syndrome (ARDS), and septic shock. Those are the causes of deaths from coronavirus, including illness with coronavirus (Covid-19), Middle East Respiratory Syndrome (Mers), and Severe Acute Respiratory Syndrome (Sars)². Although Sari's trigger species may be virus to bacteria, a subsequent growth in the case of influenza viruses, human influenza-like H5N1 and H7N9 infections, coronaviruses and other new breathing viral diseases is typically suggested in an emerging infectious disease outbreak³.

Large Sari clusters display viral outbreaks like H1N1. Sari patients who have tested negative for H1N1 are being screened for Covid-19's sentinel surveillance to assess if there is undetected community transmission Sari patients admitted to ICUs across India are being randomly checked for Covid-19 to scan for undetected community transmission⁴. The distinction is that a patient with Sari has to be treated and that an ILI is milder. In order to understand the severity of the epidemic in India, Covid 19 research will include all cases of sari in both the public and private sectors. Only then can we honestly say that there is no transmission of societies in India⁵.

Severe acute respiratory syndrome-related coronavirus (SARS-CoV or SARSr-CoV):

It is a coronavirus species that infects people, bats and certain other mammals. It is a single-stranded RNA enveloped positive-sense virus that reaches the host cell by binding to the receptor of angiotensin 2 (ACE2). It belongs to the Betacoronavirus genus and Sarbecoronavirus subgenus. Bats for the coronavirus associated with SARS as the principal host reservoir. The virus has evolved over a long time in the bat host reservoir. Recently, coronavirus SARS-related strains evolved and the cross-species jumped from bats to humans, as with the SARS-CoV and SARS-CoV-2 strains⁶. These two strains originated from one ancestor but made the cross-species leap separately into humans. SARS-CoV-2 is not a direct SARS-CoV descendant. Two virus strains have caused severe respiratory disease outbreaks in humans: severity of ARS-CoV or SARS-CoV-1, which resulted in a serious outbreak of ARS (SARS) in the 2002-2004 period, and serious acute respiratory coronavirus syndrome 2 (SARS-CoV-2) that leaded to the 2019-20 coronavirus pandemic (COVID-19). Hundreds of other strains are believed to only infect non-human primates, SARS-CoV: bats represent a major reservoir of a broad variety of SARS-related coronavirus strains, and a number of strains were found in palm civets that have been possibly ancestors of SARS-CoV. SARS-related coronavirus was one of several viruses, a new program for emergency research/development before and during the epidemic in diagnostic trials, vaccines and medicines, was one of many viruses identified in 2016, by the World Health Organization (WHO), as possibly a cause of a potential epidemic. The 2019–20 coronavirus pandemic prediction was observed⁷.

Genome:

SARS-related coronavirus is a single-stranded, enveloped RNA virus with positive senses. The genome of the RNA virus is roughly 30 kb. There are 14 open read frames in the virus, which often overlap. The genome has the typical 5′cap methylated and 3′cap polyadenylated. In 5'UTR there are 265 nucleotides and in 3'UTR 342. The 5 'methylated cap and 3' polyadenylated tail allow for direct translation of the positive-sense RNA genome by a ribosome on viral entry. SARSr-CoV is similar to the other coronaviruses because its genome expression begins by the translation, in the first two large open-reading frames (ORFs), 1a and 1b, both of them forming polyproteins, via the host cell's ribosomes. Most of the viral proteins are functions known⁸. The four main structural proteins, the Spikes, the Envelopes, the membrane, and the nucleocapsid, are encoded by ORFs 1a and 1b for polyprotein replicase / transcriptase, and later ORFs 2, 4, 5, and 9a. The ORFs later coded for 8 specific (orph3a to orf9b) protein, many of whom have no known counterparts, also include accessory protein. There is no understanding of the various roles of the accessory proteins.

Replication and transcription:

Numerous NSPs coalesce to form a multiple-protein transcriptase replication complex (RTC). The main RNA-dependent RNA polymerase (RdRp) is the replicase-transcriptase enzyme. The translation and transcription of RNA from the RNA strand is directly involved. The replication and transcription cycle is supported in many nonstructural proteins. The nsp15 protein is an exoribonuclease of 3'-5 'that offers a high degree of fidelity. The exoribonuclease provides the complex missing of the RNA-based RNA polymerase with a proofreading feature. The proteins nsp7 and nsp8 are similarly shaped as part of a complex of the hexadecameric sliding clamps that greatly enhances the RNA polymerase processivity. Due to its relatively large size of génome compared to other RNA viruses, coronaviruses need increased fidelity and processiveness during RNA Synthesis. The viral genome is one of the key functions of the complex replicase-transcriptase. RdRp mediates directly a synthesis of positive-sense RNA subgenomic sensory molecules. That is accompanied by the transcription into their corresponding positive-sense mRNAs of these negative-sense subgenomic RNA molecules. Replicating the viral genome is the other essential feature of the replication-transcriptase complex. RdRp mediates directly the synthesis of the genomic negative sense RNA of the genomic positive meaning RNA. The replication of the positive-sense genomic RNA from the negative-sense genomic RNA is observed. The genome of the progeny viruses is replicated by positive-sense genomic RNA. The specific smaller mRNAs are transcripts of the last third of the genome of a virus that adopt the ORF1a and ORF1b reading frames. The four structural proteins (S, E, M, N), including the progeny virus particles and eight other accessory proteins, (orf3 to orf9b) that assist the virus, are translated into these mRNAs⁹.

Assembly and release:

In the endoplasmic reticulum, RNA translation occurs. The S, E and M viral structural proteins move into the Golgi intermediate compartment along the secretory path. The most protein-protein interactions needed to assemble viruses after the M proteins are bound to the nucleocapsid are guided there. Progeny viruses are released from the host cell by exocytosis through secretory vesicles¹⁰.

Clinical Management of severe acute respiratory illness (SARI) in suspect/confirmed novel coronavirus (nCOV) cases:

An ARI with fever history or reported temperature of approximately 38°C and cough; initiation during the last ~10 days; and hospitalization requirement. The absence of fever does NOT rule out viral infection.

Immediate implementation of appropriate IPC measures:

IPC is a vital and integral part of patient care management and should be started at the patient's point of admission to hospital (usually the Emergency Department). Standard procedures should also be applied regularly in all health-care facilities areas. Normal precautions include hand hygiene; using PPE to prevent direct contact with the blood, body fluids, secretions (including breathing secretions) and non-intact skin of patients. Typical measures may include prevention of needle sticking or sharp injury; safe waste management; machine cleaning and disinfection; and environmental sanitation¹¹.

Early supportive therapy and monitoring:

a. Give immediate supplementary oxygen therapy to patients with SARI and respiratory distress, hypoxaemia or shock: activate 5 L/ min oxygen therapy and titrate flow rates to meet target levels of SpO2 in non-pregnant adults as well as SpO2 in pregnant patients as low as 92-95%. Children with emergency signs (obstructed or absent breathing, extreme respiratory failure, central cyanosis, shock, coma or seizures) will receive oxygen therapy during resuscitation to the SpO2 target ≥94%; otherwise, the SpO2 target is ≥90%.

b. Using conservative fluid control in SARI patients without signs of shock: SARI patients should be treated carefully with intravenous fluids due to aggressive fluid.

Management of hypoxemic respiratory failure and ARDS:

Recognize serious hypoxemic respiratory failure when the standard oxygen therapy fails in a patient with respiratory distress. Patients may continue to have increased breathing or hypoxemia function even though the oxygen is supplied via a face mask with reservoir bag (flow levels of 10-15 L/min, usually the minimum flow needed to sustain bag inflation; FiO2 0.60-0.95). Hypoxemic respiratory failure in ARDS is generally caused by mismatch or shunt intrapulmonary ventilation-perfusion, and typically involves mechanical ventilation.

Management of septic shock:

Recognize septic shock in adults when infection is suspected or confirmed AND vasopressors are required to maintain mean arterial pressure (MAP) ≥65 mmHg AND lactate is ≥2 mmol/L if hypovolemia is not present. Recognize septic shock in children with some hypotension (systolic blood pressure [SBP] < 5th centile or > 2 SD lower than normal for age) or 2-3 of the following: altered mental state; tachycardia or bradycardia (HR < 90 bpm or > 160 bpm in infants and HR < 70 bpm or > 150 bpm in children); prolonged capillary refill (> 2 sec) or warm vasodilatation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.

Specific anti-Novel-CoV treatments and clinical research:

RCTs do not currently have evidence to prescribe any particular anti-nCoV treatment for patients with suspected or confirmed nCoV. Unlicensed therapies should be performed with strict supervision only in the form of ethically-approved clinical trials or the Monitored Emergency Use of Unregistered Interventions Framework (MEURI), with strict monitoring¹².

CONCLUSION:

SARI have been identified in the World Health Organization since the majority of viral infections have generic medical symptoms that cannot be easily distinguished from other respiratory infections. Best practices for SARI including IPC and optimized supportive care for severely ill patients are essential. Clinical management of SARI can be effective, and safe supportive management of patients with nCoV, particularly those with critical illness.

ACKNOWLEDGEMENT:

I express my sincere thanks to Vice-principal Prof. Dr. S. K. Mohite for providing me all necessary facilities and valuable guidance extended to me.

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Received on 23.05.2020 Modified on 17.06.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(3):178-180.

DOI: 10.5958/0975-4377.2020.00030.0