The Science of COVID-19: COVID-19 and treatment of adults

Clinical manifestations
The clinical spectrum of COVID-19 infection ranges from asymptomatic infection to critical illness. Among patients who are symptomatic, the median incubation period is approximately four to five days, and 97.5percent have symptoms within 11.5 days after infection.
Symptoms may include fever, cough, sore throat, malaise and myalgias. Some patients have gastrointestinal symptoms, including anorexia, nausea and diarrhoea. Anosmia (loss of smell) and ageusia (loss of taste) have been reported in up to 68 percent of patients and are more common in women than in men
Risk factors for complications of COVID-19 include older age, cardiovascular disease, chronic lung disease, smoking, pregnancy, diabetes, and obesity. It is unclear whether other conditions (example, uncontrolled HIV infection or use of immunosuppressive medications) confer an increased risk of complications, but these conditions may be associated with worse outcomes after infection with other viruses.
Laboratory findings in hospitalized patients may include lymphopenia and elevated levels of d-dimer, lactate dehydrogenase, C-reactive protein and ferritin. These inflammatory markers are important to trend during the clinical course.
Evaluation of COVID-19 is guided by the severity of illness. According to data from China, 81 percent of people with COVID-19 had mild or moderate disease (including people without pneumonia and people with mild pneumonia), 14 percent had severe disease, and five percent had critical illness. Patients who have mild signs and symptoms generally do not need additional evaluation.
However, some patients who have mild symptoms initially will subsequently have precipitous clinical deterioration that occurs approximately one week after symptom onset. In patients who have risk factors for severe disease, close monitoring for clinical progression is warranted, with a low threshold for additional evaluation. If new or worsening symptoms (example, dyspnea) develop in patients with initially mild illness, additional evaluation is warranted.
Physical examination should be performed to assess for tachypnea, hypoxemia, and abnormal lung findings. In addition, testing for other pathogens (example, influenza virus, depending on the season, and other respiratory viruses) should be performed, if available, and chest imaging should be done. Typical findings are ground-glass opacifications or consolidation.
Hallmarks of moderate disease are the presence of clinical or radiographic evidence of lower respiratory tract disease, but with a blood oxygen saturation of 94 percent or higher while the patient is breathing ambient air.
Indicators of severe disease are marked tachypnea (respiratory rate, ≥30 breaths per minute), hypoxemia (oxygen saturation, ≤93 percent; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, 50 percent of the lung field involved within 24 to 48 hours).

Remdesivir, an inhibitor of RNA-dependent RNA polymerase, has activity against COVID-19 in vitro and in animals.
In the Adaptive COVID-19 Treatment Trial 1 (ACTT-1), which involved hospitalized patients with evidence of lower respiratory tract infection, those randomly assigned to receive 10 days of intravenous remdesivir recovered more rapidly than those assigned to receive placebo (median recovery time, 10 vs. 15 days); mortality estimates by day 29 were 11.4 percent and 15.2 percent, respectively. In another trial, clinical outcomes with five days of remdesivir were similar to those with 10 days of remdesivir.
Currently, remdesivir is recommended for the treatment of hospitalized patients with severe COVID-19, but consider data to be insufficient to recommend for or against the routine use of this drug for moderate disease – studies are ongoing.
Data from patients with COVID-19 who were enrolled in a large expanded-access programme for convalescent plasma in the United States suggested that mortality might be lower with receipt of plasma with a high titer of antibody than with receipt of plasma with a low titer of antibody; the data also suggested that mortality might be lower when plasma is given within three days after diagnosis than when plasma is given more than three days after diagnosis.
Ongoing randomized trials must be completed to determine the role of convalescent plasma.
Monoclonal antibodies directed against the COVID-19 spike protein are being evaluated in randomized trials as treatment for people with mild or moderate COVID-19 and as prophylaxis for household contacts of persons with COVID-19.
In the recovery trial, dexamethasone reduced mortality among hospitalized patients with COVID-19, but the benefit was limited to patients who received supplemental oxygen and was greatest among patients who underwent mechanical ventilation.
Clinical studies have shown that in 1,703 critically able patients, glucocorticoid reduced mortality versus standard of care passivity of 32 percent versus 40 percent.
Dexamethasone can be given at dose of 6 mg a day for 10 days or until discharge. Other steroids maybe similarly effective, such as hydrocortisone, methylprednisolone, and prednisone.
Dexamethasone did not improve outcomes, and may have caused harm, among patients who did not receive supplemental oxygen, and thus it is not recommended for the treatment of mild or moderate COVID-19.

Use of Concomitant Medications in People with COVID-19
Because COVID-19 enters human cells through the ACE2 receptor, questions were raised regarding whether the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) – which may increase ACE2 levels – might affect the course of COVID-19. However, large observational studies have not shown an association with increased risk.
Patients who are receiving ACE inhibitors or ARBs for another indication should not stop taking these agents, even if they have COVID-19.
Regeneron cov 2 antibody cocktail has shown to rapidly reduce viral load and associated symptoms and cause an antibody to spike protein that neutralizes the virus. Broadly direct acting antivirals are now in clinical trials. They have been shown to inhibit replication of viral pathogens from multiple RNA virus family including SARS influenza RSV, filovirus, flavivirus to name a few.
The mechanism of antiviral activities viral error catastrophe is a concept that’s predicated on increasing the viral mutation rate beyond a biologically tolerable threshold resulting in impairment of viral fitness and activity leading to viral extinction.
There are multiple other strategies for antiviral work. Another mechanism in treatment is the role of light cytokine which belongs to the TNF family, which is secreted in high-level general viral infection by reducing the cytokine. This is associated with related lung fibrosis and cytokine storm.
Infection Control and Prevention health care workers must be protected from acquiring COVID-19 when they are providing clinical care. Using telehealth when possible, reducing the number of health care workers who interact with infected patients, ensuring appropriate ventilation, and performing assiduous environmental cleaning are critical.
PPEs used while caring for patients with known or suspected COVID-19 should include, at a minimum, an isolation gown, gloves, a face mask, and eye protection (goggles or a face shield).

Article submitted as part of the Ministry of Health’s COVID-19 public information and education programme