SYMPTOMS AND DISEASE
COVID-19 (coronavirus disease) is an illness caused by the virus designated 2019-nCoV (now called SARS-CoV-2), which is a novel strain of the coronavirus group first seen in China in December 2019. This illness is similar to viral flu and therefore is called ILI (influenza-like illness). From the time of getting infected, it can take from 2 days to 2 weeks (incubation period) to manifest definite and recognizable symptoms.
ILI is defined as fever of 38 degC or more, with cough with onset within the last 10 days. Presenting symptoms of COVID include fever, dry cough, and sore throat which may be accompanied by fatigue, body ache, nasal congestion, running nose, loss of smell or taste, nausea/vomiting, loss of appetite or diarrhea. Many infected patients are often asymptomatic. Loss of smell and taste (salt and sweet), is a useful sign to look for in otherwise asymptomatic people with suspected exposure to COVID.
In about 4-5 days, the virus can spread and cause damage to the lower respiratory tract (bronchi and lungs) and decrease blood oxygen saturation. This manifests as breathlessness in addition to the other symptoms. Rarely neurological symptoms like dizziness, decreased alertness, disorientation, fits, or a stroke have also been seen.
Causes of death in COVID include ARDS (acute respiratory distress syndrome) which is respiratory failure resulting from massive lung inflammation and scarring (fibrosis), decreased oxygen in the blood, and/or sepsis leading to multi-organ failure (including heart and kidney failure). More recent research has pointed towards involvement and damage to the endothelium (the inner lining of blood vessels) as the possible cause for severe disease and mortality. Endothelial damage causes an increased risk of blood clotting (thrombosis), as well as adverse cardiovascular effects.
The overall mortality rate from COVID-19 is around 2-3% (<1% below 50 years of age). The risk of serious disease, complications, and death is higher and seen far more in older patients (>60 years) and those suffering from other underlying medical illnesses like diabetes, hypertension, cancers, and diseases of the airway/lungs, heart, kidney, liver or immune system.
The WHO in February 2020, had designated COVID-19 as a “public health emergency of international concern” (PHEIC) and labeled it a pandemic indicating that international and collaborated action will be required to tackle this infection. During the course of the pandemic in 2020, more than 100 million people have been infected globally to date. More than 90% of people have mild symptoms and almost 70% of the total cases at a given time have already recovered. Post recovery weakness, reduced work capacity, and shortness of breath have been seen for prolonged periods in some patients due to damage caused to the lung and blood vessels. There have more than 2 million deaths globally. However, a 2nd wave of resurge of COVID cases is being seen in several parts of the globe in 2021.
It is still uncertain as to how long immunity lasts after being infected with the coronavirus. There have been cases of re-infection within 3-6 months in cases who were COVID positive with mild or no symptoms. Infection rates, transmission, and symptomatic COVID in children have been seen to be very low.
By the end of 2020, vaccines have been developed for COVID, and immunization has started in several countries.
TRANSMISSION AND SPREAD
The SARS-CoV-2 is transmitted between humans through droplets and aerosols (smaller droplets usually<5 microns) emitted from infected individuals through coughing, sneezing, spitting, or talking. One gets exposed to these droplets by coming in direct contact with infected persons, infected surfaces, and suspended droplets in the air especially when at close proximity (about 1-2 meter/ 3-6 feet) of an infected patient. How far the droplets travel depends on many factors. Aerosols being smaller and lighter travel further and remain suspended longer in the air than larger droplets, however, aerosols also have less viral load per particle and can diffuse easily. A higher force of expulsion (as in sneezing and coughing, as compared to talking or breathing out), and more wind velocity can increase the degree of droplet transmission. The virus can remain on metal surfaces, plastic, and fabric for up to 12 hours.
Every country has taken immense measures to curtail the spread of COVID-19 and limit the number of cases and deaths. Measures include restricting flights or and pre-testing flyers, limiting public transport, monitoring or closing public places and institutions, imposing periodic lockdowns and curfews, disinfecting and sanitizing common areas, and stepping up testing units and hospital facilities. However, the most important thing is for the people to follow and adhere to the advisories and recommendations of their respective governments, and take the required precautions and care without panicking.
DETECTION OF VIRUS OR ANTIGEN
These include tests that detect the genetic material of the virus NAAT (nucleic acid amplification test) and those which detect antigens or surface proteins of the virus (antigen tests). A cotton swab sample from the nose-throat and/or mouth-throat junction (nasopharyngeal and/or oropharyngeal swab) is taken to test for the presence of the virus (antigen) in an individual. A person is said to be positive if the presence of the COVID-19 virus is confirmed in the nose or throat swab sample. The following are some of the tests used:
RT-PCR (Real-time Reverse Transcription Polymerase Chain Reaction) tests work by amplifying genetic fragments of the viral RNA with the help of a process called reverse transcription (conversion to DNA). Thereafter primers are added which bind to the selected DNA sequences, along with a fluorescent probe that helps in real-time antigen detection. The Ct value (cycle threshold) can give some indication about viral load and how infective a person is. Ct values above 24 usually imply a low risk of transmission. Every affected country has set up designated testing centers and reference standard laboratories for RT-PCR testing for COVID-19. It usually takes a day for getting the test results, (3-6 hours for the test plus time for transporting and processing samples). RT-PCR has the highest sensitivity among all antigen tests and is the gold standard test for declaring a person COVID negative. Recently RT-PCR with a fast turnaround time of 6-8 hours has been introduced.
CB-NAAT (Cartridge-based Nucleic acid Amplification Test) detects the E (envelope) gene as well as the key replication enzyme RNA-dependent RNA polymerase of the virus. TrueNAT is the portable form of CB-NAAT used in labs. TrueNAT is compact and uses a cartridge and microchip. Therefore it gives faster results (in 1-2 hours), is cheaper, convenient to transport, and is very useful in interior areas, to set up kiosks, camps and drive-through testing facilities.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has recently been approved with high sensitivity and specificity (96% and 98% respectively) and uses a specially adapted Cas9 protein to successfully detect the virus. The paper-strip uses cutting-edge CRISPR gene-editing technology to identify and target this genetic material of SARS-CoV-2 and can give results in less than an hour.
Virus detection tests done by RT-PCR, CRISPR, TrueNAT, or CBNAAT are considered equivalent and do not require further confirmatory tests.
Rapid Antigen Tests (RAT) are now available, which are point-of-care tests giving results immediately. They are most economical in price and are available in the form of convenient test strip packs. The test is performed for quick and mass screening, as house-to-house testing, or in institutes, large commercial establishments, and organizations. RATs also help increase detection rates in containment zones, hot spots, and migrant clusters. RAT act by detecting the spike surface protein of the coronavirus (which facilitates its entry into human cells). RATs are less sensitive than the conventional RT-PCR and though a positive result is taken as confirmed, a negative result could be false if viral load is low or the disease stage is early, and so will need confirmation by RTPCR. If the person is symptomatic, but negative on the RAT, a conventional RT-PCR should be performed.
COVIRAP is a recently introduced rapid test in India that uses isothermal amplification techniques (IAT) as alternatives to PCR to rapidly and efficiently accumulate nucleic acid sequences at a constant temperature. The test is read with colored lines on treated paper strips dipped into the processed sample to detect the virus. It is economical, faster (under 1 hour), portable, reusable (many tests from one unit), and can be handled by relatively unskilled operators on the field. It can detect low viral loads and can be useful in early stages of infection, preventing uncontrolled spread and timely isolation. It has 94% sensitivity and 98% specificity of that of RT-PCR.
Who should be tested?
People with the presence of ILI symptoms:
When community transfer is evident, ideally all people showing any ILI symptoms should be tested for COVID. However, the below categories of people must definitely be tested when showing likely COVID symptoms.
- Had known or possible contact with a lab-confirmed COVID case
- Had contact with a person returned from international travel to a COVID affected country in the last 14 days
- Is residing in a hotspot, containment zone, or building with COVID cases
- Is a migrant and returned to home-town or village in the last 14 days
- Is hospitalized and develops ILI, or has SARI (severe acute respiratory infection)
- Is a COVID healthcare worker (HCW)/front-line worker
People without symptoms (Asymptomatic):
Recommendations for testing asymptomatic people vary depending on the area and rise in cases.
People who possibly had contact with a lab-confirmed COVID positive case and are asymptomatic should be in 14-day self-isolation to observe for symptoms. The same has also been advised to asymptomatic people who have traveled in the last 14 days to a COVID affected country (or had contact with a symptomatic person who had traveled in the last 14 days to a COVID affected country). These people are tested when they develop ILI symptoms or can get themselves tested after 3-5 days of isolation if no symptoms develop.
People living in the same household as a COVID positive case are considered high-risk contacts (HRC), and should be in strict isolation for 14 days. Direct household contacts as well as those contacts having co-morbid conditions like diabetes, hypertension, cancer, or elderly>65 years, should be tested immediately on the onset of any possible ILI symptom, or at day 5 after their COVID positive contact developed symptoms.
Health care workers handling COVID positive patients should be tested if they develop symptoms. If a healthcare worker has handled a COVID positive case without adequate protection, he/she may be tested even if asymptomatic.
Asymptomatic people are to be tested for COVID if they are due to undergo any hospital procedure or surgery. However, no emergency care should be denied to any patients on grounds of waiting for or getting positive test results. Universal precautions, personal protective equipment (PPE), isolation, and hygienic measures should be taken throughout the procedure and patient’s hospital stay.
Asymptomatic people may be screened with rapid antigen tests at public areas in hot spots or places where case-clusters, or a spurt in cases is being seen. Testing by RT-PCR is a requirement for flying to certain cities and countries.
These tests work by testing antibodies (IgM and IgG) to SARS-CoV-2 proteins in the blood (serological test).
Antibody tests used commercially test for binding antibodies against S (spike surface protein) and N (nucleocapsid protein) of the coronavirus. Two types of these antibodies may be present: IgM (denotes recent infection) or IgG (denotes past infection or vaccination). The techniques used are either ELISA or ECLIA, in which purified S/N proteins of SARS-CoV-2 inactivated virus is added to the blood sample along with detecting reagents. These are also available as rapid tests.
The other type of antibody tests used in research and in clinical trials for vaccines (but not generally approved for commercial use) test for neutralizing antibodies. These tests determine the actual functional ability of antibodies to prevent virus infection by growing the sample with the virus in laboratory cultures. These include the plaque-reduction neutralization test (PRNT) and microneutralization test (MNT).
Antibody tests may be useful for screening large population groups in areas with a high number of cases to detect the extent of disease spread, and how much population has been exposed to the virus. A positive (reactive) test, can imply both active symptomatic or asymptomatic infection, as well as past exposure and immunity, developed to the virus naturally or by vaccination.
X-ray with AI-assessment and High-Resolution Chest CT scans are also being used for the detection of COVID in several countries and are also recommended to assess disease severity and complication risk.
The risk of severe disease, complications and mortality is further assessed by an increase in levels of certain blood markers like neutrophil/lymphocyte ratio, CRP (C reactive protein), D-dimer (signifies risk of thrombosis), ferritin, lactate dehydrogenase, cardiac troponin 1 and cytokine IL-6.
Types of Coronavirus
Coronavirus is a family of viruses possessing a single-stranded RNA as the genetic material and is characterized by the presence of spiked glycoproteins on its surface. This gives these viruses the appearance of wearing a crown (or corona) and makes them distinctly identifiable under the microscope. There are many types (genera) of coronaviruses found in humans (called HCoV) as well as animals like bats, birds, and pigs. These are namely alpha, beta and gamma types. Four species namely the HCoV-229E and HCoV-NL63 (alpha type), and HCoV-OC43 and HCoV-HKU1 (beta type) coronaviruses regularly circulate in humans throughout the world and cause the common viral cold.
Sometimes the coronavirus found primarily in animals and not routinely in humans, can undergo a drastic mutation (a major change in its genetic material sequencing) into a new virus species or subspecies. It can then ‘jump’ to humans, through animals that people commonly come in contact with through food products, in wet markets, farms or in various other ways including research labs. In 2002, such an occurrence originated in Guangdong, China, and that coronavirus species was called SARS (severe acute respiratory syndrome) virus. In 2012, another outbreak happened in the Middle East, where camels were supposed to be the intermediate animals. (MERS -Middle East respiratory syndrome) virus. Both of these are beta type coronaviruses.
The Coronavirus seen first in Wuhan, Hubei province of China which started infecting humans in December 2019, is also one such novel Coronavirus labeled 2019-nCoV, and the disease it causes is called COVID -19. This sub-species has been renamed SARS-CoV-2 in February 2020.
Subtle mutations are seen continuously in such viruses as part of the virus striving to adapt for better survival. Commonly these mutations are seen in the S surface spike protein to enable better entry of the virus into the cells, and over 7000 such mutations have been seen! But a novel strain or variant is considered only when the mutation changes the character/behavior of the virus. Usually, these mutant variants or strains may be more infective but generally not more severe in the symptoms, disease or damage they cause. However, if any effect on disease outcome, severity or vaccination response is expected, these variants are called VOCs (variants of concern)
New variants have been emerging and evolving through the COVID pandemic and often these strains are designated based on where they were first seen, and the position (number) and type of mutation documented by genome sequencing tests. Some recent (late 2020-early 2021) VOCs seen are B.1.1.7 from the UK (N501Y mutation), B.1.351 from South Africa (E484K and N501Y mutation), P.1 from Brazil (K417T, E484K, N501Y mutation), B.1.427/B.1.429 from California (L452R mutation) and others like from India in March 2021 showing the E484Q and L452R double mutations, and the other with the N440K mutation. These variants are now spreading across many countries. So far research has shown that these variants are not expected to significantly affect either the course and management of COVID or the immune response to the COVID vaccines developed.
The current Coronavirus SARS-CoV-2 has shown some similarity with a virus that infects the Malaria-causing parasite Plasmodium vivax, suggesting a possible inverse link with lesser number, severity and death of COVID cases in Malaria endemic regions of the world. Similarly, a link with the immune-stimulatory and protective effect of BCG vaccine has been suggested. However, the evidence is still early and more studies and research is required and ongoing.
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