Introduction:
The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus causes COVID-19 (coronavirus) disease. Coronaviruses cause illnesses that vary from the common cold to more severe conditions such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The novel coronavirus disease (COVID-19) is also known as 2019-nCoV, and the virus is transmitted via respiratory droplets (cough or sneezing) and when in close proximity with infected persons. For this reason, the World Health Organization declared a pandemic on March 11, 2020, and declared a health emergency worldwide. Many patients show the clinical symptoms of COVID-19, but when tested multiple times, the test results were negative for the virus, and after repeated tests, they were confirmed positive. Recently health professionals have been informed to start with the treatment when the infected individuals begin to show the symptoms of the disease, which can help people from more severe conditions leading to death. At present, we are in the sixth wave of COVID infections driven by the Delta and Omicron BA.2 variants. Multiple mutations in the coronavirus structure over the last few months are making parts of it unrecognizable to lab tests.
Why Do Some COVID-19 Patients Test Negative and Show Symptoms?
The Government wants to retest symptomatic individuals who had shown negative for the virus in their test reports. The COVID-19 cases can be missed for a variety of reasons, such as:
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Improper sample collection.
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Problem with the sample device.
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A positive individual is not shedding the virus yet.
The false negatives are confirmed positive to COVID-19 after multiple testing. The significant cause for retesting is the prompt diagnosis, early management to prevent disease to more severe conditions. The healthcare professionals want to start the treatment when they present the clinical symptoms and before the confirmatory tests arrive. It is important to treat people with symptoms of coronavirus even though they are tested negative as it may be risky for the patients and it increases community transmissions. The recent findings in patients said by the government doctors on COVID-19 duty are:
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Swab negative.
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Clinical symptoms of COVID-19 present.
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Clinical findings of COVID-19 in CT scans.
These patients are not officially added as COVID-19 cases, so one test-based diagnosis is not worthy. During the first and second waves 40 percent of patients admitted in the hospitals were under this category and were treated for suspected COVID-19 symptoms. Because of this condition, the hospital wards were full, and there was no sufficient space to admit and treat the infected individuals. For this reason, a single test is not sufficient, and we should look up for all the below:
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COVID-19 symptoms.
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Doctor's suggestion for the symptoms.
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CT (computed tomography) scan reports.
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X-ray reports.
How Can COVID-19 Be Diagnosed?
The diagnostic tests to confirm the presence of coronavirus are:
- RT-PCR Test (Reverse-Transcription PCR) - This test is also called a swab test, and it is considered the standard gold test as it has a sensitivity of only percent It is the most sensitive test, and it helps to identify the active infection in the body. Sometimes, there is a possibility for 25 percent false negative and false positive with RT-PCR testing. RT-PCR test undergoes a laboratory process, and the results are obtained after two days.
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Antigen Test - It can be taken within a short time but is more vulnerable to false negatives. The antigen test has a sensitivity of only 40 percent. If it is tested positive, then a confirmatory RT-PCR test is not needed.
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Antibody Test - It tests only the past infection, and it does not help in the early stages of the disease and shows the antibodies of the SARS-CoV-2 virus. The antibody tests have a sensitivity of 90 percent.
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Rapid ID Now Test - Rapid ID now test is also used to diagnose COVID-19 disease, and the results are obtained within 15 minutes, but it is not as accurate as RT-PCR testing. With the recent information, individuals tested with this rapid ID are confirmed with COVID-19 by experimenting with different methods. More false negatives tests can be observed during the fifth and the sixth wave, which has led to conclusion that the tests may not perform well against the Omicron and BA.2 variants.
As there are several false negatives for the COVID-19 disease, the healthcare professionals say that CT (computed tomography) scan reports and clinical symptoms are now an important factor for the treatment as many patients will be misdiagnosed when we depend on the above tests. As there are many false negatives and to improve the efficiency of the treatment, do not wait for the test reports to prevent the progression of the disease. Some doctors have also confirmed the disease based on COVID-19 symptoms and CT scan reports. Two to three percent of patients are tested negative for COVID-19 but have clear CT scan findings. Findings in CT scans are considered COVID-19 positive and are treated accordingly. RT-PCR tests (swab test) have 70 percent sensitivity and also have false negatives. The Indian Council of Medical Research says that COVID countings are added only when these RT-PCR tests show positive, and the considered COVID positive patients with CT scan reports are added in the category of suspected symptoms of COVID-19.
What Are the Reasons for False Negatives?
After the virus enters the body, it enters the cells. The virus interrupts the typical work pattern of the cells in the body and interrupts the operating instructions. Thus by interrupting the cell's normal function, the virus multiplies, affecting each cell. After the infection, it takes about three to five days for this affected cell to multiply and make copies to be diagnosed on the regular COVID-19 test. When a person is shedding the virus within a short time, known as the window period, and during this period, there are not enough viruses in the body to be detected by a rapid test. When a person is tested during this window period, then it will result in a false negative. Based on the available tests, the sensitivity is not 100 percent for any COVID tests. Of the available COVID-19 tests, 70 pwecent sensitivity is high, which means that nearly one-third of patients with the virus will receive a false-negative result. The PCR tests are more accurate among the COVID-19 tests and miss only 30 percent of COVID-19 cases. The Omicron variant has mutations on the S-gene that codes for the spike protein and it might not be detected by some laboratory tests. Patients with COVID-19 symptoms who received negative test results were hospitalized, and these patients received a positive test result later. Many experts have said that the COVID tests will not detect coronavirus during the early days after a person has first been exposed to a pathogen. It takes about three to five days for a test to detect the infection after the exposure.
The negative test that occurs in persons with known SARS-CoV-2 exposuresuggests no current evidence of infection, and these results could change when the same test is performed again after one or more days.
- If there is a negative result in unvaccinated individuals, they should continue to quarantine for 14 days.
- Based on evolving evidence, people who are fully vaccinated should be tested five to seven days after their last exposure or after close contact with the COVID-19 confirmed or suspected person.
In addition, an at-home rapid test could show incorrect results if the swab is not circulated or inserted far enough into the nasal cavity.
Remember that a COVID-19 test would not detect other viruses like the flu or a respiratory syncytial virus (RSV) in an individual who tests negative for COVID-19 but still manifests symptoms.
Negative testresults in people with no known exposure or without symptoms suggest no infection. Regardless of results, all persons being tested should receive counseling on the continuation of risk reduction behaviors such as wearing masks, avoiding crowds, physical distancing, etc., that help prevent the transmission of SARS-CoV-2.
Conclusion:
The negative results may not be what we think. Patients with clinical symptoms of COVID-19, CT scans showing atypical pneumonia, are suggestive of COVID-19 disease but were tested negative for three to four RT-PCR tests. Then they were found with antibodies against coronavirus, indicating the COVID infection. Thus, if the patients have COVID symptoms, more importantly when seen in older people, they should be treated immediately for COVID-19 without waiting for the test results. The Centers for Disease Control and Prevention (CDC) says that even though people are tested negative, it does not mean the virus has not infected them, and they should follow the guidelines, such as continue to practice social distancing, temperature checks, quarantining for at least 14 days, hand sanitizing, and wearing masks help the spread of the disease. When someone test negative one day, it does not mean they will not contact the new coronavirus the next. So people who tested negative should continue to follow the COVID-19 protocols.