A combination of vaccination, early multiple-round overall screening, traditional Chinese medicine intervention and “treatment window forward” can reduce the proportion of severe and critical patients with SARS-CoV-2 B.1.617.2 (Delta) variant infection—Experience from the COVID-19 treatment center of Heilongjiang Province

Abstract

TO THE EDITOR Due to no new local confirmed cases and asymptomatic infected persons, the fourth outbreak of coronavirus disease 2019 (COVID-19) in Heilongjiang Province, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) B.1.617.2 (Delta) variant infection, is coming to an end. However, the source of transmission remains unknown. A total of 89 local confirmed cases were reported, including 32 mild cases, 56 moderate cases, 1 severe case and 7 asymptomatic infected persons, indicating that the proportion of severe and critical cases was significantly lower than that previously reported at home and abroad. The only severe case was relieved into a moderate case following prompt and effective treatment in intensive care unit (ICU). In addition to individual factors, a combination of vaccination, early multiple-round overall screening, traditional Chinese medicine (TCM) intervention and “treatment window forward” is summarized and contributes to reduce the proportion of severe and critical patients with Delta variant infection and thus improve the prognosis from our clinical experience, as shown in Figure 1. This method is a combination of epidemic prevention and control measures with unique Chinese characteristics, which can be available as a global reference.Figure 1.: A combination of vaccination, early multiple-round overall screening, traditional Chinese medicine intervention and “treatment window forward” reduces the proportion of severe and critical patients with Delta variant infection.VACCINATION SARS-COV-2 is rapidly mutating, giving rise to multiple variants of the initial wild-type strain, such as Alpha, Delta, Lambda and Omicron. Adaptive mutations in the SARS-COV-2 genome have attracted worldwide attention. These mutated variants have emerged in a fairly short period of time, which indicates that it is impractical and fundamentally absurd for some countries to achieve “universal immunization” through natural infection or vaccination. Although SARS-CoV-2 mutations can lead to immune and detection escape, increased transmissibility and virulence, compromised vaccination effectiveness (VE) and breakthrough infection,[1–2] the overall VE of the two-dose vaccination against the Delta variant is still within the acceptable range, which exceeds the World Health Organization (WHO) minimal threshold of 50%.[4,5] Among them, the VE against moderate and severe COVID-19 was higher and estimated to 70.2% and 100%, respectively.[5] In addition, a third-dose boost may be a promising solution to combat SARS-CoV-2 mutations.[6] Furthermore, vaccines are highly effective in attenuating viral RNA load, reducing risk of febrile symptoms, speeding up the elimination of virus-infected cells, shortening the duration of illness, improving disease severity and preventing COVID-19-related death among those who have breakthrough infection despite vaccination.[7–8] Lastly, with the continuous in-depth understanding of the pathogenesis of SARS-CoV-2 infections and mutations, various vaccines, such as adenovirus vector vaccines and nucleic acid vaccines, are being developed, which will make up for the deficiencies of available vaccines at this stage. Considering that SARS-CoV-2 may pose a persistent threat to public health for a considerable time to come, a high rate of vaccination will be the most effective measure to prevent the recurrence of COVID-19 in the future, especially in high-risk populations. At present, China has completed more than 3432.506 million doses of vaccination against SARS-CoV-2, covering over 89.7% of the total population, which is an impressive achievement that is unmatched by other countries in the world. During the fourth outbreak of COVID-19 in Heilongjiang Province, a high rate of vaccination played an important role in preventing the spread of the epidemic and alleviating disease severity. EARLY MULTIPLE-ROUND OVERALL SCREENING COVID-19 is currently confirmed by real-time polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 nucleic acid on oropharyngeal and/or nasopharyngeal swabs, which remains the preferred method for large-scale overall screening despite the potential for false-positive and false-negative results.[10,11] COVID-19 cases confirmed following multiple rounds of negative SARS-CoV-2 nucleic acid results are common in clinical practice.[12,13] Lung computed tomography (CT), ultrasound and fluorodeoxyglucose-positron emission tomography/CT scans can be used as valuable auxiliary methods for the diagnosis of COVID-19.[14,15] However, they are only suitable for screening, diagnosis and evaluation of therapeutic effects among in-hospital patients, outpatients and high-risk populations, but not suitable for large-scale overall screening. Screening should prioritize test frequency and sample-to-answer time rather than test sensitivity, since the improvement in the latter can only slightly improve the screening effect.[16] Therefore, within 18 days after the outbreak of the epidemic, all personnel in Harbin city completed 7 rounds of SARS-CoV-2 nucleic acid testing, with a cumulative report of more than 56 million person-times. Certainly, the frequency of screening was also closely related to the severity of the epidemic, with the first four rounds of overall screening conducted every other day in the early stage of this outbreak. At present, the epidemic situation in China is characterized by sporadic confirmed cases in local areas and occasional cluster outbreaks, most of which are related to confirmed cases imported from abroad.[17] Early multiple-round overall screening facilitates early detection of COVID-19 patients, especially asymptomatic infected persons, isolation of close contacts, closure of high-risk sites and cut-off of transmission routes. Therefore, it is an important measure to contain the spread of the epidemic and initiate relevant treatment as early as possible. It is expected that more accurate and rapid diagnostic methods or more cost-effective strategies will be adopted to replace the current RT-PCR test for future overall screening of SARS-CoV-2 in large populations.[18,19] TRADITIONAL CHINESE MEDICINE INTERVENTION To date, there is no effective antiviral drug available for SARS-CoV-2 infection and even short-term corticosteroid treatment, which has been recommended in the Diagnosis and Treatment of New Coronavirus Pneumonia (the seventh edition), is controversial.[20–21] The lack of satisfactory western medicines for COVID-19 has led to the application of TCM as a potential treatment alternative.[23] It is the core of TCM intervention to explore the etiologies of patients according to the clinical symptoms, and then subsequent treatments are provided based on syndrome differentiation. The common characteristics of patients with Delta variant infection are blazing toxin, phlegm dampness and qi deficiency. The pathogenic mechanism of Delta variant infection is the coexistence of dampness, cold and toxicity and belongs to dampness-cold pathogen, namely the blazing toxin pattern in the theory of TCM. The treatment concept of TCM intervention to prevent occurrence of disease prior to onset, disease progression following onset and recurrence after recovery is especially applicable to the prevention and treatment of COVID-19 patients. It was found that TCM could exert antiviral, anti-inflammatory, immunomodulatory and organ protective activities against SARS-CoV-2 invasion by interacting with multiple targets through multiple pathways.[24–25] The role of TCM not only stays in theory, but also embodies in clinical therapeutic effects. Western medicine combined with Lianhua Qingwen granules indicated apparent clinical advantages for COVID-19 patients in symptoms, overall response rate, cure rate, severity illness rate, hospital stay and prognosis, without increasing adverse drug reactions.[27,28] Several similar studies have been conducted on other TCM applications. Therefore, all adult patients in the COVID-19 treatment center of Heilongjiang Province received Lianhua Qingwen granules and/or Fuzheng Qingwen mixture, while pediatric patients received Huatan Qingfei powder. Eventually, the integrated TCM and western medicine achieved optimal therapeutic effects. In addition, COVID-19 patients were instructed to practice Baduanjin and/or Taijiquan with physical permission for early rehabilitation in order to relieve anxiety and promote physical and mental recovery, which exhibited unique Chinese characteristics. TREATMENT WINDOW FORWARD Early multiple-round overall screening is the premise of early detection of COVID-19 patients and initiation of treatment, and also the prerequisite for “treatment window forward”. The latter suggests that the management of SARS-CoV-2 infection should not be just a passive defense, but should be advanced in the timing of treatment, including early conditioning of TCM for patients without significant clinical symptoms and apparent lung imaging changes, early implementation of conscious prone positioning for patients with mild lung imaging changes and early infusion of convalescent plasma for patients with low serum immunoglobulin G (IgG) and deterioration trend. In particular, close attention should be paid to COVID-19 patients with high-risk factors, such as advanced age, obesity, comorbidities, low lymphocyte count, T lymphocyte subsets and lymphocyte–C-reactive protein ratio (LCR) at admission.[29–30] In these patients, disease deterioration can sometimes be very rapid, without apparent stage of disease progression. In addition, individualized treatment strategy should also be implemented in COVID-19 patients due to “one size does not fit all”. In conclusion, in the absence of available specific drugs against SARS-CoV-2 infection, it is imperative to find ways to reduce the proportion of severe and critical patients in order to improve prognosis. In this study, a combination of vaccination, early multiple-round overall screening, TCM intervention and “treatment window forward” was proposed to achieve above goal from our clinical experience in the COVID-19 treatment center of Heilongjiang Province, which has unique Chinese characteristics and can be used for reference by the world.