Combination anti-HIV antibodies provide sustained virological suppression.

Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)1. However, eradication of the virus in individuals with HIV has not been possible to date2. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication3. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24 weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43 weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.

Case Report: Cytomegalovirus Reactivation and Pericarditis Following ChAdOx1 nCoV-19 Vaccination Against SARS-CoV-2.

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for vaccines to protect individuals at high risk for complications and to potentially control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge about adverse events of SARS-CoV-2 vaccines during post-marketing surveillance. Varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation has already been reported in COVID-19 patients. In addition, adverse events after SARS-CoV-2 mRNA vaccination have also been in the context of varicella zoster virus (VZV) reactivation and directly associated with the mRNA vaccine. We present the first case of CMV reactivation and pericarditis in temporal association with SARS-CoV-2 vaccination, particularly adenovirus-based DNA vector vaccine ChAdOx1 nCoV-19 against SARS-CoV-2. After initiation of antiviral therapy with oral valganciclovir, CMV viremia disappeared and clinical symptoms rapidly improved. Since huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must be in place to assess vaccine safety that is important for the detection of any events. In the context of the hundreds of millions of individuals to be vaccinated against SARS-CoV-2, a potential causal association with CMV reactivation may result in a considerable number of cases with potentially severe complications.

Sequential dynamics of virological and serological changes in the serum of SARS-CoV-2 infected patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load dynamics in respiratory samples have been studied, but knowledge about changes in serial serum samples of infected patients in relation to their immunological response is lacking. We investigated the dynamics of SARS-CoV-2 viral load and antibody response in sequential serum of coronavirus disease 2019 (COVID-19) patients and attempted to culture the virus in the serum. A total of 81 sequential serum samples from 10 confirmed COVID-19 patients (5 with mild and 5 with moderate symptoms) were analyzed. Samples were collected during hospitalization and after discharge (median follow-up of 35 days). SARS-CoV-2 ribonucleic acid in the serum was detected by real-time polymerase chain reaction. Total antibody and IgG to SARS-CoV-2 Spike protein were analyzed by Chemiluminescent Immunoassays, and neutralizing antibodies were detected using a Surrogate Virus Neutralization Test. Viremia was observed in all cases at admission, and viral copy gradually dropped to undetectable levels in patients with mild symptoms but fluctuated and remained persistent in moderate cases. The viral culture of samples with the highest viral load for each patient did not show any cytopathic change. The antibody response was faster and higher in moderate cases. This study provides a basic clue for infectious severity-dependent immune response, viremia, and antibody acquisition pattern.

Probable viremia and positive placental swabs for SARS-CoV-2 in a preterm pregnant woman with mild COVID-19.

This study aimed to report a case of mild novel coronavirus disease (COVID-19) in a pregnant woman with probable viremia, as reverse transcription-polymerase chain reaction (RT-PCR) testing of endometrial and placental swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. A 26-year-old multigravida at 35 weeks 2 days of gestation, who had extensive thigh and abdominal cellulitis, tested SARS-CoV-2 positive by RT-PCR performed on samples from the endometrium and maternal side of the placenta. However, other samples (amniotic fluid, fetal side of the placenta, umbilical cord, maternal vagina, and neonatal nasopharynx) tested negative for SARS-CoV-2. This is one of the rare reports of probable SARS-CoV-2 viremia with the presence of SARS-CoV-2 in the endometrium and placenta, but not leading to vertical transmission and neonatal infection. Because knowledge about transplacental transmission and results is very limited, we conclude that more RT-PCR tests on placental and cord blood samples are needed in order to safely make definite conclusions.

Simple workflow to repurpose SARS-CoV-2 swab/serum samples for the isolation of cost-effective antibody/antigens for proteotyping applications and diagnosis.

Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)-based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry-based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone-like strategy.

SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes.

BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).

Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients.

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48-72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8-22.6] for Roche, OR 10.3 [3.6-29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13-23.57] for TFS viremia and HR = 7.09 [3.3-14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.

Impact of COVID-19 pandemic on HIV viremia: a single-center cohort study in northern Italy.

BACKGROUND: Brescia Province, northern Italy, was one of the worst epicenters of the COVID-19 pandemic. The division of infectious diseases of ASST (Azienda Socio Sanitaria Territoriale) Spedali Civili Hospital of Brescia had to face a great number of inpatients with severe COVID-19 infection and to ensure the continuum of care for almost 4000 outpatients with HIV infection actively followed by us. In a recent manuscript we described the impact of the pandemic on continuum of care in our HIV cohort expressed as number of missed visits, number of new HIV diagnosis, drop in ART (antiretroviral therapy) dispensation and number of hospitalized HIV patients due to SARS-CoV-2 infection. In this short communication, we completed the previous article with data of HIV plasmatic viremia of the same cohort before and during pandemic. METHODS: We considered all HIV-patients in stable ART for at least 6 months and with at least 1 available HIV viremia in the time window March 01-November 30, 2019, and another group of HIV patients with the same two requisites but in different time windows of the COVID-19 period (March 01-May 31, 2020, and June 01-November 30, 2020). For patients with positive viremia (PV) during COVID-19 period, we reported also the values of viral load (VL) just before and after PV. RESULTS: the percentage of patients with PV during COVID-19 period was lower than the previous year (2.8% vs 7%). Only 1% of our outpatients surely suffered from pandemic in term of loss of previous viral suppression. CONCLUSIONS: Our efforts to limit the impact of pandemic on our HIV outpatients were effective to ensure HIV continuum of care.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

SARS-CoV-2 RNA in plasma samples of COVID-19 affected individuals: a cross-sectional proof-of-concept study.

BACKGROUND: Recent studies showed that plasma SARS-CoV-2 RNA seems to be associated with worse COVID-19 outcome. However, whether specific population can be at higher risk of viremia are to date unexplored. METHODS: This cross-sectional proof-of-concept study included 41 SARS-CoV-2-positive adult individuals (six affected by haematological malignancies) hospitalized at two major hospital in Milan, for those demographic, clinical and laboratory data were available. SARS-CoV-2 load was quantified by ddPCR in paired plasma and respiratory samples. To assess significant differences between patients with and patients without viremia, Fisher exact test and Wilcoxon test were used for categorical and continuous variables, respectively. RESULTS: Plasma SARS-CoV-2 RNA was found in 8 patients (19.5%), with a median (IQR) value of 694 (209-1023) copies/mL. Viremic patients were characterized by an higher mortality rate (50.0% vs 9.1%; p = 0.018) respect to patients without viremia. Viremic patients were more frequently affected by haematological malignancies (62.5% vs. 3.0%; p < 0.001), and had higher viral load in respiratory samples (9,404,000 [586,060-10,000,000] vs 1560 [312-25,160] copies/mL; p = 0.002). CONCLUSIONS: Even if based on a small sample population, this proof-of-concept study poses the basis for an early identification of patients at higher risk of SARS-CoV-2 viremia, and therefore likely to develop severe COVID-19, and supports the need of a quantitative viral load determination in blood and respiratory samples of haematologic patients with COVID-19 in order to predict prognosis and consequently to help their further management.

SARS-CoV-2: exposure to high external doses as determinants of higher viral loads and of increased risk for COVID-19. A systematic review of the literature.

The determinants of the risk of becoming infected by SARS-CoV-2, contracting COVID-19, and being affected by the more serious forms of the disease have been generally explored in merely qualitative terms. It seems reasonable to argue that the risk patterns for COVID-19 have to be usefully studied in quantitative terms too, whenever possible applying the same approach to the relationship 'dose of the exposure vs pathological response' commonly used for chemicals and already followed for several biological agents to SARS-CoV-2, too. Such an approach is of particular relevance in the fields of both occupational epidemiology and occupational medicine, where the identification of the sources of a dangerous exposure and of the web of causation of a disease is often questionable and questioned: it is relevant when evaluating the population risk, too. Specific occupational scenarios, basically involving health workers, exhibit important proportions of both subjects simply infected by SARS-CoV-2 and of ill subjects with, respectively, mild, moderate, and severe disease. Similar patterns have been described referring to various circumstances of community exposure, e.g., standing in crowded public places, travelling on crowded means of transport, living in accommodation or care homes, living in the same household as a COVID-19 case. The hypothesis that these findings are a consequence not only of high probabilities of exposure, but also of high doses (as a product of both intensity and duration, with possible autonomous effects of peaks of exposure) deserves to be systematically tested, in order to reconstruct the web of causation of COVID-19 individual and clustered cases and to cope with situations at critical risk for SARS-CoV-2, needing to be identified, mapped, and dealt with at the right time. A limited but consistent set of papers supporting these assumptions has been traced in the literature. Under these premises, the creation of a structured inventory of both values of viral concentrations in the air (in case and if possible, of surface contaminations too) and of viral loads in biological matrixes is proposed, with the subsequent construction of a scenario-exposure matrix. A scenario-exposure matrix for SARS-CoV-2 may represent a useful tool for research and practical risk management purposes, helping to understand the possibly critical circumstances for which no direct exposure measure is available (this is an especially frequent case, in contexts of low socio-economic level) and providing guidance to determine evidence-based public health strategies.

Two prolonged viremic SARS-CoV-2 infections with conserved viral genome for two months.

We document two cases of viremic and prolonged active infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where the viral genome was conserved for two months, but infection was with little or no symptoms. The first infection persisted for 80 days and the second for 62 days. Clearance of infection occurred 40 and 41 days, respectively, after development of detectable antibodies. Both cases were identified incidentally in an investigation of reinfection in a cohort of 133,266 laboratory-confirmed infected persons.

Presence of SARS-CoV-2 RNA in the Cornea of Viremic Patients With COVID-19.

Importance: Current recommendations are to avoid tissue for corneal transplant from donors with coronavirus disease 2019 (COVID-19) or those who were recently exposed to COVID-19 owing to the lack of knowledge about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corneal tissues. Evidence of SARS-CoV-2 in corneal tissue would seem to have clinical relevance for corneal transplant. Objectives: To investigate the presence of viral SARS-CoV-2 RNA in corneal discs of deceased patients with confirmed COVID-19 and assess viral genomic and subgenomic RNA load, possible infectivity, and histologic abnormalities. Design, Setting, and Participants: A case series was conducted of 11 deceased patients with COVID-19 who underwent autopsy between March 20 and May 14, 2020. Eleven corneal discs (1 corneal disc per patient) were harvested for molecular detection of viral genomic and subgenomic RNA, virus isolation, and immunohistochemistry. The SARS-CoV-2 RNA loads were compared with RNA loads in the conjunctival and throat swab samples and aqueous humor, vitreous humor, and blood samples. Main Outcomes and Measures: Evidence of SARS-CoV-2 RNA in human corneas. Results: This study comprised 11 patients (6 women [55%]; mean [SD] age, 68.5 [18.8] years). In 6 of 11 eyes (55%), SARS-CoV-2 genomic RNA was detected in the cornea; subgenomic RNA was present in 4 of these 6 eyes (67%). Infectivity or the presence of viral structural proteins could not be confirmed in any eye. However, patients whose corneal disc was positive for SARS-CoV-2 RNA also had positive results for SARS-CoV-2 RNA in 4 of 6 conjunctival swab samples, 1 of 3 aqueous humor samples, 3 of 5 vitreous humor samples, and 4 of 5 blood samples. Overall, conjunctival swab samples had positive results for SARS-CoV-2 RNA in 5 of 11 cases. Postmortem SARS-CoV-2 viremia was detected in 5 of 9 patients. Conclusions and Relevance: Viral genomic and subgenomic RNA of SARS-CoV-2 was detected in the cornea of patients with COVID-19 viremia. The risk of COVID-19 infection via corneal transplant is low even in donors with SARS-CoV-2 viremia, but further research is necessary to assess the rate of SARS-CoV-2 transmission via corneal transplant.

SARS-CoV-2 viral load is associated with increased disease severity and mortality.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.3 years) post transplant. Five (of 6) patients required inpatient admission, 2 patients (mortality = 33%) died. Among those with mortality, an increased concentration of inflammatory biomarkers (interleukin-6 and C-reactive protein) was noted with a lack of response to interleukin-6 blockade, remdesivir, and/or convalescent plasma. None of the kidney-only transplants (4/6; 67%) had elevation in plasma donor-derived cell-free DNA above the previously published cut-off of 1%, suggesting absence of significant allo-immune injury. Four (of 5) admitted patients had detectable SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) in blood on samples obtained at/during hospitalization. Of the 4 discharged patients, 2 patients with undetectable virus on repeat nasopharyngeal swabs had seroconversion with positive SARS-CoV-2 IgG formation at 30 to 48 days post infection. One patient had prolonged shedding of virus on nasopharyngeal swab at 28 days post discharge despite lack of symptoms. In this preliminary report, we find that immunocompromised transplant patients had higher rates of RNAemia (67%) than reported in the general population (15%), seeming absence of allo-immune injury despite systemic inflammation, and formation of IgG overtime after recovery from infection.

RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4-3.2) vs. 11.8 (IQR, 9.9-13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3-12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = -3.3, 95% CI (-5.8; 0.8), p = 0.024 and ß = -4.4, 95% CI (-7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.

The pandemic COVID-19: a tale of viremia, cellular oxidation and immune dysfunction.

COVID-19, caused by SARS-CoV-2 is a tester of the immune system. While it spares the healthy, it brings severe morbidity and in a few cases, mortality to its victims. This article aims at critically reviewing the key virulence factors of COVID-19 which are the viremia, cellular oxidation and immune dysfunction. The averse economic effect of certain disease control measures such as national lock-downs and social distancing, though beneficial, makes them unsustainable. Worse still is the fact that wild animals and domestic pets are carriers of SARS-CoV-2 suggesting that the disease would take longer than expected to be eradicated globally. A better understanding of the pathological dynamics of COVID-19 would help the general populace to prepare for possible infection by the invisible enemy. While the world prospects for vaccines and therapeutic agents against the SARS-CoV-2, clinicians should also seek to modulate the immune system for optimum performance. Immunoprophylactic and immunomodulatory strategies are recommended for the different strata of stakeholders combating the pandemic with the hope that morbidities and mortalities associated with COVID-19 would be drastically reduced.